CNOT2

Chr 12

CCR4-NOT transcription complex subunit 2

Also known as: CDC36, HSPC131, IDNADFS, NOT2, NOT2H

NCBI Gene: 4848 ENSG00000111596 UniProt: Q9NZN8

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a subunit of the multi-component CCR4-NOT complex. The CCR4-NOT complex regulates mRNA synthesis and degradation and is also thought to be involved in mRNA splicing, transport and localization. The encoded protein interacts with histone deacetylases and functions as a repressor of polymerase II transcription. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies

Clinical highlights

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

0.19

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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