CPEB3

Summary

CPEB3 (cytoplasmic polyadenylation element binding protein 3, HGNC:21746) is a protein-coding gene on chromosome 10q23.32, encoding Cytoplasmic polyadenylation element-binding protein 3 (Q8NE35). Sequence-specific RNA-binding protein which acts as a translational repressor in the basal unstimulated state but, following neuronal stimulation, acts as a translational activator.

Enables mRNA 3’-UTR binding activity and translation factor activity, RNA binding. Involved in cellular response to amino acid stimulus and regulation of gene expression. Located in several cellular components, including cytosol; midbody; and nucleoplasm. Part of CCR4-NOT complex.

Source: NCBI Gene 22849 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (No Known Disease Relationship, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 100 total
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_014912

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21746
Approved symbol	CPEB3
Name	cytoplasmic polyadenylation element binding protein 3
Location	10q23.32
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0940
Ensembl gene	ENSG00000107864
Ensembl biotype	protein_coding
OMIM	610606
Entrez	22849

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 31 protein_coding

ENST00000265997, ENST00000412050, ENST00000614585, ENST00000903860, ENST00000903863, ENST00000903866, ENST00000903867, ENST00000903868, ENST00000903869, ENST00000903870, ENST00000903871, ENST00000903872, ENST00000903873, ENST00000903874, ENST00000903875, ENST00000903876, ENST00000903877, ENST00000903878, ENST00000903879, ENST00000903880, ENST00000903881, ENST00000903882, ENST00000903883, ENST00000912186, ENST00000912187, ENST00000912188, ENST00000946416, ENST00000946417, ENST00000946418, ENST00000946419, ENST00000946420

RefSeq mRNA: 2 — MANE Select: NM_014912 NM_001178137, NM_014912

CCDS: CCDS31246, CCDS53553

Canonical transcript exons

ENST00000265997 — 10 exons

Exon	Start	End
ENSE00000713769	92111076	92111194
ENSE00000713776	92144945	92145085
ENSE00000713779	92180963	92181019
ENSE00000810688	92081320	92081501
ENSE00001162650	92046692	92052439
ENSE00001162658	92239346	92240361
ENSE00001252544	92192477	92192636
ENSE00001374446	92290926	92291078
ENSE00002487271	92091830	92091944
ENSE00002490646	92143029	92143118

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 97.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1926 / max 375.3515, expressed in 1387 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110659	2.5064	725
110658	1.9655	814
110655	1.2703	197
110651	1.1656	382
110656	0.9158	184
110648	0.4596	155
110657	0.4262	246
110647	0.2457	106
110650	0.1216	65
110660	0.0702	10

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.41	gold quality
endothelial cell	CL:0000115	96.89	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.72	gold quality
middle temporal gyrus	UBERON:0002771	92.19	gold quality
postcentral gyrus	UBERON:0002581	90.52	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.08	gold quality
substantia nigra pars compacta	UBERON:0001965	90.06	gold quality
parietal lobe	UBERON:0001872	89.77	gold quality
primary visual cortex	UBERON:0002436	89.57	gold quality
pons	UBERON:0000988	89.42	gold quality
superior frontal gyrus	UBERON:0002661	89.06	gold quality
choroid plexus epithelium	UBERON:0003911	88.28	gold quality
biceps brachii	UBERON:0001507	88.06	gold quality
entorhinal cortex	UBERON:0002728	87.93	gold quality
substantia nigra pars reticulata	UBERON:0001966	87.18	gold quality
occipital lobe	UBERON:0002021	87.16	gold quality
vastus lateralis	UBERON:0001379	85.54	gold quality
superior vestibular nucleus	UBERON:0007227	85.25	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	84.99	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.11	gold quality
quadriceps femoris	UBERON:0001377	83.35	gold quality
cerebellar vermis	UBERON:0004720	83.06	gold quality
sperm	CL:0000019	82.98	gold quality
prefrontal cortex	UBERON:0000451	82.94	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.68	gold quality
secondary oocyte	CL:0000655	82.57	gold quality
skeletal muscle organ	UBERON:0014892	82.28	gold quality
muscle organ	UBERON:0001630	82.26	gold quality
muscle of leg	UBERON:0001383	82.00	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	53.09
E-ANND-3	yes	6.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

314 targeting CPEB3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6867-5P	100.00	82.21	3464
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-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-340-5P	100.00	72.50	4437
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408

Literature-anchored findings (GeneRIF, showing 25)

• isolation of a ribozyme conserved mammalian sequence that resides in an intron of the CPEB3 gene (PMID:16990549)
• Secondary structure determination and native gel analyses reveal that the cleaved population of the CPEB3 ribozyme has a single, secondary structure that closely resembles the HDV ribozyme (PMID:20524672)
• Together, these results indicate that Tob mediates the recruitment of Caf1 to the target of CPEB3 and elicits deadenylation and decay of the mRNA. (PMID:21336257)
• cleavage of CPEB3 by NMDA-activated calpain 2 accounts for the activity-related translation of CPEB3-targeted RNAs (PMID:22711986)
• Data suggest that the RNA recognition motif (RRM) domain of CPEB3 (as a soluble peptide fragment) exhibits protein conformation distinct from those of the canonical RRM domain. (PMID:25066254)
• Data show that EGF receptor (EGFR) is involved in the microRNA miR-107 pathogenesis of hepatocellular carcinoma (HCC) through cytoplasmic polyadenylation element binding protein 3 (CPEB3). (PMID:26497556)
• Data show that the expression of cytoplasmic polyadenylation element binding protein 3 (CPEB3) positively correlated with tumor progression and malignancy but negatively correlated with protein phosphorylation in the alternatively spliced region. (PMID:27256982)
• Expression of miR-26a and miR-29a was significantly down regulated in leukoplakia and cancer tissues but up regulated in lichen planus tissues. Expression of target genes such as, ADAMTS7, ATP1B1, COL4A2, CPEB3, CDK6, DNMT3a and PI3KR1 was significantly down regulated in at least two of three disease types with respect to normal tissues. (PMID:27515006)
• SUMO1P3 was upregulated in colorectal cancer tissues and cells and bore prognostic significance. SUMO1P3 epigenetically silenced CPEB3 through EZH2. SUMO1P3 regulated proliferation and apoptosis through CPEB3. (PMID:30799082)
• miRNA-301b-3p accelerates migration and invasion of high-grade ovarian serous tumor via targeting CPEB3/EGFR axis. (PMID:30834603)
• Here, we performed deep mutational scanning of self-cleaving CPEB3 ribozyme by error-prone PCR and showed that a library of <5 x 104 single-to-triple mutants is sufficient to infer 25 of 26 base pairs including non-nested, nonhelical, and noncanonical base pairs with both sensitivity and precision at 96%. (PMID:31872260)
• NFE2L1 and NFE2L3 Complementarily Maintain Basal Proteasome Activity in Cancer Cells through CPEB3-Mediated Translational Repression. (PMID:32366381)
• LINC00641 hinders the progression of cervical cancer by targeting miR-378a-3p/CPEB3. (PMID:32367630)
• MiR-224 Executes a Tumor Accelerative Role during Hepatocellular Carcinoma Malignancy by Targeting Cytoplasmic Polyadenylation Element-Binding Protein 3. (PMID:32454494)
• CPEB3 inhibits epithelial-mesenchymal transition by disrupting the crosstalk between colorectal cancer cells and tumor-associated macrophages via IL-6R/STAT3 signaling. (PMID:32653013)
• CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression. (PMID:32968053)
• CPEB3 functions as a tumor suppressor in colorectal cancer via JAK/STAT signaling. (PMID:33146632)
• linc00968 inhibits the tumorigenesis and metastasis of lung adenocarcinoma via serving as a ceRNA against miR-9-5p and increasing CPEB3. (PMID:33159015)
• Decreased Expression of CPEB3 Predicts a Poor Prognosis in Patients with Melanoma: A Study Based on TCGA Data. (PMID:33506034)
• MiR-20b-5p promotes hepatocellular carcinoma cell proliferation, migration and invasion by down-regulating CPEB3. (PMID:33812045)
• CPEB3 overexpression caused by miR-106b-5p inhibition inhibits esophageal carcinoma in-vitro progression and metastasis. (PMID:35102025)
• CPEB3, an RNA-Binding Protein, Modulates the Behavior of Endometriosis-Derived Stromal Cells via Regulating CXCL12. (PMID:35451884)
• Conformational dynamics in the disordered region of human CPEB3 linked to memory consolidation. (PMID:35658951)
• Phase separation modulates the functional amyloid assembly of human CPEB3. (PMID:37898314)
• MicroRNA-92a-CPEB3 axis protects neurons against inflammatory neurodegeneration. (PMID:38000031)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpeb3	ENSDARG00000060103
mus_musculus	Cpeb3	ENSMUSG00000039652
rattus_norvegicus	Cpeb3	ENSRNOG00000020689
drosophila_melanogaster	orb2	FBGN0264307
caenorhabditis_elegans		WBGENE00000770
caenorhabditis_elegans		WBGENE00000771

Paralogs (3): CPEB4 (ENSG00000113742), CPEB2 (ENSG00000137449), CPEB1 (ENSG00000214575)

Protein

Protein identifiers

Cytoplasmic polyadenylation element-binding protein 3 — Q8NE35 (reviewed: Q8NE35)

All UniProt accessions (2): Q8NE35, Q5QP71

UniProt curated annotations — full annotation on UniProt →

Function. Sequence-specific RNA-binding protein which acts as a translational repressor in the basal unstimulated state but, following neuronal stimulation, acts as a translational activator. In contrast to CPEB1, does not bind to the cytoplasmic polyadenylation element (CPE), a uridine-rich sequence element within the mRNA 3’-UTR, but binds to a U-rich loop within a stem-loop structure. Required for the consolidation and maintenance of hippocampal-based long term memory. In the basal state, binds to the mRNA 3’-UTR of the glutamate receptors GRIA2/GLUR2 mRNA and negatively regulates their translation. Also represses the translation of DLG4, GRIN1, GRIN2A and GRIN2B. When activated, acts as a translational activator of GRIA1 and GRIA2. In the basal state, suppresses SUMO2 translation but activates it following neuronal stimulation. Binds to the 3’-UTR of TRPV1 mRNA and represses TRPV1 translation which is required to maintain normal thermoception. Binds actin mRNA, leading to actin translational repression in the basal state and to translational activation following neuronal stimulation. Negatively regulates target mRNA levels by binding to TOB1 which recruits CNOT7/CAF1 to a ternary complex and this leads to target mRNA deadenylation and decay. In addition to its role in translation, binds to and inhibits the transcriptional activation activity of STAT5B without affecting its dimerization or DNA-binding activity. This, in turn, represses transcription of the STAT5B target gene EGFR which has been shown to play a role in enhancing learning and memory performance. In contrast to CPEB1, CPEB2 and CPEB4, not required for cell cycle progression.

Subunit / interactions. Following synaptic activity, forms amyloid-like oligomers. Aggregation requires an intact actin cytoskeleton. Interacts with STAT5B; this inhibits STAT5B-mediated transcriptional activation. Interacts with E3 ubiquitin-protein ligase NEURL1; this leads to monoubiquitination and activation of CPEB3. Interacts with CAPN2; this leads to cleavage of CPEB3. Interacts (via C-terminal RNA-binding region) with TOB1; TOB1 also binds CNOT7/CAF1 and recruits it to CPEB3 to form a ternary complex. Interacts with SUMO-conjugating enzyme UBC9. Interacts with IPO5; the interaction is enhanced in a RAN-regulated manner following neuronal stimulation and mediates CPEB3 nuclear import. Interacts with exportin XPO1/CRM1.

Subcellular location. Cytoplasm. Nucleus. Synapse. Cell projection. Dendrite. Postsynaptic density.

Post-translational modifications. Activated by NEURL1-mediated monoubiquitination, resulting in the growth of new dendritic spines and increased levels of GRIA1 and GRIA2. NEURL1-mediated monoubiquitination facilitates synaptic plasticity and hippocampal-dependent memory storage. Under basal unstimulated conditions when CPEB3 is mainly unaggregated, sumoylated and acts as a translational repressor. Following neuronal stimulation, becomes desumoylated and aggregated which is required for the translation of mRNA targets and for dendritic filopodia formation. Following neuronal stimulation, cleaved by CAPN2 which abolishes its translational repressor activity, leading to translation of CPEB3 target mRNAs. Phosphorylation is enhanced by neuronal stimulation.

Domain organisation. The N-terminal Gln-rich region is required for the formation of amyloid-like oligomers and for the stability of long-term potentiation and spatial memory.

Miscellaneous. The CPEB3 gene contains an intron-encoded self-cleaving ribozyme which is structurally and biochemically related to human hepatitis delta virus ribozymes and which may play a role in the regulation of CPEB3 translation. A polymorphism in the ribozyme sequence which influences cleavage activity of the ribozyme may play a role in episodic memory with carriers of a rare C allele-containing ribozyme showing significantly poorer memory recall performance than T allele carriers.

Similarity. Belongs to the RRM CPEB family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NE35-1	1	yes
Q8NE35-2	2

RefSeq proteins (2): NP_001171608, NP_055727* (*=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 (49 total): mutagenesis site 13, strand 10, compositionally biased region 7, modified residue 4, site 3, domain 2, splice variant 2, region of interest 2, helix 2, chain 1, sequence variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7N2E	ELECTRON CRYSTALLOGRAPHY	1
7N2F	ELECTRON CRYSTALLOGRAPHY	1.2
7N2G	ELECTRON CRYSTALLOGRAPHY	1.2
8SPA	ELECTRON MICROSCOPY	3
2DNL	SOLUTION NMR
2RUG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NE35-F1	58.59	0.29

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 (3): 441–442 (cleavage; by capn2); 444 (required for rna-binding activity); 488 (required for rna-binding activity)

Post-translational modifications (4): 192, 195, 290, 308

Mutagenesis-validated functional residues (13):

Position	Phenotype
349	abolishes nuclear export; when associated with a-353.
353	abolishes nuclear export; when associated with a-349.
441	does not impair rna binding.
444	abolishes rna binding.
444	does not impair rna binding.
446	does not impair rna binding.
463	does not impair rna binding.
470	does not impair rna binding.
474	does not impair rna binding.
479	does not impair rna binding.
488	reduced rna binding.
488	does not impair rna binding.
528	does not impair rna binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 438 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_DENDRITE_DEVELOPMENT, GOBP_MEMORY, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_COGNITION, GOBP_BEHAVIOR, MORF_MSH3, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_ACID_CHEMICAL, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SYNAPSE_ASSEMBLY, SP3_Q3, ATACCTC_MIR202, MORF_BRCA1, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP

GO Biological Process (16): negative regulation of transcription by RNA polymerase II (GO:0000122), long-term memory (GO:0007616), negative regulation of translation (GO:0017148), positive regulation of translation (GO:0045727), regulation of synaptic plasticity (GO:0048167), positive regulation of nuclear-transcribed mRNA poly(A) tail shortening (GO:0060213), regulation of dendritic spine development (GO:0060998), positive regulation of dendritic spine development (GO:0060999), 3’-UTR-mediated mRNA destabilization (GO:0061158), cellular response to amino acid stimulus (GO:0071230), regulation of postsynapse assembly (GO:0150052), positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:1900153), negative regulation of cytoplasmic translational elongation (GO:1900248), negative regulation of cytoplasmic translation (GO:2000766), translation (GO:0006412), regulation of translation (GO:0006417)

GO Molecular Function (10): 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), RNA stem-loop binding (GO:0035613), mRNA 3’-UTR AU-rich region binding (GO:0035925), ribosome binding (GO:0043022), nucleic acid binding (GO:0003676), protein binding (GO:0005515), translation regulator activity (GO:0045182)

GO Cellular Component (14): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), CCR4-NOT complex (GO:0030014), dendrite (GO:0030425), midbody (GO:0030496), neuron projection (GO:0043005), synapse (GO:0045202), apical dendrite (GO:0097440), cell projection (GO:0042995), postsynapse (GO:0098794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
translation	4
regulation of translation	3
positive regulation of mRNA catabolic process	2
dendritic spine development	2
mRNA binding	2
RNA binding	2
binding	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
memory	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
nuclear-transcribed mRNA poly(A) tail shortening	1
regulation of nuclear-transcribed mRNA poly(A) tail shortening	1
regulation of developmental process	1
positive regulation of developmental process	1
regulation of dendritic spine development	1
mRNA destabilization	1
response to amino acid	1
cellular response to acid chemical	1
regulation of synapse assembly	1
postsynapse assembly	1
regulation of postsynapse organization	1
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
cytoplasmic translational elongation	1
negative regulation of translational elongation	1
regulation of cytoplasmic translational elongation	1
negative regulation of cytoplasmic translation	1
cytoplasmic translation	1
negative regulation of translation	1
regulation of cytoplasmic translation	1
peptidyltransferase activity	1
translational initiation	1

Protein interactions and networks

STRING

954 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPEB3	OR4K15	Q8NH41	930
CPEB3	FXR2	P51116	772
CPEB3	FXR1	P51114	770
CPEB3	FMR1	Q06787	738
CPEB3	EIF4E	P06730	715
CPEB3	DDX6	P26196	688
CPEB3	NGDN	Q8NEJ9	634
CPEB3	SYMPK	Q92797	632
CPEB3	PUM2	Q8TB72	595
CPEB3	CAMK2A	Q9UQM7	562
CPEB3	TENT2	Q6PIY7	555
CPEB3	IGF2BP1	Q9NZI8	546
CPEB3	RBFOX2	O43251	543
CPEB3	IGF1R	P08069	540
CPEB3	HNRNPA2B1	P22626	532

IntAct

14 interactions, top by confidence:

A	B	Type	Score
CNOT7	TOB1	psi-mi:“MI:0914”(association)	0.930
CPEB3	TOB1	psi-mi:“MI:0914”(association)	0.650
CPEB3	TOB1	psi-mi:“MI:0915”(physical association)	0.650
TOB1	CPEB3	psi-mi:“MI:0915”(physical association)	0.650
TOB1	CPEB3	psi-mi:“MI:0407”(direct interaction)	0.650
CPEB3	TOB2	psi-mi:“MI:0915”(physical association)	0.400
CPEB3		psi-mi:“MI:0915”(physical association)	0.370
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
CPEB4	CPEB2	psi-mi:“MI:0914”(association)	0.350
TNIK	CPEB3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): CPEB3 (Affinity Capture-RNA), CPEB3 (Biochemical Activity), CPEB3 (Biochemical Activity), Capn2 (Affinity Capture-Western), CPEB3 (Reconstituted Complex), CPEB3 (Reconstituted Complex), CPEB3 (Affinity Capture-MS), CPEB3 (Affinity Capture-RNA), CPEB3 (Affinity Capture-MS), CPEB3 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1L9WLD5, A2QUM3, A3LTE2, A7RNZ0, B0XXN8, B2ABT3, B6QFV5, B8M9Q9, C0NTV7, C7Z403, D1ZMX7, D4AZ68, E6R3N7, G4MVZ1, J9VPM2, J9VT33, M1VWN2, O00167, O54946, O95817, P02672, P0CS26, P0CS27, P36228, P81584, P91859, Q0CGY7, Q12329, Q1HVC7, Q27002, Q4P7Q1, Q4WXY0, Q4X212, Q58DB6, Q5JWF2, Q6AYU3, Q6BJD4, Q6C0K9, Q6CEV2, Q6CFG3

Diamond homologs: O01835, P0C279, P70166, Q03571, Q17RY0, Q28CH2, Q52KN7, Q5R733, Q6E3C9, Q6E3D2, Q6E3D4, Q6E3D5, Q7SXN4, Q7TN98, Q7TN99, Q7Z5Q1, Q812E0, Q8NE35, Q91572, Q967R6, Q9BZB8, Q9DED5, Q9VSR3, Q9YGX5, Q6E3C7, Q6E3D0, Q6E3F0, O14979, Q18317, Q3SWU3, Q5ZI72, Q6E3F2, Q6E3F3, Q9Z130, F4JHI7, Q96EP5, Q98SJ2, Q9JII5, Q9SJA6, P48809

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NEURL1	“up-regulates activity”	CPEB3	ubiquitination

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — BCC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	88
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3392 predictions. Top by Δscore:

Variant	Effect	Δscore
10:92081314:GCTTA:G	donor_loss	1.0000
10:92081315:CTTA:C	donor_loss	1.0000
10:92081316:TTAC:T	donor_loss	1.0000
10:92081317:TACC:T	donor_loss	1.0000
10:92081318:A:AC	donor_gain	1.0000
10:92081318:A:AT	donor_loss	1.0000
10:92081318:AC:A	donor_gain	1.0000
10:92081318:ACC:A	donor_gain	1.0000
10:92081319:C:CC	donor_gain	1.0000
10:92081319:CC:C	donor_gain	1.0000
10:92081319:CCC:C	donor_gain	1.0000
10:92081319:CCCG:C	donor_gain	1.0000
10:92081319:CCCGT:C	donor_gain	1.0000
10:92081497:TTCAA:T	acceptor_gain	1.0000
10:92081498:TCAA:T	acceptor_gain	1.0000
10:92081498:TCAAC:T	acceptor_loss	1.0000
10:92081499:CAA:C	acceptor_gain	1.0000
10:92081499:CAAC:C	acceptor_gain	1.0000
10:92081500:AA:A	acceptor_gain	1.0000
10:92081500:AACTG:A	acceptor_loss	1.0000
10:92081501:AC:A	acceptor_loss	1.0000
10:92081502:C:CC	acceptor_gain	1.0000
10:92081502:CTGCA:C	acceptor_loss	1.0000
10:92081503:T:A	acceptor_loss	1.0000
10:92081505:C:CT	acceptor_gain	1.0000
10:92081506:A:T	acceptor_gain	1.0000
10:92091822:CCACT:C	donor_loss	1.0000
10:92091823:CACTC:C	donor_loss	1.0000
10:92091824:ACTCA:A	donor_loss	1.0000
10:92091825:CTCA:C	donor_loss	1.0000

AlphaMissense

4603 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:92052257:C:A	K684N	1.000
10:92052257:C:G	K684N	1.000
10:92052259:T:C	K684E	1.000
10:92052264:A:G	L682P	1.000
10:92052264:A:T	L682Q	1.000
10:92052267:G:C	P681R	1.000
10:92052267:G:T	P681Q	1.000
10:92052268:G:A	P681S	1.000
10:92052269:T:A	K680N	1.000
10:92052269:T:G	K680N	1.000
10:92052271:T:C	K680E	1.000
10:92052272:G:C	H679Q	1.000
10:92052272:G:T	H679Q	1.000
10:92052273:T:A	H679L	1.000
10:92052273:T:C	H679R	1.000
10:92052274:G:A	H679Y	1.000
10:92052274:G:C	H679D	1.000
10:92052274:G:T	H679N	1.000
10:92052275:G:C	F678L	1.000
10:92052275:G:T	F678L	1.000
10:92052277:A:G	F678L	1.000
10:92052282:C:G	R676P	1.000
10:92052296:A:C	H671Q	1.000
10:92052296:A:T	H671Q	1.000
10:92052297:T:A	H671L	1.000
10:92052297:T:C	H671R	1.000
10:92052298:G:A	H671Y	1.000
10:92052298:G:C	H671D	1.000
10:92052298:G:T	H671N	1.000
10:92052300:A:T	I670K	1.000

dbSNP variants (sampled 300 via entrez): RS1000004377 (10:92287859 C>T), RS1000014809 (10:92242996 T>C,G), RS1000059268 (10:92143731 G>A), RS1000073035 (10:92235758 A>C), RS1000105456 (10:92136030 A>G), RS1000106542 (10:92184429 C>G,T), RS1000111652 (10:92275670 T>C), RS1000122366 (10:92241169 C>A,T), RS1000134241 (10:92210862 A>T), RS1000137699 (10:92157497 G>A), RS1000145882 (10:92082953 A>G,T), RS1000150904 (10:92087520 G>A), RS1000151309 (10:92089586 A>G), RS1000169847 (10:92189687 A>G), RS1000186943 (10:92210552 A>G)

Disease associations

OMIM: gene MIM:610606 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (1): Tourette syndrome (MONDO:0007661)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007576_273	Chronotype	2.000000e-09
GCST90002394_449	Monocyte percentage of white cells	9.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
Benzo(a)pyrene	decreases expression, decreases methylation	3
Valproic Acid	increases expression	3
Arsenic	affects methylation, increases abundance, increases expression	2
Cadmium	decreases expression, increases abundance, decreases reaction	2
Silicon Dioxide	decreases expression, increases methylation	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	affects expression, decreases expression	2
bisphenol A	affects cotreatment, increases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
nickel sulfate	decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
clothianidin	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Atrazine	increases expression	1
Calcitriol	affects cotreatment, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Copper	affects binding, increases expression	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Folic Acid	decreases expression	1

Clinical trials (associated diseases)

183 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome