COPS9
Chr 2COP9 signalosome subunit 9
Also known as: CSNAP, MYEOV2
The COPS9 protein is a component of the COP9 signalosome complex that regulates protein degradation pathways by controlling the activity of cullin-RING E3 ubiquitin ligase complexes through deneddylation. Pathogenic variants in COPS9 cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, characterized by early-onset seizures, severe developmental delay, and progressive microcephaly. This gene shows tolerance to loss-of-function variation (pLI 0.001), suggesting the disease mechanism may involve specific damaging variants rather than simple protein loss.
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 (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.
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
113 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 92 |
Likely Pathogenic | — | — | — | — | 6 |
VUS | — | — | — | — | 9 |
Likely Benign | — | — | — | — | 0 |
Benign | — | — | — | — | 0 |
| Total | — | 107 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
COPS9 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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 →No open access results found
External Resources
Links to major genomics databases and tools