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UniProtKB/Swiss-Prot P29033: Variant p.Arg75Gln

Gap junction beta-2 protein
Gene: GJB2
Variant information

Variant position:  75
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 Arginine (R) to Glutamine (Q) at position 75 (R75Q, p.Arg75Gln).
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 basic (R) to medium size and polar (Q)
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:  Keratoderma, palmoplantar, with deafness (PPKDFN) [MIM:148350]: An autosomal dominant disorder characterized by the association of palmoplantar hyperkeratosis with progressive, bilateral, high-frequency, sensorineural deafness. {ECO:0000269|PubMed:10633135, ECO:0000269|PubMed:10757647, ECO:0000269|PubMed:12372058, ECO:0000269|PubMed:12668604, ECO:0000269|PubMed:15996214, ECO:0000269|PubMed:17993581, ECO:0000269|PubMed:9856479}. 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 PPKDFN; the mutant protein completely prevents the formation of functional channels.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  75
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  226
The length of the canonical sequence.

Location on the sequence:   TLQPGCKNVCYDHYFPISHI  R LWALQLIFVSTPALLVAMHV
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                         TLQPGCKNVCYDHYFPISHIRLWALQLIFVSTPALLVAMHV

Gorilla                       TLQPGCKNVCYDHYFPISHIRLWALQLIFVSTPALLVAMHV

Rhesus macaque                TLQPGCKNVCYDHYFPISHIRLWALQLIFVSTPALLVAMHV

Mouse                         TLQPGCKNVCYDHHFPISHIRLWALQLIMVSTPALLVAMHV

Rat                           TLQPGCKNVCYDHYFPISHIRLWALQLIMVSTPALLVAMHV

Bovine                        TLQPGCKNVCYDHYFPISHIRLWALQLIFVSTPALLVAMHV

Sheep                         TLQPGCKNVCYDHYFPISHIRLWALQLIFVSTPALLVAMHV

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 – 226 Gap junction beta-2 protein
Transmembrane 74 – 94 Helical
Disulfide bond 53 – 180
Disulfide bond 60 – 174
Disulfide bond 64 – 169
Helix 73 – 83


Literature citations

The novel R75Q mutation in the GJB2 gene causes autosomal dominant hearing loss and palmoplantar keratoderma in a Turkish family.
Uyguner O.; Tukel T.; Baykal C.; Eris H.; Emiroglu M.; Hafiz G.; Ghanbari A.; Baserer N.; Yuksel-Apak M.; Wollnik B.;
Clin. Genet. 62:306-309(2002)
Cited for: VARIANT PPKDFN GLN-75;

Functional analysis of R75Q mutation in the gene coding for Connexin 26 identified in a family with nonsyndromic hearing loss.
Piazza V.; Beltramello M.; Menniti M.; Colao E.; Malatesta P.; Argento R.; Chiarella G.; Gallo L.V.; Catalano M.; Perrotti N.; Mammano F.; Cassandro E.;
Clin. Genet. 68:161-166(2005)
Cited for: VARIANT PPKDFN GLN-75; CHARACTERIZATION OF VARIANT PPKDFN GLN-75;

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.