CSN3
Chr 4casein kappa
Also known as: CNS10, CSN10, CSNK, KCA
The CSN3 protein is a component of the COP9 signalosome complex that regulates protein degradation pathways by controlling ubiquitin ligase activity and mediating phosphorylation of key cellular proteins including p53. Mutations in CSN3 cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, affecting neurological development and brain growth. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected patients.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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
63 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 | 21 | 0 | 21 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 28 | 8 | 0 | 36 |
Likely Benign | 0 | 2 | 2 | 0 | 4 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 30 | 32 | 0 | 62 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CSN3 · 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