UniProtKB/SwissProt variant VAR

Variant information

Variant position:

189

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 Serine (S) to Leucine (L) at position 189 (S189L, p.Ser189Leu).

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 small size and polar (S) to medium size and hydrophobic (L)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-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

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; moderate.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs137852367 [ dbSNP | Ensembl ]

Sequence information

Variant position:

189

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:

DPLCLTYSYLSHVDLVKDLN S GLIGALLVCREGSLAKEKTQ

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                         DPLCLTYSYLSHVDLVKDLNSGLIGALLVCREGSLAKEKTQ

                              DPPCLTYSYFSHVDLVKDLNSGLIGALLVCKEGSLAKERTQ

Mouse                         DPPCLTYSYMSHVDLVKDLNSGLIGALLVCKEGSLSKERTQ

Pig                           DPPCLTYSYLSHVDLVKDLNSGLIGALLVCREGSLTRERTQ

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.

Type	Positions	Description
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	20 – 198	Plastocyanin-like 1
Disulfide bond	172 – 198
Alternative sequence	9 – 2143	Missing. In isoform 2.

Literature citations

A novel missense mutation in exon 4 of the factor VIII:C gene resulting in moderately severe hemophilia A.
Chan V.; Chan T.K.; Tong T.M.; Todd D.;
Blood 74:2688-2691(1989)
Cited for: VARIANT HEMA LEU-189;

Molecular characterization of haemophilia A in southern Chinese.
Chan V.; Pang A.; Chan T.P.T.; Chan V.W.-Y.; Chan T.K.;
Br. J. Haematol. 93:451-456(1996)
Cited for: VARIANTS HEMA LEU-189; SER-263; ARG-947; LYS-1057; SER-1610 AND HIS-2169; VARIANT MET-2242;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P00451: Variant p.Ser189Leu