GJB6

Chr 13

gap junction protein beta 6

Also known as: CX30, DFNA3, DFNA3B, DFNB1B, ECTD2, ED2, EDH, HED

NCBI Gene: 10804 ENSG00000121742 UniProt: O95452

GJB6 encodes connexin-30, a gap junction protein that forms transmembrane channels allowing small molecules and ions to pass between adjacent cells. Mutations cause autosomal recessive or dominant nonsyndromic hearing loss and hidrotic ectodermal dysplasia, a condition affecting hair, nails, teeth, and sweat glands. This gene is not highly constrained against loss-of-function variants.

GeneReviews ResearchSummary from RefSeq, UniProt

Gap junctions allow the transport of ions and metabolites between the cytoplasm of adjacent cells. They are formed by two hemichannels, made up of six connexin proteins assembled in groups. Each connexin protein has four transmembrane segments, two extracellular loops, a cytoplasmic loop formed between the two inner transmembrane segments, and the N- and C-terminus both being in the cytoplasm. The specificity of the gap junction is determined by which connexin proteins comprise the hemichannel. In the past, connexin protein names were based on their molecular weight, however the new nomenclature uses sequential numbers based on which form (alpha or beta) of the gap junction is present. This gene encodes one of the connexin proteins. Mutations in this gene have been found in some forms of deafness and in some families with hidrotic ectodermal dysplasia. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtEctodermal dysplasia 2, Clouston type

UniProtDeafness, autosomal recessive, 1B

UniProtDeafness, autosomal dominant, 3B

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.74

LOEUF

LOF*

Mechanism· G2P

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GeneReview available — GJB6

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.74LOEUF

pLI 0.000

Z-score -0.21

OE 1.07 (0.66–1.74)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.45Z-score

OE missense 0.90 (0.78–1.03)

134 obs / 149.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.07 (0.66–1.74)

0≤0.351.4

Missense OE?0.90 (0.78–1.03)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 10 / 9.3Missense obs/exp: 134 / 149.6Syn Z: -0.49

Background carrier burden — how many people carry a rare variant somewhere in GJB6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

323 rare PASS variants

Rare truncating (LoF)

1 in 340

59 rare PASS variants

Rare synonymous (reference)

1 in 220

145 rare PASS variants

Rare missense and truncating variants are carried at similar rates in GJB6; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 200	1 in 280
South Asian	~43k	1 in 260	1 in 1,300
Remaining (unassigned)	~30k	1 in 160	1 in 320
European (Finnish)	~27k	1 in 1,600	1 in 3,800
Admixed American	~22k	1 in 140	1 in 1,700
African / African American	~21k	1 in 200	1 in 1,100
East Asian	~20k	1 in 230	1 in 900
Ashkenazi Jewish	~13k	1 in 290	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 180	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓