CPEB4
protein-codingcytoplasmic polyadenylation element binding protein 4, the group of RNA binding motif containing
Gene summary
Enables RNA binding activity. Predicted to be involved in several processes, including cellular response to glucose starvation; negative regulation of cytoplasmic translation; and response to ischemia. Located in cytoplasm and nucleus. Biomarker of liver cirrhosis; portal hypertension; and primary biliary cholangitis. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~73.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CPEB4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_030627.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 56 | 56 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 61 | 0 | 0 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_085130.2 | 10 | MANE Select | |
| Ensembl | ENSP00000265085.5 | 10 | MANE Select | |
| RefSeq | NP_001295118.1 | 9 | Standard | |
| RefSeq | NP_001295120.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Oocyte meiosis - Homo sapiens (human)
- Progesterone-mediated oocyte maturation - Homo sapiens (human)
- Glucocorticoid Receptor Pathway
- Nuclear Receptors Meta-Pathway
Biological Process
- response to ischemia
- translation
- ionotropic glutamate receptor signaling pathway
- cellular response to decreased oxygen levels
- cellular response to glucose starvation
Molecular Function
- translation repressor activity, mRNA regulatory element binding
- RNA binding
- mRNA 3'-UTR binding
- protein binding
- translation factor activity, RNA binding
Cellular Component
- nucleus
- cytoplasm
- endoplasmic reticulum
- postsynaptic density
- cell junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000265085
- Coding exons
- 10
- Length
- 73697
- Individuals with no LoFs
- 125742
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125748
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.31 | 228 | 418 | 0.545 | 0.0000225 | 4808 |
| Missense (PolyPhen) | 47 | 127.54 | 0.36851 | 1390 | ||
| Synonymous | 0.686 | 145 | 156 | 0.930 | 0.00000850 | 1432 |
| Loss of Function | 4.69 | 5 | 34.9 | 0.143 | 0.00000205 | 357 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000031 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Sequence-specific RNA-binding protein that binds to the cytoplasmic polyadenylation element (CPE), an uridine-rich sequence element (consensus sequence 5'-UUUUUAU-3') within the mRNA 3'-UTR (PubMed:24990967). RNA binding results in a clear conformational change analogous to the Venus fly trap mechanism (PubMed:24990967). Regulates activation of unfolded protein response (UPR) in the process of adaptation to ER stress in liver, by maintaining translation of CPE-regulated mRNAs in conditions in which global protein synthesis is inhibited (By similarity). Required for cell cycle progression, specifically for cytokinesis and chromosomal segregation (PubMed:26398195). Plays a role as an oncogene promoting tumor growth and progression by positively regulating translation of t-plasminogen activator/PLAT (PubMed:22138752). Stimulates proliferation of melanocytes (PubMed:27857118). In contrast to CPEB1 and CPEB3, does not play role in synaptic plasticity, learning and memory (By similarity). {ECO:0000250|UniProtKB:Q7TN98, ECO:0000269|PubMed:22138752, ECO:0000269|PubMed:24990967, ECO:0000269|PubMed:26398195, ECO:0000269|PubMed:27857118}.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- LoFtool
- 0.225
- RVIS EVS
- -0.23
- RVIS percentile EVS
- 37.32
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.964
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |