GNA12

Chr 7

G protein subunit alpha 12

Also known as: HG1M1, NNX3, RMP, gep

NCBI Gene: 2768ENSG00000146535UniProt: Q03113

Enables G protein activity; protein phosphatase 2A binding activity; and protein phosphatase activator activity. Involved in Rho-activating G protein-coupled receptor signaling pathway; regulation of TOR signaling; and regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in lateral plasma membrane; neuron projection; and neuronal cell body. Is active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2025]

97
ClinVar variants
36
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— GNA12
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 56 VUS of 97 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.28LOEUF
pLI 0.970
Z-score 3.05
OE 0.00 (0.00–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.09Z-score
OE missense 0.60 (0.52–0.69)
131 obs / 218.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.60 (0.52–0.69)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.23
0≤1.21.6
LoF obs/exp: 0 / 10.8Missense obs/exp: 131 / 218.0Syn Z: -1.74

ClinVar Variant Classifications

97 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
VUS56
Likely Benign4
Benign1
36
Pathogenic
56
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
36
0
36
Likely Pathogenic
0
0
0
0
0
VUS
0
45
11
0
56
Likely Benign
0
3
0
1
4
Benign
0
0
0
1
1
Total04847297

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GNA12 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Acid sphingomyelinase activity suggests a new antipsychotic pharmaco-treatment strategy for schizophrenia.
Chestnykh D et al.·Mol Psychiatry
2025
Genetic Risk Factors in Normal Pressure Hydrocephalus: What We Know and What Is Next.
Piccinin CC et al.·Mov Disord
2025
Identification of the clinical and genetic characteristics of gliomas with gene fusions by integrated genomic and transcriptomic analysis.
Yi GZ et al.·Eur J Med Res
2025
Examination of chromosome 7p22 candidate genes RBaK, PMS2 and GNA12 in familial hyperaldosteronism type II.
Jeske YW et al.·Clin Exp Pharmacol Physiol
2008
New IBD genetics: common pathways with other diseases.
Lees CW et al.·Gut
2011Review
G-protein genomic association with normal variation in gray matter density.
Chen J et al.·Hum Brain Mapp
2015
Variable developmental delays and characteristic facial features-A novel 7p22.3p22.2 microdeletion syndrome?
Yu AC et al.·Am J Med Genet A
2017
Epigenome-wide DNA methylation profiling of conditioned pain modulation in individuals with non-specific chronic low back pain.
Goodin BR et al.·Clin Epigenetics
2022
DNA methylation of hypertension-related genes and effect of riboflavin supplementation in adults stratified by genotype for the MTHFR C677T polymorphism.
Amenyah SD et al.·Int J Cardiol
2021
Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma.
Koma A et al.·Int J Mol Sci
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools