G3BP1

Chr 5

G3BP stress granule assembly factor 1

Also known as: G3BP, HDH-VIII

NCBI Gene: 10146ENSG00000145907UniProt: Q13283

This gene encodes one of the DNA-unwinding enzymes which prefers partially unwound 3'-tailed substrates and can also unwind partial RNA/DNA and RNA/RNA duplexes in an ATP-dependent fashion. This enzyme is a member of the heterogeneous nuclear RNA-binding proteins and is also an element of the Ras signal transduction pathway. It binds specifically to the Ras-GTPase-activating protein by associating with its SH3 domain. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

80
ClinVar variants
12
Pathogenic / LP
0.03
pLI score
0
Active trials
Clinical Summary— G3BP1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 67 VUS of 80 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.52LOEUF
pLI 0.033
Z-score 3.48
OE 0.29 (0.17–0.52)
Moderately constrained

More LoF-intolerant than ~75% 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.
1.86Z-score
OE missense 0.68 (0.60–0.77)
182 obs / 267.5 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.0.29 (0.17–0.52)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.60–0.77)
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.1.00
0≤1.21.6
LoF obs/exp: 8 / 27.8Missense obs/exp: 182 / 267.5Syn Z: 0.03

ClinVar Variant Classifications

80 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS67
Likely Benign1
11
Pathogenic
1
Likely Pathogenic
67
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
1
0
0
0
1
VUS
6
55
6
0
67
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total75518080

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

View in ClinVar →

Protein Context — Lollipop Plot

G3BP1 · 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
RIOK1 phase separation restricts PTEN translation via stress granules activating tumor growth in hepatocellular carcinoma.
Meng F et al.·Nat Cancer
2025
ALS-FTLD-linked mutations of SQSTM1/p62 disrupt selective autophagy and NFE2L2/NRF2 anti-oxidative stress pathway.
Deng Z et al.·Autophagy
2020
The roles of G3BP1 in human diseases (review).
Ge Y et al.·Gene
2022Review
Targeting autophagy in HCC treatment: exploiting the CD147 internalization pathway.
Qian M et al.·Cell Commun Signal
2024
SARS-CoV-2 nucleocapsid protein interaction with YBX1 displays oncolytic properties through PKM mRNA destabilization.
Chen X et al.·Mol Cancer
2024
Stress Granule Assembly in Pulmonary Arterial Hypertension.
Kosmas K et al.·Cells
2024
SARS-CoV-2 NSP5 and N protein counteract the RIG-I signaling pathway by suppressing the formation of stress granules.
Zheng Y et al.·Signal Transduct Target Ther
2022
Histone Demethylase UTX Suppresses Tumor Cell Proliferation by Regulating Stress Granules.
Liu X et al.·Adv Sci (Weinh)
2025
Tumor cell-intrinsic BIN1 deficiency promotes the immunosuppression and impedes ferroptosis of non-small cell lung cancer via G3BP1-mediated degradation of STAT1.
Wang J et al.·J Exp Clin Cancer Res
2025
C9orf72-linked arginine-rich dipeptide repeats aggravate pathological phase separation of G3BP1.
Van Nerom M et al.·Proc Natl Acad Sci U S A
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Anisodamine hydrobromide alleviates LPS-induced inflammation via the miR-1195/G3bp1/NF-κB axis in RAW264.7 cells.
Cai Y et al.·J Chromatogr B Analyt Technol Biomed Life Sci
2026
Alphaviral Capsid Proteins Inhibit Stress Granule Assembly via Competitive RNA Binding With G3BP1.
Zhang Y et al.·Adv Sci (Weinh)
2026
Proof of concept: targeted protein degradation of the stress granules component G3BP1 as an antiviral strategy against norovirus infection.
Echavarria-Consuegra L et al.·Antimicrob Agents Chemother
2026🔓 Open Access
RECQL4 promotes the malignant progression of lung adenocarcinoma through the YBX1/G3BP1-mediated NF-κB signaling pathway.
Li R et al.·Cell Death Discov
2026🔓 Open Access
Hypoxia-induced PRMT6 expression promotes temozolomide chemoresistance in glioblastoma via G3BP1.
Chen S et al.·J Transl Med
2026🔓 Open Access
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