GJD2

Chr 15

gap junction protein delta 2

Also known as: CX36, GJA9

NCBI Gene: 57369 ENSG00000159248 UniProt: Q9UKL4 OMIM: 607058

This gene encodes a member of the connexin protein family. Connexins are gap junction proteins which are arranged in groups of 6 around a central pore to form a connexon, a component of the gap junction intercellular channel. The channels formed by this protein allow cationic molecule exchange between human beta cells and may function in the regulation of insulin secretion. [provided by RefSeq, Oct 2012]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.70

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.70LOEUF

pLI 0.197

Z-score 2.24

OE 0.27 (0.12–0.70)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.43Z-score

OE missense 0.50 (0.42–0.59)

91 obs / 183.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.27 (0.12–0.70)

0≤0.351.4

Missense OE?0.50 (0.42–0.59)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 3 / 11.0Missense obs/exp: 91 / 183.8Syn Z: -0.81

Background carrier burden — how many people carry a rare variant somewhere in GJD2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 280

294 rare PASS variants

Rare truncating (LoF)

1 in 10,000

28 rare PASS variants

Rare synonymous (reference)

1 in 410

179 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GJD2. 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 380	1 in 6,100
South Asian	~43k	1 in 370	≈ 1 in 22,000
Remaining (unassigned)	~30k	1 in 210	≈ 1 in 10,000
European (Finnish)	~27k	1 in 1,300	≈ 1 in 27,000
Admixed American	~22k	1 in 190	none seen
African / African American	~21k	1 in 460	≈ 1 in 17,000
East Asian	~20k	1 in 310	none seen
Ashkenazi Jewish	~13k	1 in 500	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 410	none seen

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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓