CPEB1

Chr 15

cytoplasmic polyadenylation element binding protein 1

Also known as: CPE-BP1, CPEB, CPEB-1, h-CPEB, hCPEB-1

NCBI Gene: 64506 ENSG00000214575 UniProt: Q9BZB8 OMIM: 607342

The protein binds to specific RNA sequences in the 3' untranslated regions of mRNAs and regulates their translation and polyadenylation, particularly important for neuronal synaptic function and cell cycle progression. CPEB1 is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.218), but no established human disease phenotype has been definitively associated with pathogenic variants in this gene. Given its critical role in neuronal mRNA regulation and high evolutionary constraint, mutations would likely cause neurodevelopmental disorders if disease-causing variants are identified.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the cytoplasmic polyadenylation element binding protein family. This highly conserved protein binds to a specific RNA sequence, called the cytoplasmic polyadenylation element, found in the 3' untranslated region of some mRNAs. The encoded protein functions in both the cytoplasm and the nucleus. It is involved in the regulation of mRNA translation, as well as processing of the 3' untranslated region, and may play a role in cell proliferation and tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.22

Clinical Summary— CPEB1

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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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ClinVar Variants

58 VUS of 71 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.22LOEUF

pLI 0.999

Z-score 4.63

OE 0.07 (0.03–0.22)

Highly constrained

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

Missense Constraint?

2.10Z-score

OE missense 0.66 (0.58–0.74)

194 obs / 295.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.07 (0.03–0.22)

0≤0.351.4

Missense OE?0.66 (0.58–0.74)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 2 / 28.8Missense obs/exp: 194 / 295.5Syn Z: -0.33

This gene — mechanism propensity

0.3395th %ile

GOF

0.4085th %ile

LOF

0.82top 5%

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

LOFprediction above median · LOEUF 0.22

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

71 submitted variants in ClinVar

ClinVar

Classification Summary

VUS58

Likely Benign1

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	57	1	0	58
Likely Benign	0	0	1	1
Benign	0	0	1	1
Total	57	1	2	60

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 39) ClinVar copy-number / structural variants overlap CPEB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →