ARF1

Chr 1AD

ARF GTPase 1

Also known as: PVNH8

NCBI Gene: 375 ENSG00000143761 UniProt: P84077 OMIM: 103180

ADP-ribosylation factor 1 functions as a small GTPase that regulates protein trafficking between cellular compartments, particularly modulating vesicle budding and uncoating within the Golgi complex and playing roles in synaptic plasticity through AMPA receptor trafficking. Mutations cause periventricular nodular heterotopia 8, a brain malformation disorder with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to have severe consequences.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

ADP-ribosylation factor 1 (ARF1) is a member of the human ARF gene family. The family members encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking as activators of phospholipase D. The gene products, including 6 ARF proteins and 11 ARF-like proteins, constitute a family of the RAS superfamily. The ARF proteins are categorized as class I (ARF1, ARF2 and ARF3), class II (ARF4 and ARF5) and class III (ARF6), and members of each class share a common gene organization. The ARF1 protein is localized to the Golgi apparatus and has a central role in intra-Golgi transport. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Periventricular nodular heterotopia 8MIM #618185

Clinical highlights

Gene-disease validity (ClinGen)

periventricular nodular heterotopia · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.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

0.40

LOEUF

LOF

Mechanism· predicted