GNG12

Chr 1

G protein subunit gamma 12

Also known as: HG3A

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.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
8
Pubs (1 yr)
23
P/LP submissions
P/LP missense
1.05
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryGNG12
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.59) — some intolerance to loss-of-function variants.
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ClinVar Variants
23 unique Pathogenic / Likely Pathogenic· 7 VUS of 34 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
1.05LOEUF
pLI 0.589
Z-score 1.54
OE 0.00 (0.001.05)
Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint
0.67Z-score
OE missense 0.69 (0.510.96)
26 obs / 37.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.001.05)
00.351.4
Missense OE0.69 (0.510.96)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 0 / 2.8Missense obs/exp: 26 / 37.6Syn Z: -0.22
DN
0.76top 25%
GOF
0.82top 10%
LOF
0.3939th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

34 submitted variants in ClinVar

Classification Summary

Pathogenic23
VUS7
23
Pathogenic
7
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
23
Likely Pathogenic
0
VUS
7
Likely Benign
0
Benign
0
Total30

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GNG12 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC