CNOT10

Chr 3

CCR4-NOT transcription complex subunit 10

NCBI Gene: 25904 ENSG00000182973 UniProt: Q9H9A5

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.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in mRNA catabolic process and negative regulation of translation. Located in membrane. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Clinical highlights

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.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.30

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.982

Z-score 5.10

OE 0.16 (0.09–0.30)

Highly constrained

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

Missense Constraint?

1.78Z-score

OE missense 0.76 (0.69–0.83)

316 obs / 418.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.16 (0.09–0.30)

0≤0.351.4

Missense OE?0.76 (0.69–0.83)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 7 / 43.1Missense obs/exp: 316 / 418.5Syn Z: 1.57

Background carrier burden — how many people carry a rare variant somewhere in CNOT10?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 92

910 rare PASS variants

Rare truncating (LoF)

1 in 1,300

95 rare PASS variants

Rare synonymous (reference)

1 in 170

332 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CNOT10. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 1,600
South Asian	~43k	1 in 89	1 in 2,100
Remaining (unassigned)	~30k	1 in 83	1 in 1,400
European (Finnish)	~27k	1 in 300	1 in 4,800
Admixed American	~22k	1 in 93	1 in 660
African / African American	~21k	1 in 62	1 in 1,000
East Asian	~20k	1 in 96	≈ 1 in 6,400
Ashkenazi Jewish	~13k	1 in 360	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 63	≈ 1 in 2,800

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 14 of 19 coding exons well covered in gnomAD exomes; exons 6, 7, 8, 11, 13 marginal. Genomes: all 19.? see exons ↓