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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9Y6H8: Variant p.Arg76His

Gap junction alpha-3 protein
Gene: GJA3
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Variant information Variant position: help 76 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Arginine (R) to Histidine (H) at position 76 (R76H, p.Arg76His). 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: help Change from large size and basic (R) to medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 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
Variant description: help In CTRCT14; nearly abolishes formation of gap junctions; no significant effect on formation of functional hemichannels; not fully penetrant mutation. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 76 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 435 The length of the canonical sequence.
Location on the sequence: help TQQPGCENVCYDRAFPISHI R FWALQIIFVSTPTLIYLGHV 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         TQQPGCENVCYDRAFPISHIRFWALQIIFVSTPTLIYLGHV

Mouse                         TQQPGCENVCYDRAFPISHIRFWALQIIFVSTPTLIYLGHV

Rat                           TQQPGCENVCYDRAFPISHIRFWALQIIFVSTPTLIYLGHV

Bovine                        TQQPGCENVCYDRAFPISHVRFWVLQIIFVSTPTLIYLGHV

Sheep                         TQQPGCENVCYDRAFPISHVRFWVLQIIFVSTPTLIYLGHV

Chicken                       TQQPGCENVCYDKAFPISHIRFWVLQIIFVSTPTLIYLGHV
Sequence annotation in neighborhood: help 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 2 – 435 Gap junction alpha-3 protein
Transmembrane 72 – 92 Helical
Disulfide bond 54 – 192
Disulfide bond 61 – 186
Disulfide bond 65 – 181
Mutagenesis 76 – 76 R -> EK. Abolishes formation of gap junctions. No significant effect on formation of functional hemichannels.



Literature citations
A novel mutation in the Connexin 46 gene causes autosomal dominant congenital cataract with incomplete penetrance.
Burdon K.P.; Wirth M.G.; Mackey D.A.; Russell-Eggitt I.M.; Craig J.E.; Elder J.E.; Dickinson J.L.; Sale M.M.;
J. Med. Genet. 41:E106-E106(2004)
Cited for: VARIANT CTRCT14 HIS-76; Comprehensive mutational screening in a cohort of Danish families with hereditary congenital cataract.
Hansen L.; Mikkelsen A.; Nuernberg P.; Nuernberg G.; Anjum I.; Eiberg H.; Rosenberg T.;
Invest. Ophthalmol. Vis. Sci. 50:3291-3303(2009)
Cited for: VARIANTS CTRCT14 LEU-59 AND HIS-76; Alterations at Arg76 of human connexin 46, a residue associated with cataract formation, cause loss of gap junction formation but preserve hemichannel function.
Abrams C.K.; Peinado A.; Mahmoud R.; Bocarsly M.; Zhang H.; Chang P.; Botello-Smith W.M.; Freidin M.M.; Luo Y.;
Am. J. Physiol. 5:C623-C635(2018)
Cited for: CHARACTERIZATION OF VARIANTS CTRCT14 GLY-76 AND HIS-76; FUNCTION; SUBCELLULAR LOCATION; MUTAGENESIS OF ARG-76;
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.