GJB2

Protein identityUniProt · HPA

UniProt accession

P29033

Gene

GJB2

Ensembl

ENSG00000165474

Chromosome

13

Canonical length

226 aa

Protein class

Disease related genes, Human disease related genes, Potential drug targets, Predicted membrane proteins, Transporters

Subcellular location

Mitochondria

OverviewNCBI Gene

This gene encodes a member of the gap junction protein family. The gap junctions were first characterized by electron microscopy as regionally specialized structures on plasma membranes of contacting adherent cells. These structures were shown to consist of cell-to-cell channels that facilitate the transfer of ions and small molecules between cells. The gap junction proteins, also known as connexins, purified from fractions of enriched gap junctions from different tissues differ. According to sequence similarities at the nucleotide and amino acid levels, the gap junction proteins are divided into two categories, alpha and beta. Mutations in this gene are responsible for as much as 50% of pre-lingual, recessive deafness. [provided by RefSeq, Oct 2008]

Canonical amino-acid sequenceUniProt

226 residues, UniProt reviewed canonical sequence.

>P29033|GJB2
     1  MDWGTLQTIL GGVNKHSTSI GKIWLTVLFI FRIMILVVAA KEVWGDEQAD FVCNTLQPGC
    61  KNVCYDHYFP ISHIRLWALQ LIFVSTPALL VAMHVAYRRH EKKRKFIKGE IKSEFKDIEE
   121  IKTQKVRIEG SLWWTYTSSI FFRVIFEAAF MYVFYVMYDG FSMQRLVKCN AWPCPNTVDC
   181  FVSRPTEKTV FTVFMIAVSG ICILLNVTEL CYLLIRYCSG KSKKPV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GJB2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

4

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

780 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GJB2.

Disease | AllUniProt

Conditions GJB2 is implicated in, by any mechanism.

• Deafness, autosomal recessive, 1A (DFNB1A) MIM:220290
• Deafness, autosomal dominant, 3A (DFNA3A) MIM:601544
• Vohwinkel syndrome (VOWNKL) MIM:124500
• Keratoderma, palmoplantar, with deafness (PPKDFN) MIM:148350
• Keratitis-ichthyosis-deafness syndrome, autosomal dominant (KIDAD) MIM:148210
• Bart-Pumphrey syndrome (BAPS) MIM:149200
• Ichthyosis hystrix-like with deafness syndrome (HID syndrome) MIM:602540

Disease | GeneticClinVar

257 pathogenic / likely-pathogenic of 667 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive nonsyndromic hearing loss 1A
• Nonsyndromic genetic hearing loss
• 7 conditions
• Rare genetic deafness
• Autosomal dominant nonsyndromic hearing loss 3A

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.98

gnomAD pLI

0

gnomAD missense Z

-0.72

DepMap mean gene effect

-0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell-cell signaling
• gap junction assembly
• gap junction-mediated intercellular transport
• sensory perception of sound
• transmembrane transport

Molecular functions

• calcium ion binding
• gap junction channel activity
• gap junction channel activity involved in cell communication by electrical coupling
• identical protein binding

Cellular components

• connexin complex
• endoplasmic reticulum-Golgi intermediate compartment
• gap junction
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Connexin
• Connexin, N-terminal
• Connexin, conserved site
• Connexin, cysteine-rich domain
• Connexin, N-terminal domain superfamily
• Connexin
• Connexin 26

KeywordsUniProt

• Calcium
• Cell junction
• Cell membrane
• Deafness
• Disulfide bond
• Ectodermal dysplasia
• Gap junction
• Hearing
• Ichthyosis
• Membrane
• Metal-binding
• Non-syndromic deafness
• Palmoplantar keratoderma
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of GJB2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CNST