UniProtKB/SwissProt variant VAR

Variant information

Variant position:

251

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 Isoleucine (I) to Phenylalanine (F) at position 251 (I251F, p.Ile251Phe).

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 (I) to large size and aromatic (F)

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

BLOSUM score:

0

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:

Prostate cancer (PC) [MIM:176807]: A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. {ECO:0000269|PubMed:12533788}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

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 prostate cancer; germline mutation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs587780189 [ dbSNP | Ensembl ]

Sequence information

Variant position:

251

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

Protein sequence length:

543

The length of the canonical sequence.

Location on the sequence:

CGEVKLAFERKTCKKVAIKI I SKRKFAIGSAREADPALNVE

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                         CGEVKLAFERKTCKKVAIKIISKRKFAIGSAREADPALNVE

Mouse                         CGEVKMAFERKTCQKVAIKIISKRRFALGSSREADTAPSVE

Caenorhabditis elegans        FGKVLLGYKKSDRSVVAIKQLNT-QFSTRCSRAIAKTRDIR

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	1 – 543	Serine/threonine-protein kinase Chk2
Domain	220 – 486	Protein kinase
Binding site	249 – 249	ATP
Alternative sequence	75 – 392	Missing. In isoform 11.
Alternative sequence	107 – 487	Missing. In isoform 3.
Alternative sequence	148 – 543	Missing. In isoform 10.
Alternative sequence	166 – 543	Missing. In isoform 6.
Alternative sequence	204 – 543	Missing. In isoform 5.
Alternative sequence	235 – 543	Missing. In isoform 2.
Beta strand	244 – 251

Literature citations

Mutations in CHEK2 associated with prostate cancer risk.
Dong X.; Wang L.; Taniguchi K.; Wang X.; Cunningham J.M.; McDonnell S.K.; Qian C.; Marks A.F.; Slager S.L.; Peterson B.J.; Smith D.I.; Cheville J.C.; Blute M.L.; Jacobsen S.J.; Schaid D.J.; Tindall D.J.; Thibodeau S.N.; Liu W.;
Am. J. Hum. Genet. 72:270-280(2003)
Cited for: VARIANTS PROSTATE CANCER LYS-64; PRO-145; ARG-167; CYS-180; HIS-180; CYS-181; HIS-181; LYS-239; PHE-251; HIS-318; PRO-323; CYS-327 AND LYS-476; VARIANT THR-157;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O96017: Variant p.Ile251Phe