ARFGEF1

Chr 8AD

ARF guanine nucleotide exchange factor 1

Also known as: ARFGEP1, BIG1, DEDISB, P200

NCBI Gene: 10565 ENSG00000066777 UniProt: Q9Y6D6 OMIM: 604141

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP. It contains a Sec7 domain, which may be responsible for guanine-nucleotide exchange activity and also brefeldin A inhibition. [provided by RefSeq, Aug 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental delay, impaired speech, and behavioral abnormalities, with or without seizuresMIM #619964

Clinical highlights

Gene-disease validity (ClinGen)

developmental delay, impaired speech, and behavioral abnormalities, with or without seizures · ADDefinitivesufficient 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.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.14

LOEUF· LoF intol.

LOF

Mechanism· G2P