RASGEF1B

Chr 4

RasGEF domain family member 1B

Also known as: GPIG4

NCBI Gene: 153020ENSG00000138670UniProt: Q0VAM2

The protein functions as a guanine nucleotide exchange factor with specificity for RAP2A and is involved in Ras protein signal transduction. This gene is highly constrained against loss-of-function variants (pLI 0.92, LOEUF 0.35), but no established human disease associations have been reported in the provided data.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
7
Pubs (1 yr)
33
P/LP submissions
0%
P/LP missense
0.35
LOEUF· LoF intol.
—
Mechanism
Clinical Summary— RASGEF1B
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 58 VUS of 108 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.35LOEUF
pLI 0.921
Z-score 4.24
OE 0.17 (0.09–0.35)
Highly constrained

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

Missense Constraint
1.47Z-score
OE missense 0.75 (0.66–0.84)
199 obs / 266.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.09–0.35)
0≤0.351.4
Missense OE0.75 (0.66–0.84)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 5 / 30.2Missense obs/exp: 199 / 266.7Syn Z: 0.20

ClinVar Variant Classifications

108 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic2
VUS58
Likely Benign4
Benign4
31
Pathogenic
2
Likely Pathogenic
58
VUS
4
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
2
0
2
VUS
0
54
4
0
58
Likely Benign
0
3
1
0
4
Benign
0
2
1
1
4
Total05939199

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

View in ClinVar →

Protein Context — Lollipop Plot

RASGEF1B · 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

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Behavioral, neurochemical and neuroimmune features of RasGEF1b deficient mice.
Fernandes HB et al.·Prog Neuropsychopharmacol Biol Psychiatry
2024
Transcriptomic analysis reveals that RasGEF1b deletion alters basal and LPS-induced expression of genes involved in chemotaxis and cytokine responses in macrophages.
Fernandes HB et al.·Sci Rep
2023Open Access
Aberrant expression of circular RNA DHPR facilitates tumor growth and metastasis by regulating the RASGEF1B/RAS/MAPK axis in hepatocellular carcinoma.
Guo Z et al.·Cell Oncol (Dordr)
2023
Toll-like Receptor (TLR)-induced Rasgef1b expression in macrophages is regulated by NF-κB through its proximal promoter.
Leão FB et al.·Int J Biochem Cell Biol
2020
Transcriptomic analysis of the role of RasGEF1B circular RNA in the TLR4/LPS pathway.
Ng WL et al.·Sci Rep
2017Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients