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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P29033: Variant p.Met34Thr

Gap junction beta-2 protein
Gene: GJB2
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Variant information Variant position: help 34 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 Methionine (M) to Threonine (T) at position 34 (M34T, p.Met34Thr). 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 medium size and hydrophobic (M) to medium size and polar (T) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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

Variant description: help In DFNB1A; it is correctly synthesized and targeted to the plasma membrane; it inefficiently forms intercellular channels that display an abnormal electrical behavior. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 34 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 226 The length of the canonical sequence.
Location on the sequence: help NKHSTSIGKIWLTVLFIFRI M ILVVAAKEVWGDEQADFVCN 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                         NKHSTSIGKIWLTVLFIFRIMILVVAAKEVWGDEQADFVCN

Gorilla                       NKHSTSIGKIWLTVLFIFRIMILVVAAKEVWGDEQADFVCN

Rhesus macaque                NKYSTSIGKIWLTVLFIFRIMILVVAAKEVWGDEQADFVCN

Mouse                         NKHSTSIGKIWLTVLFIFRIMILVVAAKEVWGDEQADFVCN

Rat                           NKHSTSIGKIWLTVLFIFRIMILVVAAKEVWGDEQADFVCN

Bovine                        NKHSTSIGKIWLTVLFIFRIMILVVAAKEVWGDEQADFVCN

Sheep                         NKHSTSIGKIWLTVLFIFRIMILVVAAKEVWGDEQADFVCN

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 1 – 226 Gap junction beta-2 protein
Transmembrane 21 – 40 Helical
Binding site 42 – 42 in other chain
Binding site 45 – 45
Binding site 47 – 47
Mutagenesis 34 – 34 M -> A. Loss of gap junction ion conductance, probably due to very low open probability of the channels. Can form functional channels with wild-type, but with strongly reduced channel conductance. No visible effect on channel assembly and membrane insertion.
Helix 19 – 38



Literature citations
Connexin 26 mutations in hereditary non-syndromic sensorineural deafness.
Kelsell D.P.; Dunlop J.; Stevens H.P.; Lench N.J.; Liang J.N.; Parry G.; Mueller R.F.; Leigh I.M.;
Nature 387:80-83(1997)
Cited for: VARIANT DFNB1A THR-34; Connexin mutations and hearing loss.
Scott D.A.; Kraft M.L.; Tone M.M.; Sheffield V.C.; Smith R.J.H.;
Nature 391:32-32(1998)
Cited for: VARIANT DFNB1A THR-34; Identification of mutations in the connexin 26 gene that cause autosomal recessive nonsyndromic hearing loss.
Scott D.A.; Kraft M.L.; Carmi R.; Ramesh A.; Elbedour K.; Yairi Y.; Srikumari Srisailapathy C.R.; Rosengren S.S.; Markham A.F.; Mueller R.F.; Lench N.J.; van Camp G.; Smith R.J.H.; Sheffield V.C.;
Hum. Mutat. 11:387-394(1998)
Cited for: VARIANTS LEU-83 AND SER-160; VARIANT DFNB1A THR-34; Clinical evidence of the nonpathogenic nature of the M34T variant in the connexin 26 gene.
Feldmann D.; Denoyelle F.; Loundon N.; Weil D.; Garabedian E.N.; Couderc R.; Joannard A.; Schmerber S.; Delobel B.; Leman J.; Journel H.; Catros H.; Ferrec C.; Drouin-Garraud V.; Obstoy M.F.; Moati L.; Petit C.; Marlin S.;
Eur. J. Hum. Genet. 12:279-284(2004)
Cited for: VARIANT DFNB1A THR-34; Pathogenetic role of the deafness-related M34T mutation of Cx26.
Bicego M.; Beltramello M.; Melchionda S.; Carella M.; Piazza V.; Zelante L.; Bukauskas F.F.; Arslan E.; Cama E.; Pantano S.; Bruzzone R.; D'Andrea P.; Mammano F.;
Hum. Mol. Genet. 15:2569-2587(2006)
Cited for: CHARACTERIZATION OF VARIANT DFNB1A THR-34; PATHOGENIC ROLE OF VARIANT DFNB1A THR-34; FUNCTION; SUBCELLULAR LOCATION; M34T and V37I mutations in GJB2 associated hearing impairment: evidence for pathogenicity and reduced penetrance.
Pollak A.; Skorka A.; Mueller-Malesinska M.; Kostrzewa G.; Kisiel B.; Waligora J.; Krajewski P.; Oldak M.; Korniszewski L.; Skarzynski H.; Ploski R.;
Am. J. Med. Genet. A 143:2534-2543(2007)
Cited for: VARIANTS DFNB1A THR-34 AND ILE-37; Consensus interpretation of the p.Met34Thr and p.Val37Ile variants in GJB2 by the ClinGen Hearing Loss Expert Panel.
Shen J.; Oza A.M.; Del Castillo I.; Duzkale H.; Matsunaga T.; Pandya A.; Kang H.P.; Mar-Heyming R.; Guha S.; Moyer K.; Lo C.; Kenna M.; Alexander J.J.; Zhang Y.; Hirsch Y.; Luo M.; Cao Y.; Wai Choy K.; Cheng Y.F.; Avraham K.B.; Hu X.; Garrido G.; Moreno-Pelayo M.A.; Greinwald J.; Zhang K.; Zeng Y.; Brownstein Z.; Basel-Salmon L.; Davidov B.; Frydman M.; Weiden T.; Nagan N.; Willis A.; Hemphill S.E.; Grant A.R.; Siegert R.K.; DiStefano M.T.; Amr S.S.; Rehm H.L.; Abou Tayoun A.N.;
Genet. Med. 21:2442-2452(2019)
Cited for: CONFIRMED PATHOGENICITY OF VARIANTS DFNB1A THR-34 AND ILE-37;
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.