CNOT1

Chr 16AD

CCR4-NOT transcription complex subunit 1

Also known as: AD-005, CDC39, HPE12, NOT1, NOT1H, VIBOS

NCBI Gene: 23019 ENSG00000125107 UniProt: A5YKK6 OMIM: 604917

CNOT1 encodes a scaffolding component of the CCR4-NOT complex, a major cellular mRNA deadenylase that regulates mRNA degradation, translational repression, and transcription. Mutations cause autosomal dominant holoprosencephaly 12 (with or without pancreatic agenesis) and Vissers-Bodmer syndrome, affecting brain development and other organ systems. This gene is highly constrained against loss-of-function variants (pLI = 1.0), indicating intolerance to protein-disrupting mutations.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables armadillo repeat domain binding activity; molecular adaptor activity; and nuclear receptor binding activity. Contributes to poly(A)-specific ribonuclease activity. Involved in several processes, including negative regulation of intracellular signal transduction; positive regulation of cytoplasmic mRNA processing body assembly; and regulation of gene expression. Located in P-body. Part of CCR4-NOT complex. Implicated in Vissers-Bodmer syndrome and holoprosencephaly 12. [provided by Alliance of Genome Resources, Jun 2026]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Holoprosencephaly 12, with or without pancreatic agenesisMIM #618500

Vissers-Bodmer syndromeMIM #619033

Clinical highlights

Gene-disease validity (ClinGen)

holoprosencephaly 12 with or without pancreatic agenesis · ADLimitednot for standalone diagnostic reporting2 gene-disease associations curated in total

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.04

LOEUF· LoF intol.

LOF

Mechanism· predicted

📖

GeneReview available — CNOT1