ID   FA8_HUMAN               Reviewed;        2351 AA.
AC   P00451;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   10-JUN-2008, entry version 131.
DE   Coagulation factor VIII precursor (Procoagulant component)
DE   (Antihemophilic factor) (AHF) [Contains: Factor VIIIa heavy chain, 200
DE   kDa isoform; Factor VIIIa heavy chain, 92 kDa isoform; Factor VIII B
DE   chain; Factor VIIIa light chain].
GN   Name=F8; Synonyms=F8C;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=86081164; PubMed=3935400;
RA   Truett M.A., Blacher R., Burke R.L., Caput D., Chu C., Dina D.,
RA   Hartog K., Kuo C.H., Masiarz F.R., Merryweather J.P., Najarian R.,
RA   Pachl C., Potter S.J., Puma J., Quiroga M., Rall L.B., Randolph A.,
RA   Urdea M.S., Valenzuela P., Dahl H.-H.M., Favalaro J., Hansen J.,
RA   Nordfang O., Ezban M.;
RT   "Characterization of the polypeptide composition of human factor
RT   VIII:C and the nucleotide sequence and expression of the human kidney
RT   cDNA.";
RL   DNA 4:333-349(1985).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=85061548; PubMed=6438526; DOI=10.1038/312330a0;
RA   Wood W.I., Capon D.J., Simonsen C.C., Eaton D.L., Gitschier J.,
RA   Keyt B., Seeburg P.H., Smith D.H., Hollingshead P., Wion K.L.,
RA   Delwart E., Tuddenham E.G.D., Vehar G.A., Lawn R.M.;
RT   "Expression of active human factor VIII from recombinant DNA clones.";
RL   Nature 312:330-337(1984).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=85061550; PubMed=6438528; DOI=10.1038/312342a0;
RA   Toole J.J., Knopf J.L., Wozney J.M., Sultzman L.A., Buecker J.L.,
RA   Pittman D.D., Kaufman R.J., Brown E., Shoemaker C., Orr E.C.,
RA   Amphlett G.W., Foster W.B., Coe M.L., Knutson G.J., Fass D.N.,
RA   Hewick R.M.;
RT   "Molecular cloning of a cDNA encoding human antihaemophilic factor.";
RL   Nature 312:342-347(1984).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=93265012; PubMed=1303178; DOI=10.1093/hmg/1.3.199;
RA   Gitschier J., Wood W.I.;
RT   "Sequence of the exon-containing regions of the human factor VIII
RT   gene.";
RL   Hum. Mol. Genet. 1:199-200(1992).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLU-1260 AND VAL-2257.
RG   SeattleSNPs program for genomic applications;
RL   Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 2064-2070.
RA   de Water N.S., Williams R., Browett P.J.;
RT   "Factor VIII gene normal intron 20 sequence.";
RL   Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   PROTEIN SEQUENCE OF 356-378; 727-752 AND 1672-1708, MASS SPECTROMETRY,
RP   AND SULFATION AT TYR-365; TYR-737; TYR-738; TYR-742; TYR-1683 AND
RP   TYR-1699.
RX   PubMed=10368977;
RX   DOI=10.1002/(SICI)1097-0231(19990615)13:11<1016::AID-RCM599>3.0.CO;2-5;
RA   Severs J.C., Carnine M., Eguizabal H., Mock K.K.;
RT   "Characterization of tyrosine sulfate residues in antihemophilic
RT   recombinant factor VIII by liquid chromatography electrospray
RT   ionization tandem mass spectrometry and amino acid analysis.";
RL   Rapid Commun. Mass Spectrom. 13:1016-1023(1999).
RN   [8]
RP   SULFATION AT TYR-1699.
RX   MEDLINE=91093266; PubMed=1898735;
RA   Leyte A., van Schijndel H.B., Niehrs C., Huttner W.B., Verbeet M.P.,
RA   Mertens K., van Mourik J.A.;
RT   "Sulfation of Tyr1680 of human blood coagulation factor VIII is
RT   essential for the interaction of factor VIII with von Willebrand
RT   factor.";
RL   J. Biol. Chem. 266:740-746(1991).
RN   [9]
RP   SULFATION AT TYR-365; TYR-1683 AND TYR-1699, AND INTERACTION WITH VWF.
RX   MEDLINE=92207952; PubMed=1554716; DOI=10.1021/bi00128a003;
RA   Pittman D.D., Wang J.H., Kaufman R.J.;
RT   "Identification and functional importance of tyrosine sulfate residues
RT   within recombinant factor VIII.";
RL   Biochemistry 31:3315-3325(1992).
RN   [10]
RP   INTERACTION WITH VWF.
RX   PubMed=9218428; DOI=10.1074/jbc.272.29.18007;
RA   Saenko E.L., Scandella D.;
RT   "The acidic region of the factor VIII light chain and the C2 domain
RT   together form the high affinity binding site for von Willebrand
RT   factor.";
RL   J. Biol. Chem. 272:18007-18014(1997).
RN   [11]
RP   DISULFIDE BONDS.
RX   MEDLINE=95338127; PubMed=7613471;
RA   McMullen B.A., Fujikawa K., Davie E.W., Hedner U., Ezban M.;
RT   "Locations of disulfide bonds and free cysteines in the heavy and
RT   light chains of recombinant human factor VIII (antihemophilic factor
RT   A).";
RL   Protein Sci. 4:740-746(1995).
RN   [12]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-601, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Plasma;
RX   PubMed=16335952; DOI=10.1021/pr0502065;
RA   Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA   Moore R.J., Smith R.D.;
RT   "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT   hydrazide chemistry, and mass spectrometry.";
RL   J. Proteome Res. 4:2070-2080(2005).
RN   [13]
RP   STRUCTURE BY NMR OF 2322-2343.
RX   MEDLINE=95200924; PubMed=7893714; DOI=10.1021/bi00009a033;
RA   Gilbert G.E., Baleja J.D.;
RT   "Membrane-binding peptide from the C2 domain of factor VIII forms an
RT   amphipathic structure as determined by NMR spectroscopy.";
RL   Biochemistry 34:3022-3031(1995).
RN   [14]
RP   REVIEW ON MOLECULAR BASIS OF HEMA.
RX   MEDLINE=91221499; PubMed=1902642;
RA   Gitschier J.;
RT   "The molecular basis of hemophilia A.";
RL   Ann. N. Y. Acad. Sci. 614:89-96(1991).
RN   [15]
RP   REVIEW ON MOLECULAR BASIS OF HEMA.
RX   MEDLINE=89088506; PubMed=2491949;
RA   White G.C. II, Shoemaker C.B.;
RT   "Factor VIII gene and hemophilia A.";
RL   Blood 73:1-12(1989).
RN   [16]
RP   REVIEW ON MOLECULAR BASIS OF HEMA.
RX   MEDLINE=95245332; PubMed=7728145;
RA   Antonarakis S.E., Kazazian H.H. Jr., Tuddenham E.G.D.;
RT   "Molecular etiology of factor VIII deficiency in hemophilia A.";
RL   Hum. Mutat. 5:1-22(1995).
RN   [17]
RP   VARIANT HEMA GLN-2326.
RX   MEDLINE=86235434; PubMed=3012775;
RA   Gitschier J., Wood W.I., Shuman M.A., Lawn R.M.;
RT   "Identification of a missense mutation in the factor VIII gene of a
RT   mild hemophiliac.";
RL   Science 232:1415-1416(1986).
RN   [18]
RP   VARIANT HEMA PRO-2135.
RX   MEDLINE=88096539; PubMed=3122181; DOI=10.1093/nar/15.23.9797;
RA   Levinson B., Janco R.L., Phillips J.A. III, Gitschier J.;
RT   "A novel missense mutation in the factor VIII gene identified by
RT   analysis of amplified hemophilia DNA sequences.";
RL   Nucleic Acids Res. 15:9797-9805(1987).
RN   [19]
RP   VARIANT HEMA GLN-2228.
RX   MEDLINE=88191889; PubMed=2833855;
RA   Youssoufian H., Antonarakis S.E., Bell W., Griffin A.M.,
RA   Kazazian H.H. Jr.;
RT   "Nonsense and missense mutations in hemophilia A: estimate of the
RT   relative mutation rate at CG dinucleotides.";
RL   Am. J. Hum. Genet. 42:718-725(1988).
RN   [20]
RP   VARIANT HEMA GLY-291.
RX   MEDLINE=88220354; PubMed=2835904;
RA   Youssoufian H., Wong C., Aronis S., Platokoukis H., Kazazian H.H. Jr.,
RA   Antonarakis S.E.;
RT   "Moderately severe hemophilia A resulting from Glu-->Gly substitution
RT   in exon 7 of the factor VIII gene.";
RL   Am. J. Hum. Genet. 42:867-871(1988).
RN   [21]
RP   VARIANT HEMA CYS-1708.
RX   MEDLINE=89274393; PubMed=2499363;
RA   O'Brien D.P., Tuddenham E.G.;
RT   "Purification and characterization of factor VIII 1,689-Cys: a
RT   nonfunctional cofactor occurring in a patient with severe hemophilia
RT   A.";
RL   Blood 73:2117-2122(1989).
RN   [22]
RP   VARIANT HEMA CYS-391.
RX   MEDLINE=90001543; PubMed=2506948;
RA   Shima M., Ware J., Yoshioka A., Fukui H., Fulcher C.A.;
RT   "An arginine to cysteine amino acid substitution at a critical
RT   thrombin cleavage site in a dysfunctional factor VIII molecule.";
RL   Blood 74:1612-1617(1989).
RN   [23]
RP   VARIANT HEMA LEU-189.
RX   MEDLINE=90057680; PubMed=2510835;
RA   Chan V., Chan T.K., Tong T.M., Todd D.;
RT   "A novel missense mutation in exon 4 of the factor VIII:C gene
RT   resulting in moderately severe hemophilia A.";
RL   Blood 74:2688-2691(1989).
RN   [24]
RP   VARIANT HEMA LEU-2326.
RX   MEDLINE=89197216; PubMed=2495245; DOI=10.1007/BF00283686;
RA   Inaba H., Fujimaki M., Kazazian H.H. Jr., Antonarakis S.E.;
RT   "Mild hemophilia A resulting from Arg-to-Leu substitution in exon 26
RT   of the factor VIII gene.";
RL   Hum. Genet. 81:335-338(1989).
RN   [25]
RP   VARIANT HEMA HIS-391.
RX   MEDLINE=89264602; PubMed=2498882;
RA   Arai M., Inaba H., Higuchi M., Antonarakis S.E., Kazazian H.H. Jr.,
RA   Fujimaki M., Hoyer L.W.;
RT   "Direct characterization of factor VIII in plasma: detection of a
RT   mutation altering a thrombin cleavage site (arginine-
RT   372-->histidine).";
RL   Proc. Natl. Acad. Sci. U.S.A. 86:4277-4281(1989).
RN   [26]
RP   VARIANT HEMA CYS-1708.
RX   MEDLINE=90105723; PubMed=2104766;
RA   Arai M., Higuchi M., Antonarakis S.E., Kazazian H.H. Jr.,
RA   Phillips J.A. III, Janco R.L., Hoyer L.W.;
RT   "Characterization of a thrombin cleavage site mutation (Arg 1689 to
RT   Cys) in the factor VIII gene of two unrelated patients with cross-
RT   reacting material-positive hemophilia A.";
RL   Blood 75:384-389(1990).
RN   [27]
RP   VARIANTS HEMA GLN-2228 AND LEU-2326.
RX   MEDLINE=90123183; PubMed=2105106;
RA   Casula L., Murru S., Pecorara M., Ristaldi M.S., Restagno G.,
RA   Mancuso G., Morfini M., de Biasi R., Baudo F., Carbonara A.;
RT   "Recurrent mutations and three novel rearrangements in the factor VIII
RT   gene of hemophilia A patients of Italian descent.";
RL   Blood 75:662-670(1990).
RN   [28]
RP   VARIANT HEMA CYS-391.
RX   MEDLINE=90329422; PubMed=1973901;
RA   Pattinson J.K., McVey J.H., Boon M., Ajani A., Tuddenham E.G.;
RT   "CRM+ haemophilia A due to a missense mutation (372-->Cys) at the
RT   internal heavy chain thrombin cleavage site.";
RL   Br. J. Haematol. 75:73-77(1990).
RN   [29]
RP   VARIANTS HEMA PHE-1699 AND CYS-1708.
RX   MEDLINE=90152691; PubMed=2105906; DOI=10.1016/0888-7543(90)90448-4;
RA   Higuchi M., Wong C., Kochhan L., Olek K., Aronis S., Kasper C.K.,
RA   Kazazian H.H. Jr., Antonarakis S.E.;
RT   "Characterization of mutations in the factor VIII gene by direct
RT   sequencing of amplified genomic DNA.";
RL   Genomics 6:65-71(1990).
RN   [30]
RP   VARIANTS HEMA CYS-1728 AND ASP-1941.
RX   MEDLINE=90169988; PubMed=2106480; DOI=10.1016/0888-7543(90)90569-G;
RA   Traystman M.D., Higuchi M., Kasper C.K., Antonarakis S.E.,
RA   Kazazian H.H. Jr.;
RT   "Use of denaturing gradient gel electrophoresis to detect point
RT   mutations in the factor VIII gene.";
RL   Genomics 6:293-301(1990).
RN   [31]
RP   VARIANTS HEMA LEU-345 AND ARG-348.
RX   MEDLINE=90192753; PubMed=2107542;
RA   Kogan S., Gitschier J.;
RT   "Mutations and a polymorphism in the factor VIII gene discovered by
RT   denaturing gradient gel electrophoresis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:2092-2096(1990).
RN   [32]
RP   VARIANTS HEMA LYS-1723 AND SER-2319.
RX   MEDLINE=91348684; PubMed=1908817; DOI=10.1007/BF00197155;
RA   Paynton C., Sarkar G., Sommer S.S.;
RT   "Identification of mutations in two families with sporadic hemophilia
RT   A.";
RL   Hum. Genet. 87:397-400(1991).
RN   [33]
RP   VARIANTS HEMA THR-108; VAL-110; GLY-285; HIS-301; SER-312; ARG-444;
RP   HIS-492; GLY-561; CYS-612; THR-723; PHE-1699; HIS-1800; TYR-1803;
RP   ASP-1941; SER-1941; HIS-2169; GLN-2228 AND CYS-2323.
RX   MEDLINE=91334474; PubMed=1908096;
RA   Higuchi M., Kazazian H.H. Jr., Kasch L., Warren T.C., McGinniss M.J.,
RA   Phillips J.A. III, Kasper C., Janco R., Antonarakis S.E.;
RT   "Molecular characterization of severe hemophilia A suggests that about
RT   half the mutations are not within the coding regions and splice
RT   junctions of the factor VIII gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:7405-7409(1991).
RN   [34]
RP   VARIANTS.
RX   MEDLINE=92020842; PubMed=1924291;
RA   Higuchi M., Antonarakis S.E., Kasch L., Oldenburg J.,
RA   Economou-Petersen E., Olek K., Arai M., Inaba H., Kazazian H.H. Jr.;
RT   "Molecular characterization of mild-to-moderate hemophilia A:
RT   detection of the mutation in 25 of 29 patients by denaturing gradient
RT   gel electrophoresis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:8307-8311(1991).
RN   [35]
RP   VARIANTS HEMA CYS-1708 AND HIS-1708.
RX   MEDLINE=91228147; PubMed=1851341; DOI=10.1016/0049-3848(91)90098-H;
RA   Schwaab R., Ludwig M., Kochhan L., Oldenburg J., McVey J.H., Egli H.,
RA   Brackmann H.H., Olek K.;
RT   "Detection and characterisation of two missense mutations at a
RT   cleavage site in the factor VIII light chain.";
RL   Thromb. Res. 61:225-234(1991).
RN   [36]
RP   VARIANTS HEMA LYS-291 AND GLN-1960.
RX   PubMed=1356412;
RA   Krepelova A., Vorlova Z., Acquila M., Mori P.;
RT   "GAA(Glu)272->AAA(Lys) and CGA(Arg)1941->CAA(Gln) in the factor VIII
RT   gene in two haemophilia A patients of Czech origin.";
RL   Br. J. Haematol. 81:458-458(1992).
RN   [37]
RP   VARIANTS HEMA PRO-1845 AND PRO-2224 DEL.
RX   MEDLINE=92347913; PubMed=1639429; DOI=10.1016/0888-7543(92)90189-Y;
RA   Economou E.P., Kazazian H.H. Jr., Antonarakis S.E.;
RT   "Detection of mutations in the factor VIII gene using single-stranded
RT   conformational polymorphism (SSCP).";
RL   Genomics 13:909-911(1992).
RN   [38]
RP   VARIANT HEMA GLY-1715.
RX   MEDLINE=92250024; PubMed=1349567; DOI=10.1007/BF00207049;
RA   Reiner A.P., Thompson A.R.;
RT   "Screening for nonsense mutations in patients with severe hemophilia A
RT   can provide rapid, direct carrier detection.";
RL   Hum. Genet. 89:88-94(1992).
RN   [39]
RP   VARIANT HEMA LEU-1960.
RX   MEDLINE=93244837; PubMed=1301194;
RA   Nafa K., Baudis M., Deburgrave N., Bardin J.M., Sultan Y.,
RA   Kaplan J.C., Delpech M.;
RT   "A novel mutation (Arg-->Leu in exon 18) in factor VIII gene
RT   responsible for moderate hemophilia A.";
RL   Hum. Mutat. 1:77-78(1992).
RN   [40]
RP   VARIANTS HEMA VAL-30; VAL-89; VAL-92; ASP-104; VAL-164; MET-181;
RP   CYS-550; GLY-554; CYS-612; TRP-717; PHE-1808; SER-1941; ARG-2065;
RP   HIS-2169; CYS-2178 AND CYS-2248.
RX   MEDLINE=93250816; PubMed=1301932;
RA   Diamond C., Kogan S., Levinson B., Gitschier J.;
RT   "Amino acid substitutions in conserved domains of factor VIII and
RT   related proteins: study of patients with mild and moderately severe
RT   hemophilia A.";
RL   Hum. Mutat. 1:248-257(1992).
RN   [41]
RP   VARIANTS HEMA CYS-1800 AND ILE-2173.
RX   MEDLINE=93250855; PubMed=1301960;
RA   Jonsdottir S., Diamond C., Levinson B., Magnusson S., Jensson O.,
RA   Gitschier J.;
RT   "Missense mutations causing mild hemophilia A in Iceland detected by
RT   denaturing gradient gel electrophoresis.";
RL   Hum. Mutat. 1:506-508(1992).
RN   [42]
RP   VARIANTS HEMA LEU-308; HIS-391; TRP-546; PHE-577; ALA-653; MET-653;
RP   PHE-671 DEL; LYS-1460 AND CYS-2178.
RX   MEDLINE=93194188; PubMed=8449505; DOI=10.1006/geno.1993.1073;
RA   McGinniss M.J., Kazazian H.H. Jr., Hoyer L.W., Bi L., Inaba H.,
RA   Antonarakis S.E.;
RT   "Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A.";
RL   Genomics 15:392-398(1993).
RN   [43]
RP   VARIANTS HEMA ILE-299 AND ASN-450.
RX   MEDLINE=93310754; PubMed=8322269;
RA   Pieneman W.C., Reitsma P.H., Briet E.;
RT   "Double strand conformation polymorphism (DSCP) detects two point
RT   mutations at codon 280 (AAC-->ATC) and at codon 431 (TAC-->AAC) of the
RT   blood coagulation factor VIII gene.";
RL   Thromb. Haemost. 69:473-475(1993).
RN   [44]
RP   VARIANTS HEMA ARG-113; ASN-202; LEU-275; GLY-285; CYS-301; ASP-637;
RP   PHE-1808; PRO-1867; GLN-1960; HIS-2169; CYS-2178; VAL-2257 AND
RP   THR-2281.
RX   PubMed=7579394;
RA   Arruda V.R., Pieneman W.C., Reitsma P.H., Deutz-Terlouw P.P.,
RA   Annichino-Bizzacchi J.M., Brieet E., Costa F.F.;
RT   "Eleven novel mutations in the factor VIII gene from Brazilian
RT   hemophilia A patients.";
RL   Blood 86:3015-3020(1995).
RN   [45]
RP   VARIANTS HEMA HIS-217; ILE-299; ASN-450; TRP-546; CYS-612; VAL-705;
RP   CYS-1708; TRP-2016 AND ARG-2119.
RX   PubMed=7794769;
RA   Pieneman W.C., Deutz-Terlouw P.P., Reitsma P.H., Brieet E.;
RT   "Screening for mutations in haemophilia A patients by multiplex PCR-
RT   SSCP, Southern blotting and RNA analysis: the detection of a genetic
RT   abnormality in the factor VIII gene in 30 out of 35 patients.";
RL   Br. J. Haematol. 90:442-449(1995).
RN   [46]
RP   VARIANTS HEMA GLU-75; MET-181; ASP-720; THR-1853 AND ILE-1888.
RX   PubMed=7759074; DOI=10.1007/BF00223865;
RA   Bidichandani S.I., Lanyon W.G., Shiach C.R., Lowe G.D.O., Connor J.M.;
RT   "Detection of mutations in ectopic factor VIII transcripts from nine
RT   haemophilia A patients and the correlation with phenotype.";
RL   Hum. Genet. 95:531-538(1995).
RN   [47]
RP   VARIANTS HEMA ARG-26; LYS-48; ASP-89; ASP-99; VAL-101; ARG-117;
RP   GLY-135; ASP-219; ARG-278; LEU-301; GLN-302 DEL; PRO-327; PRO-659;
RP   LEU-1012; GLU-1260; CYS-1708; ASN-1865; ARG-1873; THR-1971; TRP-2016;
RP   GLN-2228; LEU-2326 AND SER-2344.
RX   PubMed=8644728;
RA   Becker J., Schwaab R., Moeller-Taube A., Schwaab U., Schmidt W.,
RA   Brackmann H.H., Grimm T., Olek K., Oldenburg J.;
RT   "Characterization of the factor VIII defect in 147 patients with
RT   sporadic hemophilia A: family studies indicate a mutation type-
RT   dependent sex ratio of mutation frequencies.";
RL   Am. J. Hum. Genet. 58:657-670(1996).
RN   [48]
RP   VARIANTS HEMA LEU-189; SER-263; ARG-947; LYS-1057; SER-1610 AND
RP   HIS-2169, AND VARIANT MET-2242.
RX   PubMed=8639447; DOI=10.1046/j.1365-2141.1996.4981042.x;
RA   Chan V., Pang A., Chan T.P.T., Chan V.W.-Y., Chan T.K.;
RT   "Molecular characterization of haemophilia A in southern Chinese.";
RL   Br. J. Haematol. 93:451-456(1996).
RN   [49]
RP   VARIANTS HEMA GLU-303; LEU-308; HIS-550; LEU-717; TRP-717 AND
RP   PHE-1951.
RX   PubMed=8759905; DOI=10.1046/j.1365-2141.1996.d01-1792.x;
RA   Rudzki Z., Duncan E.M., Casey G.J., Neumann M., Favaloro E.J.,
RA   Lloyd J.V.;
RT   "Mutations in a subgroup of patients with mild haemophilia A and a
RT   familial discrepancy between the one-stage and two-stage factor VIII:C
RT   methods.";
RL   Br. J. Haematol. 94:400-406(1996).
RN   [50]
RP   VARIANTS HEMA PRO-303; TRP-546; HIS-550 AND ILE-1966.
RX   PubMed=9029040;
RA   Mazurier C., Gaucher C., Jorieux S., Parquet-Gernez A.;
RT   "Mutations in the FVIII gene in seven families with mild haemophilia
RT   A.";
RL   Br. J. Haematol. 96:426-427(1997).
RN   [51]
RP   VARIANTS HEMA CYS-274; CYS-492; ARG-498; HIS-550; ARG-686; CYS-1708;
RP   GLN-1960; HIS-2169; CYS-2178; ALA-2264 AND VAL-2304.
RX   PubMed=9326186; DOI=10.1046/j.1365-2141.1997.2963113.x;
RA   Morichika S., Shima M., Kamisue S., Tanaka I., Imanaka Y., Suzuki H.,
RA   Shibata H., Pemberton S., Gale K., McVey J., Tuddenham E.G.D.,
RA   Yoshioka A.;
RT   "Factor VIII gene analysis in Japanese CRM-positive and CRM-reduced
RT   haemophilia A patients by single-strand conformation polymorphism.";
RL   Br. J. Haematol. 98:901-906(1997).
RN   [52]
RP   VARIANTS HEMA GLY-33; CYS-639; HIS-1800; LEU-1908 AND ARG-2106.
RX   PubMed=9341862; DOI=10.1007/s004390050543;
RA   Tavassoli K., Eigel A., Pollmann H., Horst J.;
RT   "Mutational analysis of ectopic factor VIII transcripts from
RT   hemophilia A patients: identification of cryptic splice site, exon
RT   skipping and novel point mutations.";
RL   Hum. Genet. 100:508-511(1997).
RN   [53]
RP   VARIANTS HEMA LYS-98; GLY-101; CYS-133; HIS-145; ALA-159; LYS-163;
RP   ASP-164; PRO-179; MET-181; LYS-291; ALA-297; GLU-303; SER-312;
RP   HIS-391; ILE-427; TRP-437; ASN-450; ILE-454; LEU-470; SER-541;
RP   TRP-546; CYS-550; HIS-550; PRO-553; THR-560; ALA-578; ARG-603;
RP   ILE-633; ASN-683; LEU-721; CYS-742; THR-1698; GLY-1715; ARG-1779;
RP   THR-1791; HIS-1800; ALA-1801; PHE-1901; GLN-1960; GLN-1985; ILE-2007;
RP   TRP-2016; ASP-2022; ASN-2030 AND SER-2038.
RX   PubMed=9886318; DOI=10.1046/j.1365-2141.1998.01122.x;
RA   Liu M., Murphy M.E.P., Thompson A.R.;
RT   "A domain mutations in 65 haemophilia A families and molecular
RT   modelling of dysfunctional factor VIII proteins.";
RL   Br. J. Haematol. 103:1051-1060(1998).
RN   [54]
RP   VARIANTS HEMA VAL-129; LYS-631 AND HIS-1800.
RX   MEDLINE=98111374; PubMed=9450898;
RX   DOI=10.1002/(SICI)1098-1004(1998)11:1<18::AID-HUMU3>3.3.CO;2-Z;
RA   Maugard C., Tuffery S., Aguilar-Martinez P., Schved J.-F., Gris J.-C.,
RA   Demaille J., Claustres M.;
RT   "Protein truncation test: detection of severe haemophilia a mutation
RT   and analysis of factor VIII transcripts.";
RL   Hum. Mutat. 11:18-22(1998).
RN   [55]
RP   VARIANT HEMA HIS-2182.
RX   MEDLINE=99229539; PubMed=10215414;
RX   DOI=10.1002/(SICI)1098-1004(1998)11:4<334::AID-HUMU21>3.3.CO;2-O;
RA   Theophilus B.D.M., Enayat M.S., Higuchi M., Kazazian H.H. Jr.,
RA   Antonarakis S.E., Hill F.G.H.;
RT   "Independent occurrence of the novel Arg2163 to His mutation in the
RT   factor VIII gene in three unrelated families with haemophilia A with
RT   different phenotypes.";
RL   Hum. Mutat. 11:334-334(1998).
RN   [56]
RP   VARIANTS HEMA ASP-132; PHE-253; ILE-314; VAL-331; ARG-474; ARG-498;
RP   VAL-644; VAL-699; ASP-720; PHE-727 AND ASN-2105.
RX   MEDLINE=98264603; PubMed=9603440;
RX   DOI=10.1002/(SICI)1098-1004(1998)11:6<470::AID-HUMU8>3.3.CO;2-1;
RA   Freson K., Peerlinck K., Aguirre T., Arnout J., Vermylen J.,
RA   Cassiman J.-J., Matthijs G.;
RT   "Fluorescent chemical cleavage of mismatches for efficient screening
RT   of the factor VIII gene.";
RL   Hum. Mutat. 11:470-479(1998).
RN   [57]
RP   VARIANTS HEMA GLY-550; THR-723; GLY-1894; SER-2107 AND THR-2204.
RX   MEDLINE=98112483; PubMed=9452104;
RA   Tavassoli K., Eigel A., Dworniczak B., Valtseva E., Horst J.;
RT   "Identification of four novel mutations in the factor VIII gene: three
RT   missense mutations (E1875G, G2088S, I2185T) and a 2-bp deletion
RT   (1780delTC).";
RL   Hum. Mutat. Suppl. 1:S260-S262(1998).
RN   [58]
RP   VARIANTS HEMA.
RX   MEDLINE=99006891; PubMed=9792405;
RX   DOI=10.1002/(SICI)1098-1004(1998)12:5<301::AID-HUMU2>3.3.CO;2-3;
RA   Tavassoli K., Eigel A., Wilke K., Pollmann H., Horst J.;
RT   "Molecular diagnostics of 15 hemophilia A patients: characterization
RT   of eight novel mutations in the factor VIII gene, two of which result
RT   in exon skipping.";
RL   Hum. Mutat. 12:301-303(1998).
RN   [59]
RP   VARIANTS HEMA VAL-439; CYS-1800; HIS-2169; HIS-2182 AND SER-2319.
RX   MEDLINE=99045373; PubMed=9829908;
RX   DOI=10.1002/(SICI)1098-1004(1998)12:6<393::AID-HUMU5>3.0.CO;2-A;
RA   Laprise S.L., Mak E.K., Killoran K.A., Layman L.C., Gray M.R.;
RT   "Use of denaturing gradient gel blots to screen for point mutations in
RT   the factor VIII gene.";
RL   Hum. Mutat. 12:393-402(1998).
RN   [60]
RP   VARIANTS HEMA LYS-223; VAL-2045 AND CYS-2279, AND VARIANT VAL-2257.
RX   PubMed=9569180;
RA   Williams I.J., Abuzenadah A., Winship P.R., Preston F.E., Dolan G.,
RA   Wright J., Peake I.R., Goodeve A.C.;
RT   "Precise carrier diagnosis in families with haemophilia A: use of
RT   conformation sensitive gel electrophoresis for mutation screening and
RT   polymorphism analysis.";
RL   Thromb. Haemost. 79:723-726(1998).
RN   [61]
RP   VARIANTS HEMA CYS-612; PHE-682; ARG-2028; CYS-2124; HIS-2169;
RP   HIS-2182; ASP-2200; CYS-2248 AND ILE-2279.
RX   PubMed=9569189;
RG   UK haemophilia centre directors organisation;
RA   Hay C.R.M., Ludlam C.A., Colvin B.T., Hill F.G.H., Preston F.E.,
RA   Wasseem N., Bagnall R., Peake I.R., Berntorp E.,
RA   Mauser Bunschoten E.P., Fijnvandraat K., Kasper C.K., White G.,
RA   Santagostino E.;
RT   "Factor VIII inhibitors in mild and moderate-severity haemophilia A.";
RL   Thromb. Haemost. 79:762-766(1998).
RN   [62]
RP   VARIANT HEMA LEU-1973.
RX   PubMed=10554831; DOI=10.1046/j.1365-2141.1999.01460.x;
RA   Keeling D.M., Sukhu K., Kemball-Cook G., Waseem N., Bagnall R.,
RA   Lloyd J.V.;
RT   "Diagnostic importance of the two-stage factor VIII:C assay
RT   demonstrated by a case of mild haemophilia associated with
RT   His1954-->Leu substitution in the factor VIII A3 domain.";
RL   Br. J. Haematol. 105:1123-1126(1999).
RN   [63]
RP   VARIANTS HEMA ARG-19; HIS-301; LEU-308; HIS-2169; GLN-2228 AND
RP   GLN-2326.
RX   PubMed=10338101;
RX   DOI=10.1002/(SICI)1098-1004(1999)13:5<413::AID-HUMU15>3.3.CO;2-5;
RA   Strmecki L., Benedik-Dolnicar M., Vouk K., Komel R.;
RT   "Screen of 55 Slovenian haemophilia A patients: identification of 2
RT   novel mutations (S-1R and IVS23+1G-->A) and discussion of mutation
RT   spectrum.";
RL   Hum. Mutat. 13:413-413(1999).
RN   [64]
RP   VARIANTS HEMA ARG-202 AND HIS-301.
RX   MEDLINE=99335269; PubMed=10408784;
RX   DOI=10.1002/(SICI)1098-1004(1999)13:6<504::AID-HUMU14>3.3.CO;2-0;
RA   Moeller-Morlang K., Tavassoli K., Eigel A., Pollmann H., Horst J.;
RT   "Mutational-screening in the factor VIII gene resulting in the
RT   identification of three novel mutations, one of which is a donor
RT   splice mutation.";
RL   Hum. Mutat. 13:504-504(1999).
RN   [65]
RP   VARIANTS HEMA CYS-24; ARG-26; TYR-113; SER-121; TRP-172; PRO-176;
RP   MET-181; VAL-214; THR-219; LYS-291; ALA-314; VAL-315; LYS-340;
RP   PHE-405; GLY-412; THR-470; GLU-474; ASN-478; CYS-484; GLY-490;
RP   ARG-498; TRP-546; CYS-550; HIS-561; ARG-584; THR-585; GLY-588;
RP   ASP-601; LYS-601; GLY-602; HIS-605; CYS-612; TRP-717; CYS-1708;
RP   GLN-1751; HIS-1800; CYS-1802; THR-1853; GLU-1864; PRO-1882; ILE-1888;
RP   LEU-1973; TRP-2016; ALA-2035; TYR-2040; CYS-2120; CYS-2145; HIS-2169;
RP   CYS-2178; HIS-2182; VAL-2183; VAL-2198; CYS-2248 AND GLY-2326.
RX   PubMed=10404764;
RG   The haemophilia centres;
RA   Waseem N.H., Bagnall R., Green P.M., Giannelli F.;
RT   "Start of UK confidential haemophilia A database: analysis of 142
RT   patients by solid phase fluorescent chemical cleavage of mismatch.";
RL   Thromb. Haemost. 81:900-905(1999).
RN   [66]
RP   VARIANTS HEMA SER-2117; TYR-2138; SER-2148; HIS-2169 AND GLN-2172, AND
RP   CHARACTERIZATION OF VARIANTS HEMA SER-2117; TYR-2138 AND HIS-2169.
RX   PubMed=10910910;
RA   Jacquemin M., Lavend'homme R., Benhida A., Vanzieleghem B.,
RA   d'Oiron R., Lavergne J.-M., Brackmann H.H., Schwaab R.,
RA   VandenDriessche T., Chuah M.K.L., Hoylaerts M., Gilles J.G.G.,
RA   Peerlinck K., Vermylen J., Saint-Remy J.-M.R.;
RT   "A novel cause of mild/moderate hemophilia A: mutations scattered in
RT   the factor VIII C1 domain reduce factor VIII binding to von Willebrand
RT   factor.";
RL   Blood 96:958-965(2000).
RN   [67]
RP   VARIANTS HEMA GLU-2106; CYS-2109; CYS-2169; CYS-2178; CYS-2182;
RP   ARG-2183; ILE-2192; PRO-2220; ALA-2251; LEU-2319; CYS-2323; GLY-2323;
RP   GLN-2326 AND THR-2339.
RX   PubMed=10910913;
RA   Liu M.-L., Shen B.W., Nakaya S., Pratt K.P., Fujikawa K., Davie E.W.,
RA   Stoddard B.L., Thompson A.R.;
RT   "Hemophilic factor VIII C1- and C2-domain missense mutations and their
RT   modeling to the 1.5-angstrom human C2-domain crystal structure.";
RL   Blood 96:979-987(2000).
RN   [68]
RP   VARIANTS HEMA CYS-612 AND SER-637, AND CHARACTERIZATION OF VARIANTS
RP   HEMA CYS-612 AND SER-637.
RX   PubMed=10691849; DOI=10.1046/j.1365-2141.2000.01834.x;
RA   Roelse J.C., De Laaf R.T.M., Timmermans S.M.H., Peters M.,
RA   Van Mourik J.A., Voorberg J.;
RT   "Intracellular accumulation of factor VIII induced by missense
RT   mutations Arg593-->Cys and Asn618-->Ser explains cross-reacting
RT   material-reduced haemophilia A.";
RL   Br. J. Haematol. 108:241-246(2000).
RN   [69]
RP   VARIANT HEMA ILE-713.
RX   PubMed=10886198; DOI=10.1046/j.1365-2141.2000.02021.x;
RA   Schwaab R., Oldenburg J., Kemball-Cook G., Albert T., Juhler C.,
RA   Hanfland P., Ingerslev J.;
RT   "Assay discrepancy in mild haemophilia A due to a factor VIII missense
RT   mutation (Asn694Ile) in a large Danish family.";
RL   Br. J. Haematol. 109:523-528(2000).
RN   [70]
RP   VARIANTS HEMA HIS-35; LEU-295; SER-307; CYS-1909; PRO-2058; GLN-2228
RP   AND ARG-2332.
RX   PubMed=10800171;
RA   Tagariello G., Belvini D., Salviato R., Are A., De Biasi E.,
RA   Goodeve A., Davoli P.;
RT   "Experience of a single Italian center in genetic counseling for
RT   hemophilia: from linkage analysis to molecular diagnosis.";
RL   Haematologica 85:525-529(2000).
RN   [71]
RP   VARIANTS HEMA PRO-69; TYR-75; ARG-585; PRO-664; GLU-1779; ALA-2000;
RP   HIS-2169 AND PRO-2228.
RX   PubMed=10896236;
RG   Recombinate PUP study group;
RA   Goodeve A.C., Williams I., Bray G.L., Peake I.R.;
RT   "Relationship between factor VIII mutation type and inhibitor
RT   development in a cohort of previously untreated patients treated with
RT   recombinant factor VIII (Recombinate).";
RL   Thromb. Haemost. 83:844-848(2000).
RN   [72]
RP   VARIANTS HEMA TYR-561; VAL-1869 AND CYS-2344.
RX   MEDLINE=20081067; PubMed=10612839;
RX   DOI=10.1002/(SICI)1098-1004(200001)15:1<117::AID-HUMU27>3.0.CO;2-E;
RA   Akkarapatumwong V., Oranwiroon S., Pung-amritt P., Treesucon A.,
RA   Thanootarakul P., Veerakul G., Mahasandana C., Panyim S.,
RA   Yenchitsomanus P.;
RT   "Mutations of the factor VIII gene in Thai hemophilia A patients.";
RL   Hum. Mutat. 15:117-118(2000).
RN   [73]
RP   VARIANTS HEMA ASP-89; ASP-99; HIS-101; TYR-135; PRO-327; GLY-409;
RP   ARG-498; ARG-603; ASP-637; GLY-1894; VAL-2045; LEU-2067; ARG-2172;
RP   CYS-2182; SER-2185; CYS-2279; LEU-2319; LEU-2326 AND PRO-2326.
RX   PubMed=11410838; DOI=10.1086/321285;
RA   Leuer M., Oldenburg J., Lavergne J.-M., Ludwig M., Fregin A.,
RA   Eigel A., Ljung R., Goodeve A., Peake I., Olek K.;
RT   "Somatic mosaicism in hemophilia A: a fairly common event.";
RL   Am. J. Hum. Genet. 69:75-87(2001).
RN   [74]
RP   VARIANTS HEMA VAL-255; GLU-323; CYS-391; CYS-550; VAL-586; CYS-1708;
RP   CYS-1800; ALA-1942; PRO-1963; CYS-2036; CYS-2124; ARG-2172; CYS-2182;
RP   GLN-2228 AND ALA-2307.
RX   MEDLINE=21194898; PubMed=11298607;
RX   DOI=10.1046/j.1365-2141.2001.02671.x;
RA   Ivaskevicius V., Jurgutis R., Rost S., Muller A., Schmitt C.,
RA   Wulff K., Herrmann F.H., Muller C.R., Schwaab R., Oldenburg J.;
RT   "Lithuanian haemophilia A and B registry comprising phenotypic and
RT   genotypic data.";
RL   Br. J. Haematol. 112:1062-1070(2001).
RN   [75]
RP   VARIANTS HEMA ASP-132; LYS-141; GLU-466; THR-470; HIS-503; GLY-602;
RP   THR-1853; GLN-1985; ARG-2004; TRP-2016; TYR-2093; HIS-2169; HIS-2182;
RP   VAL-2198 AND GLN-2228.
RX   PubMed=11442643; DOI=10.1046/j.1365-2516.2001.00528.x;
RA   Theophilus B.D.M., Enayat M.S., Williams M.D., Hill F.G.H.;
RT   "Site and type of mutations in the factor VIII gene in patients and
RT   carriers of haemophilia A.";
RL   Haemophilia 7:381-391(2001).
RN   [76]
RP   VARIANT HEMA ALA-92.
RX   PubMed=11442647;
RA   Bauduer F., Ducout L., Bendriss P., Falaises B., Lavergne J.-M.;
RT   "Mild haemophilia A discovered in a previously multi-operated 73-year-
RT   old man: characterization of a new mutation.";
RL   Haemophilia 7:419-421(2001).
RN   [77]
RP   VARIANTS HEMA ASN-67; PHE-117; ALA-137; TYR-267; CYS-301; HIS-301;
RP   TYR-348; LYS-475; ALA-579; CYS-612; CYS-683; LEU-698; TRP-710;
RP   CYS-1708; HIS-1788; LEU-1876; TRP-2016; GLU-2045; CYS-2178; CYS-2182;
RP   HIS-2182; PRO-2182; ALA-2307 AND LEU-2323.
RX   PubMed=11554935; DOI=10.1046/j.1365-2516.2001.00548.x;
RA   Timur A.A., Guergey A., Aktuglu G., Kavakli K., Canatan D., Olek K.,
RA   Caglayan S.H.;
RT   "Molecular pathology of haemophilia A in Turkish patients:
RT   identification of 36 independent mutations.";
RL   Haemophilia 7:475-481(2001).
RN   [78]
RP   VARIANTS HEMA MET-181; THR-339; CYS-455; TRP-546; CYS-554; CYS-2178
RP   AND PRO-2326.
RX   PubMed=11748850; DOI=10.1002/humu.1234;
RA   Bogdanova N., Lemcke B., Markoff A., Pollmann H., Dworniczak B.,
RA   Eigel A., Horst J.;
RT   "Seven novel and four recurrent point mutations in the factor VIII
RT   (F8C) gene.";
RL   Hum. Mutat. 18:546-546(2001).
RN   [79]
RP   VARIANTS HEMA ARG-193; CYS-391; CYS-550; CYS-612; HIS-1705; ARG-1782;
RP   GLU-1872; TRP-2016; PRO-2016; HIS-2169 AND HIS-2182.
RX   PubMed=11341489;
RA   Vidal F., Farssac E., Altisent C., Puig L., Gallardo D.;
RT   "Rapid hemophilia A molecular diagnosis by a simple DNA sequencing
RT   procedure: identification of 14 novel mutations.";
RL   Thromb. Haemost. 85:580-583(2001).
RN   [80]
RP   ERRATUM.
RA   Vidal F., Farssac E., Altisent C., Puig L., Gallardo D.;
RL   Thromb. Haemost. 86:727-727(2001).
RN   [81]
RP   VARIANT HEMA CYS-35.
RX   PubMed=12351418; DOI=10.1182/blood-2002-01-0277;
RA   Valleix S., Vinciguerra C., Lavergne J.-M., Leuer M., Delpech M.,
RA   Negrier C.;
RT   "Skewed X-chromosome inactivation in monochorionic diamniotic twin
RT   sisters results in severe and mild hemophilia A.";
RL   Blood 100:3034-3036(2002).
RN   [82]
RP   VARIANT HEMA GLY-198.
RX   PubMed=12406074; DOI=10.1046/j.1365-2141.2002.03819.x;
RA   Mazurier C., Parquet-Gernez A., Gaucher C., Lavergne J.-M.,
RA   Goudemand J.;
RT   "Factor VIII deficiency not induced by FVIII gene mutation in a female
RT   first cousin of two brothers with haemophilia A.";
RL   Br. J. Haematol. 119:390-392(2002).
RN   [83]
RP   VARIANTS HEMA PRO-97 AND GLY-2193.
RX   MEDLINE=22188717; PubMed=12199686;
RX   DOI=10.1046/j.1365-2516.2002.00661.x;
RA   Sukarova-Stefanovska E., Zisovski N., Muratovska O., Kostova S.,
RA   Efremov G.D.;
RT   "Three novel point mutations causing haemophilia A.";
RL   Haemophilia 8:715-718(2002).
RN   [84]
RP   VARIANTS HEMA THR-22; CYS-25; PRO-26; VAL-111; ARG-138; GLY-186;
RP   LYS-284; VAL-327; CYS-365; SER-431; PRO-437; CYS-455; HIS-579;
RP   HIS-584; PHE-650; ILE-681; GLN-725; VAL-1727; GLY-1740; CYS-1858;
RP   ASP-1869; ARG-1968; CYS-1998; ASN-2056; VAL-2070; ASN-2082; CYS-2145;
RP   ASP-2157; ALA-2173 AND PRO-2330.
RX   PubMed=11857744; DOI=10.1002/humu.10056;
RA   Cutler J.A., Mitchell M.J., Smith M.P., Savidge G.F.;
RT   "The identification and classification of 41 novel mutations in the
RT   factor VIII gene (F8C).";
RL   Hum. Mutat. 19:274-278(2002).
RN   [85]
RP   VARIANTS HEMA VAL-477; SER-1714; PRO-1777 AND PRO-2330.
RX   PubMed=12203998; DOI=10.1002/humu.9052;
RA   Frusconi S., Passerini I., Girolami F., Masieri M., Linari S.,
RA   Longo G., Morfini M., Torricelli F.;
RT   "Identification of seven novel mutations of F8C by DHPLC.";
RL   Hum. Mutat. 20:231-232(2002).
RN   [86]
RP   VARIANTS HEMA TRP-172; LYS-291; CYS-301; ALA-345; HIS-391; VAL-439;
RP   CYS-442; LEU-470; GLY-532; MET-653; CYS-683; LYS-1336; HIS-1708;
RP   PRO-1875; ARG-1877; ILE-1965; PHE-2117; CYS-2182; TRP-2185; LEU-2224;
RP   GLU-2251; LEU-2290; CYS-2323 AND TYR-2345.
RX   PubMed=12325022; DOI=10.1002/humu.10119;
RA   Citron M., Godmilow L., Ganguly T., Ganguly A.;
RT   "High throughput mutation screening of the factor VIII gene (F8C) in
RT   hemophilia A: 37 novel mutations and genotype-phenotype correlation.";
RL   Hum. Mutat. 20:267-274(2002).
RN   [87]
RP   VARIANTS HEMA GLU-67; 84-ARG-PRO-85 DEL; PRO-85 DEL; MET-181; TYR-186;
RP   GLY-220; LEU-262; ARG-412; PHE-438; ASP-439; ARG-470; SER-513;
RP   SER-541; CYS-550; GLY-554; SER-583; GLN-594; ILE-609; CYS-612;
RP   ASN-635; THR-699; ILE-701; ILE-721; ARG-1779; LEU-1780; THR-1791;
RP   PRO-1798; HIS-1800; GLY-1848; ARG-1907; CYS-1907; THR-1939; VAL-1939;
RP   ILE-1982; GLN-1985; CYS-2015; TRP-2016; SER-2038; HIS-2169; ILE-2192
RP   AND LEU-2326.
RX   PubMed=11858487;
RA   Liu M.-L., Nakaya S., Thompson A.R.;
RT   "Non-inversion factor VIII mutations in 80 hemophilia A families
RT   including 24 with alloimmune responses.";
RL   Thromb. Haemost. 87:273-276(2002).
RN   [88]
RP   VARIANTS HEMA ASP-147; CYS-301; CYS-612; VAL-1945; CYS-2178 AND
RP   GLN-2326, AND VARIANT GLU-1260.
RX   PubMed=12195713;
RA   Klopp N., Oldenburg J., Uen C., Schneppenheim R., Graw J.;
RT   "11 hemophilia A patients without mutations in the factor VIII
RT   encoding gene.";
RL   Thromb. Haemost. 88:357-360(2002).
RN   [89]
RP   VARIANTS HEMA LYS-72; HIS-155; GLU-181; ILE-254; SER-439; GLU-529;
RP   THR-567; SER-1804; SER-2051; ASN-2141 AND GLN-2262 INS.
RX   MEDLINE=22811549; PubMed=12930394;
RX   DOI=10.1046/j.1365-2141.2003.04494.x;
RA   Bicocchi M.P., Pasino M., Lanza T., Bottini F., Boeri E., Mori P.G.,
RA   Molinari A.C., Rosano C., Acquila M.;
RT   "Analysis of 18 novel mutations in the factor VIII gene.";
RL   Br. J. Haematol. 122:810-817(2003).
RN   [90]
RP   VARIANTS HEMA ARG-26; PRO-326; PHE-329; HIS-391; GLY-401; TYR-522;
RP   THR-540; TRP-546; TYR-588; CYS-683; SER-720; TYR-1066; HIS-1768;
RP   PRO-1771; HIS-1800; ASP-1904; PRO-1980; CYS-2169; HIS-2169; ASP-2174;
RP   CYS-2178; HIS-2178; CYS-2182; GLY-2228; PHE-2229; LEU-2319; CYS-2323;
RP   HIS-2323 AND SER-2345.
RX   PubMed=12871415; DOI=10.1046/j.1538-7836.2003.00149.x;
RA   Habart D., Kalabova D., Novotny M., Vorlova Z.;
RT   "Thirty-four novel mutations detected in factor VIII gene by multiplex
RT   CSGE: modeling of 13 novel amino acid substitutions.";
RL   J. Thromb. Haemost. 1:773-781(2003).
RN   [91]
RP   VARIANTS HEMA ILE-252; TYR-561; VAL-1869; SER-2248 AND CYS-2344.
RX   PubMed=12614369; DOI=10.1046/j.1365-2516.2003.00729.x;
RA   Yenchitsomanus P., Akkarapatumwong V., Pung-Amritt P., Intorasoot S.,
RA   Thanootarakul P., Oranwiroon S., Veerakul G., Mahasandana C.;
RT   "Genotype and phenotype of haemophilia A in Thai patients.";
RL   Haemophilia 9:179-186(2003).
RN   [92]
RP   VARIANTS HEMA THR-111; ASP-450; CYS-612; HIS-1800; CYS-1802 AND
RP   ALA-2251.
RX   PubMed=15682412; DOI=10.1002/ajh.20234;
RA   Bicocchi M.P., Pasino M., Lanza T., Bottini F., Molinari A.C.,
RA   Caprino D., Rosano C., Acquila M.;
RT   "Small FVIII gene rearrangements in 18 hemophilia A patients: five
RT   novel mutations.";
RL   Am. J. Hematol. 78:117-122(2005).
RN   [93]
RP   VARIANTS HEMA CYS-365; THR-470; SER-541; GLY-602; TRP-717; LYS-1701;
RP   CYS-1708; VAL-1727; ILE-1888; VAL-1966; TRP-2016; GLY-2018; LEU-2067;
RP   LEU-2162 AND HIS-2182.
RX   PubMed=15810915; DOI=10.1111/j.1365-2516.2005.01069.x;
RA   Hill M., Deam S., Gordon B., Dolan G.;
RT   "Mutation analysis in 51 patients with haemophilia A: report of 10
RT   novel mutations and correlations between genotype and clinical
RT   phenotype.";
RL   Haemophilia 11:133-141(2005).
RN   [94]
RP   VARIANT HEMA PRO-1994.
RX   PubMed=16805874; DOI=10.1111/j.1538-7836.2006.02105.x;
RA   Cai X.-H., Wang X.-F., Dai J., Fang Y., Ding Q.-L., Xie F.,
RA   Wang H.-L.;
RT   "Female haemophilia A heterozygous for a de novo frameshift and a
RT   novel missense mutation of factor VIII.";
RL   J. Thromb. Haemost. 4:1969-1974(2006).
CC   -!- FUNCTION: Factor VIII, along with calcium and phospholipid, acts
CC       as a cofactor for factor IXa when it converts factor X to the
CC       activated form, factor Xa.
CC   -!- SUBUNIT: Interacts with VWF. VWF binding is essential for the
CC       stabilization of F8 in circulation.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC   -!- DOMAIN: Domain F5/8 type C 2 is responsible for phospholipid-
CC       binding and essential for factor VIII activity.
CC   -!- PTM: Sulfation on Tyr-1699 is essential for binding VWF.
CC   -!- MASS SPECTROMETRY: Mass=1367.6; Method=Electrospray; Range=356-
CC       378; Note=Nonsulfated; Source=PubMed:10368977;
CC   -!- MASS SPECTROMETRY: Mass=1407.4; Method=Electrospray; Range=356-
CC       378; Note=Sulfated; Source=PubMed:10368977;
CC   -!- MASS SPECTROMETRY: Mass=2975.4; Method=Electrospray; Range=400-
CC       424; Note=Nonsulfated; Source=PubMed:10368977;
CC   -!- MASS SPECTROMETRY: Mass=3024; Method=Electrospray; Range=727-752;
CC       Note=Nonsulfated; Source=PubMed:10368977;
CC   -!- MASS SPECTROMETRY: Mass=3104; Method=Electrospray; Range=727-752;
CC       Note=Monosulfated; Source=PubMed:10368977;
CC   -!- MASS SPECTROMETRY: Mass=3183.5; Method=Electrospray; Range=727-
CC       752; Note=Disulfated; Source=PubMed:10368977;
CC   -!- MASS SPECTROMETRY: Mass=3262.5; Method=Electrospray; Range=727-
CC       752; Note=Trisulfated; Source=PubMed:10368977;
CC   -!- MASS SPECTROMETRY: Mass=2460.9; Method=Electrospray; Range=1672-
CC       1692; Note=Nonsulfated; Source=PubMed:10368977;
CC   -!- MASS SPECTROMETRY: Mass=2540.7; Method=Electrospray; Range=1672-
CC       1692; Note=Sulfated; Source=PubMed:10368977;
CC   -!- MASS SPECTROMETRY: Mass=2000.7; Method=Electrospray; Range=1691-
CC       1708; Note=Nonsulfated; Source=PubMed:10368977;
CC   -!- MASS SPECTROMETRY: Mass=2080.7; Method=Electrospray; Range=1691-
CC       1708; Note=Sulfated; Source=PubMed:10368977;
CC   -!- DISEASE: Defects in F8 are the cause of hemophilia A (HEMA)
CC       [MIM:306700]. HEMA is a common recessive X-linked coagulation
CC       disorder. The frequency of hemophilia A is 1-2 in 10,000 male
CC       births in all ethnic groups. About 50% of patients have severe
CC       hemophilia A with F8C activity less than 1% of normal; they have
CC       frequent spontaneous bleeding into joints, muscles and internal
CC       organs. Moderately severe hemophilia A occurs in about 10% of
CC       patients; F8C activity is 2-5% of normal, and there is bleeding
CC       after minor trauma. Mild hemophilia A, which occurs in 30-40% of
CC       patients, is associated with F8C activity of 5-30% and bleeding
CC       occurs only after significant trauma or surgery. Of particular
CC       interest for the understanding of the function of F8C is the
CC       category of CRM (cross-reacting material) positive patients
CC       (approximately 5%) that have considerable amount of F8C in their
CC       plasma (at least 30% of normal), but the protein is non-
CC       functional; i.e., the F8C activity is much less than the plasma
CC       protein level. CRM-reduced is another category of patients in
CC       which the F8C antigen and activity are reduced to approximately
CC       the same level. Most mutations are CRM negative, and probably
CC       affect the folding and stability of the protein.
CC   -!- PHARMACEUTICAL: Available under the names Kogenate (Bayer) and
CC       Recombinate (Baxter and American Home Products). Used to treat
CC       hemophilia A.
CC   -!- SIMILARITY: Belongs to the multicopper oxidase family.
CC   -!- SIMILARITY: Contains 3 F5/8 type A domains.
CC   -!- SIMILARITY: Contains 2 F5/8 type C domains.
CC   -!- SIMILARITY: Contains 6 plastocyanin-like domains.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Factor VIII entry;
CC       URL="http://en.wikipedia.org/wiki/Factor_VIII";
CC   -!- WEB RESOURCE: Name=HAMSters; Note=Factor VIII mutation db;
CC       URL="http://europium.csc.mrc.ac.uk/WebPages/Main/main.htm";
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.genetests.org/query?gene=F8";
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/f8/";
CC   -----------------------------------------------------------------------
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DR   EMBL; M14113; AAA52485.1; -; mRNA.
DR   EMBL; X01179; CAA25619.1; -; mRNA.
DR   EMBL; K01740; AAA52484.1; -; mRNA.
DR   EMBL; M88648; AAA52420.1; -; Genomic_DNA.
DR   EMBL; M88628; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88629; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88630; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88631; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88632; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88633; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88634; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88635; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88636; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88638; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88639; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88640; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88641; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88642; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88643; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88644; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88645; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88646; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; M88647; AAA52420.1; JOINED; Genomic_DNA.
DR   EMBL; AY769950; AAV85964.1; -; Genomic_DNA.
DR   EMBL; U80228; AAB61261.1; -; Genomic_DNA.
DR   PIR; I54318; EZHU.
DR   RefSeq; NP_000123.1; -.
DR   UniGene; Hs.654450; -.
DR   PDB; 1CFG; NMR; -; A=2322-2343.
DR   PDB; 1D7P; X-ray; 1.50 A; M=2190-2348.
DR   PDB; 1FAC; NMR; -; A=2322-2342.
DR   PDB; 1IQD; X-ray; 2.00 A; C=2193-2348.
DR   PDBsum; 1CFG; -.
DR   PDBsum; 1D7P; -.
DR   PDBsum; 1FAC; -.
DR   PDBsum; 1IQD; -.
DR   GlycoSuiteDB; P00451; -.
DR   PhosphoSite; P00451; -.
DR   Ensembl; ENSG00000185010; Homo sapiens.
DR   GeneID; 2157; -.
DR   KEGG; hsa:2157; -.
DR   H-InvDB; HIX0056228; -.
DR   HGNC; HGNC:3546; F8.
DR   HPA; HPA001108; -.
DR   MIM; 134500; phenotype.
DR   MIM; 306700; gene+phenotype.
DR   Orphanet; 448; Hemophilia.
DR   PharmGKB; PA134914298; -.
DR   HOGENOM; P00451; -.
DR   HOVERGEN; P00451; -.
DR   Reactome; REACT_604; Hemostasis.
DR   DrugBank; DB00025; Antihemophilic Factor.
DR   DrugBank; DB00100; Coagulation Factor IX.
DR   DrugBank; DB00055; Drotrecogin alfa.
DR   ArrayExpress; P00451; -.
DR   CleanEx; HS_F8; -.
DR   GermOnline; ENSG00000185010; Homo sapiens.
DR   GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; EXP:Reactome.
DR   GO; GO:0031093; C:platelet alpha granule lumen; EXP:Reactome.
DR   GO; GO:0005515; F:protein binding; IPI:UniProtKB.
DR   GO; GO:0007596; P:blood coagulation; TAS:ProtInc.
DR   InterPro; IPR000421; Coagulation_factor_5/8-type_C.
DR   InterPro; IPR001117; Cu-oxidase.
DR   InterPro; IPR011706; Cu-oxidase_2.
DR   InterPro; IPR011707; Cu-oxidase_3.
DR   InterPro; IPR002355; Cu_oxidase_Cu_BS.
DR   InterPro; IPR008972; Cupredoxin.
DR   InterPro; IPR014707; Factor_VIII.
DR   Gene3D; G3DSA:2.60.40.420; Cupredoxin; 6.
DR   PANTHER; PTHR10127:SF50; Factor_VIII; 1.
DR   Pfam; PF00394; Cu-oxidase; 1.
DR   Pfam; PF07731; Cu-oxidase_2; 1.
DR   Pfam; PF07732; Cu-oxidase_3; 1.
DR   Pfam; PF00754; F5_F8_type_C; 2.
DR   SMART; SM00231; FA58C; 2.
DR   PROSITE; PS01285; FA58C_1; 2.
DR   PROSITE; PS01286; FA58C_2; 2.
DR   PROSITE; PS50022; FA58C_3; 2.
DR   PROSITE; PS00079; MULTICOPPER_OXIDASE1; 3.
PE   1: Evidence at protein level;
KW   3D-structure; Acute phase; Blood coagulation; Calcium;
KW   Direct protein sequencing; Disease mutation; Glycoprotein; Hemophilia;
KW   Metal-binding; Pharmaceutical; Polymorphism; Repeat; Secreted; Signal;
KW   Sulfation.
FT   SIGNAL        1     19
FT   CHAIN        20   2351       Coagulation factor VIII.
FT                                /FTId=PRO_0000002967.
FT   CHAIN        20   1332       Factor VIIIa heavy chain, 200 kDa
FT                                isoform.
FT                                /FTId=PRO_0000002968.
FT   CHAIN        20    759       Factor VIIIa heavy chain, 92 kDa isoform.
FT                                /FTId=PRO_0000002969.
FT   CHAIN       760   1332       Factor VIII B chain.
FT                                /FTId=PRO_0000002970.
FT   CHAIN      1668   2351       Factor VIIIa light chain.
FT                                /FTId=PRO_0000002971.
FT   DOMAIN       20    348       F5/8 type A 1.
FT   DOMAIN       20    198       Plastocyanin-like 1.
FT   DOMAIN      206    348       Plastocyanin-like 2.
FT   DOMAIN      399    730       F5/8 type A 2.
FT   DOMAIN      399    573       Plastocyanin-like 3.
FT   DOMAIN      583    730       Plastocyanin-like 4.
FT   DOMAIN     1713   2040       F5/8 type A 3.
FT   DOMAIN     1713   1877       Plastocyanin-like 5.
FT   DOMAIN     1887   2040       Plastocyanin-like 6.
FT   DOMAIN     2040   2188       F5/8 type C 1.
FT   DOMAIN     2193   2345       F5/8 type C 2.
FT   REGION      760   1667       B.
FT   SITE        391    392       Cleavage; by thrombin.
FT   SITE        759    760       Cleavage; by thrombin.
FT   SITE       1332   1333       Cleavage (activation).
FT   SITE       1667   1668       Cleavage (activation).
FT   SITE       1708   1709       Cleavage; by thrombin.
FT   MOD_RES     365    365       Sulfotyrosine.
FT   MOD_RES     737    737       Sulfotyrosine.
FT   MOD_RES     738    738       Sulfotyrosine.
FT   MOD_RES     742    742       Sulfotyrosine.
FT   MOD_RES    1683   1683       Sulfotyrosine.
FT   MOD_RES    1699   1699       Sulfotyrosine.
FT   CARBOHYD     60     60       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    258    258       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    601    601       N-linked (GlcNAc...).
FT   CARBOHYD    776    776       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    803    803       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    847    847       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    919    919       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    962    962       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    982    982       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD   1020   1020       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD   1024   1024       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD   1074   1074       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD   1085   1085       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD   1204   1204       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD   1274   1274       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD   1278   1278       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD   1301   1301       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD   1319   1319       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD   1431   1431       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD   1461   1461       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD   1829   1829       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD   2137   2137       N-linked (GlcNAc...) (Potential).
FT   DISULFID    172    198
FT   DISULFID    267    348
FT   DISULFID    547    573
FT   DISULFID    649    730
FT   DISULFID   1851   1877
FT   DISULFID   1918   1922
FT   DISULFID   2040   2188
FT   DISULFID   2193   2345       By similarity.
FT   VARIANT      19     19       S -> R (in HEMA).
FT                                /FTId=VAR_028447.
FT   VARIANT      22     22       R -> T (in HEMA; severe).
FT                                /FTId=VAR_028448.
FT   VARIANT      24     24       Y -> C (in HEMA).
FT                                /FTId=VAR_028449.
FT   VARIANT      25     25       Y -> C (in HEMA; mild).
FT                                /FTId=VAR_028450.
FT   VARIANT      26     26       L -> P (in HEMA; severe).
FT                                /FTId=VAR_028451.
FT   VARIANT      26     26       L -> R (in HEMA; severe).
FT                                /FTId=VAR_001045.
FT   VARIANT      30     30       E -> V (in HEMA; mild).
FT                                /FTId=VAR_001046.
FT   VARIANT      33     33       W -> G (in HEMA; moderate).
FT                                /FTId=VAR_028452.
FT   VARIANT      35     35       Y -> C (in HEMA; mild/severe).
FT                                /FTId=VAR_028453.
FT   VARIANT      35     35       Y -> H (in HEMA; severe).
FT                                /FTId=VAR_028454.
FT   VARIANT      41     41       G -> C (in HEMA; severe/moderate).
FT                                /FTId=VAR_001047.
FT   VARIANT      48     48       R -> C (in HEMA; severe).
FT                                /FTId=VAR_001048.
FT   VARIANT      48     48       R -> K (in HEMA).
FT                                /FTId=VAR_028455.
FT   VARIANT      67     67       K -> E (in HEMA; severe).
FT                                /FTId=VAR_028456.
FT   VARIANT      67     67       K -> N (in HEMA).
FT                                /FTId=VAR_028457.
FT   VARIANT      69     69       L -> P (in HEMA; moderate-severe).
FT                                /FTId=VAR_028458.
FT   VARIANT      72     72       E -> K (in HEMA; moderate).
FT                                /FTId=VAR_017330.
FT   VARIANT      75     75       D -> E (in HEMA; moderate).
FT                                /FTId=VAR_028459.
FT   VARIANT      75     75       D -> V (in dbSNP:rs1800288).
FT                                /FTId=VAR_001049.
FT   VARIANT      75     75       D -> Y (in HEMA; moderate-severe).
FT                                /FTId=VAR_028460.
FT   VARIANT      84     85       Missing (in HEMA; severe).
FT                                /FTId=VAR_028461.
FT   VARIANT      85     85       Missing (in HEMA; moderate).
FT                                /FTId=VAR_028462.
FT   VARIANT      89     89       G -> D (in HEMA; severe).
FT                                /FTId=VAR_001050.
FT   VARIANT      89     89       G -> V (in HEMA; mild).
FT                                /FTId=VAR_001051.
FT   VARIANT      92     92       G -> A (in HEMA).
FT                                /FTId=VAR_028463.
FT   VARIANT      92     92       G -> V (in HEMA; mild).
FT                                /FTId=VAR_028464.
FT   VARIANT      97     97       A -> P (in HEMA).
FT                                /FTId=VAR_017331.
FT   VARIANT      98     98       E -> K (in HEMA; severe).
FT                                /FTId=VAR_028465.
FT   VARIANT      99     99       V -> D (in HEMA; severe).
FT                                /FTId=VAR_001052.
FT   VARIANT     101    101       D -> G (in HEMA; severe).
FT                                /FTId=VAR_028466.
FT   VARIANT     101    101       D -> H (in HEMA; severe sporadic).
FT                                /FTId=VAR_028467.
FT   VARIANT     101    101       D -> V (in HEMA).
FT                                /FTId=VAR_028468.
FT   VARIANT     104    104       V -> D (in HEMA; mild).
FT                                /FTId=VAR_001053.
FT   VARIANT     108    108       K -> T (in HEMA; mild).
FT                                /FTId=VAR_001054.
FT   VARIANT     110    110       M -> V (in HEMA; moderate).
FT                                /FTId=VAR_001055.
FT   VARIANT     111    111       A -> T (in HEMA; severe).
FT                                /FTId=VAR_028469.
FT   VARIANT     111    111       A -> V (in HEMA; moderate).
FT                                /FTId=VAR_028470.
FT   VARIANT     113    113       H -> R (in HEMA; mild).
FT                                /FTId=VAR_028471.
FT   VARIANT     113    113       H -> Y (in HEMA).
FT                                /FTId=VAR_028472.
FT   VARIANT     117    117       L -> F (in HEMA; mild).
FT                                /FTId=VAR_028473.
FT   VARIANT     117    117       L -> R (in HEMA; severe).
FT                                /FTId=VAR_001056.
FT   VARIANT     121    121       G -> S (in HEMA).
FT                                /FTId=VAR_028474.
FT   VARIANT     129    129       E -> V (in HEMA; severe).
FT                                /FTId=VAR_001057.
FT   VARIANT     130    130       G -> R (in HEMA; severe).
FT                                /FTId=VAR_001058.
FT   VARIANT     132    132       E -> D (in HEMA; severe).
FT                                /FTId=VAR_001059.
FT   VARIANT     133    133       Y -> C (in HEMA; mild).
FT                                /FTId=VAR_001060.
FT   VARIANT     135    135       D -> G (in HEMA; severe).
FT                                /FTId=VAR_001061.
FT   VARIANT     135    135       D -> Y (in HEMA; severe sporadic).
FT                                /FTId=VAR_028475.
FT   VARIANT     137    137       T -> A (in HEMA; severe).
FT                                /FTId=VAR_028476.
FT   VARIANT     137    137       T -> I (in HEMA; moderate).
FT                                /FTId=VAR_001062.
FT   VARIANT     138    138       S -> R (in HEMA; mild).
FT                                /FTId=VAR_028477.
FT   VARIANT     141    141       E -> K (in HEMA; severe familial).
FT                                /FTId=VAR_028478.
FT   VARIANT     145    145       D -> H (in HEMA; moderate).
FT                                /FTId=VAR_028479.
FT   VARIANT     147    147       V -> D (in HEMA; severe).
FT                                /FTId=VAR_028480.
FT   VARIANT     155    155       Y -> H (in HEMA; moderate).
FT                                /FTId=VAR_017332.
FT   VARIANT     159    159       V -> A (in HEMA; moderate).
FT                                /FTId=VAR_028481.
FT   VARIANT     163    163       N -> K (in HEMA; moderate).
FT                                /FTId=VAR_028482.
FT   VARIANT     164    164       G -> D (in HEMA; moderate).
FT                                /FTId=VAR_028483.
FT   VARIANT     164    164       G -> V (in HEMA; mild).
FT                                /FTId=VAR_001063.
FT   VARIANT     165    165       P -> S (in HEMA; severe).
FT                                /FTId=VAR_001064.
FT   VARIANT     172    172       C -> W (in HEMA).
FT                                /FTId=VAR_028484.
FT   VARIANT     176    176       S -> P (in HEMA).
FT                                /FTId=VAR_028485.
FT   VARIANT     179    179       S -> P (in HEMA; moderate).
FT                                /FTId=VAR_028486.
FT   VARIANT     181    181       V -> E (in HEMA; mild).
FT                                /FTId=VAR_017333.
FT   VARIANT     181    181       V -> M (in HEMA; mild/moderate).
FT                                /FTId=VAR_001065.
FT   VARIANT     185    185       K -> T (in HEMA; mild).
FT                                /FTId=VAR_001066.
FT   VARIANT     186    186       D -> G (in HEMA; mild).
FT                                /FTId=VAR_028487.
FT   VARIANT     186    186       D -> Y (in HEMA; severe).
FT                                /FTId=VAR_028488.
FT   VARIANT     189    189       S -> L (in HEMA; moderate).
FT                                /FTId=VAR_001067.
FT   VARIANT     193    193       G -> R (in HEMA; severe familial).
FT                                /FTId=VAR_028489.
FT   VARIANT     198    198       C -> G (in HEMA; severe).
FT                                /FTId=VAR_028490.
FT   VARIANT     202    202       S -> N (in HEMA; mild).
FT                                /FTId=VAR_028491.
FT   VARIANT     202    202       S -> R (in HEMA; mild).
FT                                /FTId=VAR_008123.
FT   VARIANT     214    214       F -> V (in HEMA).
FT                                /FTId=VAR_028492.
FT   VARIANT     217    217       L -> H (in HEMA; moderate).
FT                                /FTId=VAR_028493.
FT   VARIANT     219    219       A -> D (in HEMA).
FT                                /FTId=VAR_028494.
FT   VARIANT     219    219       A -> T (in HEMA).
FT                                /FTId=VAR_028495.
FT   VARIANT     220    220       V -> G (in HEMA; mild).
FT                                /FTId=VAR_028496.
FT   VARIANT     222    222       D -> V (in HEMA; moderate).
FT                                /FTId=VAR_001068.
FT   VARIANT     223    223       E -> K (in HEMA; severe).
FT                                /FTId=VAR_028497.
FT   VARIANT     224    224       G -> W (in HEMA; moderate).
FT                                /FTId=VAR_001069.
FT   VARIANT     252    252       T -> I (in HEMA; moderate).
FT                                /FTId=VAR_028498.
FT   VARIANT     253    253       V -> F (in HEMA; severe).
FT                                /FTId=VAR_001070.
FT   VARIANT     254    254       N -> I (in HEMA; severe).
FT                                /FTId=VAR_017334.
FT   VARIANT     255    255       G -> V (in HEMA; severe).
FT                                /FTId=VAR_015127.
FT   VARIANT     262    262       P -> L (in HEMA; moderate).
FT                                /FTId=VAR_028499.
FT   VARIANT     263    263       G -> S (in HEMA).
FT                                /FTId=VAR_028500.
FT   VARIANT     266    266       G -> E (in HEMA; severe).
FT                                /FTId=VAR_001071.
FT   VARIANT     267    267       C -> Y (in HEMA; moderate).
FT                                /FTId=VAR_028501.
FT   VARIANT     274    274       W -> C (in HEMA).
FT                                /FTId=VAR_028502.
FT   VARIANT     275    275       H -> L (in HEMA; mild).
FT                                /FTId=VAR_028503.
FT   VARIANT     278    278       G -> R (in HEMA; severe).
FT                                /FTId=VAR_001072.
FT   VARIANT     284    284       E -> K (in HEMA; moderate).
FT                                /FTId=VAR_028504.
FT   VARIANT     285    285       V -> G (in HEMA; mild).
FT                                /FTId=VAR_001073.
FT   VARIANT     291    291       E -> G (in HEMA; mild).
FT                                /FTId=VAR_001074.
FT   VARIANT     291    291       E -> K (in HEMA; mild).
FT                                /FTId=VAR_028505.
FT   VARIANT     294    294       T -> I (in HEMA; moderate).
FT                                /FTId=VAR_001075.
FT   VARIANT     295    295       F -> L (in HEMA; moderate).
FT                                /FTId=VAR_028506.
FT   VARIANT     297    297       V -> A (in HEMA; mild).
FT                                /FTId=VAR_028507.
FT   VARIANT     299    299       N -> I (in HEMA; mild).
FT                                /FTId=VAR_001076.
FT   VARIANT     301    301       R -> C (in HEMA; severe/mild).
FT                                /FTId=VAR_028508.
FT   VARIANT     301    301       R -> H (in HEMA; severe).
FT                                /FTId=VAR_001077.
FT   VARIANT     301    301       R -> L (in HEMA; severe).
FT                                /FTId=VAR_001078.
FT   VARIANT     302    302       Missing (in HEMA).
FT                                /FTId=VAR_028509.
FT   VARIANT     303    303       A -> E (in HEMA; mild).
FT                                /FTId=VAR_028510.
FT   VARIANT     303    303       A -> P (in HEMA; mild).
FT                                /FTId=VAR_028511.
FT   VARIANT     307    307       I -> S (in HEMA; moderate).
FT                                /FTId=VAR_028512.
FT   VARIANT     308    308       S -> L (in HEMA; moderate).
FT                                /FTId=VAR_001079.
FT   VARIANT     312    312       F -> S (in HEMA; mild/moderate).
FT                                /FTId=VAR_001080.
FT   VARIANT     314    314       T -> A (in HEMA; mild).
FT                                /FTId=VAR_001081.
FT   VARIANT     314    314       T -> I (in HEMA; moderate).
FT                                /FTId=VAR_001082.
FT   VARIANT     315    315       A -> V (in HEMA).
FT                                /FTId=VAR_028513.
FT   VARIANT     320    320       Missing (in HEMA; severe).
FT                                /FTId=VAR_028514.
FT   VARIANT     323    323       G -> E (in HEMA; severe).
FT                                /FTId=VAR_015128.
FT   VARIANT     326    326       L -> P (in HEMA).
FT                                /FTId=VAR_028515.
FT   VARIANT     327    327       L -> P (in HEMA; severe).
FT                                /FTId=VAR_001083.
FT   VARIANT     327    327       L -> V (in HEMA; mild).
FT                                /FTId=VAR_028516.
FT   VARIANT     329    329       C -> F (in HEMA).
FT                                /FTId=VAR_028517.
FT   VARIANT     331    331       I -> V (in HEMA; mild).
FT                                /FTId=VAR_001084.
FT   VARIANT     339    339       M -> T (in HEMA; moderate).
FT                                /FTId=VAR_028518.
FT   VARIANT     340    340       E -> K (in HEMA).
FT                                /FTId=VAR_028519.
FT   VARIANT     345    345       V -> A (in HEMA).
FT                                /FTId=VAR_028520.
FT   VARIANT     345    345       V -> L (in HEMA; severe).
FT                                /FTId=VAR_001085.
FT   VARIANT     348    348       C -> R (in HEMA; severe).
FT                                /FTId=VAR_001086.
FT   VARIANT     348    348       C -> S (in HEMA; moderate).
FT                                /FTId=VAR_001087.
FT   VARIANT     348    348       C -> Y (in HEMA; mild/severe).
FT                                /FTId=VAR_001088.
FT   VARIANT     365    365       Y -> C (in HEMA; mild).
FT                                /FTId=VAR_028521.
FT   VARIANT     391    391       R -> C (in HEMA; Okayama; moderate/
FT                                severe; abolishes the normal cleavage by
FT                                thrombin).
FT                                /FTId=VAR_001089.
FT   VARIANT     391    391       R -> H (in HEMA; Kumamoto; mild/moderate;
FT                                abolishes the normal cleavage by
FT                                thrombin).
FT                                /FTId=VAR_001090.
FT   VARIANT     391    391       R -> P (in HEMA; severe; abolishes the
FT                                normal cleavage by thrombin).
FT                                /FTId=VAR_001091.
FT   VARIANT     392    392       S -> L (in HEMA; mild; abolishes normal
FT                                cleavage by thrombin).
FT                                /FTId=VAR_001092.
FT   VARIANT     392    392       S -> P (in HEMA; mild; dbSNP:rs28933669).
FT                                /FTId=VAR_001093.
FT   VARIANT     401    401       W -> G (in HEMA).
FT                                /FTId=VAR_028522.
FT   VARIANT     405    405       I -> F (in HEMA).
FT                                /FTId=VAR_028523.
FT   VARIANT     405    405       I -> S (in HEMA; severe;
FT                                dbSNP:rs28933670).
FT                                /FTId=VAR_001094.
FT   VARIANT     409    409       E -> G (in HEMA; severe/moderate;
FT                                dbSNP:rs28933671).
FT                                /FTId=VAR_001095.
FT   VARIANT     412    412       W -> G (in HEMA).
FT                                /FTId=VAR_028524.
FT   VARIANT     412    412       W -> R (in HEMA; severe).
FT                                /FTId=VAR_028525.
FT   VARIANT     427    427       K -> I (in HEMA; mild).
FT                                /FTId=VAR_028526.
FT   VARIANT     431    431       L -> F (in HEMA; moderate).
FT                                /FTId=VAR_001096.
FT   VARIANT     431    431       L -> S (in HEMA; moderate).
FT                                /FTId=VAR_028527.
FT   VARIANT     437    437       R -> P (in HEMA; severe).
FT                                /FTId=VAR_028528.
FT   VARIANT     437    437       R -> W (in HEMA; mild).
FT                                /FTId=VAR_028529.
FT   VARIANT     438    438       I -> F (in HEMA; not severe).
FT                                /FTId=VAR_028530.
FT   VARIANT     439    439       G -> D (in HEMA; severe).
FT                                /FTId=VAR_028531.
FT   VARIANT     439    439       G -> S (in HEMA; moderate).
FT                                /FTId=VAR_017335.
FT   VARIANT     439    439       G -> V (in HEMA; severe).
FT                                /FTId=VAR_001097.
FT   VARIANT     442    442       Y -> C (in HEMA).
FT                                /FTId=VAR_028532.
FT   VARIANT     444    444       K -> R (in HEMA; severe).
FT                                /FTId=VAR_001098.
FT   VARIANT     450    450       Y -> D (in HEMA; severe).
FT                                /FTId=VAR_028533.
FT   VARIANT     450    450       Y -> N (in HEMA; mild/moderate;
FT                                dbSNP:rs28937273).
FT                                /FTId=VAR_001099.
FT   VARIANT     454    454       T -> I (in HEMA; mild).
FT                                /FTId=VAR_028534.
FT   VARIANT     455    455       F -> C (in HEMA; mild-moderate/severe).
FT                                /FTId=VAR_028535.
FT   VARIANT     466    466       G -> E (in HEMA; severe sporadic).
FT                                /FTId=VAR_028536.
FT   VARIANT     470    470       P -> L (in HEMA; mild).
FT                                /FTId=VAR_028537.
FT   VARIANT     470    470       P -> R (in HEMA; mild).
FT                                /FTId=VAR_028538.
FT   VARIANT     470    470       P -> T (in HEMA; mild sporadic).
FT                                /FTId=VAR_028539.
FT   VARIANT     474    474       G -> E (in HEMA).
FT                                /FTId=VAR_028540.
FT   VARIANT     474    474       G -> R (in HEMA; severe).
FT                                /FTId=VAR_001100.
FT   VARIANT     475    475       E -> K (in HEMA; moderate).
FT                                /FTId=VAR_028541.
FT   VARIANT     477    477       G -> V (in HEMA; moderate).
FT                                /FTId=VAR_028542.
FT   VARIANT     478    478       D -> N (in HEMA).
FT                                /FTId=VAR_028543.
FT   VARIANT     479    479       T -> R (in HEMA).
FT                                /FTId=VAR_028544.
FT   VARIANT     484    484       F -> C (in HEMA).
FT                                /FTId=VAR_028545.
FT   VARIANT     488    488       A -> G (in HEMA; moderate).
FT                                /FTId=VAR_001101.
FT   VARIANT     490    490       R -> G (in HEMA).
FT                                /FTId=VAR_028546.
FT   VARIANT     492    492       Y -> C (in HEMA; moderate).
FT                                /FTId=VAR_001103.
FT   VARIANT     492    492       Y -> H (in HEMA; mild).
FT                                /FTId=VAR_001102.
FT   VARIANT     494    494       I -> T (in HEMA; mild).
FT                                /FTId=VAR_001104.
FT   VARIANT     498    498       G -> R (in HEMA; severe/moderate).
FT                                /FTId=VAR_001105.
FT   VARIANT     503    503       R -> H (in HEMA).
FT                                /FTId=VAR_028547.
FT   VARIANT     513    513       G -> S (in HEMA; moderate).
FT                                /FTId=VAR_028548.
FT   VARIANT     522    522       I -> Y (in HEMA; requires 2 nucleotide
FT                                substitutions).
FT                                /FTId=VAR_028549.
FT   VARIANT     529    529       K -> E (in HEMA; moderate).
FT                                /FTId=VAR_017336.
FT   VARIANT     532    532       W -> G (in HEMA).
FT                                /FTId=VAR_028550.
FT   VARIANT     540    540       P -> T (in HEMA).
FT                                /FTId=VAR_028551.
FT   VARIANT     541    541       T -> S (in HEMA; mild).
FT                                /FTId=VAR_028552.
FT   VARIANT     544    544       D -> N (in HEMA; moderate).
FT                                /FTId=VAR_001106.
FT   VARIANT     546    546       R -> W (in HEMA; mild).
FT                                /FTId=VAR_001107.
FT   VARIANT     550    550       R -> C (in HEMA; mild/moderate).
FT                                /FTId=VAR_001108.
FT   VARIANT     550    550       R -> G (in HEMA; mild).
FT                                /FTId=VAR_001109.
FT   VARIANT     550    550       R -> H (in HEMA; mild/moderate).
FT                                /FTId=VAR_001110.
FT   VARIANT     553    553       S -> P (in HEMA; severe).
FT                                /FTId=VAR_028553.
FT   VARIANT     554    554       S -> C (in HEMA; moderate).
FT                                /FTId=VAR_028554.
FT   VARIANT     554    554       S -> G (in HEMA; mild).
FT                                /FTId=VAR_001111.
FT   VARIANT     556    556       V -> D (in HEMA; moderate).
FT                                /FTId=VAR_001112.
FT   VARIANT     560    560       R -> T (in HEMA; mild).
FT                                /FTId=VAR_028555.
FT   VARIANT     561    561       D -> G (in HEMA; severe).
FT                                /FTId=VAR_028556.
FT   VARIANT     561    561       D -> H (in HEMA).
FT                                /FTId=VAR_028557.
FT   VARIANT     561    561       D -> Y (in HEMA; severe).
FT                                /FTId=VAR_008967.
FT   VARIANT     567    567       I -> T (in HEMA; mild).
FT                                /FTId=VAR_017337.
FT   VARIANT     577    577       S -> F (in HEMA; mild).
FT                                /FTId=VAR_001113.
FT   VARIANT     578    578       V -> A (in HEMA; mild).
FT                                /FTId=VAR_028558.
FT   VARIANT     579    579       D -> A (in HEMA; mild).
FT                                /FTId=VAR_028559.
FT   VARIANT     579    579       D -> H (in HEMA; mild).
FT                                /FTId=VAR_028560.
FT   VARIANT     583    583       N -> S (in HEMA; mild).
FT                                /FTId=VAR_028561.
FT   VARIANT     584    584       Q -> H (in HEMA; mild).
FT                                /FTId=VAR_028562.
FT   VARIANT     584    584       Q -> K (in HEMA; moderate).
FT                                /FTId=VAR_001114.
FT   VARIANT     584    584       Q -> R (in HEMA).
FT                                /FTId=VAR_028563.
FT   VARIANT     585    585       I -> R (in HEMA; moderate-severe).
FT                                /FTId=VAR_028564.
FT   VARIANT     585    585       I -> T (in HEMA; severe/moderate).
FT                                /FTId=VAR_001115.
FT   VARIANT     586    586       M -> V (in HEMA; mild).
FT                                /FTId=VAR_015129.
FT   VARIANT     588    588       D -> G (in HEMA).
FT                                /FTId=VAR_028565.
FT   VARIANT     588    588       D -> Y (in HEMA).
FT                                /FTId=VAR_028566.
FT   VARIANT     594    594       L -> Q (in HEMA; mild).
FT                                /FTId=VAR_028567.
FT   VARIANT     596    596       S -> P (in HEMA; severe).
FT                                /FTId=VAR_001116.
FT   VARIANT     601    601       N -> D (in HEMA).
FT                                /FTId=VAR_028568.
FT   VARIANT     601    601       N -> K (in HEMA).
FT                                /FTId=VAR_028569.
FT   VARIANT     602    602       R -> G (in HEMA; mild familial).
FT                                /FTId=VAR_028570.
FT   VARIANT     603    603       S -> I (in HEMA).
FT                                /FTId=VAR_001117.
FT   VARIANT     603    603       S -> R (in HEMA; severe).
FT                                /FTId=VAR_028571.
FT   VARIANT     604    604       W -> C (in HEMA; severe).
FT                                /FTId=VAR_001118.
FT   VARIANT     605    605       Y -> H (in HEMA).
FT                                /FTId=VAR_028572.
FT   VARIANT     605    605       Y -> S (in HEMA; severe).
FT                                /FTId=VAR_001119.
FT   VARIANT     609    609       N -> I (in HEMA; moderate).
FT                                /FTId=VAR_028573.
FT   VARIANT     612    612       R -> C (in HEMA; mild/moderate; secretion
FT                                impaired).
FT                                /FTId=VAR_001120.
FT   VARIANT     631    631       N -> K (in HEMA; severe).
FT                                /FTId=VAR_001121.
FT   VARIANT     631    631       N -> S (in HEMA).
FT                                /FTId=VAR_001122.
FT   VARIANT     633    633       M -> I (in HEMA; mild).
FT                                /FTId=VAR_028574.
FT   VARIANT     635    635       S -> N (in HEMA; mild).
FT                                /FTId=VAR_028575.
FT   VARIANT     637    637       N -> D (in HEMA; severe sporadic/
FT                                moderate).
FT                                /FTId=VAR_028576.
FT   VARIANT     637    637       N -> S (in HEMA; mild; secretion
FT                                impaired).
FT                                /FTId=VAR_028577.
FT   VARIANT     639    639       Y -> C (in HEMA; moderate).
FT                                /FTId=VAR_028578.
FT   VARIANT     644    644       L -> V (in HEMA; mild).
FT                                /FTId=VAR_001123.
FT   VARIANT     650    650       L -> F (in HEMA; mild).
FT                                /FTId=VAR_028579.
FT   VARIANT     653    653       V -> A (in HEMA; mild).
FT                                /FTId=VAR_001124.
FT   VARIANT     653    653       V -> M (in HEMA; severe).
FT                                /FTId=VAR_001125.
FT   VARIANT     659    659       L -> P (in HEMA).
FT                                /FTId=VAR_028580.
FT   VARIANT     663    663       A -> V (in HEMA; mild).
FT                                /FTId=VAR_001126.
FT   VARIANT     664    664       Q -> P (in HEMA; moderate-severe).
FT                                /FTId=VAR_028581.
FT   VARIANT     671    671       Missing (in HEMA; severe).
FT                                /FTId=VAR_001127.
FT   VARIANT     677    677       F -> L (in HEMA; moderate).
FT                                /FTId=VAR_001128.
FT   VARIANT     681    681       M -> I (in HEMA; mild).
FT                                /FTId=VAR_028582.
FT   VARIANT     682    682       V -> F (in HEMA).
FT                                /FTId=VAR_028583.
FT   VARIANT     683    683       Y -> C (in HEMA; severe).
FT                                /FTId=VAR_028584.
FT   VARIANT     683    683       Y -> N (in HEMA; mild).
FT                                /FTId=VAR_028585.
FT   VARIANT     686    686       T -> R (in HEMA).
FT                                /FTId=VAR_028586.
FT   VARIANT     698    698       F -> L (in HEMA).
FT                                /FTId=VAR_028587.
FT   VARIANT     699    699       M -> T (in HEMA; mild).
FT                                /FTId=VAR_028588.
FT   VARIANT     699    699       M -> V (in HEMA; severe).
FT                                /FTId=VAR_001129.
FT   VARIANT     701    701       M -> I (in HEMA; mild).
FT                                /FTId=VAR_028589.
FT   VARIANT     705    705       G -> V (in HEMA; moderate).
FT                                /FTId=VAR_028590.
FT   VARIANT     710    710       G -> W (in HEMA).
FT                                /FTId=VAR_028591.
FT   VARIANT     713    713       N -> I (in HEMA; mild).
FT                                /FTId=VAR_028592.
FT   VARIANT     717    717       R -> L (in HEMA; mild).
FT                                /FTId=VAR_028593.
FT   VARIANT     717    717       R -> W (in HEMA; mild).
FT                                /FTId=VAR_001130.
FT   VARIANT     720    720       G -> D (in HEMA; severe/moderate).
FT                                /FTId=VAR_001131.
FT   VARIANT     720    720       G -> S (in HEMA).
FT                                /FTId=VAR_028594.
FT   VARIANT     721    721       M -> I (in HEMA; severe).
FT                                /FTId=VAR_028595.
FT   VARIANT     721    721       M -> L (in HEMA; mild).
FT                                /FTId=VAR_028596.
FT   VARIANT     723    723       A -> T (in HEMA; moderate).
FT                                /FTId=VAR_001132.
FT   VARIANT     725    725       L -> Q (in HEMA; severe).
FT                                /FTId=VAR_028597.
FT   VARIANT     727    727       V -> F (in HEMA; severe).
FT                                /FTId=VAR_001133.
FT   VARIANT     739    739       E -> K (in HEMA; mild; dbSNP:rs28937285).
FT                                /FTId=VAR_001134.
FT   VARIANT     742    742       Y -> C (in HEMA; mild).
FT                                /FTId=VAR_028598.
FT   VARIANT     795    795       R -> G (in dbSNP:rs2228152).
FT                                /FTId=VAR_024380.
FT   VARIANT     947    947       P -> R (in HEMA).
FT                                /FTId=VAR_028599.
FT   VARIANT    1012   1012       V -> L (in HEMA).
FT                                /FTId=VAR_028600.
FT   VARIANT    1057   1057       E -> K (in HEMA; moderate;
FT                                dbSNP:rs28933673).
FT                                /FTId=VAR_001135.
FT   VARIANT    1066   1066       H -> Y (in HEMA).
FT                                /FTId=VAR_028601.
FT   VARIANT    1260   1260       D -> E (in dbSNP:rs1800291).
FT                                /FTId=VAR_001136.
FT   VARIANT    1336   1336       Q -> K (in HEMA).
FT                                /FTId=VAR_028602.
FT   VARIANT    1460   1460       N -> K (in HEMA).
FT                                /FTId=VAR_028603.
FT   VARIANT    1481   1481       L -> P (in dbSNP:rs1800294).
FT                                /FTId=VAR_001137.
FT   VARIANT    1610   1610       A -> S (in HEMA).
FT                                /FTId=VAR_028604.
FT   VARIANT    1698   1698       I -> T (in HEMA; mild).
FT                                /FTId=VAR_028605.
FT   VARIANT    1699   1699       Y -> C (in HEMA; severe).
FT                                /FTId=VAR_001138.
FT   VARIANT    1699   1699       Y -> F (in HEMA; moderate;
FT                                dbSNP:rs28935203).
FT                                /FTId=VAR_001139.
FT   VARIANT    1701   1701       E -> K (in HEMA; mild).
FT                                /FTId=VAR_028606.
FT   VARIANT    1705   1705       Q -> H (in HEMA; mild sporadic).
FT                                /FTId=VAR_028607.
FT   VARIANT    1708   1708       R -> C (in HEMA; East Hartford; severe/
FT                                moderate/mild; abolishes thrombin
FT                                cleavage at the light chain).
FT                                /FTId=VAR_001140.
FT   VARIANT    1708   1708       R -> H (in HEMA; mild; abolishes thrombin
FT                                cleavage at the light chain;
FT                                dbSNP:rs28937286).
FT                                /FTId=VAR_001141.
FT   VARIANT    1714   1714       T -> S (in HEMA; moderate).
FT                                /FTId=VAR_028608.
FT   VARIANT    1715   1715       R -> G (in HEMA; mild).
FT                                /FTId=VAR_001142.
FT   VARIANT    1723   1723       E -> K (in HEMA; severe).
FT                                /FTId=VAR_001143.
FT   VARIANT    1727   1727       D -> V (in HEMA; mild).
FT                                /FTId=VAR_028609.
FT   VARIANT    1728   1728       Y -> C (in HEMA; moderate).
FT                                /FTId=VAR_001144.
FT   VARIANT    1740   1740       R -> G (in HEMA; mild).
FT                                /FTId=VAR_028610.
FT   VARIANT    1751   1751       K -> Q (in HEMA).
FT                                /FTId=VAR_028611.
FT   VARIANT    1768   1768       R -> H (in HEMA).
FT                                /FTId=VAR_028612.
FT   VARIANT    1769   1769       G -> R (in HEMA; mild).
FT                                /FTId=VAR_001145.
FT   VARIANT    1771   1771       L -> P (in HEMA).
FT                                /FTId=VAR_028613.
FT   VARIANT    1775   1775       L -> F (in HEMA; mild).
FT                                /FTId=VAR_001147.
FT   VARIANT    1775   1775       L -> V (in HEMA; moderate).
FT                                /FTId=VAR_001146.
FT   VARIANT    1777   1777       L -> P (in HEMA; moderate).
FT                                /FTId=VAR_028614.
FT   VARIANT    1779   1779       G -> E (in HEMA; severe/moderate).
FT                                /FTId=VAR_001148.
FT   VARIANT    1779   1779       G -> R (in HEMA; severe).
FT                                /FTId=VAR_028615.
FT   VARIANT    1780   1780       P -> L (in HEMA; moderate).
FT                                /FTId=VAR_028616.
FT   VARIANT    1782   1782       I -> R (in HEMA; severe sporadic).
FT                                /FTId=VAR_028617.
FT   VARIANT    1788   1788       D -> H (in HEMA; mild).
FT                                /FTId=VAR_028618.
FT   VARIANT    1791   1791       M -> T (in HEMA; severe).
FT                                /FTId=VAR_001149.
FT   VARIANT    1798   1798       A -> P (in HEMA; severe).
FT                                /FTId=VAR_028619.
FT   VARIANT    1799   1799       S -> H (in HEMA; requires 2 nucleotide
FT                                substitutions).
FT                                /FTId=VAR_028620.
FT   VARIANT    1800   1800       R -> C (in HEMA; moderate).
FT                                /FTId=VAR_001151.
FT   VARIANT    1800   1800       R -> G (in HEMA; mild).
FT                                /FTId=VAR_001152.
FT   VARIANT    1800   1800       R -> H (in HEMA; moderate/severe).
FT                                /FTId=VAR_001150.
FT   VARIANT    1801   1801       P -> A (in HEMA; mild).
FT                                /FTId=VAR_028621.
FT   VARIANT    1802   1802       Y -> C (in HEMA; moderate).
FT                                /FTId=VAR_028622.
FT   VARIANT    1803   1803       S -> Y (in HEMA; severe).
FT                                /FTId=VAR_001153.
FT   VARIANT    1804   1804       F -> S (in HEMA; severe).
FT                                /FTId=VAR_017338.
FT   VARIANT    1808   1808       L -> F (in HEMA; mild).
FT                                /FTId=VAR_001154.
FT   VARIANT    1842   1842       M -> I (in HEMA; moderate;
FT                                dbSNP:rs28933674).
FT                                /FTId=VAR_001155.
FT   VARIANT    1844   1844       P -> S (in HEMA; mild; dbSNP:rs28933675).
FT                                /FTId=VAR_001156.
FT   VARIANT    1845   1845       T -> P (in HEMA; mild; dbSNP:rs28933676).
FT                                /FTId=VAR_001157.
FT   VARIANT    1848   1848       E -> G (in HEMA; mild).
FT                                /FTId=VAR_028623.
FT   VARIANT    1853   1853       A -> T (in HEMA; moderate/severe).
FT                                /FTId=VAR_001158.
FT   VARIANT    1853   1853       A -> V (in HEMA; mild; dbSNP:rs28933677).
FT                                /FTId=VAR_001159.
FT   VARIANT    1858   1858       S -> C (in HEMA; moderate).
FT                                /FTId=VAR_028624.
FT   VARIANT    1864   1864       K -> E (in HEMA).
FT                                /FTId=VAR_028625.
FT   VARIANT    1865   1865       D -> N (in HEMA; severe).
FT                                /FTId=VAR_001160.
FT   VARIANT    1865   1865       D -> Y (in HEMA; severe).
FT                                /FTId=VAR_001161.
FT   VARIANT    1867   1867       H -> P (in HEMA; mild).
FT                                /FTId=VAR_028626.
FT   VARIANT    1867   1867       H -> R (in HEMA; moderate;
FT                                dbSNP:rs28933679).
FT                                /FTId=VAR_001162.
FT   VARIANT    1869   1869       G -> D (in HEMA; severe).
FT                                /FTId=VAR_028627.
FT   VARIANT    1869   1869       G -> V (in HEMA; severe).
FT                                /FTId=VAR_001163.
FT   VARIANT    1872   1872       G -> E (in HEMA; severe sporadic).
FT                                /FTId=VAR_028628.
FT   VARIANT    1873   1873       P -> R (in HEMA; severe;
FT                                dbSNP:rs28933680).
FT                                /FTId=VAR_001164.
FT   VARIANT    1875   1875       L -> P (in HEMA).
FT                                /FTId=VAR_028629.
FT   VARIANT    1876   1876       V -> L (in HEMA; mild).
FT                                /FTId=VAR_028630.
FT   VARIANT    1877   1877       C -> R (in HEMA).
FT                                /FTId=VAR_028631.
FT   VARIANT    1882   1882       L -> P (in HEMA).
FT                                /FTId=VAR_028632.
FT   VARIANT    1888   1888       R -> I (in HEMA; severe).
FT                                /FTId=VAR_001165.
FT   VARIANT    1894   1894       E -> G (in HEMA; moderate).
FT                                /FTId=VAR_001166.
FT   VARIANT    1901   1901       I -> F (in HEMA; mild).
FT                                /FTId=VAR_028633.
FT   VARIANT    1904   1904       E -> D (in HEMA).
FT                                /FTId=VAR_028634.
FT   VARIANT    1904   1904       E -> K (in HEMA; severe;
FT                                dbSNP:rs28933681).
FT                                /FTId=VAR_001167.
FT   VARIANT    1907   1907       S -> C (in HEMA; moderate).
FT                                /FTId=VAR_028635.
FT   VARIANT    1907   1907       S -> R (in HEMA; severe).
FT                                /FTId=VAR_028636.
FT   VARIANT    1908   1908       W -> L (in HEMA; mild).
FT                                /FTId=VAR_028637.
FT   VARIANT    1909   1909       Y -> C (in HEMA; moderate).
FT                                /FTId=VAR_028638.
FT   VARIANT    1939   1939       A -> T (in HEMA; severe).
FT                                /FTId=VAR_028639.
FT   VARIANT    1939   1939       A -> V (in HEMA; second mutation; could
FT                                be a polymorphism).
FT                                /FTId=VAR_028640.
FT   VARIANT    1941   1941       N -> D (in HEMA; severe/moderate).
FT                                /FTId=VAR_001168.
FT   VARIANT    1941   1941       N -> S (in HEMA; severe/moderate;
FT                                dbSNP:rs28933682).
FT                                /FTId=VAR_001169.
FT   VARIANT    1942   1942       G -> A (in HEMA; moderate).
FT                                /FTId=VAR_015130.
FT   VARIANT    1945   1945       M -> V (in HEMA; moderate).
FT                                /FTId=VAR_028641.
FT   VARIANT    1951   1951       L -> F (in HEMA; mild).
FT                                /FTId=VAR_028642.
FT   VARIANT    1960   1960       R -> L (in HEMA; moderate).
FT                                /FTId=VAR_001171.
FT   VARIANT    1960   1960       R -> Q (in HEMA; mild/moderate;
FT                                dbSNP:rs28937294).
FT                                /FTId=VAR_001170.
FT   VARIANT    1963   1963       L -> P (in HEMA; severe).
FT                                /FTId=VAR_015131.
FT   VARIANT    1965   1965       S -> I (in HEMA).
FT                                /FTId=VAR_028643.
FT   VARIANT    1966   1966       M -> I (in HEMA; mild).
FT                                /FTId=VAR_028644.
FT   VARIANT    1966   1966       M -> V (in HEMA; mild).
FT                                /FTId=VAR_028645.
FT   VARIANT    1967   1967       G -> D (in HEMA; moderate;
FT                                dbSNP:rs28937295).
FT                                /FTId=VAR_001172.
FT   VARIANT    1968   1968       S -> R (in HEMA; mild).
FT                                /FTId=VAR_028646.
FT   VARIANT    1971   1971       N -> T (in HEMA).
FT                                /FTId=VAR_028647.
FT   VARIANT    1973   1973       H -> L (in HEMA; mild).
FT                                /FTId=VAR_028648.
FT   VARIANT    1979   1979       G -> V (in HEMA; moderate).
FT                                /FTId=VAR_001173.
FT   VARIANT    1980   1980       H -> P (in HEMA).
FT                                /FTId=VAR_028649.
FT   VARIANT    1980   1980       H -> Y (in HEMA; mild).
FT                                /FTId=VAR_001174.
FT   VARIANT    1982   1982       F -> I (in HEMA; mild).
FT                                /FTId=VAR_028650.
FT   VARIANT    1985   1985       R -> Q (in HEMA; mild).
FT                                /FTId=VAR_028651.
FT   VARIANT    1994   1994       L -> P (in HEMA; moderate).
FT                                /FTId=VAR_028652.
FT   VARIANT    1998   1998       Y -> C (in HEMA; mild).
FT                                /FTId=VAR_028653.
FT   VARIANT    2000   2000       G -> A (in HEMA; moderate-severe).
FT                                /FTId=VAR_028654.
FT   VARIANT    2004   2004       T -> R (in HEMA; sporadic).
FT                                /FTId=VAR_028655.
FT   VARIANT    2007   2007       M -> I (in HEMA; mild).
FT                                /FTId=VAR_028656.
FT   VARIANT    2015   2015       W -> C (in HEMA; moderate).
FT                                /FTId=VAR_028657.
FT   VARIANT    2016   2016       R -> P (in HEMA; severe familial).
FT                                /FTId=VAR_028658.
FT   VARIANT    2016   2016       R -> W (in HEMA; severe/moderate/mild).
FT                                /FTId=VAR_001175.
FT   VARIANT    2018   2018       E -> G (in HEMA; moderate).
FT                                /FTId=VAR_028659.
FT   VARIANT    2022   2022       G -> D (in HEMA; severe).
FT                                /FTId=VAR_028660.
FT   VARIANT    2028   2028       G -> R (in HEMA).
FT                                /FTId=VAR_028661.
FT   VARIANT    2030   2030       S -> N (in HEMA; mild).
FT                                /FTId=VAR_028662.
FT   VARIANT    2035   2035       V -> A (in HEMA).
FT                                /FTId=VAR_028663.
FT   VARIANT    2036   2036       Y -> C (in HEMA; moderate).
FT                                /FTId=VAR_015132.
FT   VARIANT    2038   2038       N -> S (in HEMA; mild/moderate).
FT                                /FTId=VAR_001176.
FT   VARIANT    2040   2040       C -> Y (in HEMA).
FT                                /FTId=VAR_028664.
FT   VARIANT    2045   2045       G -> E (in HEMA; mild).
FT                                /FTId=VAR_028665.
FT   VARIANT    2045   2045       G -> V (in HEMA; severe sporadic).
FT                                /FTId=VAR_028666.
FT   VARIANT    2051   2051       I -> S (in HEMA; severe).
FT                                /FTId=VAR_017339.
FT   VARIANT    2056   2056       I -> N (in HEMA; severe).
FT                                /FTId=VAR_028667.
FT   VARIANT    2058   2058       A -> P (in HEMA; moderate).
FT                                /FTId=VAR_028668.
FT   VARIANT    2065   2065       W -> R (in HEMA; moderate).
FT                                /FTId=VAR_001177.
FT   VARIANT    2067   2067       P -> L (in HEMA; severe sporadic).
FT                                /FTId=VAR_028669.
FT   VARIANT    2070   2070       A -> V (in HEMA; mild).
FT                                /FTId=VAR_028670.
FT   VARIANT    2082   2082       S -> N (in HEMA; severe).
FT                                /FTId=VAR_028671.
FT   VARIANT    2088   2088       S -> F (in HEMA; severe).
FT                                /FTId=VAR_001178.
FT   VARIANT    2093   2093       D -> G (in HEMA; mild).
FT                                /FTId=VAR_001179.
FT   VARIANT    2093   2093       D -> Y (in HEMA; severe familial).
FT                                /FTId=VAR_028672.
FT   VARIANT    2105   2105       T -> N (in HEMA; moderate).
FT                                /FTId=VAR_001180.
FT   VARIANT    2106   2106       Q -> E (in HEMA; mild).
FT                                /FTId=VAR_028673.
FT   VARIANT    2106   2106       Q -> R (in HEMA; mild).
FT                                /FTId=VAR_028674.
FT   VARIANT    2107   2107       G -> S (in HEMA; severe).
FT                                /FTId=VAR_001181.
FT   VARIANT    2109   2109       R -> C (in HEMA; mild).
FT                                /FTId=VAR_028675.
FT   VARIANT    2117   2117       I -> F (in HEMA).
FT                                /FTId=VAR_028676.
FT   VARIANT    2117   2117       I -> S (in HEMA; mild-moderate; affinity
FT                                for VWF reduced 8-fold).
FT                                /FTId=VAR_028677.
FT   VARIANT    2119   2119       Q -> R (in HEMA; moderate).
FT                                /FTId=VAR_028678.
FT   VARIANT    2120   2120       F -> C (in HEMA).
FT                                /FTId=VAR_028679.
FT   VARIANT    2120   2120       F -> L (in HEMA; mild).
FT                                /FTId=VAR_001182.
FT   VARIANT    2124   2124       Y -> C (in HEMA; mild).
FT                                /FTId=VAR_001183.
FT   VARIANT    2135   2135       R -> P (in HEMA; severe).
FT                                /FTId=VAR_001184.
FT   VARIANT    2138   2138       S -> Y (in HEMA; moderate; affinity for
FT                                VWF reduced 80-fold).
FT                                /FTId=VAR_001185.
FT   VARIANT    2141   2141       T -> N (in HEMA; severe).
FT                                /FTId=VAR_017340.
FT   VARIANT    2145   2145       F -> C (in HEMA; mild).
FT                                /FTId=VAR_028680.
FT   VARIANT    2148   2148       N -> S (in HEMA; moderate).
FT                                /FTId=VAR_001186.
FT   VARIANT    2157   2157       N -> D (in HEMA; mild).
FT                                /FTId=VAR_028681.
FT   VARIANT    2162   2162       P -> L (in HEMA; severe).
FT                                /FTId=VAR_028682.
FT   VARIANT    2169   2169       R -> C (in HEMA; mild).
FT                                /FTId=VAR_028683.
FT   VARIANT    2169   2169       R -> H (in HEMA; severe/mild; affinity
FT                                for VWF reducced 3-fold).
FT                                /FTId=VAR_001187.
FT   VARIANT    2172   2172       P -> Q (in HEMA; moderate).
FT                                /FTId=VAR_001188.
FT   VARIANT    2172   2172       P -> R (in HEMA; severe).
FT                                /FTId=VAR_015133.
FT   VARIANT    2173   2173       T -> A (in HEMA; mild).
FT                                /FTId=VAR_028684.
FT   VARIANT    2173   2173       T -> I (in HEMA; mild).
FT                                /FTId=VAR_001189.
FT   VARIANT    2174   2174       H -> D (in HEMA).
FT                                /FTId=VAR_028685.
FT   VARIANT    2178   2178       R -> C (in HEMA; mild/moderate).
FT                                /FTId=VAR_001190.
FT   VARIANT    2178   2178       R -> H (in HEMA; mild).
FT                                /FTId=VAR_001191.
FT   VARIANT    2178   2178       R -> L (in HEMA; mild).
FT                                /FTId=VAR_001192.
FT   VARIANT    2182   2182       R -> C (in HEMA; severe/moderate).
FT                                /FTId=VAR_001193.
FT   VARIANT    2182   2182       R -> H (in HEMA; severe/moderate).
FT                                /FTId=VAR_001194.
FT   VARIANT    2182   2182       R -> P (in HEMA; moderate/severe).
FT                                /FTId=VAR_028686.
FT   VARIANT    2183   2183       M -> R (in HEMA; moderate).
FT                                /FTId=VAR_028687.
FT   VARIANT    2183   2183       M -> V (in HEMA; mild).
FT                                /FTId=VAR_001195.
FT   VARIANT    2185   2185       L -> S (in HEMA; severe).
FT                                /FTId=VAR_001196.
FT   VARIANT    2185   2185       L -> W (in HEMA).
FT                                /FTId=VAR_028688.
FT   VARIANT    2192   2192       S -> I (in HEMA; mild).
FT                                /FTId=VAR_028689.
FT   VARIANT    2193   2193       C -> G (in HEMA).
FT                                /FTId=VAR_017341.
FT   VARIANT    2196   2196       P -> R (in HEMA).
FT                                /FTId=VAR_028690.
FT   VARIANT    2198   2198       G -> V (in HEMA; severe sporadic).
FT                                /FTId=VAR_028691.
FT   VARIANT    2200   2200       E -> D (in HEMA).
FT                                /FTId=VAR_028692.
FT   VARIANT    2204   2204       I -> T (in HEMA; mild).
FT                                /FTId=VAR_001197.
FT   VARIANT    2209   2209       I -> N (in HEMA; moderate).
FT                                /FTId=VAR_001198.
FT   VARIANT    2211   2211       A -> P (in HEMA; moderate).
FT                                /FTId=VAR_001199.
FT   VARIANT    2220   2220       A -> P (in HEMA; mild).
FT                                /FTId=VAR_028693.
FT   VARIANT    2223   2223       Missing (in HEMA; severe/moderate).
FT                                /FTId=VAR_001200.
FT   VARIANT    2224   2224       P -> L (in HEMA).
FT                                /FTId=VAR_028695.
FT   VARIANT    2224   2224       Missing (in HEMA; moderate).
FT                                /FTId=VAR_028694.
FT   VARIANT    2228   2228       R -> G (in HEMA; severe).
FT                                /FTId=VAR_001201.
FT   VARIANT    2228   2228       R -> L (in HEMA; moderate).
FT                                /FTId=VAR_001202.
FT   VARIANT    2228   2228       R -> P (in HEMA; moderate-severe).
FT                                /FTId=VAR_028696.
FT   VARIANT    2228   2228       R -> Q (in HEMA; severe/moderate).
FT                                /FTId=VAR_001203.
FT   VARIANT    2229   2229       L -> F (in HEMA).
FT                                /FTId=VAR_028697.
FT   VARIANT    2242   2242       V -> M.
FT                                /FTId=VAR_001204.
FT   VARIANT    2248   2248       W -> C (in HEMA; moderate).
FT                                /FTId=VAR_001205.
FT   VARIANT    2248   2248       W -> S (in HEMA; moderate).
FT                                /FTId=VAR_028698.
FT   VARIANT    2251   2251       V -> A (in HEMA; mild).
FT                                /FTId=VAR_028699.
FT   VARIANT    2251   2251       V -> E (in HEMA).
FT                                /FTId=VAR_028700.
FT   VARIANT    2257   2257       M -> V (in HEMA; moderate; could be a
FT                                polymorphism; dbSNP:rs1800297).
FT                                /FTId=VAR_021356.
FT   VARIANT    2262   2262       V -> VQ (in HEMA; moderate).
FT                                /FTId=VAR_017342.
FT   VARIANT    2264   2264       T -> A (in HEMA).
FT                                /FTId=VAR_028701.
FT   VARIANT    2265   2265       Q -> R (in HEMA; moderate).
FT                                /FTId=VAR_001206.
FT   VARIANT    2279   2279       F -> C (in HEMA; severe sporadic).
FT                                /FTId=VAR_028702.
FT   VARIANT    2279   2279       F -> I (in HEMA).
FT                                /FTId=VAR_028703.
FT   VARIANT    2281   2281       I -> T (in HEMA; severe).
FT                                /FTId=VAR_028704.
FT   VARIANT    2290   2290       W -> L (in HEMA).
FT                                /FTId=VAR_028705.
FT   VARIANT    2304   2304       G -> V (in HEMA).
FT                                /FTId=VAR_028706.
FT   VARIANT    2307   2307       D -> A (in HEMA; moderate/mild).
FT                                /FTId=VAR_015134.
FT   VARIANT    2319   2319       P -> L (in HEMA; mild/severe).
FT                                /FTId=VAR_001207.
FT   VARIANT    2319   2319       P -> S (in HEMA; mild).
FT                                /FTId=VAR_001208.
FT   VARIANT    2323   2323       R -> C (in HEMA; severe/moderate; may
FT                                cause reduced phospholipid binding).
FT                                /FTId=VAR_001209.
FT   VARIANT    2323   2323       R -> G (in HEMA; moderate).
FT                                /FTId=VAR_028707.
FT   VARIANT    2323   2323       R -> H (in HEMA; mild; may cause reduced
FT                                phospholipid binding).
FT                                /FTId=VAR_001210.
FT   VARIANT    2323   2323       R -> L (in HEMA; mild).
FT                                /FTId=VAR_028708.
FT   VARIANT    2326   2326       R -> G (in HEMA).
FT                                /FTId=VAR_028709.
FT   VARIANT    2326   2326       R -> L (in HEMA; severe/moderate; may
FT                                cause reduced phospholipid binding).
FT                                /FTId=VAR_001211.
FT   VARIANT    2326   2326       R -> P (in HEMA; severe sporadic).
FT                                /FTId=VAR_028710.
FT   VARIANT    2326   2326       R -> Q (in HEMA; moderate/mild; may cause
FT                                reduced phospholipid binding).
FT                                /FTId=VAR_001212.
FT   VARIANT    2330   2330       Q -> P (in HEMA; severe).
FT                                /FTId=VAR_028711.
FT   VARIANT    2332   2332       W -> R (in HEMA; severe).
FT                                /FTId=VAR_028712.
FT   VARIANT    2339   2339       R -> T (in HEMA; moderate).
FT                                /FTId=VAR_028713.
FT   VARIANT    2344   2344       G -> C (in HEMA; moderate).
FT                                /FTId=VAR_008968.
FT   VARIANT    2344   2344       G -> S (in HEMA).
FT                                /FTId=VAR_028714.
FT   VARIANT    2345   2345       C -> S (in HEMA).
FT                                /FTId=VAR_028715.
FT   VARIANT    2345   2345       C -> Y (in HEMA).
FT                                /FTId=VAR_028716.
FT   CONFLICT    768    768       P -> R (in Ref. 2; CAA25619).
FT   CONFLICT   1922   1922       C -> S (in Ref. 4; AAA52420).
FT   TURN       2199   2201
FT   HELIX      2206   2208
FT   STRAND     2209   2212
FT   STRAND     2215   2217
FT   STRAND     2220   2222
FT   HELIX      2224   2226
FT   STRAND     2249   2265
FT   STRAND     2267   2269
FT   STRAND     2272   2289
FT   STRAND     2306   2309
FT   STRAND     2312   2335
FT   STRAND     2338   2346
SQ   SEQUENCE   2351 AA;  267009 MW;  75FB6A2955C74CB0 CRC64;
     MQIELSTCFF LCLLRFCFSA TRRYYLGAVE LSWDYMQSDL GELPVDARFP PRVPKSFPFN
     TSVVYKKTLF VEFTDHLFNI AKPRPPWMGL LGPTIQAEVY DTVVITLKNM ASHPVSLHAV
     GVSYWKASEG AEYDDQTSQR EKEDDKVFPG GSHTYVWQVL KENGPMASDP LCLTYSYLSH
     VDLVKDLNSG LIGALLVCRE GSLAKEKTQT LHKFILLFAV FDEGKSWHSE TKNSLMQDRD
     AASARAWPKM HTVNGYVNRS LPGLIGCHRK SVYWHVIGMG TTPEVHSIFL EGHTFLVRNH
     RQASLEISPI TFLTAQTLLM DLGQFLLFCH ISSHQHDGME AYVKVDSCPE EPQLRMKNNE
     EAEDYDDDLT DSEMDVVRFD DDNSPSFIQI RSVAKKHPKT WVHYIAAEEE DWDYAPLVLA
     PDDRSYKSQY LNNGPQRIGR KYKKVRFMAY TDETFKTREA IQHESGILGP LLYGEVGDTL
     LIIFKNQASR PYNIYPHGIT DVRPLYSRRL PKGVKHLKDF PILPGEIFKY KWTVTVEDGP
     TKSDPRCLTR YYSSFVNMER DLASGLIGPL LICYKESVDQ RGNQIMSDKR NVILFSVFDE
     NRSWYLTENI QRFLPNPAGV QLEDPEFQAS NIMHSINGYV FDSLQLSVCL HEVAYWYILS
     IGAQTDFLSV FFSGYTFKHK MVYEDTLTLF PFSGETVFMS MENPGLWILG CHNSDFRNRG
     MTALLKVSSC DKNTGDYYED SYEDISAYLL SKNNAIEPRS FSQNSRHPST RQKQFNATTI
     PENDIEKTDP WFAHRTPMPK IQNVSSSDLL MLLRQSPTPH GLSLSDLQEA KYETFSDDPS
     PGAIDSNNSL SEMTHFRPQL HHSGDMVFTP ESGLQLRLNE KLGTTAATEL KKLDFKVSST
     SNNLISTIPS DNLAAGTDNT SSLGPPSMPV HYDSQLDTTL FGKKSSPLTE SGGPLSLSEE
     NNDSKLLESG LMNSQESSWG KNVSSTESGR LFKGKRAHGP ALLTKDNALF KVSISLLKTN
     KTSNNSATNR KTHIDGPSLL IENSPSVWQN ILESDTEFKK VTPLIHDRML MDKNATALRL
     NHMSNKTTSS KNMEMVQQKK EGPIPPDAQN PDMSFFKMLF LPESARWIQR THGKNSLNSG
     QGPSPKQLVS LGPEKSVEGQ NFLSEKNKVV VGKGEFTKDV GLKEMVFPSS RNLFLTNLDN
     LHENNTHNQE KKIQEEIEKK ETLIQENVVL PQIHTVTGTK NFMKNLFLLS TRQNVEGSYD
     GAYAPVLQDF RSLNDSTNRT KKHTAHFSKK GEEENLEGLG NQTKQIVEKY ACTTRISPNT
     SQQNFVTQRS KRALKQFRLP LEETELEKRI IVDDTSTQWS KNMKHLTPST LTQIDYNEKE
     KGAITQSPLS DCLTRSHSIP QANRSPLPIA KVSSFPSIRP IYLTRVLFQD NSSHLPAASY
     RKKDSGVQES SHFLQGAKKN NLSLAILTLE MTGDQREVGS LGTSATNSVT YKKVENTVLP
     KPDLPKTSGK VELLPKVHIY QKDLFPTETS NGSPGHLDLV EGSLLQGTEG AIKWNEANRP
     GKVPFLRVAT ESSAKTPSKL LDPLAWDNHY GTQIPKEEWK SQEKSPEKTA FKKKDTILSL
     NACESNHAIA AINEGQNKPE IEVTWAKQGR TERLCSQNPP VLKRHQREIT RTTLQSDQEE
     IDYDDTISVE MKKEDFDIYD EDENQSPRSF QKKTRHYFIA AVERLWDYGM SSSPHVLRNR
     AQSGSVPQFK KVVFQEFTDG SFTQPLYRGE LNEHLGLLGP YIRAEVEDNI MVTFRNQASR
     PYSFYSSLIS YEEDQRQGAE PRKNFVKPNE TKTYFWKVQH HMAPTKDEFD CKAWAYFSDV
     DLEKDVHSGL IGPLLVCHTN TLNPAHGRQV TVQEFALFFT IFDETKSWYF TENMERNCRA
     PCNIQMEDPT FKENYRFHAI NGYIMDTLPG LVMAQDQRIR WYLLSMGSNE NIHSIHFSGH
     VFTVRKKEEY KMALYNLYPG VFETVEMLPS KAGIWRVECL IGEHLHAGMS TLFLVYSNKC
     QTPLGMASGH IRDFQITASG QYGQWAPKLA RLHYSGSINA WSTKEPFSWI KVDLLAPMII
     HGIKTQGARQ KFSSLYISQF IIMYSLDGKK WQTYRGNSTG TLMVFFGNVD SSGIKHNIFN
     PPIIARYIRL HPTHYSIRST LRMELMGCDL NSCSMPLGME SKAISDAQIT ASSYFTNMFA
     TWSPSKARLH LQGRSNAWRP QVNNPKEWLQ VDFQKTMKVT GVTTQGVKSL LTSMYVKEFL
     ISSSQDGHQW TLFFQNGKVK VFQGNQDSFT PVVNSLDPPL LTRYLRIHPQ SWVHQIALRM
     EVLGCEAQDL Y
//
