CNOT8

Chr 5

CCR4-NOT transcription complex subunit 8

Also known as: CAF1, CALIF, Caf1b, POP2, hCAF1

NCBI Gene: 9337ENSG00000155508UniProt: Q9UFF9

Enables poly(A)-specific ribonuclease activity. Involved in miRNA-mediated gene silencing by mRNA destabilization and positive regulation of cell population proliferation. Located in nucleus. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Jul 2025]

30
ClinVar variants
11
Pathogenic / LP
0.22
pLI score
0
Active trials
Clinical Summary— CNOT8
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 17 VUS of 30 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.58LOEUF
pLI 0.217
Z-score 2.75
OE 0.25 (0.12–0.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.16Z-score
OE missense 0.51 (0.42–0.61)
78 obs / 153.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.25 (0.12–0.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.51 (0.42–0.61)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.90
0≤1.21.6
LoF obs/exp: 4 / 15.8Missense obs/exp: 78 / 153.5Syn Z: 0.60

ClinVar Variant Classifications

30 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
VUS17
Likely Benign2
11
Pathogenic
17
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
0
0
0
VUS
0
14
3
0
17
Likely Benign
0
0
1
1
2
Benign
0
0
0
0
0
Total01415130

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

View in ClinVar →

Protein Context — Lollipop Plot

CNOT8 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Cnot8 eliminates naïve regulation networks and is essential for naïve-to-formative pluripotency transition.
Quan Y et al.·Nucleic Acids Res
2022🔓 Open Access
CNOT7 Outcompetes Its Paralog CNOT8 for Integration into The CCR4-NOT Complex.
Stoney PN et al.·J Mol Biol
2022
Importance of CNOT8 Deadenylase Subunit in DNA Damage Responses Following Ionizing Radiation (IR).
Eskandarian S et al.·Rep Biochem Mol Biol
2020
A mutation in cnot8, component of the Ccr4-not complex regulating transcript stability, affects expression levels of developmental regulators and reveals a role of Fgf3 in development of caudal hypothalamic dopaminergic neurons.
Koch P et al.·PLoS One
2014🔓 Open Access
The anti-proliferative activity of BTG/TOB proteins is mediated via the Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not complex.
Doidge R et al.·PLoS One
2012🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools