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

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.

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]

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

0.22

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?

0.22LOEUF

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

Background carrier burden — how many people carry a rare variant somewhere in CPEB1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 80

741 rare PASS variants

Rare truncating (LoF)

1 in 490

74 rare PASS variants

Rare synonymous (reference)

1 in 140

342 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CPEB1. 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 1,300
South Asian	~43k	1 in 77	1 in 440
Remaining (unassigned)	~30k	1 in 82	1 in 930
European (Finnish)	~27k	1 in 110	≈ 1 in 27,000
Admixed American	~22k	1 in 95	1 in 820
African / African American	~21k	1 in 94	1 in 380
East Asian	~20k	1 in 100	≈ 1 in 9,400
Ashkenazi Jewish	~13k	1 in 230	1 in 770
Middle Eastern	~2,884	1 in 82	≈ 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): 10 of 12 coding exons well covered in gnomAD exomes; exon 2 poorly covered; exon 7 marginal. Genomes: all 12.? see exons ↓