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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P00451: Variant p.Arg2228Gln

Coagulation factor VIII
Gene: F8
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Variant information Variant position: help 2228 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 Glutamine (Q) at position 2228 (R2228Q, p.Arg2228Gln). 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 (Q) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 1 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; severe/moderate. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 2228 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 QITASSYFTNMFATWSPSKA R LHLQGRSNAWRPQVNNPKEW 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                         QITASSYFTNMFATWSPSKARLHLQGRSNAWRPQVNNPKEW

                              QITASSYLSSMLATWSPSQARLHLQGRTNAWRPQANNPKEW

Mouse                         QITASSYFTNMFATWSPSQARLHLQGRTNAWRPQVNDPKQW

Pig                           QITASSHLSNIFATWSPSQARLHLQGRTNAWRPRVSSAEEW
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 2193 – 2345 F5/8 type C 2
Disulfide bond 2193 – 2345



Literature citations
Nonsense and missense mutations in hemophilia A: estimate of the relative mutation rate at CG dinucleotides.
Youssoufian H.; Antonarakis S.E.; Bell W.; Griffin A.M.; Kazazian H.H. Jr.;
Am. J. Hum. Genet. 42:718-725(1988)
Cited for: VARIANT HEMA GLN-2228; Recurrent mutations and three novel rearrangements in the factor VIII gene of hemophilia A patients of Italian descent.
Casula L.; Murru S.; Pecorara M.; Ristaldi M.S.; Restagno G.; Mancuso G.; Morfini M.; de Biasi R.; Baudo F.; Carbonara A.;
Blood 75:662-670(1990)
Cited for: VARIANTS HEMA GLN-2228 AND LEU-2326; Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.
Higuchi M.; Kazazian H.H. Jr.; Kasch L.; Warren T.C.; McGinniss M.J.; Phillips J.A. III; Kasper C.; Janco R.; Antonarakis S.E.;
Proc. Natl. Acad. Sci. U.S.A. 88:7405-7409(1991)
Cited for: VARIANTS HEMA THR-108; VAL-110; GLY-285; HIS-301; SER-312; ARG-444; HIS-492; GLY-561; CYS-612; THR-723; PHE-1699; HIS-1800; TYR-1803; ASP-1941; SER-1941; HIS-2169; GLN-2228 AND CYS-2323; Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: family studies indicate a mutation type-dependent sex ratio of mutation frequencies.
Becker J.; Schwaab R.; Moeller-Taube A.; Schwaab U.; Schmidt W.; Brackmann H.H.; Grimm T.; Olek K.; Oldenburg J.;
Am. J. Hum. Genet. 58:657-670(1996)
Cited for: VARIANTS HEMA ARG-26; LYS-48; ASP-89; ASP-99; VAL-101; ARG-117; GLY-135; ASP-219; ARG-278; LEU-301; GLN-302 DEL; PRO-327; PRO-659; LEU-1012; GLU-1260; CYS-1708; ASN-1865; ARG-1873; THR-1971; TRP-2016; GLN-2228; LEU-2326 AND SER-2344; Screen of 55 Slovenian haemophilia A patients: identification of 2 novel mutations (S-1R and IVS23+1G-->A) and discussion of mutation spectrum.
Strmecki L.; Benedik-Dolnicar M.; Vouk K.; Komel R.;
Hum. Mutat. 13:413-413(1999)
Cited for: VARIANTS HEMA ARG-19; HIS-301; LEU-308; HIS-2169; GLN-2228 AND GLN-2326; Experience of a single Italian center in genetic counseling for hemophilia: from linkage analysis to molecular diagnosis.
Tagariello G.; Belvini D.; Salviato R.; Are A.; De Biasi E.; Goodeve A.; Davoli P.;
Haematologica 85:525-529(2000)
Cited for: VARIANTS HEMA HIS-35; LEU-295; SER-307; CYS-1909; PRO-2058; GLN-2228 AND ARG-2332; Lithuanian haemophilia A and B registry comprising phenotypic and genotypic data.
Ivaskevicius V.; Jurgutis R.; Rost S.; Muller A.; Schmitt C.; Wulff K.; Herrmann F.H.; Muller C.R.; Schwaab R.; Oldenburg J.;
Br. J. Haematol. 112:1062-1070(2001)
Cited for: VARIANTS HEMA VAL-255; GLU-323; CYS-391; CYS-550; VAL-586; CYS-1708; CYS-1800; ALA-1942; PRO-1963; CYS-2036; CYS-2124; ARG-2172; CYS-2182; GLN-2228 AND ALA-2307; Site and type of mutations in the factor VIII gene in patients and carriers of haemophilia A.
Theophilus B.D.M.; Enayat M.S.; Williams M.D.; Hill F.G.H.;
Haemophilia 7:381-391(2001)
Cited for: VARIANTS HEMA ASP-132; LYS-141; GLU-466; THR-470; HIS-503; GLY-602; THR-1853; GLN-1985; ARG-2004; TRP-2016; TYR-2093; HIS-2169; HIS-2182; VAL-2198 AND GLN-2228;
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.