CNOT10

Chr 3

CCR4-NOT transcription complex subunit 10

CNOT10 encodes a component of the CCR4-NOT complex, which functions as a major cellular mRNA deadenylase and regulates mRNA degradation, miRNA-mediated repression, and translational control. The gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.31), suggesting mutations would likely cause severe developmental disorders. However, specific disease associations and inheritance patterns for CNOT10 mutations have not been established in the provided data.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.30
Clinical SummaryCNOT10
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 81 VUS of 130 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.982
Z-score 5.10
OE 0.16 (0.090.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.78Z-score
OE missense 0.76 (0.690.83)
316 obs / 418.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.16 (0.090.30)
00.351.4
Missense OE0.76 (0.690.83)
00.61.4
Synonymous OE0.84
01.21.6
LoF obs/exp: 7 / 43.1Missense obs/exp: 316 / 418.5Syn Z: 1.57
DN
0.3495th %ile
GOF
0.2995th %ile
LOF
0.73top 10%

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

LOFprediction above median · LOEUF 0.30

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

130 submitted variants in ClinVar

Classification Summary

Pathogenic16
VUS81
Likely Benign2
16
Pathogenic
81
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
0
0
0
VUS
1
77
3
0
81
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Total17819199

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CNOT10 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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