UniProtKB/SwissProt variant VAR

Variant information

Variant position:

46

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

Type of variant:

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:

From Arginine (R) to Serine (S) at position 46 (R46S, p.Arg46Ser).

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 large size and basic (R) to small size and polar (S)

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

Variant description:

In HEMB; severe; Cambridge; impaired processing of the propeptide; impaired gamma-carboxylation; decreased protein abundance; loss of function in blood coagulation.

Any additional useful information about the variant.

Sequence information

Variant position:

46

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

Protein sequence length:

461

The length of the canonical sequence.

Location on the sequence:

AECTVFLDHENANKILNRPK R YNSGKLEEFVQGNLERECME

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                         AECTVFLDHENANKILNRPKRYNSGKLEEFVQGNLERECME

                              AECAVFLDRENATKILSRPKRYNSGKLEEFVRGNLERECIE

Chimpanzee                    AECTVFLDHENANKILNRPKRYNSGKLEEFVQGNLERECME

Mouse                         TECAVFLDRENATKILTRPKRYNSGKLEEFVRGNLERECIE

Rat                           TECAVFLDRENATKILTRPKRYNSGKLEEFVQGNLERECIE

Bovine                        AECTVFLDRENATKILHRPKRYNSGKLEEFVRGNLERECKE

Cat                           ADCTVFLDHEDATKVLSRPKRYNSGKLEEFVQGNLERECME

Chicken                       AESTVFIENKEASTVLSRTRRGNSNRLEELIPGNLERECIE

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
Propeptide	29 – 46
Metal binding	47 – 47	Calcium 1; via carbonyl oxygen
Metal binding	48 – 48	Calcium 2
Metal binding	53 – 53	Calcium 1; via 4-carboxyglutamate
Metal binding	53 – 53	Calcium 2; via 4-carboxyglutamate
Metal binding	54 – 54	Calcium 2; via 4-carboxyglutamate
Metal binding	54 – 54	Calcium 3; via 4-carboxyglutamate
Metal binding	61 – 61	Calcium 4 or magnesium 1; via 4-carboxyglutamate
Metal binding	63 – 63	Calcium 1; via 4-carboxyglutamate
Metal binding	63 – 63	Calcium 2; via 4-carboxyglutamate
Metal binding	63 – 63	Calcium 3; via 4-carboxyglutamate
Metal binding	66 – 66	Calcium 4 or magnesium 1; via 4-carboxyglutamate
Modified residue	53 – 53	4-carboxyglutamate
Modified residue	54 – 54	4-carboxyglutamate
Modified residue	61 – 61	4-carboxyglutamate
Modified residue	63 – 63	4-carboxyglutamate
Modified residue	66 – 66	4-carboxyglutamate

Literature citations

Comprehensive analysis of phenotypes and genetics in 21 Chinese families with haemophilia B: characterization of five novel mutations.
Guo Z.P.; Yang L.H.; Qin X.Y.; Liu X.E.; Chen J.F.; Zhang Y.F.;
Haemophilia 20:859-865(2014)
Cited for: VARIANTS HEMB SER-20; TYR-28; SER-46; ASP-54; GLU-58; ARG-84; HIS-138; GLN-226; ILE-284 DEL; MET-296; LYS-328; TYR-328; THR-414 AND TYR-THR-LYS-VAL-447 INS; CHARACTERIZATION OF VARIANTS HEMB SER-20; TYR-28; SER-46; ASP-54; GLU-58; ARG-84; HIS-138; GLN-226; ILE-284 DEL; MET-296; LYS-328; TYR-328; THR-414 AND TYR-THR-LYS-VAL-447 INS;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P00740: Variant p.Arg46Ser