ARFRP1

Chr 20

ARF related protein 1

Also known as: ARL18, ARP, Arp1

NCBI Gene: 10139ENSG00000101246UniProt: Q13795

The protein is a trans-Golgi-associated GTPase that regulates protein sorting and controls targeting of ARL1 and its effector to the trans-Golgi, and is required for lipidation of chylomicrons in the intestine and VLDL in the liver. Mutations cause autosomal recessive perioral dermatitis with intestinal lipodystrophy. The gene shows moderate constraint against loss-of-function variants.

Summary from RefSeq, UniProt
Research Assistant →
MultiplemechanismLOEUF 0.64
Clinical Summary— ARFRP1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
41 unique Pathogenic / Likely Pathogenic· 48 VUS of 103 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.64LOEUF
pLI 0.137
Z-score 2.52
OE 0.28 (0.14–0.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.85Z-score
OE missense 0.79 (0.67–0.93)
103 obs / 130.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.28 (0.14–0.64)
0≤0.351.4
Missense OE0.79 (0.67–0.93)
0≤0.61.4
Synonymous OE1.16
0≤1.21.6
LoF obs/exp: 4 / 14.3Missense obs/exp: 103 / 130.4Syn Z: -0.95
DN
0.76top 25%
GOF
0.7029th %ile
LOF
0.2971th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

103 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic8
VUS48
Likely Benign1
Benign1
Conflicting1
33
Pathogenic
8
Likely Pathogenic
48
VUS
1
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
8
0
8
VUS
0
33
15
0
48
Likely Benign
0
1
0
0
1
Benign
0
0
0
1
1
Conflicting
—1
Total03456192

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

View in ClinVar →

Protein Context — Lollipop Plot

ARFRP1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients