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UniProtKB/Swiss-Prot Q8IXK2: Variant p.Tyr396Cys

Polypeptide N-acetylgalactosaminyltransferase 12
Gene: GALNT12
Chromosomal location: 9q22.33
Variant information

Variant position:  396
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 Tyrosine (Y) to Cysteine (C) at position 396 (Y396C, p.Tyr396Cys).
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 aromatic (Y) to medium size and polar (C)
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:  Colorectal cancer 1 (CRCS1) [MIM:608812]: 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. {ECO:0000269|PubMed:19617566, ECO:0000269|PubMed:22461326, ECO:0000269|PubMed:24115450}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. The role of GALNT12 in colon cancer susceptibility is however subject to discussion: studies on 103 probants with colorectal cancer 1 (CRCS1) suggest that it does not act as a major contributor of CRCS1 (PubMed:24115450). {ECO:0000269|PubMed:24115450}.
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 CRCS1.
Any additional useful information about the variant.



Sequence information

Variant position:  396
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  581
The length of the canonical sequence.

Location on the sequence:   ALANSVRAAEVWMDEFKELY  Y HRNPRARLEPFGDVTERKQL
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                         ALANSVRAAEVWMDEFKELYYHRNPRARLEPFGDVTERKQL

Mouse                         ALANSVRAAEVWMDEFKELYYHRNPQARLEPFGDVTERKKL

Drosophila                    KSRNLKRIIEVWTGDLKSAIYKYQPHLLNISEGDLNEPRKL

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 – 581 Polypeptide N-acetylgalactosaminyltransferase 12
Topological domain 38 – 581 Lumenal
Disulfide bond 349 – 422


Literature citations

Inherited deleterious variants in GALNT12 are associated with CRC susceptibility.
Clarke E.; Green R.C.; Green J.S.; Mahoney K.; Parfrey P.S.; Younghusband H.B.; Woods M.O.;
Hum. Mutat. 33:1056-1058(2012)
Cited for: VARIANTS CRCS1 ASN-303 AND CYS-396;

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.