UniProtKB/Swiss-Prot P17302: Variant p.Gly2Val

Gap junction alpha-1 protein
Gene: GJA1
Chromosomal location: 6q21-q23.2
Variant information

Variant position:  2
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 Valine (V) at position 2 (G2V, p.Gly2Val).
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 hydrophobic (V)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Oculodentodigital dysplasia (ODDD) [MIM:164200]: A disease characterized by a typical facial appearance and variable involvement of the eyes, dentition, and fingers. Characteristic facial features include a narrow, pinched nose with hypoplastic alae nasi, prominent columella and thin anteverted nares together with a narrow nasal bridge, and prominent epicanthic folds giving the impression of hypertelorism. The teeth are usually small and carious. Typical eye findings include microphthalmia and microcornea. The characteristic digital malformation is complete syndactyly of the fourth and fifth fingers (syndactyly type III) but the third finger may be involved and associated camptodactyly is a common finding. Cardiac abnormalities are observed in rare instances. {ECO:0000269|PubMed:12457340, ECO:0000269|PubMed:14729836, ECO:0000269|PubMed:15108203, ECO:0000269|PubMed:15637728, ECO:0000269|PubMed:16219735, ECO:0000269|PubMed:16222672, ECO:0000269|PubMed:16378922, ECO:0000269|PubMed:16709485, ECO:0000269|PubMed:16813608, ECO:0000269|PubMed:16816024, ECO:0000269|PubMed:17509830, ECO:0000269|PubMed:18161618, ECO:0000269|PubMed:19338053, ECO:0000269|PubMed:21670345, ECO:0000269|PubMed:23550541, ECO:0000269|PubMed:24508941, ECO:0000269|PubMed:28258662}. Note=The disease is caused by mutations 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 ODDD.
Any additional useful information about the variant.

Sequence information

Variant position:  2
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  382
The length of the canonical sequence.

Location on the sequence:   M  G DWSALGKLLDKVQAYSTAGG
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                         MGDWSALGKLLDKVQAYSTAGG


Mouse                         MGDWSALGKLLDKVQAYSTAGG

Rat                           MGDWSALGKLLDKVQAYSTAGG

Pig                           MGDWSALGKLLDKVQAYSTAGG

Bovine                        MGDWSALGKLLDKVQAYSTAGG

Rabbit                        MGDWSALGKLLDKVQAYSTAGG

Chicken                       MGDWSALGKLLDKVQAYSTAGG

Xenopus laevis                MGDWSALGRLLDKVQAYSTAGG

Zebrafish                     MGDWSALGRLLDKVQAYSTAGG

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 – 382 Gap junction alpha-1 protein
Topological domain 1 – 13 Cytoplasmic
Modified residue 5 – 5 Phosphoserine

Literature citations

Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia.
Paznekas W.A.; Boyadjiev S.A.; Shapiro R.E.; Daniels O.; Wollnik B.; Keegan C.E.; Innis J.W.; Dinulos M.B.; Christian C.; Hannibal M.C.; Jabs E.W.;
Am. J. Hum. Genet. 72:408-418(2003)

A new GJA1 (connexin 43) mutation causing oculodentodigital dysplasia associated to uncommon features.
de la Parra D.R.; Zenteno J.C.;
Ophthalmic Genet. 28:198-202(2007)
Cited for: VARIANT ODDD VAL-2;

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.