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UniProtKB/Swiss-Prot P0DP91: Variant p.Gly746Asp

Chimeric ERCC6-PGBD3 protein
Gene: CSB-PGBD3
Chromosomal location: 10q11
Variant information

Variant position:  746
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 Glycine (G) to Aspartate (D) at position 746 (G746D, p.Gly746Asp).
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 glycine (G) to medium size and acidic (D)
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:  Premature ovarian failure 11 (POF11) [MIM:616946]: An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. {ECO:0000269|PubMed:26218421}. Note=The protein represented in this entry is involved in disease pathogenesis. Disease-causing variants affect isoform CSB-PGBD3, which is a chimeric protein between ERCC6 N-terminus and the entire PGBD3 sequence. {ECO:0000269|PubMed:26218421}.
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 POF11; weaker cellular response to DNA damage as indicated by delayed recruitement of mutant protein to DNA damaged sites, compared to ERCC6 isoform 1; no effect on interaction with RNA polymerase II either after UV or H(2)O(2) damage.
Any additional useful information about the variant.



Sequence information

Variant position:  746
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1061
The length of the canonical sequence.

Location on the sequence:   MKFVPNETYFSFDEFMVPYF  G RHGCKQFIRGKPIRFGYKFW
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.

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 – 1061 Chimeric ERCC6-PGBD3 protein


Literature citations

CSB-PGBD3 mutations cause premature ovarian failure.
Qin Y.; Guo T.; Li G.; Tang T.S.; Zhao S.; Jiao X.; Gong J.; Gao F.; Guo C.; Simpson J.L.; Chen Z.J.;
PLoS Genet. 11:E1005419-E1005419(2015)
Cited for: INVOLVEMENT IN POF11; VARIANTS POF11 ASP-746 AND ILE-1056; CHARACTERIZATION OF VARIANTS POF11 ASP-746 AND ILE-1056; SUBCELLULAR LOCATION; TISSUE SPECIFICITY;

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.