ADP-ribosylation factor 3 encodes a small GTP-binding protein that regulates vesicle trafficking and modulates vesicle budding and uncoating within the Golgi apparatus. Mutations cause autosomal recessive periventricular nodular heterotopia with intellectual disability and seizures, typically presenting in infancy with developmental delays and brain malformations affecting neuronal migration.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.72
Clinical SummaryARF3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.72LOEUF
pLI 0.353
Z-score 2.12
OE 0.23 (0.090.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.82Z-score
OE missense 0.25 (0.180.34)
28 obs / 112.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.23 (0.090.72)
00.351.4
Missense OE0.25 (0.180.34)
00.61.4
Synonymous OE0.77
01.21.6
LoF obs/exp: 2 / 8.8Missense obs/exp: 28 / 112.2Syn Z: 1.19
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateARF3-related neurodevelopmental disorderDNAD
DN
0.75top 25%
GOF
0.5465th %ile
LOF
0.4233th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ARF3 · 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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