ARFGEF2

Chr 20

ARF guanine nucleotide exchange factor 2

Also known as: BIG2, PVNH2, dJ1164I10.1

NCBI Gene: 10564 ENSG00000124198 UniProt: Q9Y6D5

This protein functions as a guanine nucleotide exchange factor that activates ARF proteins to regulate vesicular trafficking between the Golgi, endosomes, and plasma membrane. Biallelic mutations cause autosomal recessive periventricular heterotopia with microcephaly. The gene is highly constrained against loss-of-function variants in the general population.

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 and is involved in Golgi transport. It contains a Sec7 domain, which may be responsible for its guanine-nucleotide exchange activity and also brefeldin A inhibition. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPeriventricular nodular heterotopia 2

Clinical highlights

Gene-disease validity (ClinGen)

periventricular heterotopia with microcephaly, autosomal recessive · ARDefinitivesufficient 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)

—

P/LP submissions

—

P/LP missense

0.25

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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