EPC2

Summary

EPC2 (enhancer of polycomb 2, HGNC:24543) is a protein-coding gene on chromosome 2q23.1, encoding Enhancer of polycomb homolog 2 (Q52LR7). May play a role in transcription or DNA repair. It is a selective cancer dependency (DepMap: 27.2% of cell lines).

Predicted to enable protein-macromolecule adaptor activity. Involved in positive regulation of double-strand break repair via homologous recombination and regulation of cell cycle. Predicted to be located in nucleus. Predicted to be part of NuA4 histone acetyltransferase complex and piccolo histone acetyltransferase complex.

Source: NCBI Gene 26122 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 104 total — 4 pathogenic, 2 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 4 tissues, sQTL in 17 (q < 0.05)
• Cancer dependency (DepMap): dependent in 27.2% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.20 (highly constrained)
• MANE Select transcript: NM_015630
• Notable: 104 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24543
Approved symbol	EPC2
Name	enhancer of polycomb 2
Location	2q23.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP566F2124
Ensembl gene	ENSG00000135999
Ensembl biotype	protein_coding
OMIM	611000
Entrez	26122

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000258484

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

ENST00000258484, ENST00000397424, ENST00000409654, ENST00000449013, ENST00000457184, ENST00000491099, ENST00000902236, ENST00000902237, ENST00001077479, ENST00001144688

RefSeq mRNA: 1 — MANE Select: NM_015630 NM_015630

CCDS: CCDS46422

Canonical transcript exons

ENST00000258484 — 14 exons

Exon	Start	End
ENSE00001153925	148786305	148787569
ENSE00001153931	148743622	148743767
ENSE00001689981	148644751	148645170
ENSE00001758796	148753927	148754133
ENSE00003595825	148690214	148690373
ENSE00004282159	148784668	148785001
ENSE00004282160	148764955	148765146
ENSE00004282161	148781644	148781780
ENSE00004282162	148769151	148769240
ENSE00004282163	148761782	148761930
ENSE00004282164	148783597	148783756
ENSE00004282165	148762670	148762802
ENSE00004282166	148771044	148771387
ENSE00004282167	148770792	148770937

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 95.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.2969 / max 669.3664, expressed in 1811 samples.

Highest expression (Bgee): germinal epithelium of ovary, calcaneal tendon, ganglionic eminence, ventricular zone, cortical plate.

Genetic regulation across tissues (GTEx eQTL / sQTL)

EPC2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 4 tissues and its splicing (sQTL) in 17 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 21 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	sqtl	1.0e-08	+0.42	2:148691616:G:A
Breast Mammary Tissue	sqtl	8.0e-08	+0.44	2:148691616:G:A
Nerve Tibial	sqtl	2.8e-06	+0.38	2:148691616:G:A
Whole Blood	eqtl	4.4e-05	+0.09	2:148691616:G:A
Artery Tibial	sqtl	7.6e-05	+0.29	2:148691616:G:A
Skin Sun Exposed Lower leg	sqtl	2.4e-04	+0.29	2:148691616:G:A
Liver	eqtl	1.0e-03	-0.65	2:149623783:C:T
Adipose Visceral Omentum	sqtl	2.1e-03	+0.31	2:148691616:G:A
Brain Cerebellum	sqtl	4.1e-03	-1.99	2:149236393:T:C
Testis	sqtl	5.5e-03	+0.38	2:148691616:G:A
Lung	sqtl	6.2e-03	+0.26	2:148795570:G:A
Whole Blood	sqtl	6.2e-03	+0.28	2:148691616:G:A
Esophagus Gastroesophageal Junction	sqtl	1.3e-02	-1.20	2:148514734:G:A
Cells Cultured fibroblasts	sqtl	2.2e-02	+0.28	2:148662079:C:G
Heart Atrial Appendage	sqtl	2.2e-02	+0.34	2:148691616:G:A
Brain Hippocampus	eqtl	2.3e-02	-0.27	2:148660340:G:T
Cells Cultured fibroblasts	eqtl	2.7e-02	-0.38	2:148860757:G:A
Ovary	sqtl	2.8e-02	+0.46	2:148691616:G:A
Brain Cortex	sqtl	2.9e-02	-0.54	2:148619295:T:C
Artery Coronary	sqtl	4.7e-02	-0.43	2:148691616:G:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
22957	22.2969	1811

Top tissues by expression

showing 100 of 258 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	95.73	gold quality
calcaneal tendon	UBERON:0003701	95.44	gold quality
ganglionic eminence	UBERON:0004023	94.44	gold quality
ventricular zone	UBERON:0003053	93.98	gold quality
cortical plate	UBERON:0005343	93.74	gold quality
endothelial cell	CL:0000115	93.20	silver quality
sural nerve	UBERON:0015488	93.20	gold quality
bone marrow cell	CL:0002092	91.63	gold quality
tendon	UBERON:0000043	91.37	gold quality
corpus callosum	UBERON:0002336	91.19	gold quality
amniotic fluid	UBERON:0000173	90.45	gold quality
monocyte	CL:0000576	89.98	gold quality
ovary	UBERON:0000992	89.79	gold quality
thymus	UBERON:0002370	89.79	gold quality
leukocyte	CL:0000738	89.69	gold quality
gingival epithelium	UBERON:0001949	89.68	silver quality
left ovary	UBERON:0002119	89.63	gold quality
middle temporal gyrus	UBERON:0002771	89.56	gold quality
smooth muscle tissue	UBERON:0001135	89.02	gold quality
visceral pleura	UBERON:0002401	88.99	gold quality
parietal pleura	UBERON:0002400	88.86	gold quality
superficial temporal artery	UBERON:0001614	88.83	gold quality
bone marrow	UBERON:0002371	88.77	gold quality
right ovary	UBERON:0002118	88.69	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.52	gold quality
urethra	UBERON:0000057	88.50	gold quality
popliteal artery	UBERON:0002250	88.36	gold quality
pericardium	UBERON:0002407	88.35	gold quality
tibial artery	UBERON:0007610	88.35	gold quality
saphenous vein	UBERON:0007318	88.34	gold quality
cerebellar vermis	UBERON:0004720	88.32	gold quality
adrenal tissue	UBERON:0018303	88.19	gold quality
islet of Langerhans	UBERON:0000006	88.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.79	gold quality
occipital lobe	UBERON:0002021	87.56	gold quality
uterine cervix	UBERON:0000002	87.47	gold quality
body of uterus	UBERON:0009853	87.44	gold quality
primary visual cortex	UBERON:0002436	87.25	gold quality
tonsil	UBERON:0002372	87.16	gold quality
aorta	UBERON:0000947	87.13	gold quality
cardiac muscle of right atrium	UBERON:0003379	87.07	silver quality
left ventricle myocardium	UBERON:0006566	87.04	silver quality
gingiva	UBERON:0001828	86.97	silver quality
endocervix	UBERON:0000458	86.84	gold quality
uterus	UBERON:0000995	86.78	gold quality
endometrium	UBERON:0001295	86.57	gold quality
myometrium	UBERON:0001296	86.53	gold quality
penis	UBERON:0000989	86.49	gold quality
colonic epithelium	UBERON:0000397	86.48	gold quality
trigeminal ganglion	UBERON:0001675	86.47	gold quality
lymph node	UBERON:0000029	86.41	gold quality
tibial nerve	UBERON:0001323	86.36	gold quality
vena cava	UBERON:0004087	86.34	silver quality
female reproductive system	UBERON:0000474	86.30	gold quality
descending thoracic aorta	UBERON:0002345	86.30	gold quality
epithelium of nasopharynx	UBERON:0001951	86.17	gold quality
urinary bladder	UBERON:0001255	86.16	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.06	gold quality
layer of synovial tissue	UBERON:0007616	86.04	gold quality
ectocervix	UBERON:0012249	85.99	gold quality
cardia of stomach	UBERON:0001162	85.98	gold quality
gall bladder	UBERON:0002110	85.91	gold quality
cerebellum	UBERON:0002037	85.85	gold quality
right lung	UBERON:0002167	85.71	gold quality
rectum	UBERON:0001052	85.68	gold quality
gastrocnemius	UBERON:0001388	85.54	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.51	gold quality
muscle of leg	UBERON:0001383	85.49	gold quality
thoracic aorta	UBERON:0001515	85.47	gold quality
myocardium	UBERON:0002349	85.46	silver quality
cerebellar cortex	UBERON:0002129	85.45	gold quality
superior vestibular nucleus	UBERON:0007227	85.38	gold quality
seminal vesicle	UBERON:0000998	85.36	gold quality
ascending aorta	UBERON:0001496	85.36	gold quality
cerebellar hemisphere	UBERON:0002245	85.32	gold quality
left uterine tube	UBERON:0001303	85.30	gold quality
tendon of biceps brachii	UBERON:0008188	85.24	silver quality
epithelial cell of pancreas	CL:0000083	85.12	silver quality
dorsal root ganglion	UBERON:0000044	85.12	gold quality
coronary artery	UBERON:0001621	85.10	gold quality
left coronary artery	UBERON:0001626	85.10	gold quality
right coronary artery	UBERON:0001625	85.04	gold quality
deltoid	UBERON:0001476	85.00	silver quality
skeletal muscle organ	UBERON:0014892	85.00	gold quality
superior surface of tongue	UBERON:0007371	84.88	gold quality
peritoneum	UBERON:0002358	84.70	gold quality
omental fat pad	UBERON:0010414	84.68	gold quality
adrenal gland	UBERON:0002369	84.65	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.63	gold quality
prefrontal cortex	UBERON:0000451	84.62	gold quality
mucosa of stomach	UBERON:0001199	84.48	gold quality
vermiform appendix	UBERON:0001154	84.47	gold quality
lung	UBERON:0002048	84.44	gold quality
prostate gland	UBERON:0002367	84.38	gold quality
thyroid gland	UBERON:0002046	84.37	gold quality
caecum	UBERON:0001153	84.32	gold quality
left adrenal gland	UBERON:0001234	84.30	gold quality
adipose tissue of abdominal region	UBERON:0007808	84.26	gold quality
synovial joint	UBERON:0002217	84.24	gold quality
pons	UBERON:0000988	84.17	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.44
E-HCAD-5	no	2.22

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	47.4	high
Cerebellum	tissue	31.8	medium
Postcentral gyrus	tissue	30.6
Nucleus accumbens	tissue	29.0
Cerebral cortex	tissue	27.6	medium
Occipital cortex	tissue	27.6
Ovary	tissue	27.3	high
Frontal cortex	tissue	27.3
Somatosensory cortex	tissue	27.1
Hippocampus	tissue	26.2	high
Choroid plexus	tissue	26.1
Hippocampal formation	tissue	26.1
Entorhinal cortex	tissue	26.1
Motor cortex	tissue	25.9
Prefrontal cortex	tissue	25.0
Septum	tissue	24.8
Locus coeruleus	tissue	24.6
Putamen	tissue	24.2
Retrosplenial and cingulate cortex	tissue	24.2
Endometrium 1	tissue	23.9	high
Temporal cortex	tissue	23.6
Basal ganglia	tissue	23.4	medium
Ventral forebrain	tissue	23.3
Caudate putamen	tissue	23.1
Retrosplenial cortex	tissue	22.8
Midbrain	tissue	21.8
Hypothalamus	tissue	21.8
Periaqueductal gray	tissue	21.6
Thymus	tissue	21.5
Amygdala	tissue	21.4
Olfactory bulb	tissue	21.4
Pons	tissue	21.3
Insular cortex	tissue	21.2
Thalamus	tissue	21.1
Corpus callosum	tissue	21.1
Superior colliculi	tissue	20.6
Medulla oblongata	tissue	19.2
Substantia nigra	tissue	19.1
Spinal cord	tissue	18.6
Thyroid gland	tissue	18.1	high
Smooth muscle	tissue	17.8	medium
Tongue	tissue	17.3
Placenta	tissue	17.3	high
Lymph node	tissue	16.8	medium
Cervix	tissue	16.6	high
Breast	tissue	16.1	medium
Adipose tissue	tissue	15.4	medium
Prostate	tissue	15.2	medium
Spleen	tissue	15.0	high
Tonsil	tissue	14.9	high
Seminal vesicle	tissue	14.6	high
Urinary bladder	tissue	14.6	medium
Heart muscle	tissue	14.5	medium
Gallbladder	tissue	14.4	high
Fallopian tube	tissue	14.4	high
Lung	tissue	13.8	high
Testis	tissue	13.3	high
Epididymis	tissue	13.3	high
Adrenal gland	tissue	13.2	high
Rectum	tissue	13.0	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Cerebellar cortex (55.1), Vermis (52.2), Flocculonodular lobe (49.6), Corpus callosum, genu (white matter) (38.6), Corpus callosum, splenium (white matter) (37.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting EPC2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 177 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4668-3P	100.00	68.74	2635
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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1277-5P	100.00	73.95	5056
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-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.203, missense Z 2.5 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000258484 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈2% 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
2:148,645,018–148,690,244	36 / 84.0	0.43	no
2:148,690,245–148,781,654	509 / 607.7	0.84	no
2:148,781,655–148,781,706	3 / 19.3	0.16	yes (p 2.0e-04)
2:148,781,707–148,786,374	207 / 260.5	0.79	no
DepMap (CRISPR cell-line fitness): dependent in 27.2% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): NCI-H82 (-1.981), HCC-33 (-1.934), EWS502 (-1.851), BPH-1 (-1.508), NGP (-1.464), JVM-3 (-1.372), NP 8 (-1.337), CHL-1-DM (-1.306), NB-4 (-1.257), HCC-95 (-1.256), KNS-81 (-1.251), SK-NEP-1 (-1.235), SNU-C1 (-1.22), H314 (-1.217), WPE1-NA22 (-1.211).

Literature-anchored findings (GeneRIF, showing 1)

• EPC1 and EPC2 are components of a complex that directly or indirectly serves to prevent MYC accumulation and AML cell apoptosis, thus sustaining oncogenic potential (PMID:24166297)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	epc2	ENSDARG00000007485
mus_musculus	Epc2	ENSMUSG00000069495
rattus_norvegicus	Epc2	ENSRNOG00000029447
rattus_norvegicus	Epc2l1	ENSRNOG00000050758
drosophila_melanogaster	E(Pc)	FBGN0000581
caenorhabditis_elegans		WBGENE00007030

Paralogs (1): EPC1 (ENSG00000120616)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1278321) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal lens morphology	1
cataract	1
abnormal retina morphology	1
decreased locomotor activity	1
increased thigmotaxis	1
abnormal vertebral arch morphology	1
abnormal behavior	1
decreased lactate dehydrogenase level	1
increased pulmonary respiratory rate	1
abnormal retina blood vessel morphology	1
increased respiratory quotient	1
preweaning lethality, complete penetrance	1
decreased total retina thickness	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
Cryptococcus deneoformans JEC21	P0CN58	98.6%	Diamond
Cryptococcus deneoformans B-3501A	P0CN59	98.6%	Diamond
Xenopus laevis	Q66JA8	95.8%	Diamond
Xenopus tropicalis	Q6DJR9	95.8%	Diamond
Aspergillus fumigatus Af293	Q4WDF1	70.0%	Diamond
Aspergillus nidulans FGSC A4	Q5AYR3	70.0%	Diamond
Schizosaccharomyces pombe 972h-	Q9UU94	38.2%	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
MBD5	protein-coding	55777

Protein

Protein identifiers

Enhancer of polycomb homolog 2 — Q52LR7 (reviewed: Q52LR7)

Alternative names: EPC-like

All UniProt accessions (5): C9J1X4, E7ETK1, E9PBA8, Q52LR7, H7C0K5

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in transcription or DNA repair.

Subcellular location. Nucleus.

Similarity. Belongs to the enhancer of polycomb family.

RefSeq proteins (1): NP_056445* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009607	Enhancer_polycomb_C	Domain
IPR019542	Enhancer_polycomb-like_N	Domain
IPR024943	Enhancer_polycomb	Family

Pfam: PF06752, PF10513

UniProt features (14 total): cross-link 4, region of interest 3, compositionally biased region 3, modified residue 2, chain 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q52LR7-F1	58.35	0.15

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear speckles

Antibody reliability (HPA): IH uncertain · 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.

Post-translational modifications (6)

Type	Positions
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	195, 324, 362, 135
Phosphoserine	538, 754

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: 239 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_REGULATION_OF_DNA_RECOMBINATION, ACTACCT_MIR196A_MIR196B, GCM_GSPT1, TGCACTT_MIR519C_MIR519B_MIR519A, GCM_ZNF198, GTTAAAG_MIR302B, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, CHANDRAN_METASTASIS_DN, GOBP_REGULATION_OF_DNA_REPAIR, ATGTTAA_MIR302C, CTAGGAA_MIR384, CATTTCA_MIR203

GO Biological Process (10): DNA repair (GO:0006281), chromatin organization (GO:0006325), DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), regulation of apoptotic process (GO:0042981), positive regulation of DNA-templated transcription (GO:0045893), regulation of cell cycle (GO:0051726), positive regulation of double-strand break repair via homologous recombination (GO:1905168), regulation of double-strand break repair (GO:2000779), DNA damage response (GO:0006974)

GO Molecular Function (1): protein-macromolecule adaptor activity (GO:0030674)

GO Cellular Component (3): nucleus (GO:0005634), piccolo histone acetyltransferase complex (GO:0032777), NuA4 histone acetyltransferase complex (GO:0035267)

GO top-level categories

25 GO namespaces:

Category	Terms
regulation of DNA-templated transcription	2
DNA metabolic process	1
DNA damage response	1
cellular component organization	1
gene expression	1
RNA biosynthetic process	1
transcription by RNA polymerase II	1
apoptotic process	1
regulation of programmed cell death	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cell cycle	1
regulation of cellular process	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
positive regulation of DNA recombination	1
positive regulation of double-strand break repair	1
regulation of DNA repair	1
double-strand break repair	1
cellular response to stress	1
protein binding	1
molecular adaptor activity	1
intracellular membrane-bounded organelle	1
protein-containing complex	1
H4/H2A histone acetyltransferase complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 14 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
positive regulation of double-strand break repair via homologous recombination	BP	direct assay
regulation of cell cycle	BP	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 974 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPC2	MEAF6	Q9HAF1	777
EPC2	BRD8	Q9H0E9	715
EPC2	DMAP1	Q9NPF5	671
EPC2	TRRAP	Q9Y4A5	638
EPC2	ING3	Q9NXR8	612
EPC2	YEATS4	O95619	586
EPC2	EP400	Q96L91	568
EPC2	ACTL6A	O96019	565
EPC2	DSG1	Q02413	550
EPC2	KAT5	Q92993	545
EPC2	CAPN14	A8MX76	541
EPC2	RUVBL1	P82276	541
EPC2	MORF4L1	Q9UBU8	537
EPC2	LYPD6B	Q8NI32	525
EPC2	CDX1	P47902	511

IntAct

Human interaction partners of EPC2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
YEATS4	association	0.640	2
CEP63	physical association	0.000	1

BioGRID (126 interactions; top human partners by supporting records): KAT5 (Affinity Capture-MS; 6 records), MORF4L1 (Affinity Capture-MS; 6 records), MORF4L2 (Affinity Capture-MS; 5 records), FOXR1 (Affinity Capture-MS; 4 records), MYC (Proximity Label-MS; 4 records), YEATS4 (Affinity Capture-MS; 4 records), DMAP1 (Affinity Capture-MS; 3 records), FOXR2 (Affinity Capture-MS; 3 records), HIST1H2BA (Affinity Capture-MS; 3 records), ING3 (Affinity Capture-MS; 3 records), JAZF1 (Affinity Capture-MS; 3 records), MBTD1 (Affinity Capture-MS; 3 records), MRGBP (Affinity Capture-MS; 3 records), PLAC1 (Affinity Capture-MS; 3 records), RUVBL1 (Affinity Capture-MS; 3 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
EPC2	“form complex”	“NuA4 complex”	binding

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
H2A.Z histone-exchange complex p400/TIP60	27	ZNHIT1, ACTL6A, DMAP1, MORF4L1, MRGBP, RUVBL1, VPS72, YEATS4, BRD8, H4C1, ING3, IPO9, PRKDC, SRCAP, ANP32E, EP400, EPC1, EPC2, H2AZ1, H2BC4, H3C1, KAT5, MORF4L2, RUVBL2, TRRAP, XRCC5, XRCC6
NuA4/Tip60-HAT complex A	15	DMAP1, ING3, MEAF6, RUVBL2, TRRAP, YEATS4, BRD8, EPC1, EPC2, RUVBL1, ACTL6A, MORF4L1, MRGBP, EP400, KAT5
NuA4/Tip60 HAT complex	14	EP400, EPC1, KAT5, YEATS4, ACTL6A, EPC2, ING3, MEAF6, MORF4L1, RUVBL1, RUVBL2, TRRAP, BRD8, DMAP1

Disease & clinical

Genetic variants

Variant evidence for EPC2: 104 ClinVar records (6 pathogenic / likely pathogenic); 12 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	81
Likely benign	0
Benign	5

Top pathogenic / likely-pathogenic (6)

Showing all 6 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
403692	Single allele	Pathogenic	criteria provided, single submitter	1
2506556	GRCh37/hg19 2q23.1(chr2:149220152-149633312)	Likely pathogenic	criteria provided, single submitter	1
150817	GRCh38/hg38 2q23.1-23.2(chr2:148440874-149091788)x1	Pathogenic	no assertion criteria provided	1
183383	NC_000002.10:g.148447496_149377297del	Pathogenic	no assertion criteria provided	1
395440	GRCh37/hg19 2q23.1-23.3(chr2:148842506-152370040)x1	Pathogenic	no assertion criteria provided	1
562615	GRCh37/hg19 2q23.1(chr2:148704099-149545055)x3	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore EPC2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 1,275):

Position(s)	Effect	Δscore	Sites
2:148690206	acceptor_gain	1.0000
2:148690212–148690213	acceptor_loss	1.0000	5
2:148690336	donor_gain	1.0000
2:148690374–148690375	donor_loss	1.0000	5
2:148743620–148743621	acceptor_loss	1.0000	6
2:148743768–148743769	donor_loss	1.0000	5
2:148753925–148753926	acceptor_loss	1.0000	6
2:148754134–148754135	donor_loss	1.0000	5
2:148762668	acceptor_gain	1.0000
2:148764929–148764930	acceptor_gain	1.0000	2

AlphaMissense

2,061 missense substitutions predicted likely pathogenic (of 5,334 scored), across 453 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
M218	9	0.998	1.000
M45	9	0.994	1.000
M234	9	0.980	1.000
M41	9	0.959	1.000
M804	9	0.948	0.997
M593	9	0.901	0.995
M72	9	0.871	0.989
M142	9	0.864	0.994
H54	8	0.999	1.000
F211	8	0.999	1.000
D121	8	0.998	1.000
F6	8	0.997	1.000
D12	8	0.997	1.000
N223	8	0.994	1.000
D277	8	0.994	0.999
N226	8	0.992	1.000
F400	8	0.989	0.999
D463	8	0.989	0.997
D227	8	0.987	0.999
D118	8	0.980	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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	2.09e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000455

Disease associations

OMIM: gene MIM:611000 | disease phenotypes: MIM:156200

GenCC curated gene-disease

Mondo (1): intellectual disability, autosomal dominant 1 (MONDO:0007974)

Orphanet (1): 2q23.1 microdeletion syndrome (Orphanet:228402)

GWAS associations

12 associations:

Study	Trait	p-value
GCST007272_40	Pulse pressure	3e-25
GCST007272_44	Pulse pressure	6e-24
GCST010118_66	Type 2 diabetes	1e-9
GCST007576_7	Chronotype	2e-9
GCST007847_82	Type 2 diabetes	5e-9
GCST007201_314	Schizophrenia	8e-9
GCST006803_82	Schizophrenia	8e-7
GCST000900_1	Alzheimer’s disease biomarkers	1e-6
GCST000900_4	Alzheimer’s disease biomarkers	1e-6
GCST006397_6	Relative amplitude of rest-activity cycles	3e-6
GCST000189_36	Protein quantitative trait loci	4e-6
GCST009391_2092	Metabolite levels	9e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0004811	interleukin-8 measurement
EFO:0004760	t-tau measurement
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0005763	pulse pressure measurement
EFO:0008328	chronotype measurement
EFO:0010378	phosphatidylcholine 34:4 measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C566947	Mental Retardation, Autosomal Dominant 1 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	5
trichostatin A	affects cotreatment, decreases expression, affects expression	3
sodium arsenite	decreases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Formaldehyde	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
TL8-506	affects cotreatment, increases expression	1
propionaldehyde	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Caffeine	affects phosphorylation	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	increases abundance, increases expression	1

Clinical trials (associated diseases)

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