CNOT3
Chr 19ADCCR4-NOT transcription complex subunit 3
Also known as: IDDSADF, LENG2, NOT3, NOT3H
CNOT3 encodes a component of the CCR4-NOT complex, a major cellular mRNA deadenylase that regulates mRNA degradation, translational repression, and transcriptional regulation, and is involved in stem cell maintenance and mitotic progression. Mutations cause autosomal dominant intellectual developmental disorder with speech delay, autism, and dysmorphic facies. The gene is highly constrained against loss-of-function variants (pLI >0.99, LOEUF 0.076), indicating that even single functional copies are critical for normal development.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CNOT3 · 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
External Resources
Links to major genomics databases and tools