ARHGEF7

Chr 13

Rho guanine nucleotide exchange factor 7

Also known as: BETA-PIX, COOL-1, COOL1, Nbla10314, P50, P50BP, P85, P85COOL1

NCBI Gene: 8874ENSG00000102606UniProt: Q14155

The protein acts as a RAC1 guanine nucleotide exchange factor that regulates cell migration, attachment, and synaptic development in hippocampal neurons. Mutations cause autosomal dominant intellectual disability with epilepsy and abnormal behavior, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.19), indicating intolerance to protein-disrupting mutations.

Summary from RefSeq, UniProt
Research Assistant →
1
Active trials
5
Pubs (1 yr)
55
P/LP submissions
0%
P/LP missense
0.19
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— ARHGEF7
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
55 unique Pathogenic / Likely Pathogenic· 57 VUS of 138 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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
0.19LOEUF
pLI 1.000
Z-score 5.54
OE 0.07 (0.03–0.19)
Highly constrained

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

Missense Constraint
2.57Z-score
OE missense 0.67 (0.61–0.73)
313 obs / 469.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.07 (0.03–0.19)
0≤0.351.4
Missense OE0.67 (0.61–0.73)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 3 / 41.5Missense obs/exp: 313 / 469.9Syn Z: 0.20
DN
0.3991th %ile
GOF
0.5169th %ile
LOF
0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.19

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

138 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic1
VUS57
Likely Benign1
54
Pathogenic
1
Likely Pathogenic
57
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
54
0
54
Likely Pathogenic
0
0
1
0
1
VUS
0
55
2
0
57
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total056570113

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

View in ClinVar →

Protein Context — Lollipop Plot

ARHGEF7 · protein map & ClinVar variants

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

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
Arhgef7 is essential for granule cell precursor proliferation and migration during cerebellum development.
Jiménez-Amilburu V et al.·iScience
2026Open Access
Arhgef7 as a key target for enriched environment rescuing spatial cognitive deficits and anxiety-like behaviors in a mouse model of Alzheimer's disease following early social isolation.
Wang Y et al.·Alzheimers Res Ther
2025Open AccessFunctional
β-PIX-d, a Member of the ARHGEF7 Guanine Nucleotide Exchange Factor Family, Activates Rac1 and Induces Neuritogenesis in Primary Cortical Neurons.
Kim S et al.·Exp Neurobiol
2024Open Access
Ubiquitin ligase KLHL2 promotes the degradation and ubiquitination of ARHGEF7 protein to suppress renal cell carcinoma progression.
Zhang E et al.·Am J Cancer Res
2020
ARHGEF7 (β-PIX) Is Required for the Maintenance of Podocyte Architecture and Glomerular Function.
Matsuda J et al.·J Am Soc Nephrol
2020
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