Home  |  Contact

UniProtKB/Swiss-Prot P00451: Variant p.Val253Phe

Coagulation factor VIII
Gene: F8
Variant information

Variant position:  253
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Valine (V) to Phenylalanine (F) at position 253 (V253F, p.Val253Phe).
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:  Change from medium size and hydrophobic (V) to large size and aromatic (F)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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

Involvement in disease:  Hemophilia A (HEMA) [MIM:306700]: A disorder of blood coagulation characterized by a permanent tendency to hemorrhage. About 50% of patients have severe hemophilia resulting in frequent spontaneous bleeding into joints, muscles and internal organs. Less severe forms are characterized by bleeding after trauma or surgery. {ECO:0000269|PubMed:10215414, ECO:0000269|PubMed:10338101, ECO:0000269|PubMed:10404764, ECO:0000269|PubMed:10408784, ECO:0000269|PubMed:10554831, ECO:0000269|PubMed:10612839, ECO:0000269|PubMed:10691849, ECO:0000269|PubMed:10800171, ECO:0000269|PubMed:10886198, ECO:0000269|PubMed:10896236, ECO:0000269|PubMed:10910910, ECO:0000269|PubMed:10910913, ECO:0000269|PubMed:11298607, ECO:0000269|PubMed:11341489, ECO:0000269|PubMed:11410838, ECO:0000269|PubMed:11442643, ECO:0000269|PubMed:11442647, ECO:0000269|PubMed:11554935, ECO:0000269|PubMed:11748850, ECO:0000269|PubMed:11857744, ECO:0000269|PubMed:11858487, ECO:0000269|PubMed:12195713, ECO:0000269|PubMed:12199686, ECO:0000269|PubMed:12203998, ECO:0000269|PubMed:12325022, ECO:0000269|PubMed:12351418, ECO:0000269|PubMed:12406074, ECO:0000269|PubMed:12614369, ECO:0000269|PubMed:12871415, ECO:0000269|PubMed:12930394, ECO:0000269|PubMed:1301194, ECO:0000269|PubMed:1301932, ECO:0000269|PubMed:1301960, ECO:0000269|PubMed:1349567, ECO:0000269|PubMed:1356412, ECO:0000269|PubMed:15682412, ECO:0000269|PubMed:15810915, ECO:0000269|PubMed:1639429, ECO:0000269|PubMed:16805874, ECO:0000269|PubMed:18184865, ECO:0000269|PubMed:1851341, ECO:0000269|PubMed:1908096, ECO:0000269|PubMed:1908817, ECO:0000269|PubMed:1973901, ECO:0000269|PubMed:2104766, ECO:0000269|PubMed:2105106, ECO:0000269|PubMed:2105906, ECO:0000269|PubMed:2106480, ECO:0000269|PubMed:2107542, ECO:0000269|PubMed:21371196, ECO:0000269|PubMed:2495245, ECO:0000269|PubMed:2498882, ECO:0000269|PubMed:2499363, ECO:0000269|PubMed:2506948, ECO:0000269|PubMed:2510835, ECO:0000269|PubMed:25550078, ECO:0000269|PubMed:26278069, ECO:0000269|PubMed:2833855, ECO:0000269|PubMed:2835904, ECO:0000269|PubMed:3012775, ECO:0000269|PubMed:3122181, ECO:0000269|PubMed:7579394, ECO:0000269|PubMed:7759074, ECO:0000269|PubMed:7794769, ECO:0000269|PubMed:8322269, ECO:0000269|PubMed:8449505, ECO:0000269|PubMed:8639447, ECO:0000269|PubMed:8644728, ECO:0000269|PubMed:8759905, ECO:0000269|PubMed:9029040, ECO:0000269|PubMed:9326186, ECO:0000269|PubMed:9341862, ECO:0000269|PubMed:9450898, ECO:0000269|PubMed:9452104, ECO:0000269|PubMed:9569180, ECO:0000269|PubMed:9569189, ECO:0000269|PubMed:9603440, ECO:0000269|PubMed:9792405, ECO:0000269|PubMed:9829908, ECO:0000269|PubMed:9886318}. Note=The disease is caused by mutations affecting the gene represented in this entry. Of particular interest for the understanding of the function of F8 is the category of CRM (cross-reacting material) positive patients (approximately 5%) that have considerable amount of F8 in their plasma (at least 30% of normal), but the protein is non-functional; i.e. The F8 activity is much less than the plasma protein level. CRM-reduced is another category of patients in which the F8C antigen and activity are reduced to approximately the same level. Most mutations are CRM negative, and probably affect the folding and stability of the protein.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In HEMA; severe.
Any additional useful information about the variant.



Sequence information

Variant position:  253
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2351
The length of the canonical sequence.

Location on the sequence:   NSLMQDRDAASARAWPKMHT  V NGYVNRSLPGLIGCHRKSVY
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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         NSLMQDRDAASARAWPKMHTVNGYVNRSLPGLIGCHRKSVY

                              ASLTQ------AEAQHELHTINGYVNRSLPGLTVCHKRSVY

Mouse                         DSYTQSMDSASARDWPKMHTVNGYVNRSLPGLIGCHRKSVY

Pig                           DSWTRAMDPAPARAQPAMHTVNGYVNRSLPGLIGCHKKSVY

Sequence annotation in neighborhood:  
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 20 – 1332 Factor VIIIa heavy chain, 200 kDa isoform
Chain 20 – 759 Factor VIIIa heavy chain, 92 kDa isoform
Domain 20 – 348 F5/8 type A 1
Domain 206 – 348 Plastocyanin-like 2
Glycosylation 258 – 258 N-linked (GlcNAc...) asparagine
Alternative sequence 9 – 2143 Missing. In isoform 2.


Literature citations

Fluorescent chemical cleavage of mismatches for efficient screening of the factor VIII gene.
Freson K.; Peerlinck K.; Aguirre T.; Arnout J.; Vermylen J.; Cassiman J.-J.; Matthijs G.;
Hum. Mutat. 11:470-479(1998)
Cited for: VARIANTS HEMA ASP-132; PHE-253; ILE-314; VAL-331; ARG-474; ARG-498; VAL-644; VAL-699; ASP-720; PHE-727 AND ASN-2105;

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.