UniProtKB/Swiss-Prot P10914: Variant p.Met8Leu

Interferon regulatory factor 1
Gene: IRF1
Chromosomal location: 5q31.1
Variant information

Variant position:  8
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Methionine (M) to Leucine (L) at position 8 (M8L, p.Met8Leu).
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:  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:  Gastric cancer (GASC) [MIM:613659]: A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. {ECO:0000269|PubMed:10395927, ECO:0000269|PubMed:9679752}. 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 GASC; somatic mutation; produces a protein with markedly reduced transcriptional activity but unaltered DNA-binding activity.
Any additional useful information about the variant.



Sequence information

Variant position:  8
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  325
The length of the canonical sequence.

Location on the sequence:   MPITRMR  M RPWLEMQINSNQIPGLIWIN
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                         MPITRMRMRPWLEMQINSNQIPGLIWIN

Mouse                         MPITRMRMRPWLEMQINSNQIPGLIWIN

Rat                           MPITRMRMRPWLEMQINSNQIPGLSWIN

Pig                           MPITRMRMRPWLEMQINSNQIPGLIWIN

Bovine                        MPITRMRMRPWLEMQINSNQIPGLIWIN

Chicken                       MPVSRMRMRPWLEMQINSNQIPGLIWIN

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.

TypePositionsDescription
Chain 1 – 325 Interferon regulatory factor 1
DNA binding 5 – 113 IRF tryptophan pentad repeat


Literature citations

Functionally inactivating point mutation in the tumor-suppressor IRF-1 gene identified in human gastric cancer.
Nozawa H.; Oda E.; Ueda S.; Tamura G.; Maesawa C.; Muto T.; Taniguchi T.; Tanaka N.;
Int. J. Cancer 77:522-527(1998)
Cited for: VARIANT GASC LEU-8; CHARACTERIZATION OF VARIANT GASC LEU-8;

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.