GJB2 gap junction protein, beta 2, 26kDa [Homo sapiens] - Gene

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Summary

Official Symbol: GJB2provided by HGNC
Official Full Name: gap junction protein, beta 2, 26kDaprovided by HGNC
Primary source: HGNC:4284
See related: Ensembl:ENSG00000165474; HPRD:00413; MIM:121011; Vega:OTTHUMG00000016513
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HID; KID; PPK; CX26; DFNA3; DFNB1; NSRD1; DFNA3A; DFNB1A
Summary: 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]

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Genomic context

Location :: 13q11-q12

Sequence :: Chromosome: 13; NC_000013.10 (20761602..20767114, complement)

See GJB2 in Epigenomics, MapViewer

Chromosome 13 - NC_000013.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

genetic analysis of the GJB2 gene identified connexin 26 mutations in 22 patients out of 45 with cochlear implants.
Title: Prevalence of mutations located at the dfnb1 locus in a population of cochlear implanted children in eastern Romania.
MUltiplex ligation dependent probe amplification screening of deaf Brazilian patients found 46 with mutations in only one GJB2 allele, 13 with different pathogenic mutations in c.35delG, and 2 with digenic heterozygous mutations.
Title: Searching for digenic inheritance in deaf Brazilian individuals using the multiplex ligation-dependent probe amplification technique.
A de novo GJB2 p.R184Q mutation can cause severe-to-profound bilateral sensorineural hearing impairment, although not common in Chinese patients.
Title: De novo dominant mutation of GJB2 in two Chinese families with nonsyndromic hearing loss.
A digenic effect of MITF and GJB2 genes may contribute to deafness of the proband in a large Chinese family with Waardenburg syndrome type II.
Title: A novel mutation in the MITF may be digenic with GJB2 mutations in a large Chinese family of Waardenburg syndrome type II.
Preimplantation genetic diagnosis (PGD) of monogenic disorders is a very efficient method, especially for patients whose previous child is homozygous for genetic disorders.
Title: [Preimplantaion genetic diagnosis of hearing loss with 35delG mutation in GJB2 gene - preliminary report].
GJB2 235delC heterozygous carriers may be a risk group for high-frequency hearing loss.
Title: [Tonal audiometry of GJB2 235delC single heterozygous mutation carriers].
A neonatal hearing screening program in Campania, Italy confirmed that GJB2 c.35delG homozygotes tend to have severe symmetrical hearing loss, whereas hearing impairment is milder in compound heterozygotes.
Title: Mutational analysis for GJB2, GJB6, and GJB3 genes in Campania within a universal neonatal hearing screening programme.
The frequency of GJB2 mutation is relatively low in these consanguineous families, most of which were minorities. Our results suggest that screening for responsible genes other than GJB2 may be necessary for NSHI in these minorities.
Title: Low frequency of GJB2 mutations in thirty-five students with hearing loss in Chinese consanguineous families.
These findings characterize Eastern Siberia as the region with the most extensive accumulation of the splice site mutation IVS1+1G>A mutation in the GJB2 gene as a result of founder effect.
Title: Autosomal recessive deafness 1A (DFNB1A) in Yakut population isolate in Eastern Siberia: extensive accumulation of the splice site mutation IVS1+1G>A in GJB2 gene as a result of founder effect.
IVS1+1G>A, a splice site mutation of GJB2, was assessed for its significance as the autosomal recessive non-syndromic genetic load among Iranian Azeri Turkish patients
Title: Prevalence of IVS1+1G>A mutation among Iranian Azeri Turkish patients with autosomal recessive non-syndromic hearing loss (ARNSHL).

Submit: New GeneRIF Correction See all (335)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Deafness, autosomal dominant 3A

MIM: 601544

Deafness, autosomal recessive 1A

MIM: 220290

Summary from GeneReviews:

Disease Characteristics

Nonsyndromic hearing loss and deafness (DFNB1) is characterized by congenital, non-progressive, mild-to-profound sensorineural hearing impairment. No other associated medical findings are present.

Diagnosis of DFNB1 depends on molecular genetic testing to identify deafness-causing mutations in GJB2 and/or GJB6 that alter the gap junction beta-2 protein (connexin 26) and the gap junction beta-6 protein (connexin 30), respectively. Clinically available molecular genetic testing of GJB2 and GJB6 detects more than 99% of deafness-causing mutations in these genes.

Genetic Counseling

DFNB1 is inherited in an autosomal recessive or possibly digenic manner. In each pregnancy, the parents of a proband have a 25% chance of having a deaf child, a 50% chance of having a hearing child who is a carrier, and a 25% chance of having a hearing child who is not a carrier. Once an at-risk sib is known to be hearing, the chance of his/her being a carrier is 2/3. When the mutations causing DFNB1 are detected in one family member, carrier testing for at-risk family members and prenatal testing for at-risk pregnancies are possible.

Interactions

Products	Interactant	Other Gene	Source	Pubs	Description
P29033	Q03135	CAV1	HPRD	PubMed
P29033	P08034	GJB1	HPRD	PubMed
P29033	O95452	GJB6	HPRD	PubMed
BioGRID:108972	BioGRID:107305	CAV1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108972	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

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General gene information

Markers

RH78858 (e-PCR)
- UniSTS:83384

GJB2 (e-PCR)
- UniSTS:480198

Genotypes

See GJB2 SNP Geneview Report
See GJB2 SNP Genotype Report
See GJB2 SNP Variation Viewer Report

Homology

Map Viewer (Mouse, Rat)

Pathways from BioSystems

Calcium Regulation in the Cardiac Cell, organism-specific biosystem (from WikiPathways)
Calcium Regulation in the Cardiac Cell, organism-specific biosystemCalcium is a common signaling mechanism, as once it enters the cytoplasm it exerts allosteric regulatory affects on many enzymes and proteins. Calcium can act in signal transduction after influx resu...
Gap junction assembly, organism-specific biosystem (from REACTOME)
Gap junction assembly, organism-specific biosystemThe assembly of gap junctions involves (1) synthesis of connexin polypeptides at endoplasmic reticulum membranes, (2) oligomerization into homomeric- and heteromeric gap junction connexons (hemi-chan...
Gap junction trafficking, organism-specific biosystem (from REACTOME)
Gap junction trafficking, organism-specific biosystemGap junctions are intercellular communication channels formed from Cx (connexin) protein subunits (see Segretain and Falk 2004 and Evans et al. 2006 for comprehensive reviews). Connexins are transpor...
Gap junction trafficking and regulation, organism-specific biosystem (from REACTOME)
Gap junction trafficking and regulation, organism-specific biosystemGap junctions are clusters of intercellular channels connecting adjacent cells and permitting the direct exchange of ions and small molecules between cells. These channels are composed of two hemicha...
Membrane Trafficking, organism-specific biosystem (from REACTOME)
Membrane Trafficking, organism-specific biosystemThe secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is ma...
Oligomerization of connexins into connexons, organism-specific biosystem (from REACTOME)
Oligomerization of connexins into connexons, organism-specific biosystemThe mechanism of connexin assembly into connexons has been well characterized. Two different types of connexons can be formed. A connexon containing six identical connexin molecules is referred to as...
Transport of connexins along the secretory pathway, organism-specific biosystem (from REACTOME)
Transport of connexins along the secretory pathway, organism-specific biosystemConnexins follow the classical secretory transport route from the ER to the plasma membrane: ER -> ERGIC -> Golgi -> TGN (Trans Golgi Network) -> PM (Plasma Membrane). All connexins assemble or oli...
Transport of connexons to the plasma membrane, organism-specific biosystem (from REACTOME)
Transport of connexons to the plasma membrane, organism-specific biosystemFollowing connexon oligomerization, the hemichannels must be transported to the plasma membrane. This has been shown to occur in transport vesicles called "cargo containers". Most of post-Golgi carg...

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
gap junction channel activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
cell-cell signaling	IEA Inferred from Electronic Annotation more info
cellular membrane organization	TAS Traceable Author Statement more info
gap junction assembly	TAS Traceable Author Statement more info
male genitalia development	IEA Inferred from Electronic Annotation more info
sensory perception of sound	IEA Inferred from Electronic Annotation more info
transport	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
cell junction	IEA Inferred from Electronic Annotation more info
connexon complex	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum-Golgi intermediate compartment	TAS Traceable Author Statement more info
integral to membrane	IEA Inferred from Electronic Annotation more info
lateral plasma membrane	IEA Inferred from Electronic Annotation more info
plasma membrane	TAS Traceable Author Statement more info

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General protein information

Preferred Names: gap junction beta-2 protein

Names: gap junction beta-2 protein; connexin 26; gap junction protein beta 2

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008358.1 RefSeqGene

Range

5001..10513

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_004004.5 → NP_003995.2 gap junction beta-2 protein

Status: REVIEWED

Source sequence(s)

AA962716, BC017048, BC071703, BI491091, DA287424

Consensus CDS

CCDS9290.1

UniProtKB/Swiss-Prot

P29033

Related

ENSP00000372299, OTTHUMP00000018093, ENST00000382848, OTTHUMT00000044063

Conserved Domains (2) summary

cl02435
Location:2 – 108
Blast Score: 531

Connexin; Connexin

cl11207
Location:146 – 213
Blast Score: 304

Connexin_CCC; Gap junction channel protein cysteine-rich domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000013.10 Reference GRCh37.p5 Primary Assembly

Range

20761602..20767114, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000145.1 Alternate HuRef

Range

1567054..1572566, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AF281280.1	AAF91440.1
genomic	AF479776.1	AAL87696.1
genomic	AL138688.27	CAC16959.1
genomic	AY255853.1	AAP34178.1
genomic	AY275646.1	AAQ94940.1
genomic	AY275648.1	AAQ94942.1
genomic	AY275649.1	AAQ94943.1
genomic	AY275650.1	AAQ94944.1
genomic	AY275651.1	AAQ94945.1
genomic	AY275652.1	AAQ94946.1
genomic	AY275653.1	AAQ94947.1
genomic	AY275654.1	AAQ94948.1
genomic	AY280971.1	AAQ17213.1
genomic	AY953438.1	AAY25169.1
genomic	AY953441.1	AAY25170.1
genomic	CH471075.1	EAX08252.1
		EAX08253.1
genomic	JQ595559.1	AFG29041.1
genomic	U43932.1	AAD14840.1
mRNA	AA947181.1	None
mRNA	AA962716.1	None
mRNA	AK225966.1	None
mRNA	AK313595.1	BAG36361.1
mRNA	BC017048.1	AAH17048.1
mRNA	BC071703.1	AAH71703.1
mRNA	BI491091.1	None
mRNA	BT006732.1	AAP35378.1
mRNA	DA287424.1	None
mRNA	JQ342677.1	AFG29040.1
mRNA	M86849.2	AAD21314.1
other-genetic	DQ891797.2	ABM82723.1
other-genetic	DQ894980.2	ABM85906.1