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FLASH GENE
Symbol GJB2 contributors: mct/pgu - updated : 04-09-2017
HGNC name gap junction protein, beta 2, 26kDa
HGNC id 4284
DNA
TYPE functioning gene
STRUCTURE 5.51 kb     2 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
2 - 2347 - 226 - -
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Hearing/Equilibriumearinnercochlea highly Homo sapiensAdult
Reproductivemale systemmale genital tractepididymis   Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • four putative membrane spanning alpha helices (TM4)
  • N terminal intracellular domain
  • two extracellular loops
  • a VVAA motif of GJB2 in the TM1 is critical for TM1 dimerization, hexamer formation, and channel function
  • a C terminal intracellular domain
  • mono polymer heteromer , hexamer
    HOMOLOGY
    interspecies homolog to C.elegans T23D8.2
    intraspecies homolog to GJB6
    Homologene
    FAMILY
  • connexin family
  • beta-type (group 1) subfamily
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,gap
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    basic FUNCTION
  • oligomerizing to form intercellular channel that are clustered at gap junctions
  • playing a major role in homeostasis of the cortilymph through the epithelial cell system and in the function of the organ of Corti
  • maybe involved in cornified envelope formation
  • play a crucial role in inner ear Ca2+ signaling: as hemichannels, they promote ATP release, sustaining long-range intercellular Ca2+ signals propagation
  • play an important role in lymphatic invasion as well as lymph node and distant metastases in squamous lung cancer and breast cancer
  • both GJB2 and GJB6 play essential roles in normal cochlear functions
  • plays an essential role in the postnatal development of the normal cochlear sensory epithelium, the organ of Corti
  • plays an essential role in the development of the auditory sensory epithelium and its unique developmental functions required for normal hearing is not replaceable by GJB6
  • GJB2, and GJB6 have dramatically different temporal and cellular expression patterns during early postnatal cochlear development
  • GJB2- hemichannels may play a role in Ca(2+) influx into cells under conditions that lead to hemichannel activation, such as ischemic damage
  • appears to be essential for normal development of the auditory sensory epithelium, but may be dispensable during normal hearing
  • in the cochlea, GJB2, GJB6 largely co-assemble into heteromeric gap junctions, which connect adjacent non-sensory epithelial cells
  • presence of non-junctional GJB2/GJB6 oligomers within lipid raft-enriched tricellular junction sites
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cell to cell transport
    PATHWAY
    metabolism
    signaling sensory transduction/hearing
    a component
  • monomer constituent of the connexon (six subunits including GJA3, GJA8, GJB1, GJB2) and CX30/CX26 heteromer
  • GJB6 homomeric and GJB2/GJB6 heteromeric gap junctions exhibit distinct assembly mechanisms in the cochlea
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PTK2 modulates radial glia-dependent neuronal migration through GJB2
  • TCF12 functions as a regulator of EMT by affecting the expression of CDH1 as well as that of GJA1 and GJB2
  • GJB2-DNM2 interaction involves the C-terminus of GJB2 and the GTPase effector domain of DNM2, which is of particular importance for the regulation of the endocytic pathway, and DNM2 regulates GJB2 endocytosis and ubiquitination
  • cell & other
    REGULATION
    Other regulated by a Ca2+-dependent control in the expression of inner ear connexins implicated in hereditary deafness GJB2 and GJB6
    ASSOCIATED DISORDERS
    corresponding disease(s) DFNA3 , DFNB1 , KHM2 , KID , HID
    related resource Hereditary Hearing Loss Homepage
    Hereditary Hearing Loss at GeneDis
    The Connexin-deafness homepage
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    increasing cell survival
    tumoral     --low  
    in hepatocellular carcinoma
    Susceptibility
  • to hearing loss with GJB6 deletion associated
  • to hearing impairment
  • Variant & Polymorphism other
  • heterozygote mutation of DFNB1 increasing cell survival
  • variant M34T significantly associated with hearing impairment
  • a heterozygous mutation 32G->A transversion leading to the G11E substitution. Mutated protein shows abnormal properties in protein trafficking and membrane localization
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS