ARF1

Chr 1AD

ARF GTPase 1

Also known as: PVNH8

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.401 OMIM phenotype
Clinical SummaryARF1
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Gene-Disease Validity (ClinGen)
periventricular nodular heterotopia · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.90) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint
0.40LOEUF
pLI 0.900
Z-score 2.53
OE 0.00 (0.000.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.39Z-score
OE missense 0.14 (0.090.21)
17 obs / 122.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.000.40)
00.351.4
Missense OE0.14 (0.090.21)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 0 / 7.4Missense obs/exp: 17 / 122.5Syn Z: -0.37
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongARF1-related periventricular nodular heterotopiaOTHERAD
DN
0.5674th %ile
GOF
0.4875th %ile
LOF
0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.40

Literature Evidence

LOFThese clinical features showed similarities to those of three previously reported cases with ARF1 missense variants, confirming that haploinsufficiency of this gene causes a recognisable neurological disorder with abnormal neuronal migration and variable clinical expressivity.PMID:34353862

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

ARF1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗