UniProtKB/SwissProt variant VAR

Variant information

Variant position:

180

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 Arginine (R) to Histidine (H) at position 180 (R180H, p.Arg180His).

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 medium size and polar (H)

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; somatic mutation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs137853009 [ dbSNP | Ensembl ]

Sequence information

Variant position:

180

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:

IEDHSGNGTFVNTELVGKGK R RPLNNNSEIALSLSRNKVFV

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                         IEDHSGNGTFVNTELVGKGKRRPLNNNSEIALSLSRNKVFV

Mouse                         IEDHSGNGTFVNTELIGKGKRCPLSNNSEIALSLCRNKVFV

Caenorhabditis elegans        LHDHSRNGTLVNQEMIGKGLSRELMNGDLISIGIPALIIFV

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
Alternative sequence	1 – 221	Missing. In isoform 13.
Alternative sequence	75 – 392	Missing. In isoform 11.
Alternative sequence	107 – 487	Missing. In isoform 3.
Alternative sequence	107 – 197	Missing. In isoform 4.
Alternative sequence	148 – 543	Missing. In isoform 10.
Alternative sequence	166 – 543	Missing. In isoform 6.
Beta strand	180 – 182

Literature citations

CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours.
Sodha N.; Bullock S.; Taylor R.; Mitchell G.; Guertl-Lackner B.; Williams R.D.; Bevan S.; Bishop K.; McGuire S.; Houlston R.S.; Eeles R.A.;
Br. J. Cancer 87:1445-1448(2002)
Cited for: VARIANTS GLY-117; GLN-137 AND HIS-180;

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;

Homozygosity for a CHEK2*1100delC mutation identified in familial colorectal cancer does not lead to a severe clinical phenotype.
van Puijenbroek M.; van Asperen C.J.; van Mil A.; Devilee P.; van Wezel T.; Morreau H.;
J. Pathol. 206:198-204(2005)
Cited for: VARIANTS GLY-117; GLN-137; TRP-145; THR-157 AND HIS-180;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O96017: Variant p.Arg180His