ARFGEF1
Chr 8ADARF guanine nucleotide exchange factor 1
Also known as: ARFGEP1, BIG1, DEDISB, P200
The protein encoded by ARFGEF1 promotes guanine-nucleotide exchange on ARF1 and ARF3 to activate these proteins for vesicular trafficking, maintains Golgi structure, and is required for integrin beta-1 maturation. Mutations cause autosomal dominant developmental delay, impaired speech, and behavioral abnormalities with or without seizures. This gene is highly constrained against loss-of-function variants (pLI >0.99), indicating that functional copies are critical for normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Extremely missense-constrained (top ~0.01%)
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
ARFGEF1 · 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