ARRDC1
Chr 9arrestin domain containing 1
The ARRDC1 protein functions as an adapter that recruits ubiquitin ligases to specific substrates and plays a role in extracellular vesicle biogenesis and negative regulation of Notch signaling. Mutations cause autosomal recessive developmental delay with seizures and microcephaly, typically presenting in infancy with neurological manifestations. This gene is highly intolerant to loss-of-function variation, suggesting complete loss of protein function has severe developmental consequences.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
276 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 132 | 0 | 132 |
Likely Pathogenic | 0 | 0 | 15 | 0 | 15 |
VUS | 0 | 95 | 13 | 0 | 108 |
Likely Benign | 0 | 6 | 0 | 0 | 6 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 3 | |||
| Total | 0 | 101 | 160 | 0 | 264 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ARRDC1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools