CNOT2
Chr 12ADCCR4-NOT transcription complex subunit 2
Also known as: CDC36, HSPC131, IDNADFS, NOT2, NOT2H
The protein is a component of the CCR4-NOT complex, which regulates mRNA deadenylation, degradation, and transcriptional repression, and is required for maintaining the complex's structural integrity. Mutations cause autosomal dominant intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
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
111 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 | 3 | 0 | 14 | 0 | 17 |
Likely Pathogenic | 3 | 0 | 5 | 0 | 8 |
VUS | 1 | 49 | 5 | 0 | 55 |
Likely Benign | 0 | 5 | 3 | 2 | 10 |
Benign | 0 | 0 | 1 | 0 | 1 |
Conflicting | — | 2 | |||
| Total | 7 | 54 | 28 | 2 | 93 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CNOT2 · 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