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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P00451: Variant p.Arg2326Leu

Coagulation factor VIII
Gene: F8
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Variant information Variant position: help 2326 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 Leucine (L) at position 2326 (R2326L, p.Arg2326Leu). 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 hydrophobic (L) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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; may cause reduced phospholipid binding. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 2326 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 QDSFTPVVNSLDPPLLTRYL R IHPQSWVHQIALRMEVLGCE 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                         QDSFTPVVNSLDPPLLTRYLRIHPQSWVHQIALRMEVLGCE

                              RDSSTPVRNRLEPPLVARYVRLHPQSWAHHIALRLEVLGCD

Mouse                         QDSSTPMMNSLDPPLLTRYLRIHPQIWEHQIALRLEILGCE

Pig                           QDSSTPVVNALDPPLFTRYLRIHPTSWAQHIALRLEVLGCE
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
Beta strand 2312 – 2335



Literature citations
Mild hemophilia A resulting from Arg-to-Leu substitution in exon 26 of the factor VIII gene.
Inaba H.; Fujimaki M.; Kazazian H.H. Jr.; Antonarakis S.E.;
Hum. Genet. 81:335-338(1989)
Cited for: VARIANT HEMA LEU-2326; 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; 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; Somatic mosaicism in hemophilia A: a fairly common event.
Leuer M.; Oldenburg J.; Lavergne J.-M.; Ludwig M.; Fregin A.; Eigel A.; Ljung R.; Goodeve A.; Peake I.; Olek K.;
Am. J. Hum. Genet. 69:75-87(2001)
Cited for: VARIANTS HEMA ASP-89; ASP-99; HIS-101; TYR-135; PRO-327; GLY-409; ARG-498; ARG-603; ASP-637; GLY-1894; VAL-2045; LEU-2067; ARG-2172; CYS-2182; SER-2185; CYS-2279; LEU-2319; LEU-2326 AND PRO-2326; Non-inversion factor VIII mutations in 80 hemophilia A families including 24 with alloimmune responses.
Liu M.-L.; Nakaya S.; Thompson A.R.;
Thromb. Haemost. 87:273-276(2002)
Cited for: VARIANTS HEMA GLU-67; 84-ARG-PRO-85 DEL; PRO-85 DEL; MET-181; TYR-186; GLY-220; LEU-262; ARG-412; PHE-438; ASP-439; ARG-470; SER-513; SER-541; CYS-550; GLY-554; SER-583; GLN-594; ILE-609; CYS-612; ASN-635; THR-699; ILE-701; ILE-721; ARG-1779; LEU-1780; THR-1791; PRO-1798; HIS-1800; GLY-1848; ARG-1907; CYS-1907; THR-1939; VAL-1939; ILE-1982; GLN-1985; CYS-2015; TRP-2016; SER-2038; HIS-2169; ILE-2192 AND LEU-2326;
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.