GNG12

Chr 1

G protein subunit gamma 12

Also known as: HG3A

NCBI Gene: 55970 ENSG00000172380 UniProt: Q9UBI6

The protein is a gamma subunit of heterotrimeric G proteins that modulates transmembrane signaling by facilitating GTPase activity and effector interactions in G protein-coupled receptor pathways. Currently, no established human diseases have been definitively linked to mutations in this gene. The gene shows moderate tolerance to loss-of-function variants based on population genetics data.

ResearchSummary from RefSeq, UniProt

Enables PDZ domain binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]

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

1.05

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?

1.05LOEUF

pLI 0.589

Z-score 1.54

OE 0.00 (0.00–1.05)

Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint?

0.67Z-score

OE missense 0.69 (0.51–0.96)

26 obs / 37.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.05)

0≤0.351.4

Missense OE?0.69 (0.51–0.96)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 0 / 2.8Missense obs/exp: 26 / 37.6Syn Z: -0.22

Background carrier burden — how many people carry a rare variant somewhere in GNG12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 580

72 rare PASS variants

Rare truncating (LoF)

1 in 49,000

5 rare PASS variants

Rare synonymous (reference)

1 in 460

29 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GNG12. 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 570	1 in 46,000
South Asian	~43k	1 in 2,200	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 630	none seen
European (Finnish)	~27k	1 in 670	none seen
Admixed American	~22k	1 in 790	≈ 1 in 22,000
African / African American	~21k	1 in 650	≈ 1 in 17,000
East Asian	~20k	1 in 1,500	none seen
Middle Eastern	~2,884	1 in 320	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): 1 of 2 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 2.? see exons ↓