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UniProtKB/Swiss-Prot Q07864: Variant p.Leu424Val

DNA polymerase epsilon catalytic subunit A
Gene: POLE
Variant information

Variant position:  424
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 Leucine (L) to Valine (V) at position 424 (L424V, p.Leu424Val).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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:  Colorectal cancer 12 (CRCS12) [MIM:615083]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. CRCS12 is characterized by a high-penetrance predisposition to the development of colorectal adenomas and carcinomas, with a variable tendency to develop multiple and large tumors. Onset is usually before age 40 years. The histologic features of the tumors are unremarkable. {ECO:0000269|PubMed:23263490, ECO:0000269|PubMed:24501277, ECO:0000269|PubMed:25860647, ECO:0000269|PubMed:27573199}. 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 CRCS12; associated with disease susceptibility.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.

Sequence information

Variant position:  424
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2286
The length of the canonical sequence.

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.





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.

Chain 1 – 2286 DNA polymerase epsilon catalytic subunit A

Literature citations

Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas.
Palles C.; Cazier J.B.; Howarth K.M.; Domingo E.; Jones A.M.; Broderick P.; Kemp Z.; Spain S.L.; Guarino Almeida E.; Salguero I.; Sherborne A.; Chubb D.; Carvajal-Carmona L.G.; Ma Y.; Kaur K.; Dobbins S.; Barclay E.; Gorman M.; Martin L.; Kovac M.B.; Humphray S.; Lucassen A.; Holmes C.C.; Bentley D.; Donnelly P.; Taylor J.; Petridis C.; Roylance R.; Sawyer E.J.; Kerr D.J.; Clark S.; Grimes J.; Kearsey S.E.; Thomas H.J.; McVean G.; Houlston R.S.; Tomlinson I.;
Nat. Genet. 45:136-144(2013)
Cited for: VARIANTS CRCS12 LEU-411 AND VAL-424; VARIANTS THR-189; HIS-231; HIS-286; SER-367; ARG-436; PHE-459; TRP-762; ASN-777; ASN-1008; VAL-1255; MET-1368; SER-1421; ASN-1752; ASN-2013; THR-2056 AND VAL-2213;

New insights into POLE and POLD1 germline mutations in familial colorectal cancer and polyposis.
Valle L.; Hernandez-Illan E.; Bellido F.; Aiza G.; Castillejo A.; Castillejo M.I.; Navarro M.; Segui N.; Vargas G.; Guarinos C.; Juarez M.; Sanjuan X.; Iglesias S.; Alenda C.; Egoavil C.; Segura A.; Juan M.J.; Rodriguez-Soler M.; Brunet J.; Gonzalez S.; Jover R.; Lazaro C.; Capella G.; Pineda M.; Soto J.L.; Blanco I.;
Hum. Mol. Genet. 23:3506-3512(2014)
Cited for: VARIANT CRCS12 VAL-424;

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.