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 — RefSeq curated summary.

At a glance

• GWAS associations: 79
• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_030627

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: 13 — 9 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

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

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.

FANTOM5 promoters (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

261 total, 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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

196 targeting CPEB4, 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-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

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)

Protein

Protein identifiers

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

All UniProt accessions (8): A0A590UJI5, A0A590UJN2, A0A590UK96, B7ZLQ8, Q17RY0, 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 16, binding site 8, modified residue 8, helix 6, compositionally biased region 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.

PDB	Method	Resolution (Å)
5DIF	X-RAY DIFFRACTION	2.09
2MKI	SOLUTION NMR
2MKJ	SOLUTION NMR

Predicted structure (AlphaFold)

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

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): 473 (rna-binding); 561 (important for the positioning of rrm1 relative to rrm2)

Ligand- & substrate-binding residues (8): 667; 675; 684; 689; 694; 697; 702; 710

Post-translational modifications (8): 97, 99, 137, 252, 255, 326, 330, 332

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

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 (13): 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), cell projection (GO:0042995), postsynapse (GO:0098794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
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

Protein interactions and networks

STRING

1198 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPEB4	FXR1	P51114	757
CPEB4	FXR2	P51116	745
CPEB4	EIF4E	P06730	726
CPEB4	FMR1	Q06787	721
CPEB4	DDX6	P26196	719
CPEB4	SYMPK	Q92797	659
CPEB4	NGDN	Q8NEJ9	634
CPEB4	TENT2	Q6PIY7	627
CPEB4	CAMK2A	Q9UQM7	552
CPEB4	RBFOX2	O43251	540
CPEB4	EIF2S3	P41091	533
CPEB4	IGF2BP1	Q9NZI8	527
CPEB4	CPSF2	Q9P2I0	515
CPEB4	HNRNPA2B1	P22626	514
CPEB4	PAPOLB	Q9NRJ5	490

IntAct

17 interactions, top by confidence:

A	B	Type	Score
SAV1	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
TOB1	CPEB4	psi-mi:“MI:0915”(physical association)	0.540
TOB1	CPEB4	psi-mi:“MI:0407”(direct interaction)	0.540
HOMEZ	CPEB4	psi-mi:“MI:0914”(association)	0.530
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
NBEAL2	HAX1	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
BSCL2	TMEM223	psi-mi:“MI:0914”(association)	0.350
PURG	ZNF320	psi-mi:“MI:0914”(association)	0.350
FAM120A	GTPBP10	psi-mi:“MI:0914”(association)	0.350
HOMEZ	KCNQ1	psi-mi:“MI:0914”(association)	0.350
CPEB4	CPEB2	psi-mi:“MI:0914”(association)	0.350
	NFIB	psi-mi:“MI:0914”(association)	0.350
LIN28B	MEX3A	psi-mi:“MI:2364”(proximity)	0.270
CPEB4	uup	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (194): CPEB4 (Affinity Capture-MS), CPEB4 (Biochemical Activity), CPEB4 (Affinity Capture-MS), CPEB4 (Affinity Capture-RNA), CPEB4 (Proximity Label-MS), CPEB4 (Proximity Label-MS), CPEB4 (Proximity Label-MS), CPEB4 (Proximity Label-MS), CPEB4 (Proximity Label-MS), CPEB4 (Proximity Label-MS), CPEB4 (Proximity Label-MS), CPEB4 (Proximity Label-MS), AGO1 (Proximity Label-MS), AGO2 (Proximity Label-MS), AGO3 (Proximity Label-MS)

ESM2 similar proteins: A2YX04, G5EDE9, O01835, O60291, P04150, P06536, P06537, P24345, P48001, P49115, P49843, P49844, P59667, Q09446, Q14693, Q17RY0, Q43484, Q5R9P5, Q5RJX2, Q5XIQ4, Q680Q4, Q6E3D2, Q6E3D4, Q6E3D5, Q6NN85, Q6NPP4, Q6Z8M8, Q6ZK57, Q700C2, Q75LH6, Q75LX7, Q7TN98, Q7TN99, Q7XC57, Q7XHR2, Q7YZA2, Q7ZUL9, Q8BFX3, Q8MQX9, Q8RY95

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
MAPK1	“up-regulates activity”	CPEB4	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1654 predictions. Top by Δscore:

Variant	Effect	Δscore
5:173910520:CAGG:C	acceptor_loss	1.0000
5:173910521:A:AG	acceptor_gain	1.0000
5:173910521:AG:A	acceptor_gain	1.0000
5:173910521:AGGAT:A	acceptor_loss	1.0000
5:173910522:G:GG	acceptor_gain	1.0000
5:173910522:G:T	acceptor_loss	1.0000
5:173910522:GG:G	acceptor_gain	1.0000
5:173910522:GGATC:G	acceptor_gain	1.0000
5:173910604:GGT:G	donor_loss	1.0000
5:173910605:G:GA	donor_loss	1.0000
5:173910605:G:GG	donor_gain	1.0000
5:173910606:T:A	donor_loss	1.0000
5:173944960:A:AG	acceptor_gain	1.0000
5:173944963:CCAG:C	acceptor_loss	1.0000
5:173944964:CAG:C	acceptor_loss	1.0000
5:173944965:A:AG	acceptor_gain	1.0000
5:173944965:AG:A	acceptor_gain	1.0000
5:173944966:G:GA	acceptor_gain	1.0000
5:173944966:GG:G	acceptor_gain	1.0000
5:173944966:GGT:G	acceptor_gain	1.0000
5:173944966:GGTC:G	acceptor_gain	1.0000
5:173944966:GGTCA:G	acceptor_gain	1.0000
5:173945137:GAAG:G	donor_gain	1.0000
5:173945141:G:GG	donor_gain	1.0000
5:173945142:T:G	donor_loss	1.0000
5:173949504:TTA:T	acceptor_loss	1.0000
5:173949505:TA:T	acceptor_loss	1.0000
5:173949506:A:AC	acceptor_loss	1.0000
5:173949506:A:AG	acceptor_gain	1.0000
5:173949506:AGAT:A	acceptor_gain	1.0000

AlphaMissense

4821 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:173945096:C:T	S471F	1.000
5:173945101:A:C	K473Q	1.000
5:173945101:A:G	K473E	1.000
5:173945103:G:C	K473N	1.000
5:173945103:G:T	K473N	1.000
5:173945105:T:A	V474E	1.000
5:173945107:T:A	F475I	1.000
5:173945107:T:C	F475L	1.000
5:173945107:T:G	F475V	1.000
5:173945108:T:C	F475S	1.000
5:173945108:T:G	F475C	1.000
5:173945109:T:A	F475L	1.000
5:173945109:T:G	F475L	1.000
5:173945111:T:A	V476E	1.000
5:173945113:G:C	G477R	1.000
5:173945113:G:T	G477C	1.000
5:173945114:G:A	G477D	1.000
5:173945114:G:T	G477V	1.000
5:173945116:G:A	G478R	1.000
5:173945116:G:C	G478R	1.000
5:173945117:G:A	G478E	1.000
5:173945117:G:T	G478V	1.000
5:173945120:T:C	L479S	1.000
5:173945120:T:G	L479W	1.000
5:173945122:C:A	P480T	1.000
5:173945122:C:T	P480S	1.000
5:173945123:C:A	P480H	1.000
5:173945123:C:G	P480R	1.000
5:173945126:C:A	P481Q	1.000
5:173945128:G:C	D482H	1.000

dbSNP variants (sampled 300 via entrez): RS1000031740 (5:173961479 T>C), RS1000081230 (5:173915925 T>C), RS1000095673 (5:173911942 A>G), RS1000176169 (5:173901598 C>A,T), RS1000209149 (5:173905142 A>G), RS1000247852 (5:173957737 C>A,T), RS1000284950 (5:173889869 A>C,G,T), RS1000334225 (5:173893962 A>G), RS1000340644 (5:173889509 A>C), RS1000376661 (5:173946806 C>A), RS1000421071 (5:173950186 G>A), RS1000429172 (5:173946483 G>A), RS1000446388 (5:173912241 C>T), RS1000451290 (5:173916428 A>G), RS1000579531 (5:173918049 T>A,C)

Disease associations

OMIM: gene MIM:610607 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

79 associations (top):

Study	Trait	p-value
GCST000829_16	Waist-hip ratio	2.000000e-09
GCST000879_20	Crohn’s disease	3.000000e-12
GCST001729_28	Crohn’s disease	5.000000e-09
GCST001762_66	Obesity-related traits	2.000000e-06
GCST002782_167	Waist-to-hip ratio adjusted for body mass index	2.000000e-08
GCST002782_168	Waist-to-hip ratio adjusted for body mass index	2.000000e-07
GCST002782_177	Waist-to-hip ratio adjusted for body mass index	5.000000e-14
GCST002782_178	Waist-to-hip ratio adjusted for body mass index	4.000000e-07
GCST002782_179	Waist-to-hip ratio adjusted for body mass index	3.000000e-08
GCST002782_180	Waist-to-hip ratio adjusted for body mass index	2.000000e-13
GCST004063_11	Waist circumference adjusted for body mass index	3.000000e-10
GCST004063_34	Waist circumference adjusted for body mass index	8.000000e-11
GCST004280_88	Diastolic blood pressure	2.000000e-11
GCST004500_122	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	8.000000e-06
GCST004500_52	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	2.000000e-06
GCST004501_15	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	4.000000e-06
GCST004501_16	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	9.000000e-06
GCST004505_31	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	8.000000e-07
GCST004505_32	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	7.000000e-07
GCST004602_40	Mean corpuscular volume	8.000000e-16
GCST004621_88	Red cell distribution width	1.000000e-09
GCST004630_76	Mean corpuscular hemoglobin	2.000000e-14
GCST004863_108	Mosquito bite size	2.000000e-06
GCST004904_30	Body mass index	5.000000e-10
GCST005532_1	Sjögren’s syndrome	9.000000e-07
GCST005537_239	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	1.000000e-08
GCST005993_78	Mean corpuscular hemoglobin	9.000000e-12
GCST006011_110	Mean corpuscular volume	3.000000e-11
GCST006666_10	Lipid traits (pleiotropy) (HIPO component 1)	4.000000e-08
GCST006979_482	Heel bone mineral density	1.000000e-09

EFO canonical traits (22, from GWAS)

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 (VIP=true, CPIC=false)

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
Arsenic	affects expression, decreases methylation, increases abundance	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	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
oxamflatin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1

Clinical trials (associated diseases)

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