GJA3

Chr 13

gap junction protein alpha 3

Also known as: CTRCT14, CX46, CZP3

NCBI Gene: 2700 ENSG00000121743 UniProt: Q9Y6H8

This gene encodes connexin 43, a structural component of gap junctions that form dodecameric channels connecting the cytoplasm of adjacent lens fiber cells, allowing diffusion of small molecules and ions. Mutations cause autosomal dominant cataracts with multiple morphologic types, including zonular pulverulent cataracts. The gene shows low constraint to loss-of-function variants, consistent with a dominant inheritance pattern affecting lens development and transparency.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a connexin and is a component of lens fiber gap junctions. Defects in this gene are a cause of zonular pulverulent cataract type 3 (CZP3). [provided by RefSeq, Jan 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCataract 14, multiple types

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.49

LOEUF

Multiple*

Mechanism· predicted

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?

1.49LOEUF

pLI 0.001

Z-score 0.68

OE 0.72 (0.38–1.49)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.71Z-score

OE missense 0.70 (0.62–0.80)

186 obs / 264.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.38–1.49)

0≤0.351.4

Missense OE?0.70 (0.62–0.80)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 5 / 6.9Missense obs/exp: 186 / 264.3Syn Z: 0.87

Background carrier burden — how many people carry a rare variant somewhere in GJA3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

613 rare PASS variants

Rare truncating (LoF)

1 in 4,500

63 rare PASS variants

Rare synonymous (reference)

1 in 120

319 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GJA3. 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 160	1 in 4,200
South Asian	~43k	1 in 130	1 in 1,800
Remaining (unassigned)	~30k	1 in 150	1 in 4,900
European (Finnish)	~27k	1 in 570	1 in 4,900
Admixed American	~22k	1 in 120	1 in 2,400
African / African American	~21k	1 in 80	≈ 1 in 5,100
East Asian	~20k	1 in 92	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 550	none seen
Middle Eastern	~2,884	1 in 280	≈ 1 in 2,900

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 ↓