OPHN1
Chr XXLRoligophrenin 1
Also known as: ARHGAP41, MRX60, MRXSBL, OPN1
This gene encodes a Rho-GTPase-activating protein that stimulates GTP hydrolysis of Rho family members and is critical for dendritic spine stabilization, synaptic function, and synaptic vesicle endocytosis. Mutations cause X-linked intellectual developmental disorder with cerebellar hypoplasia and distinctive facial dysmorphism (Billuart type). The gene shows extreme constraint against loss-of-function variants and follows X-linked recessive inheritance.
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
OPHN1 · 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