The protein functions as a gamma subunit of heterotrimeric G-proteins, enabling G-protein beta-subunit binding and participating in G protein-coupled receptor signaling pathways at the plasma membrane. Mutations in this gene cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, seizures, and developmental delay. The gene shows low constraint against loss-of-function variants, which is consistent with the recessive inheritance pattern observed in affected patients.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.96
Clinical SummaryGNG10
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.96LOEUF
pLI 0.000
Z-score -1.60
OE 2.13 (0.851.96)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.74Z-score
OE missense 0.63 (0.440.92)
20 obs / 31.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE2.13 (0.851.96)
00.351.4
Missense OE0.63 (0.440.92)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 5 / 2.4Missense obs/exp: 20 / 31.7Syn Z: 0.09
DN
0.75top 25%
GOF
0.82top 10%
LOF
0.2777th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GNG10 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found