GNG4

Chr 1

G protein subunit gamma 4

Also known as: HG3C

NCBI Gene: 2786ENSG00000168243UniProt: P50150

Predicted to enable G-protein beta-subunit binding activity. Involved in negative regulation of cell growth. Located in extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]

74
ClinVar variants
51
Pathogenic / LP
0.16
pLI score
0
Active trials
Clinical Summary— GNG4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.16) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
51 Pathogenic / Likely Pathogenic· 21 VUS of 74 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.71LOEUF
pLI 0.156
Z-score 0.72
OE 0.47 (0.16–1.71)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.68Z-score
OE missense 0.72 (0.54–0.96)
32 obs / 44.7 exp
Tolerant

Mild missense constraint

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.0.47 (0.16–1.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.54–0.96)
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.0.59
0≤1.21.6
LoF obs/exp: 1 / 2.1Missense obs/exp: 32 / 44.7Syn Z: 1.26

ClinVar Variant Classifications

74 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic2
VUS21
Likely Benign2
49
Pathogenic
2
Likely Pathogenic
21
VUS
2
Likely Benign

Curated Variants Distribution

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

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————49
Likely Pathogenic
————2
VUS
————21
Likely Benign
————2
Benign
————0
Total—74

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GNG4 · 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
📖
GeneReview available — GNG4
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
High GNG4 expression is associated with poor prognosis in patients with lung adenocarcinoma.
Zhou B et al.·Thorac Cancer
2022Cohort
Clinical Characteristics and Outcomes of Acute Myeloid Leukemia Patients Harboring NPM1/FLT3-ITD/DNMT3A Triple Mutations and the Potential Prognostic Value of GNG4.
Niu Y et al.·Cancer Control
2025Cohort
GNG4, as a potential predictor of prognosis, is correlated with immune infiltrates in colon adenocarcinoma.
Wang J et al.·J Cell Mol Med
2023
Identifying GNG4 might play an important role in colorectal cancer TMB.
Zhao H et al.·Cancer Biomark
2021
Targeting GNG4 inhibits tumor progression and restores enzalutamide sensitivity in prostate cancer by suppressing autophagy.
Chen L et al.·Cell Death Dis
2026
Construction of circRNA-miRNA-mRNA network in the pathogenesis of recurrent implantation failure using integrated bioinformatics study.
Ahmadi M et al.·J Cell Mol Med
2022
Identification of differentially methylated genes as diagnostic and prognostic biomarkers of breast cancer.
Mao XH et al.·World J Surg Oncol
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