ARF3

Chr 12

ARF GTPase 3

NCBI Gene: 377ENSG00000134287UniProt: P61204

ADP-ribosylation factor 3 (ARF3) is a member of the human ARF gene family. These genes encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking and as activators of phospholipase D. The gene products include 6 ARF proteins and 11 ARF-like proteins and constitute one 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. [provided by RefSeq, Oct 2022]

41
ClinVar variants
17
Pathogenic / LP
0.35
pLI score
0
Active trials
Clinical Summary— ARF3
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 21 VUS of 41 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.72LOEUF
pLI 0.353
Z-score 2.12
OE 0.23 (0.09–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.82Z-score
OE missense 0.25 (0.18–0.34)
28 obs / 112.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.23 (0.09–0.72)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.25 (0.18–0.34)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.77
0≤1.21.6
LoF obs/exp: 2 / 8.8Missense obs/exp: 28 / 112.2Syn Z: 1.19

ClinVar Variant Classifications

41 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic4
VUS21
Benign2
Conflicting1
13
Pathogenic
4
Likely Pathogenic
21
VUS
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
4
9
0
13
Likely Pathogenic
0
3
1
0
4
VUS
0
16
5
0
21
Likely Benign
0
0
0
0
0
Benign
0
0
1
1
2
Conflicting
—1
Total02316141

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

ARF3-related neurodevelopmental disorder

moderate
ADDominant NegativeAltered Gene Product Structure, Decreased Gene Product Level
Dev. Disorders
G2P ↗
missense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genome Sequencing of Idiopathic Speech Delay.
Eising E et al.·Hum Mutat
2024
Newly identified ARF3 variants strengthen the causal link between Golgi fragmentation and brain malformations.
Muto V et al.·Eur J Hum Genet
2026
Transcriptomic signatures in peripheral CD4(+)T-lymphocytes may reflect melanoma staging and immunotherapy responsiveness prior to ICI initiation.
Palli E et al.·Front Immunol
2025
BIG1 controls macrophage pro-inflammatory responses through ARF3-mediated PI(4,5)P2 synthesis.
Liu L et al.·Cell Death Dis
2020
Neurodevelopmental disorder associated with gene ARF3: A case report.
Dos Santos Henrique S et al.·Am J Med Genet A
2024Case report
Identification of core genes and clinical roles in pregnancy-associated breast cancer based on integrated analysis of different microarray profile datasets.
Zhang J et al.·Biosci Rep
2019
Identification of class II ADP-ribosylation factors as cellular factors required for hepatitis C virus replication.
Farhat R et al.·Cell Microbiol
2016
Protein expression analysis of chromosome 12 candidate genes in chronic lymphocytic leukemia (CLL).
Winkler D et al.·Leukemia
2005
An AGEF-1/Arf GTPase/AP-1 ensemble antagonizes LET-23 EGFR basolateral localization and signaling during C. elegans vulva induction.
Skorobogata O et al.·PLoS Genet
2014
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools