CPEB4

Summary

CPEB4 (cytoplasmic polyadenylation element binding protein 4, HGNC:21747) is a protein-coding gene on chromosome 5q35.2, encoding Cytoplasmic polyadenylation element-binding protein 4 (Q17RY0). 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.

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.

Source: NCBI Gene 80315 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 79 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 71 total
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈3% of expected missense variation)
• GTEx eGene: eQTL in 13 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.29 (highly constrained)
• MANE Select transcript: NM_030627
• Notable: 71 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21747
Approved symbol	CPEB4
Name	cytoplasmic polyadenylation element binding protein 4
Location	5q35.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1673
Ensembl gene	ENSG00000113742
Ensembl biotype	protein_coding
OMIM	610607
Entrez	80315

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000265085

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 1, TSL 3: 2, TSL 5: 2

ENST00000265085, ENST00000334035, ENST00000517880, ENST00000518141, ENST00000519152, ENST00000519467, ENST00000519835, ENST00000520867, ENST00000522336, ENST00000522344, ENST00000656232, ENST00000657000, ENST00000659882, ENST00001132768

RefSeq mRNA: 5 — MANE Select: NM_030627 NM_001308189, NM_001308191, NM_001308192, NM_001308193, NM_030627

CCDS: CCDS4390, CCDS78086, CCDS78087, CCDS83043, CCDS83044

Canonical transcript exons

ENST00000265085 — 10 exons

Exon	Start	End
ENSE00001332359	173932450	173932500
ENSE00001821369	173955910	173961980
ENSE00002123650	173888349	173890858
ENSE00003461841	173949960	173950078
ENSE00003537747	173910523	173910604
ENSE00003560849	173951824	173951938
ENSE00003600356	173949508	173949597
ENSE00003631575	173944967	173945140
ENSE00003649497	173943026	173943049
ENSE00003654057	173953091	173953272

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 99.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 60.9198 / max 1573.9504, expressed in 1820 samples.

Highest expression (Bgee): adrenal tissue, ventricle myocardium, secondary oocyte, kidney epithelium, pigmented layer of retina.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CPEB4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

15 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Heart Left Ventricle	eqtl	7.7e-14	-0.23	5:173878429:T:C
Whole Blood	eqtl	4.8e-11	-0.16	5:173778315:G:A
Testis	eqtl	1.0e-10	-0.20	5:173917150:T:C
Pancreas	eqtl	6.9e-09	+0.27	5:173860760:G:A
Cells EBV-transformed lymphocytes	eqtl	5.6e-06	+0.23	5:173835213:AG:A
Colon Transverse	sqtl	2.6e-03	-1.23	5:174853287:C:T
Cells Cultured fibroblasts	eqtl	6.9e-03	+0.12	5:173916897:G:C
Esophagus Muscularis	eqtl	2.1e-02	+0.11	5:173931151:G:A
Prostate	eqtl	2.7e-02	+0.14	5:173931151:G:A
Thyroid	eqtl	2.7e-02	+0.12	5:173972722:C:T
Stomach	eqtl	3.2e-02	+0.13	5:173860760:G:A
Brain Anterior cingulate cortex BA24	eqtl	3.3e-02	+0.90	5:174143836:C:A
Lung	eqtl	3.5e-02	+0.34	5:174751897:C:A
Skin Not Sun Exposed Suprapubic	sqtl	4.2e-02	+0.86	5:174136561:C:T
Skin Not Sun Exposed Suprapubic	eqtl	5.0e-02	+0.39	5:173435208:G:C

FANTOM5 promoters

showing 10 of 15 alternative TSS:

Promoter ID	TPM avg	Samples expressed
60297	50.3457	1807
60296	5.4031	1500
60310	1.5313	825
60311	0.7498	423
60304	0.3837	173
60299	0.3443	136
60300	0.3212	140
60301	0.3095	120
60306	0.3058	133
60312	0.2679	29

Top tissues by expression

showing 100 of 261 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.11	gold quality
left ventricle myocardium	UBERON:0006566	98.35	gold quality
secondary oocyte	CL:0000655	98.31	gold quality
kidney epithelium	UBERON:0004819	97.70	gold quality
pigmented layer of retina	UBERON:0001782	97.38	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.13	gold quality
tibialis anterior	UBERON:0001385	97.01	gold quality
endothelial cell	CL:0000115	96.69	gold quality
upper arm skin	UBERON:0004263	96.38	gold quality
medial globus pallidus	UBERON:0002477	96.32	gold quality
myocardium	UBERON:0002349	96.07	gold quality
bone marrow cell	CL:0002092	96.06	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.86	gold quality
globus pallidus	UBERON:0001875	95.85	gold quality
eye	UBERON:0000970	95.65	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.65	gold quality
epithelial cell of pancreas	CL:0000083	95.60	gold quality
deltoid	UBERON:0001476	95.60	gold quality
heart right ventricle	UBERON:0002080	95.55	gold quality
adrenal gland	UBERON:0002369	95.28	gold quality
corpus callosum	UBERON:0002336	95.22	gold quality
biceps brachii	UBERON:0001507	95.17	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.14	gold quality
trabecular bone tissue	UBERON:0002483	95.11	gold quality
adrenal cortex	UBERON:0001235	95.09	gold quality
palpebral conjunctiva	UBERON:0001812	95.09	gold quality
body of tongue	UBERON:0011876	95.07	gold quality
left adrenal gland cortex	UBERON:0035825	95.07	gold quality
left adrenal gland	UBERON:0001234	95.00	gold quality
amniotic fluid	UBERON:0000173	94.93	gold quality
vastus lateralis	UBERON:0001379	94.90	gold quality
right adrenal gland cortex	UBERON:0035827	94.76	gold quality
gastrocnemius	UBERON:0001388	94.69	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.64	gold quality
skeletal muscle tissue	UBERON:0001134	94.61	gold quality
bone marrow	UBERON:0002371	94.59	gold quality
quadriceps femoris	UBERON:0001377	94.54	gold quality
oviduct epithelium	UBERON:0004804	94.49	gold quality
right adrenal gland	UBERON:0001233	94.39	gold quality
renal medulla	UBERON:0000362	94.35	gold quality
muscle tissue	UBERON:0002385	94.02	gold quality
superficial temporal artery	UBERON:0001614	93.95	gold quality
subthalamic nucleus	UBERON:0001906	93.89	gold quality
skeletal muscle organ	UBERON:0014892	93.89	gold quality
tongue	UBERON:0001723	93.80	gold quality
buccal mucosa cell	CL:0002336	93.77	gold quality
cortical plate	UBERON:0005343	93.70	gold quality
muscle of leg	UBERON:0001383	93.67	gold quality
medulla oblongata	UBERON:0001896	93.62	gold quality
islet of Langerhans	UBERON:0000006	93.57	gold quality
occipital lobe	UBERON:0002021	93.49	gold quality
superior vestibular nucleus	UBERON:0007227	93.41	gold quality
lower lobe of lung	UBERON:0008949	93.28	gold quality
primary visual cortex	UBERON:0002436	93.23	gold quality
entorhinal cortex	UBERON:0002728	93.13	gold quality
esophagus squamous epithelium	UBERON:0006920	93.13	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.09	gold quality
lateral globus pallidus	UBERON:0002476	93.03	gold quality
dorsal plus ventral thalamus	UBERON:0001897	93.00	gold quality
oral cavity	UBERON:0000167	92.96	gold quality
epithelium of nasopharynx	UBERON:0001951	92.94	gold quality
nasopharynx	UBERON:0001728	92.92	gold quality
cerebellar vermis	UBERON:0004720	92.90	gold quality
pons	UBERON:0000988	92.81	gold quality
ventral tegmental area	UBERON:0002691	92.81	gold quality
inferior vagus X ganglion	UBERON:0005363	92.76	gold quality
pancreatic ductal cell	CL:0002079	92.66	gold quality
substantia nigra pars compacta	UBERON:0001965	92.65	gold quality
parietal lobe	UBERON:0001872	92.49	gold quality
cardiac ventricle	UBERON:0002082	92.44	gold quality
postcentral gyrus	UBERON:0002581	92.32	gold quality
heart left ventricle	UBERON:0002084	92.31	gold quality
cauda epididymis	UBERON:0004360	92.23	gold quality
germinal epithelium of ovary	UBERON:0001304	92.22	gold quality
superior surface of tongue	UBERON:0007371	92.22	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.98	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.89	gold quality
superior frontal gyrus	UBERON:0002661	91.85	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.76	gold quality
gingival epithelium	UBERON:0001949	91.72	gold quality
sperm	CL:0000019	91.61	gold quality
tonsil	UBERON:0002372	91.31	gold quality
heart	UBERON:0000948	91.29	gold quality
kidney	UBERON:0002113	91.03	gold quality
nasal cavity epithelium	UBERON:0005384	90.96	gold quality
gingiva	UBERON:0001828	90.92	gold quality
nasal cavity mucosa	UBERON:0001826	90.88	gold quality
saphenous vein	UBERON:0007318	90.88	gold quality
sural nerve	UBERON:0015488	90.86	gold quality
middle temporal gyrus	UBERON:0002771	90.79	gold quality
seminal vesicle	UBERON:0000998	90.71	gold quality
visceral pleura	UBERON:0002401	90.65	gold quality
cardiac atrium	UBERON:0002081	90.60	gold quality
parotid gland	UBERON:0001831	90.44	gold quality
monocyte	CL:0000576	90.36	gold quality
oocyte	CL:0000023	90.34	gold quality
pharyngeal mucosa	UBERON:0000355	90.15	gold quality
right atrium auricular region	UBERON:0006631	90.10	gold quality
temporal lobe	UBERON:0001871	90.06	gold quality
nipple	UBERON:0002030	90.03	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-11	yes	421.55
E-CURD-119	yes	62.71
E-CURD-122	yes	36.61
E-ENAD-17	no	566.24
E-MTAB-10042	no	267.81
E-MTAB-9067	no	4.70
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Choroid plexus	tissue	164.7
Cerebellum	tissue	161.8
Postcentral gyrus	tissue	119.0
Nucleus accumbens	tissue	115.6
Hippocampal formation	tissue	104.7
Entorhinal cortex	tissue	104.7
Hippocampus	tissue	103.5
Locus coeruleus	tissue	102.9
Cerebral cortex	tissue	101.8
Occipital cortex	tissue	101.8
Prefrontal cortex	tissue	100.9
Insular cortex	tissue	99.7
Temporal cortex	tissue	98.4
Motor cortex	tissue	96.5
Retrosplenial and cingulate cortex	tissue	95.6
Somatosensory cortex	tissue	95.6
Olfactory bulb	tissue	90.8
Retrosplenial cortex	tissue	88.5
Amygdala	tissue	86.3
Putamen	tissue	80.4
Basal ganglia	tissue	80.2
Ventral forebrain	tissue	78.5
Liver	tissue	73.8
Septum	tissue	70.1
Parathyroid gland	tissue	68.7
Bone marrow	tissue	68.0
Adrenal gland	tissue	62.4
Tongue	tissue	58.3
Midbrain	tissue	57.8
Thalamus	tissue	55.5
Hypothalamus	tissue	55.2
Superior colliculi	tissue	55.0
Pons	tissue	51.7
Medulla oblongata	tissue	51.7
Substantia nigra	tissue	51.7
Spinal cord	tissue	51.7
Frontal cortex	tissue	51.3
Corpus callosum	tissue	50.4
Caudate putamen	tissue	49.6
Periaqueductal gray	tissue	49.3
Kidney	tissue	47.3
Heart muscle	tissue	43.6
Retina	tissue	38.6
Pancreas	tissue	34.5
Thyroid gland	tissue	31.2
Esophagus	tissue	28.9
Skeletal muscle	tissue	25.8
Salivary gland	tissue	21.6
Urinary bladder	tissue	20.7
Adipose tissue	tissue	18.8
Gallbladder	tissue	18.7
Stomach 1	tissue	18.1
Placenta	tissue	17.1
Appendix	tissue	16.7
Cervix	tissue	16.3
Breast	tissue	16.1
Lung	tissue	15.6
Tonsil	tissue	15.3
Smooth muscle	tissue	15.2
Testis	tissue	14.7

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Cerebellar cortex (162.6), Flocculonodular lobe (161.9), Vermis (148.1), Angular gyrus (white matter) (136.3), Cerebellar white matter (133.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CPEB4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 196 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-32-5P	99.98	75.21	1964

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.287, missense Z 3.47 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000265085 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈3% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
5:173,889,734–173,889,804	7 / 26.1	0.27	yes (p 1.8e-04)
5:173,889,805–173,945,092	458 / 548.6	0.83	no
5:173,945,093–173,949,989	25 / 68.9	0.36	no
5:173,949,990–173,950,046	23 / 21.8	1.05	no
5:173,950,047–173,956,134	101 / 243.1	0.42	no

Literature-anchored findings (GeneRIF, showing 32)

• CPEB4, an RNA binding protein that mediates meiotic mRNA cytoplasmic polyadenylation and translation, is overexpressed in pancreatic ductal adenocarcinomas and glioblastomas, where it supports tumor growth, vascularization and invasion. (PMID:22138752)
• Knockdown of CPEB4 expression significantly facilitated HCC cell migration and invasion. (PMID:23145039)
• CPEB4 is a candidate biomarker for defining metastatic cancers and directing personalized therapies. (PMID:24045092)
• Evidence that CPEB4 uses both its RNA recognition motifs to maintain optimal RNA binding. (PMID:25081215)
• findings imply that posttranscriptional deregulation of CPEB4 contributes to the inhibited cell proliferation and the enhanced cell apoptosis in colorectal cancer, and directly targeting CPEB4 by miR-203 might be a strategy in colorectal cancer treatment (PMID:26361147)
• CPEB1, 2, and 4, are essential to successful mitotic cell division. (PMID:26398195)
• Our studies first validated that CPEB4 interacts with Vimentin and indicated that high CPEB4 expression in astrocytic tumors correlates closely with a clinically aggressive future, and that CPEB4 might represent a valuable prognostic marker for patients with astrocytic tumors. (PMID:26546435)
• Identify a mechanism of VEGF overexpression in liver and mesentery that promotes pathologic, but not physiologic, angiogenesis, via sequential and nonredundant functions of CPEB1 and CPEB4. (PMID:26627607)
• Low CPEB4 expression and high CPEB1 expression were independent predictors of overall survival in glioma patients. (PMID:27000226)
• CPEB4 and IRF4 expression in peripheral mononuclear cells are potential prognostic factors for advanced lung cancer (PMID:27113098)
• downregulation of CPEB4 likely occurs at the late cancer stage to facilitate HCC progression. Biphasic alteration of CPEB4 expression during HCC progression suggests its complicated role in tumorigenesis (PMID:27158894)
• high expression of CPEB4 was found to be an independent prognostic biomarker for overall survival in colorectal cancer patients (PMID:27771769)
• This study identified a lineage-specific requirement of CPEB4 in malignant melanoma. (PMID:27857118)
• positive cytoplasmic polyadenylation element binding protein 4 expression predicted a worse prognosis in glioma patients, and cytoplasmic polyadenylation element binding protein 4 could represent a useful biomarker or therapeutic target for glioma. (PMID:28381179)
• The results implicate the potential role of CPEB4 and Vimentin in breast cancer metastasis, which is further confirmed by the finding that there is a physical interaction between the two proteins. (PMID:28536077)
• Survival analysis revealed a significant association between progression free survival (PFS) and overall survival (OS) and CPEB4 immunohistochemical expression, which was independent in the multivariate analysis. CPEB4 behaves as a significant predictor of prognosis in stage IV colorectal carcinoma. (PMID:28551384)
• Silencing of CPEB4 induces reactive oxygen species generation, thus suppressing the Akt expression, which finally prevents non-small cell lung cancer cells invasion and migration. (PMID:29286212)
• Increased expression of CPEB4 in primary glioblastoma is a novel biomarker for predicting poor outcome of patients. (PMID:29642043)
• data identify CPEB4 as a regulator of autism spectrum disorder risk genes (PMID:30111840)
• Silencing lncRNA FOXD2-AS1 inhibits proliferation, migration, invasion and drug resistance of drug-resistant glioma cells and promotes their apoptosis via microRNA-98-5p/CPEB4 axis. (PMID:31770107)
• CPEB4 can inhibit the proliferation and promote the apoptosis of K562 cells, the AKT, p-AKT, BCL-2 and caspase-3 are involved in the regulation mechanism (PMID:31839038)
• LncRNA RP11-361F15.2 promotes osteosarcoma tumorigenesis by inhibiting M2-Like polarization of tumor-associated macrophages of CPEB4. (PMID:31904478)
• CPEB1 and CPEB4 are involved in the regulation of the TAK1 and Smad signalings in human macrophages and dermal fibroblasts (PMID:32113875)
• CPEB4 Increases Expression of PFKFB3 to Induce Glycolysis and Activate Mouse and Human Hepatic Stellate Cells, Promoting Liver Fibrosis. (PMID:32169429)
• LncRNA EWSAT1 upregulates CPEB4 via miR-330-5p to promote cervical cancer development. (PMID:32556917)
• Polyadenylation of mRNA as a novel regulatory mechanism of gene expression in temporal lobe epilepsy. (PMID:32594159)
• [Effect of CPEB4 on Migration and Cycle of Chronic Myeloid Leukemia Cell]. (PMID:32798388)
• Investigation of the expression levels of CPEB4, APC, TRIP13, EIF2S3, EIF4A1, IFNg, PIK3CA and CTNNB1 genes in different stage colorectal tumors (PMID:33237662)
• Targeting the cytoplasmic polyadenylation element-binding protein CPEB4 protects against diet-induced obesity and microbiome dysbiosis. (PMID:34774811)
• Macrophage inflammation resolution requires CPEB4-directed offsetting of mRNA degradation. (PMID:35442882)
• Antitumor T-cell function requires CPEB4-mediated adaptation to chronic endoplasmic reticulum stress. (PMID:36919984)
• Down-Regulation of CPEB4 Alleviates Preeclampsia through the Inhibition of Ferroptosis by PFKFB3. (PMID:38305290)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpeb4a	ENSDARG00000056691
mus_musculus	Cpeb4	ENSMUSG00000020300
rattus_norvegicus	Cpeb4	ENSRNOG00000033169
drosophila_melanogaster	orb2	FBGN0264307
caenorhabditis_elegans		WBGENE00000770
caenorhabditis_elegans		WBGENE00000771

Paralogs (3): CPEB3 (ENSG00000107864), CPEB2 (ENSG00000137449), CPEB1 (ENSG00000214575)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1914829) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 23 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating calcium level	1
abnormal neuromuscular synapse morphology	1
decreased body weight	1
decreased body size	1
impaired coordination	1
abnormal suckling behavior	1
respiratory distress	1
abnormal seminal vesicle morphology	1
abnormal axon extension	1
abnormal bone structure	1
abnormal cell physiology	1
abnormal neurite morphology	1
decreased survivor rate	1
absent gastric milk in neonates	1
abnormal dendritic spine morphology	1
postnatal lethality, incomplete penetrance	1
neonatal lethality, incomplete penetrance	1
preweaning lethality, complete penetrance	1
lethality during fetal growth through weaning, incomplete penetrance	1
abnormal fetal derived definitive erythrocyte morphology	1
decreased fetal derived definitive erythrocyte cell number	1
abnormal phrenic nerve innervation pattern to diaphragm	1
impaired erythrocyte maturation	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R733	98.4%	Diamond
Xenopus laevis	Q52KN7	96.8%	Diamond
Carassius auratus	Q9DED5	95.3%	Diamond
Xenopus tropicalis	Q28CH2	86.0%	Diamond
Caenorhabditis briggsae	Q6E3F3	72.0%	Diamond
Caenorhabditis remanei	Q6E3F2	71.3%	Diamond
Aplysia californica	Q967R6	66.8%	Diamond
Caenorhabditis japonica	Q6E3F0	65.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
C5orf47	protein-coding	133491
NSG2	protein-coding	51617
LINC01484	ncRNA	101928136
LINC01485	ncRNA	101928154
LINC01942	ncRNA	105377736

Protein

Protein identifiers

Cytoplasmic polyadenylation element-binding protein 4 — Q17RY0 (reviewed: Q17RY0)

All UniProt accessions (8): Q17RY0, A0A590UJI5, A0A590UJN2, A0A590UK96, B7ZLQ8, E5RFP2, E5RJM0, H0YBG1

UniProt curated annotations — full annotation on UniProt →

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. RNA binding results in a clear conformational change analogous to the Venus fly trap mechanism. 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. Required for cell cycle progression, specifically for cytokinesis and chromosomal segregation. Plays a role as an oncogene promoting tumor growth and progression by positively regulating translation of t-plasminogen activator/PLAT. Stimulates proliferation of melanocytes. In contrast to CPEB1 and CPEB3, does not play role in synaptic plasticity, learning and memory.

Subunit / interactions. Interacts with TOB1.

Subcellular location. Cytoplasm. Cell projection. Dendrite. Dendritic spine. Postsynaptic density. Axon. Growth cone. Endoplasmic reticulum. Perinuclear region.

Tissue specificity. Expressed in pancreas in islets and ductal cells (at protein level). Expressed in melanocytes.

Domain organisation. The 2 RRM domains and the C-terminal region mediate interaction with CPE-containing RNA. The interdomain linker (564-579) acts as a hinge to fix the relative orientation of the 2 RRMs. The ZZ domain (509-566) coordinates 2 Zn ions and is probably implicated in mediating interactions with other proteins in addition to increasing the affinity of the RRMs for the CPEs. Unlike in CPEB1, a continuous polar interface is formed between the 2 RRMs.

Similarity. Belongs to the RRM CPEB family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q17RY0-1	1	yes
Q17RY0-2	2
Q17RY0-3	3

RefSeq proteins (5): NP_001295118, NP_001295120, NP_001295121, NP_001295122, NP_085130* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR032296	CEBP_ZZ	Domain
IPR034819	CPEB	Family
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR038446	CEBP_ZZ_sf	Homologous_superfamily

Pfam: PF16366, PF16367

UniProt features (58 total): strand 17, binding site 8, modified residue 8, compositionally biased region 5, helix 5, region of interest 4, splice variant 3, domain 2, site 2, turn 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
5DIF	Crystal Structure of CPEB4 NES Peptide in complex with CRM1-Ran-RanBP1	X-RAY DIFFRACTION	2.09
2MKI	Solution structure of tandem RRM domains of cytoplasmic polyadenylation element binding …	SOLUTION NMR
2MKJ	Solution structure of tandem RRM domains of cytoplasmic polyadenylation element binding …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q17RY0-F1	57.58	0.30

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; nucleoplasm; vesicles

Antibody reliability (HPA): IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2)

Position	Role
473	rna-binding
561	important for the positioning of rrm1 relative to rrm2

Ligand- & substrate-binding residues (8)

Position	Role
667	Zn(2+)
675	Zn(2+)
684	Zn(2+)
689	Zn(2+)
694	Zn(2+)
697	Zn(2+)
702	Zn(2+)
710	Zn(2+)

Post-translational modifications (8)

Type	Positions
Phosphoserine	97, 99, 137, 252, 255, 330, 332
Phosphothreonine	326

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 423 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_RESPONSE_TO_ACID_CHEMICAL, CMYB_01, TTTGTAG_MIR520D, ATACCTC_MIR202, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, TATTATA_MIR374, CAFFAREL_RESPONSE_TO_THC_UP, MEF2_02, GOBP_CELLULAR_RESPONSE_TO_ACID_CHEMICAL, CACCAGC_MIR138, CAGCTG_AP4_Q5, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP

GO Biological Process (9): response to ischemia (GO:0002931), ionotropic glutamate receptor signaling pathway (GO:0035235), cellular response to decreased oxygen levels (GO:0036294), cellular response to glucose starvation (GO:0042149), negative regulation of neuron apoptotic process (GO:0043524), cellular response to amino acid stimulus (GO:0071230), negative regulation of cytoplasmic translation (GO:2000766), translation (GO:0006412), regulation of translation (GO:0006417)

GO Molecular Function (9): mRNA regulatory element binding translation repressor activity (GO:0000900), RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), translation factor activity, RNA binding (GO:0008135), ribosome binding (GO:0043022), metal ion binding (GO:0046872), nucleic acid binding (GO:0003676), protein binding (GO:0005515), translation regulator activity (GO:0045182)

GO Cellular Component (12): nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), postsynaptic density (GO:0014069), dendrite (GO:0030425), growth cone (GO:0030426), neuron projection (GO:0043005), dendritic spine (GO:0043197), synapse (GO:0045202), perinuclear region of cytoplasm (GO:0048471), axon (GO:0030424), postsynapse (GO:0098794)

GO top-level categories

52 GO namespaces:

Category	Terms
cellular anatomical structure	3
translation	2
mRNA binding	2
binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
neuron projection	2
response to stress	1
glutamate-gated receptor activity	1
glutamate receptor signaling pathway	1
ligand-gated ion channel signaling pathway	1
response to decreased oxygen levels	1
cellular response to oxygen levels	1
cellular response to starvation	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
response to amino acid	1
cellular response to acid chemical	1
cytoplasmic translation	1
negative regulation of translation	1
regulation of cytoplasmic translation	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
translation repressor activity	1
nucleic acid binding	1
RNA binding	1
translation factor activity	1
ribonucleoprotein complex binding	1
cation binding	1
molecular_function	1
regulation of translation	1
intracellular anatomical structure	1
endomembrane system	1
asymmetric synapse	1
postsynaptic specialization	1
dendritic tree	1
site of polarized growth	1
distal axon	1
plasma membrane bounded cell projection	1
dendrite	1
neuron spine	1
postsynapse	1
cell junction	1
synapse	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 30 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
cytoplasm	CC	direct assay
nucleus	CC	direct assay
RNA binding	MF	high-throughput assay

Protein interactions and networks

STRING

showing 16 of 1,058 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPEB4	FXR1	P51114	612
CPEB4	TENT2	Q6PIY7	565
CPEB4	FMR1	Q06787	473
CPEB4	FXR2	P51116	457
CPEB4	SYMPK	Q92797	429
CPEB4	PAPOLA	P51003	426
CPEB4	PAPOLB	Q9NRJ5	422
CPEB4	PAPOLG	Q9BWT3	420
CPEB4	NGDN	Q8NEJ9	417
CPEB4	EIF4E	P06730	387
CPEB4	PUM2	Q8TB72	387
CPEB4	PABPC1	P11940	385
CPEB4	LYPLAL1	Q5VWZ2	383
CPEB4	DDX6	P26196	377
CPEB4	CTIF	O43310	370
CPEB4	P2RY6	Q15077	370

IntAct

Human interaction partners of CPEB4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
TOB1	physical association	0.540	2
HOMEZ	association	0.530	1
CPEB2	association	0.350	1

BioGRID (207 interactions; top human partners by supporting records): VIM (Affinity Capture-MS; 4 records), FAM120A (Proximity Label-MS; 3 records), AGO2 (Proximity Label-MS; 2 records), ALG13 (Proximity Label-MS; 2 records), ANKRD17 (Proximity Label-MS; 2 records), ATXN2 (Proximity Label-MS; 2 records), CNOT2 (Proximity Label-MS; 2 records), CNOT7 (Proximity Label-MS; 2 records), EIF4ENIF1 (Proximity Label-MS; 2 records), FAM120C (Proximity Label-MS; 2 records), FMR1 (Proximity Label-MS; 2 records), FUBP3 (Proximity Label-MS; 2 records), FXR2 (Proximity Label-MS; 2 records), HELZ (Proximity Label-MS; 2 records), IGF2BP2 (Proximity Label-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
MAPK1	“up-regulates activity”	CPEB4	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for CPEB4: 71 ClinVar records (0 pathogenic / likely pathogenic); 79 GWAS associations.

ClinVar

71 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 43 predictions of 896):

Position(s)	Effect	Δscore	Sites
5:173910521–173910522	acceptor_loss	1.0000	6
5:173910605–173910606	donor_loss	1.0000	3
5:173944965–173944966	acceptor_loss	1.0000	3
5:173945141–173945142	donor_loss	1.0000	5
5:173949506–173949507	acceptor_loss	1.0000	6
5:173949958–173949959	acceptor_loss	1.0000	6
5:173950071	donor_gain	1.0000
5:173950079–173950080	donor_loss	1.0000	5
5:173953086–173953087	acceptor_gain	1.0000	2
5:173953089–173953090	acceptor_loss	1.0000	6

AlphaMissense

2,150 missense substitutions predicted likely pathogenic (of 4,821 scored), across 448 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M600	9	0.993	1.000
D613	8	1.000	1.000
F629	8	1.000	1.000
H710	8	1.000	1.000
F475	8	0.999	1.000
D482	8	0.999	1.000
F583	8	0.999	1.000
H702	8	0.999	1.000
F492	8	0.998	1.000
F519	8	0.998	1.000
D615	8	0.998	1.000
D668	8	0.998	1.000
F683	8	0.998	1.000
D501	8	0.997	0.999
F512	8	0.997	1.000
S548	8	0.997	1.000
F522	8	0.996	1.000
H504	8	0.995	1.000
F643	8	0.995	1.000
D663	8	0.995	1.000

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Kidney Chromophobe)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.2e-08
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	2.71e-06

Disease associations

OMIM: gene MIM:610607 | disease phenotypes:

GWAS associations

showing 30 of 79 associations:

Study	Trait	p-value
GCST90020024_383	A body shape index	6e-34
GCST90020027_140	Waist-hip index	2e-32
GCST90020025_997	Waist-to-hip ratio adjusted for BMI	4e-31
GCST90020029_1183	Waist circumference adjusted for body mass index	1e-28
GCST90020024_390	A body shape index	8e-22
GCST90020027_146	Waist-hip index	5e-20
GCST90020025_1653	Waist-to-hip ratio adjusted for BMI	6e-19
GCST90020024_387	A body shape index	2e-17
GCST90020024_384	A body shape index	5e-17
GCST90020024_385	A body shape index	1e-16
GCST90020027_141	Waist-hip index	3e-16
GCST004602_219	Mean corpuscular volume	8e-16
GCST90020027_144	Waist-hip index	9e-16
GCST90020025_998	Waist-to-hip ratio adjusted for BMI	1e-15
GCST90002403_210	Red blood cell count	2e-15
GCST90020025_1651	Waist-to-hip ratio adjusted for BMI	3e-15
GCST90020027_145	Waist-hip index	4e-15
GCST90020029_1182	Waist circumference adjusted for body mass index	4e-15
GCST90020029_1186	Waist circumference adjusted for body mass index	6e-15
GCST90020024_386	A body shape index	9e-15
GCST90020025_1652	Waist-to-hip ratio adjusted for BMI	1e-14
GCST90020027_142	Waist-hip index	1e-14
GCST004630_80	Mean corpuscular hemoglobin	2e-14
GCST002782_191	Waist-to-hip ratio adjusted for body mass index	5e-14
GCST90020025_999	Waist-to-hip ratio adjusted for BMI	5e-14
GCST007094_173	Diastolic blood pressure	1e-13
GCST90020029_1185	Waist circumference adjusted for body mass index	1e-13
GCST002782_194	Waist-to-hip ratio adjusted for body mass index	2e-13
GCST90020029_1184	Waist circumference adjusted for body mass index	2e-13
GCST90020029_1189	Waist circumference adjusted for body mass index	2e-13

EFO canonical traits (from GWAS)

22 canonical traits:

EFO ID	Trait name
EFO:0004343	waist-hip ratio
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference
EFO:0006336	diastolic blood pressure
EFO:0004318	smoking behavior
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0008378	mosquito bite reaction size measurement
EFO:0004340	body mass index
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0008579	risk-taking behaviour
EFO:0008354	cognitive function measurement
EFO:0003959	cleft lip
EFO:0009793	isoleucine measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004842	eosinophil count
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

77 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	6
Cyclosporine	increases expression	3
Aflatoxin B1	decreases methylation, increases expression	3
Acetaminophen	increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, increases expression	2
Arsenic	affects expression, decreases methylation, increases abundance	2
Ozone	increases oxidation, increases abundance, increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Tretinoin	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
FR900359	affects phosphorylation	1
urushiol	increases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
Huang Qi	affects cotreatment, decreases expression, decreases reaction	1
cupric oxide	increases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.