ARHGEF9
Chr XX-linkedCdc42 guanine nucleotide exchange factor 9
Also known as: COLLYBISTIN, DEE8, EIEE8, HPEM-2, PEM-2, PEM2
The protein acts as a guanine nucleotide exchange factor for CDC42 and facilitates recruitment of gephyrin at GABAergic and glycinergic synapses. Mutations cause developmental and epileptic encephalopathy 8 through an X-linked inheritance pattern, predominantly through loss-of-function mechanisms. The gene shows high constraint against loss-of-function variants, consistent with haploinsufficiency being pathogenic in this X-linked disorder.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ARHGEF9 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools