EPOP

Summary

EPOP (elongin BC and polycomb repressive complex 2 associated protein, HGNC:34493) is a protein-coding gene on chromosome 17q12, encoding Elongin BC and Polycomb repressive complex 2-associated protein (A6NHQ4). Scaffold protein that serves as a bridging partner between the PRC2/EZH2 complex and the elongin BC complex: required to fine-tune the transcriptional status of Polycomb group (PcG) target genes in embryonic stem cells (ESCs). It is a selective cancer dependency (DepMap: 56.5% of cell lines).

Predicted to enable chromatin binding activity. Predicted to be involved in neuron fate commitment; regulation of transcription by RNA polymerase II; and stem cell differentiation. Predicted to be located in chromosome and nucleus. Predicted to be part of ESC/E(Z) complex and elongin complex.

Source: NCBI Gene 100170841 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 4 total
• Cancer dependency (DepMap): dependent in 56.5% of screened cell lines
• MANE Select transcript: NM_001130677

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34493
Approved symbol	EPOP
Name	elongin BC and polycomb repressive complex 2 associated protein
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	LOC100170841, PRR28
Ensembl gene	ENSG00000273604
Ensembl biotype	protein_coding
OMIM	617795
Entrez	100170841

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000621654

RefSeq mRNA: 1 — MANE Select: NM_001130677 NM_001130677

CCDS: CCDS45661

Canonical transcript exons

ENST00000613024 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 82.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.9135 / max 87.8434, expressed in 1245 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165531	3.9767	1108
165530	1.9367	656

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	82.90	gold quality
prefrontal cortex	UBERON:0000451	81.76	gold quality
frontal cortex	UBERON:0001870	81.05	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.96	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.21	gold quality
anterior cingulate cortex	UBERON:0009835	79.89	gold quality
right frontal lobe	UBERON:0002810	79.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.76	gold quality
cerebral cortex	UBERON:0000956	78.05	gold quality
primary visual cortex	UBERON:0002436	75.47	gold quality
left testis	UBERON:0004533	75.29	gold quality
testis	UBERON:0000473	75.22	gold quality
right testis	UBERON:0004534	75.18	gold quality
temporal lobe	UBERON:0001871	71.28	gold quality
amygdala	UBERON:0001876	71.07	gold quality
putamen	UBERON:0001874	68.97	gold quality
lymph node	UBERON:0000029	68.65	gold quality
right lobe of liver	UBERON:0001114	68.23	gold quality
islet of Langerhans	UBERON:0000006	67.97	gold quality
brain	UBERON:0000955	67.93	gold quality
cortical plate	UBERON:0005343	67.64	gold quality
granulocyte	CL:0000094	67.33	gold quality
pancreas	UBERON:0001264	67.32	gold quality
ganglionic eminence	UBERON:0004023	67.07	gold quality
body of pancreas	UBERON:0001150	66.55	gold quality
left adrenal gland	UBERON:0001234	66.38	gold quality
liver	UBERON:0002107	66.33	gold quality
left adrenal gland cortex	UBERON:0035825	66.17	gold quality
placenta	UBERON:0001987	66.03	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting EPOP, 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-4533	100.00	69.48	2758
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 56.5% of screened cell lines.

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Epop	ENSMUSG00000043439
rattus_norvegicus	Epop	ENSRNOG00000048187

Paralogs (2): SIMC1 (ENSG00000170085), SKIDA1 (ENSG00000180592)

Protein

Protein identifiers

Elongin BC and Polycomb repressive complex 2-associated protein — A6NHQ4 (reviewed: A6NHQ4)

Alternative names: Proline-rich protein 28

All UniProt accessions (1): A6NHQ4

UniProt curated annotations — full annotation on UniProt →

Function. Scaffold protein that serves as a bridging partner between the PRC2/EZH2 complex and the elongin BC complex: required to fine-tune the transcriptional status of Polycomb group (PcG) target genes in embryonic stem cells (ESCs). Plays a key role in genomic regions that display both active and repressive chromatin properties in pluripotent stem cells by sustaining low level expression at PcG target genes: acts by recruiting the elongin BC complex, thereby restricting excessive activity of the PRC2/EZH2 complex. Interaction with USP7 promotes deubiquitination of H2B at promoter sites. Acts as a regulator of neuronal differentiation.

Subunit / interactions. Associates with the PRC2 complex, which consists of the core components EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP. Within the complex, interacts with SUZ12 (via C2H2 zinc finger domain); competes with JARID2 for SUZ12 binding. Associates with the elongin BC complex. Interacts with USP7.

Subcellular location. Nucleus. Chromosome.

Domain organisation. The BC-box, which mediates binding to the elongin BC complex.

RefSeq proteins (1): NP_001124149* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027971	EPOP	Family
IPR052119	ElonginBC-PRC2_ViralRestrict	Family

Pfam: PF15223

UniProt features (13 total): region of interest 6, modified residue 3, compositionally biased region 3, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9LAF	X-RAY DIFFRACTION	2.14
9XZI	X-RAY DIFFRACTION	2.69

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NHQ4-F1	59.12	0.01

Functional residue map

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

Post-translational modifications (3): 15, 19, 52

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212300	PRC2 methylates histones and DNA

MSigDB gene sets: 94 (showing top): GOBP_NEUROGENESIS, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS, SANSOM_APC_TARGETS_UP, GOBP_STEM_CELL_DIFFERENTIATION, GOBP_NEURON_FATE_COMMITMENT, YAMAZAKI_TCEB3_TARGETS_UP, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, GOBP_CELL_FATE_COMMITMENT, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOMF_CHROMATIN_BINDING, GOCC_TRANSFERASE_COMPLEX, GOCC_PCG_PROTEIN_COMPLEX, GOCC_HISTONE_METHYLTRANSFERASE_COMPLEX

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), neuron fate commitment (GO:0048663), stem cell differentiation (GO:0048863), transcription elongation-coupled chromatin remodeling (GO:0140673)

GO Molecular Function (2): chromatin binding (GO:0003682), protein-containing complex binding (GO:0044877)

GO Cellular Component (4): chromosome (GO:0005694), ESC/E(Z) complex (GO:0035098), elongin complex (GO:0070449), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
neuron differentiation	1
cell fate commitment	1
cell differentiation	1
chromatin remodeling	1
transcription elongation by RNA polymerase II	1
intracellular membraneless organelle	1
PcG protein complex	1
histone methyltransferase complex	1
transcription elongation factor complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPOP	MTF2	Q9Y483	988
EPOP	PHF19	Q5T6S3	988
EPOP	PHF1	O43189	978
EPOP	AEBP2	Q6ZN18	866
EPOP	JARID2	Q92833	817
EPOP	LCOR	Q96JN0	799
EPOP	RBBP4	P31149	745
EPOP	SUZ12	Q15022	741
EPOP	EZH1	Q92800	708
EPOP	EZH2	Q15910	642
EPOP	ELOB	Q15370	607
EPOP	EZHIP	Q86X51	583
EPOP	USP7	Q93009	577
EPOP	RBBP7	Q16576	571
EPOP	YAF2	Q8IY57	520

IntAct

21 interactions, top by confidence:

A	B	Type	Score
EZH2	EPOP	psi-mi:“MI:0914”(association)	0.730
SUZ12	EPOP	psi-mi:“MI:0914”(association)	0.640
EED	EPOP	psi-mi:“MI:0914”(association)	0.530
RBBP7	EPOP	psi-mi:“MI:0914”(association)	0.530
PHF19	EPOP	psi-mi:“MI:0914”(association)	0.530
PHF1	EPOP	psi-mi:“MI:0914”(association)	0.530
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
EPOP	HAT1	psi-mi:“MI:0914”(association)	0.350
MTF2	EPOP	psi-mi:“MI:0914”(association)	0.350

BioGRID (54): C17orf96 (Affinity Capture-RNA), C17orf96 (Affinity Capture-RNA), C17orf96 (Affinity Capture-MS), C17orf96 (Affinity Capture-MS), C17orf96 (Affinity Capture-MS), CHD3 (Affinity Capture-MS), CUL3 (Affinity Capture-MS), EED (Affinity Capture-MS), TCEB2 (Affinity Capture-MS), TCEB1 (Affinity Capture-MS), EZH1 (Affinity Capture-MS), EZH2 (Affinity Capture-MS), HAT1 (Affinity Capture-MS), HDAC2 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RRK4, A0A1W2PPE3, A0A1W2PR82, A0A2R8Y2Y2, A0A494C0N9, A0A494C0Y3, A0JNN8, A6NF83, A6NHQ4, A6QPM6, A8E4L3, A8MTW9, B2KGE5, C9JVW0, I3L1E1, O43541, O75474, O75638, P0C7X2, P70339, P89439, Q02080, Q05215, Q12950, Q3SYB3, Q5T230, Q5VV16, Q6NZ36, Q6NZY7, Q6P1X6, Q6VB84, Q6VUC0, Q6VUP9, Q6ZSJ8, Q7RTU5, Q7TNS8, Q80WY3, Q86SI9, Q86UU5, Q8K025

Diamond homologs: A6NHQ4, Q1XH10, Q7TNS8, Q80YR3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

127 predictions. Top by Δscore:

Variant	Effect	Δscore
17:38673468:C:CA	donor_gain	0.7500
17:38674661:C:CA	donor_gain	0.7400
17:38674673:T:A	donor_gain	0.6400
17:38674922:C:A	donor_gain	0.5700
17:38674899:T:TA	donor_gain	0.5200
17:38673247:AGCTC:A	acceptor_loss	0.4900
17:38673248:GCTCC:G	acceptor_loss	0.4900
17:38673249:CTCCT:C	acceptor_loss	0.4900
17:38673250:TCCTA:T	acceptor_loss	0.4900
17:38673251:CCTAA:C	acceptor_loss	0.4900
17:38673252:C:A	acceptor_loss	0.4900
17:38673253:T:C	acceptor_loss	0.4900
17:38673254:A:C	acceptor_loss	0.4800
17:38673259:G:C	acceptor_loss	0.4800
17:38674674:C:A	donor_gain	0.4700
17:38674921:T:TA	donor_gain	0.4600
17:38674137:T:TA	donor_gain	0.4500
17:38673256:A:C	acceptor_loss	0.4400
17:38673276:ATGT:A	acceptor_loss	0.4400
17:38673275:AATGT:A	acceptor_loss	0.4300
17:38673158:CCT:C	acceptor_gain	0.4200
17:38673159:CTC:C	acceptor_gain	0.4200
17:38673160:TCT:T	acceptor_gain	0.4200
17:38673278:GTGA:G	acceptor_loss	0.4200
17:38673280:G:GC	acceptor_loss	0.4200
17:38673279:T:C	acceptor_loss	0.4100
17:38674395:T:TA	donor_gain	0.4100
17:38673159:CT:C	acceptor_gain	0.4000
17:38673161:C:CC	acceptor_gain	0.4000
17:38673277:TGTG:T	acceptor_loss	0.4000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000118139 (17:38674011 G>A,C,T), RS1000700633 (17:38675536 T>A), RS1000976911 (17:38675173 G>T), RS1001463769 (17:38671650 A>C,G), RS1001530153 (17:38675182 C>A,G,T), RS1001535934 (17:38671364 C>A), RS1002920901 (17:38672025 C>T), RS1003491572 (17:38674098 G>A), RS1003772098 (17:38673825 G>A), RS1003865254 (17:38676636 G>A,T), RS1004702403 (17:38671925 C>T), RS1005755129 (17:38673101 A>T), RS1005971635 (17:38673801 G>A,T), RS1006699823 (17:38674852 C>G,T), RS1006963911 (17:38674658 G>A,T)

Disease associations

OMIM: gene MIM:617795 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003075_28	Cognitive decline rate in late mild cognitive impairment	6.000000e-07
GCST007600_68	Alzheimer’s disease	2.000000e-06
GCST007600_70	Alzheimer’s disease	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	6
trichostatin A	affects cotreatment, increases expression	3
Nickel	increases expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
sodium arsenite	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
ferrous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
gardiquimod	increases expression, decreases reaction	1
Leflunomide	decreases expression	1
Ethanol	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, decreases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Malathion	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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