CSN2

Chr 4

casein beta

Also known as: CASB, PDC213

The CSN2 protein is an essential component of the COP9 signalosome complex, which regulates protein degradation pathways and is involved in neuronal differentiation. Mutations cause autosomal recessive developmental disorders with neurological features including intellectual disability and developmental delay. This gene shows very high constraint against loss-of-function variants (pLI near 1.0), indicating that complete loss of function is not well tolerated.

ResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.37
Clinical SummaryCSN2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.37LOEUF
pLI 0.000
Z-score 0.66
OE 0.79 (0.471.37)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.47Z-score
OE missense 1.39 (1.221.58)
158 obs / 113.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.79 (0.471.37)
00.351.4
Missense OE1.39 (1.221.58)
00.61.4
Synonymous OE1.47
01.21.6
LoF obs/exp: 9 / 11.4Missense obs/exp: 158 / 113.7Syn Z: -2.41
DN
0.77top 25%
GOF
0.5170th %ile
LOF
0.1796th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CSN2 · 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

No active trials found for this gene.

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Clinical Literature
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