GNG3

Chr 11

G protein subunit gamma 3

Also known as: HG3D

NCBI Gene: 2785 ENSG00000162188 UniProt: P63215

The protein encoded by GNG3 is the gamma subunit of heterotrimeric G proteins that modulates transmembrane signaling by determining specificity of signaling pathways and enabling GTPase activity and effector interactions. Mutations cause autosomal recessive cone dystrophy with supernormal rod response, a retinal disorder affecting color vision and central visual acuity.

ResearchSummary from RefSeq, UniProt

Guanine nucleotide binding proteins are heterotrimeric signal-transducing molecules consisting of alpha, beta, and gamma subunits. The gamma subunit determines the specificity of which signaling pathways will be affected by this particular complex. The protein encoded by this gene represents the gamma subunit of both inhibitory and stimulatory complexes. [provided by RefSeq, Jan 2012]

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

1.22

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

Moderate LoF intolerance

LoF Constraint?

1.22LOEUF

pLI 0.542

Z-score 1.41

OE 0.00 (0.00–1.22)

Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint?

1.16Z-score

OE missense 0.52 (0.38–0.73)

24 obs / 46.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.22)

0≤0.351.4

Missense OE?0.52 (0.38–0.73)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 0 / 2.3Missense obs/exp: 24 / 46.2Syn Z: -0.31

Background carrier burden — how many people carry a rare variant somewhere in GNG3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 3,300

69 rare PASS variants

Rare truncating (LoF)

1 in 73,000

8 rare PASS variants

Rare synonymous (reference)

1 in 590

31 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GNG3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 8 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 4,400	1 in 69,000
South Asian	~43k	1 in 1,600	none seen
Remaining (unassigned)	~30k	≈ 1 in 15,000	≈ 1 in 30,000
Admixed American	~22k	1 in 2,800	none seen
African / African American	~21k	1 in 1,400	none seen
East Asian	~20k	1 in 1,600	none seen
Ashkenazi Jewish	~13k	none seen	≈ 1 in 13,000
Middle Eastern	~2,884	≈ 1 in 2,900	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 ↓