CNOT1

Chr 16AD

CCR4-NOT transcription complex subunit 1

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

NCBI Gene: 23019ENSG00000125107UniProt: A5YKK6OMIM: 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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.042 OMIM phenotypes
Clinical Summary— CNOT1
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Gene-Disease Validity (ClinGen)
holoprosencephaly 12 with or without pancreatic agenesis · ADLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.04LOEUF
pLI 1.000
Z-score 10.28
OE 0.01 (0.00–0.04)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
7.25Z-score
OE missense 0.43 (0.40–0.46)
561 obs / 1295.9 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.01 (0.00–0.04)
0≤0.351.4
Missense OE0.43 (0.40–0.46)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 1 / 125.0Missense obs/exp: 561 / 1295.9Syn Z: -0.51
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCNOT1-related neurodevelopmental disorderOTHERAD
strongCNOT1-related holoprosencephaly with or without pancreatic agenesisOTHERAD
DN
0.2099th %ile
GOF
0.3193th %ile
LOF
0.82top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.04

Literature Evidence

LOFAn integrated omics approach of patient-derived genomics and transcriptomics data suggested only minimal effects on endonucleolytic nonsense-mediated mRNA decay components, suggesting that de novo CNOT1 variants are likely haploinsufficient hypomorph or neomorph, rather than dominant negative.PMID:32553196

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

ClinVar

Protein Context — Lollipop Plot

CNOT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients