OPHN1

Chr X

oligophrenin 1

Also known as: ARHGAP41, MRX60, MRXSBL, OPN1

NCBI Gene: 4983ENSG00000079482UniProt: O60890

This gene encodes a Rho-GTPase-activating protein that promotes GTP hydrolysis of Rho subfamily members. Rho proteins are important mediators of intracellular signal transduction, which affects cell migration and cell morphogenesis. Mutations in this gene are responsible for OPHN1-related X-linked cognitive disability with cerebellar hypoplasia and distinctive facial dysmorhphism. [provided by RefSeq, Jul 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, X-linked, syndromic, Billuart type

Clinical highlights

Gene-disease validity (ClinGen)
X-linked intellectual disability-cerebellar hypoplasia syndrome · XLDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
9
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.16
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — OPHN1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.16LOEUF
pLI 1.000
Z-score 4.86
OE 0.03 (0.01–0.16)
Highly constrained

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

Missense Constraint?
2.59Z-score
OE missense 0.58 (0.51–0.66)
174 obs / 300.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.03 (0.01–0.16)
0≤0.351.4
Missense OE?0.58 (0.51–0.66)
0≤0.61.4
Synonymous OE?0.98
0≤1.21.6
LoF obs/exp: 1 / 29.5Missense obs/exp: 174 / 300.5Syn Z: 0.18

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

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