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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P00451: Variant p.Arg2178Cys

Coagulation factor VIII
Gene: F8
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Variant information Variant position: help 2178 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change: help From Arginine (R) to Cysteine (C) at position 2178 (R2178C, p.Arg2178Cys). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from large size and basic (R) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description: help In HEMA; mild/moderate. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 2178 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 2351 The length of the canonical sequence.
Location on the sequence: help IFNPPIIARYIRLHPTHYSI R STLRMELMGCDLNSCSMPLG The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         IFNPPIIARYIRLHPTHYSIRSTLRMELMGCDLNSCSMPLG

                              IFNPPIIAQYIRLHPTHYSIRSTLRMELLGCDFNSCSMPLG

Mouse                         SFNPPIIARYIRLHPTHSSIRSTLRMELMGCDLNSCSIPLG

Pig                           IFNPPIVARYIRLHPTHYSIRSTLRMELMGCDLNSCSMPLG

Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 20 – 2351 Coagulation factor VIII
Chain 1668 – 2351 Factor VIIIa light chain
Domain 2040 – 2188 F5/8 type C 1
Disulfide bond 2040 – 2188
Beta strand 2155 – 2178



Literature citations
Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.
Higuchi M.; Antonarakis S.E.; Kasch L.; Oldenburg J.; Economou-Petersen E.; Olek K.; Arai M.; Inaba H.; Kazazian H.H. Jr.;
Proc. Natl. Acad. Sci. U.S.A. 88:8307-8311(1991)
Cited for: VARIANTS HEMA THR-185; TRP-224; ALA-314; PHE-431; CYS-492; TRP-546; CYS-550; GLY-550; LYS-584; VAL-663; LYS-1057; SER-1844; ARG-1867; TRP-2016; LEU-2120; TYR-2138; HIS-2169; CYS-2178 AND LEU-2319; Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A.
Diamond C.; Kogan S.; Levinson B.; Gitschier J.;
Hum. Mutat. 1:248-257(1992)
Cited for: VARIANTS HEMA VAL-30; VAL-89; VAL-92; ASP-104; VAL-164; MET-181; CYS-550; GLY-554; CYS-612; TRP-717; PHE-1808; SER-1941; ARG-2065; HIS-2169; CYS-2178 AND CYS-2248; Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A.
McGinniss M.J.; Kazazian H.H. Jr.; Hoyer L.W.; Bi L.; Inaba H.; Antonarakis S.E.;
Genomics 15:392-398(1993)
Cited for: VARIANTS HEMA LEU-308; HIS-391; TRP-546; PHE-577; ALA-653; MET-653; PHE-671 DEL; LYS-1460 AND CYS-2178; Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A patients.
Arruda V.R.; Pieneman W.C.; Reitsma P.H.; Deutz-Terlouw P.P.; Annichino-Bizzacchi J.M.; Brieet E.; Costa F.F.;
Blood 86:3015-3020(1995)
Cited for: VARIANTS HEMA ARG-113; ASN-202; LEU-275; GLY-285; CYS-301; ASP-637; PHE-1808; PRO-1867; GLN-1960; HIS-2169; CYS-2178 AND THR-2281; VARIANT VAL-2257; Factor VIII gene analysis in Japanese CRM-positive and CRM-reduced haemophilia A patients by single-strand conformation polymorphism.
Morichika S.; Shima M.; Kamisue S.; Tanaka I.; Imanaka Y.; Suzuki H.; Shibata H.; Pemberton S.; Gale K.; McVey J.; Tuddenham E.G.D.; Yoshioka A.;
Br. J. Haematol. 98:901-906(1997)
Cited for: VARIANTS HEMA CYS-274; CYS-492; ARG-498; HIS-550; ARG-686; CYS-1708; GLN-1960; HIS-2169; CYS-2178; ALA-2264 AND VAL-2304; Start of UK confidential haemophilia A database: analysis of 142 patients by solid phase fluorescent chemical cleavage of mismatch.
Waseem N.H.; Bagnall R.; Green P.M.; Giannelli F.;
Thromb. Haemost. 81:900-905(1999)
Cited for: VARIANTS HEMA CYS-24; ARG-26; TYR-113; SER-121; TRP-172; PRO-176; MET-181; VAL-214; THR-219; LYS-291; ALA-314; VAL-315; LYS-340; PHE-405; GLY-412; THR-470; GLU-474; ASN-478; CYS-484; GLY-490; ARG-498; TRP-546; CYS-550; HIS-561; ARG-584; THR-585; GLY-588; ASP-601; LYS-601; GLY-602; HIS-605; CYS-612; TRP-717; CYS-1708; GLN-1751; HIS-1800; CYS-1802; THR-1853; GLU-1864; PRO-1882; ILE-1888; LEU-1973; TRP-2016; ALA-2035; TYR-2040; CYS-2120; CYS-2145; HIS-2169; CYS-2178; HIS-2182; VAL-2183; VAL-2198; CYS-2248 AND GLY-2326; Hemophilic factor VIII C1- and C2-domain missense mutations and their modeling to the 1.5-angstrom human C2-domain crystal structure.
Liu M.-L.; Shen B.W.; Nakaya S.; Pratt K.P.; Fujikawa K.; Davie E.W.; Stoddard B.L.; Thompson A.R.;
Blood 96:979-987(2000)
Cited for: VARIANTS HEMA GLU-2106; CYS-2109; CYS-2169; CYS-2178; CYS-2182; ARG-2183; ILE-2192; PRO-2220; ALA-2251; LEU-2319; CYS-2323; GLY-2323; GLN-2326 AND THR-2339; Molecular pathology of haemophilia A in Turkish patients: identification of 36 independent mutations.
Timur A.A.; Guergey A.; Aktuglu G.; Kavakli K.; Canatan D.; Olek K.; Caglayan S.H.;
Haemophilia 7:475-481(2001)
Cited for: VARIANTS HEMA ASN-67; PHE-117; ALA-137; TYR-267; CYS-301; HIS-301; TYR-348; LYS-475; ALA-579; CYS-612; CYS-683; LEU-698; TRP-710; CYS-1708; HIS-1788; LEU-1876; TRP-2016; GLU-2045; CYS-2178; CYS-2182; HIS-2182; PRO-2182; ALA-2307 AND LEU-2323; Seven novel and four recurrent point mutations in the factor VIII (F8C) gene.
Bogdanova N.; Lemcke B.; Markoff A.; Pollmann H.; Dworniczak B.; Eigel A.; Horst J.;
Hum. Mutat. 18:546-546(2001)
Cited for: VARIANTS HEMA MET-181; THR-339; CYS-455; TRP-546; CYS-554; CYS-2178 AND PRO-2326; 11 hemophilia A patients without mutations in the factor VIII encoding gene.
Klopp N.; Oldenburg J.; Uen C.; Schneppenheim R.; Graw J.;
Thromb. Haemost. 88:357-360(2002)
Cited for: VARIANTS HEMA ASP-147; CYS-301; CYS-612; VAL-1945; CYS-2178 AND GLN-2326; VARIANT GLU-1260; Thirty-four novel mutations detected in factor VIII gene by multiplex CSGE: modeling of 13 novel amino acid substitutions.
Habart D.; Kalabova D.; Novotny M.; Vorlova Z.;
J. Thromb. Haemost. 1:773-781(2003)
Cited for: VARIANTS HEMA ARG-26; PRO-326; PHE-329; HIS-391; GLY-401; TYR-522; THR-540; TRP-546; TYR-588; CYS-683; SER-720; TYR-1066; HIS-1768; PRO-1771; HIS-1800; ASP-1904; PRO-1980; CYS-2169; HIS-2169; ASP-2174; CYS-2178; HIS-2178; CYS-2182; GLY-2228; PHE-2229; LEU-2319; CYS-2323; HIS-2323 AND SER-2345;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.