CNOT3

Chr 19AD

CCR4-NOT transcription complex subunit 3

Also known as: IDDSADF, LENG2, NOT3, NOT3H

NCBI Gene: 4849 ENSG00000088038 UniProt: O75175 OMIM: 604910

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Involved in regulation of stem cell population maintenance. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder with speech delay, autism, and dysmorphic faciesMIM #618672

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.08

LOEUF· LoF intol.

LOF

Mechanism· G2P