UniProtKB/Swiss-Prot Q9BYW2: Variant p.Ser1769Pro

Histone-lysine N-methyltransferase SETD2
Gene: SETD2
Chromosomal location: 3p21.31
Variant information

Variant position:  1769
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 Serine (S) to Proline (P) at position 1769 (S1769P, p.Ser1769Pro).
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 small size and polar (S) to medium size and hydrophobic (P)
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:  Renal cell carcinoma (RCC) [MIM:144700]: Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype. {ECO:0000269|PubMed:20054297, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:23792563, ECO:0000269|PubMed:25728682}. Note=The disease may be caused by mutations affecting the gene represented in this entry. Defects of SETD2 are associated with loss of DNA methylation at non-promoter regions (PubMed:23792563). SETD2 defects lead to aberrant and reduced nucleosome compaction and chromatin association of key replication proteins, such as MCM7 and DNA polymerase delta, leading to hinder replication fork progression and prevent loading of RAD51 homologous recombination repair factor at DNA breaks (PubMed:25728682). {ECO:0000269|PubMed:23792563, ECO:0000269|PubMed:25728682}.
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 RCC; defects in recruitment of the MutS alpha complex.
Any additional useful information about the variant.



Sequence information

Variant position:  1769
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2564
The length of the canonical sequence.

Location on the sequence:   EQKLTCLELIQNTHSQSCLK  S FLERHGLSLLWIWMAELGDG
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                         EQKLTCLELIQNTHSQSCLKSFLERHGLSLLWIWMAELGDG

Mouse                         EQKLTCLKLIQNTHSQSCLKSFLERHGLSLLWIWMAELGDG

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 – 2564 Histone-lysine N-methyltransferase SETD2
Alternative sequence 1573 – 2564 Missing. In isoform 3.
Alternative sequence 1715 – 2564 Missing. In isoform 2.


Literature citations

The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSalpha.
Li F.; Mao G.; Tong D.; Huang J.; Gu L.; Yang W.; Li G.M.;
Cell 153:590-600(2013)
Cited for: FUNCTION; INVOLVEMENT IN RCC; VARIANTS RCC ASP-1733 AND PRO-1769; CHARACTERIZATION OF VARIANTS RCC ASP-1733 AND PRO-1769;

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.