ARHGEF28
Chr 5Rho guanine nucleotide exchange factor 28
Also known as: RGNEF, RIP2, p190RHOGEF
This protein functions as a RHOA-specific guanine nucleotide exchange factor that regulates axonal branching, synapse formation, and dendritic morphogenesis. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay, following an autosomal dominant inheritance pattern. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to cause significant developmental impairment.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ARHGEF28 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools