COPS3
Chr 17COP9 signalosome subunit 3
Also known as: CSN3, SGN3
The COPS3 protein is a component of the COP9 signalosome complex that regulates protein degradation pathways by controlling ubiquitin ligase activity and phosphorylating key signaling proteins including p53 and c-Jun. Mutations in COPS3 cause autosomal dominant syndromic intellectual disability with developmental delay and dysmorphic features. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to have significant clinical consequences.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
164 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 | 114 | 0 | 114 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 1 | 22 | 6 | 0 | 29 |
Likely Benign | 0 | 0 | 1 | 1 | 2 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 1 | 22 | 121 | 2 | 146 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
COPS3 · 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