APRG1

Chr 3

APRG1 tumor suppressor candidate

Also known as: C3orf35

NCBI Gene: 339883ENSG00000198590UniProt: Q8IVJ8OMIM: 611429

The APRG1 protein is predicted to be located in cellular membranes, though its specific function remains unclear. Mutations in this gene have not been definitively associated with any recognized human genetic diseases. This gene appears to tolerate loss-of-function variants well based on population genetics data.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 1.68
Clinical Summary— APRG1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.05) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 11 VUS of 25 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
1.68LOEUF
pLI 0.049
Z-score 0.64
OE 0.62 (0.25–1.68)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.11Z-score
OE missense 0.97 (0.81–1.16)
89 obs / 91.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.62 (0.25–1.68)
0≤0.351.4
Missense OE0.97 (0.81–1.16)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 2 / 3.2Missense obs/exp: 89 / 91.9Syn Z: 0.32
DN
0.6938th %ile
GOF
0.6638th %ile
LOF
0.4528th %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

25 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS11
Likely Benign1
11
Pathogenic
1
Likely Pathogenic
11
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————11
Likely Pathogenic
————1
VUS
————11
Likely Benign
————1
Benign
————0
Total—24

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

APRG1 · 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 →

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