EP400

Summary

EP400 (E1A binding protein p400, HGNC:11958) is a protein-coding gene on chromosome 12q24.33, encoding E1A-binding protein p400 (Q96L91). Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. It is a common-essential gene (DepMap: required in 94.3% of cancer cell lines).

Predicted to enable chromatin binding activity. Involved in positive regulation of double-strand break repair via homologous recombination and regulation of cell cycle. Part of NuA4 histone acetyltransferase complex; Swr1 complex; and nucleosome.

Source: NCBI Gene 57634 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with or without early-onset generalized epilepsy (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 9
• Clinical variants (ClinVar): 670 total
• Cancer dependency (DepMap): dependent in 94.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_015409

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11958
Approved symbol	EP400
Name	E1A binding protein p400
Location	12q24.33
Locus type	gene with protein product
Status	Approved
Aliases	CAGH32, KIAA1498, P400, KIAA1818, DKFZP434I225
Ensembl gene	ENSG00000183495
Ensembl biotype	protein_coding
OMIM	606265
Entrez	57634

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 4 retained_intron

ENST00000330386, ENST00000332482, ENST00000333577, ENST00000389561, ENST00000611118, ENST00000611739, ENST00000611841, ENST00000616136, ENST00000703283, ENST00000935960

RefSeq mRNA: 1 — MANE Select: NM_015409 NM_015409

CCDS: CCDS31929

Canonical transcript exons

ENST00000389561 — 53 exons

Exon	Start	End
ENSE00001290726	132005077	132005184
ENSE00001291050	132023777	132023941
ENSE00001291944	132006700	132006877
ENSE00001292814	132013009	132013178
ENSE00001293593	132017535	132017721
ENSE00001294299	132062466	132062701
ENSE00001294729	131960585	131961954
ENSE00001295342	132066774	132066969
ENSE00001295450	132050599	132050655
ENSE00001296640	132053343	132053597
ENSE00001298179	132055099	132055208
ENSE00001298875	131992173	131992230
ENSE00001299035	131986514	131986807
ENSE00001300850	131981489	131981596
ENSE00001302486	132027437	132027531
ENSE00001308755	132029701	132029903
ENSE00001309364	132021079	132021321
ENSE00001309396	132013777	132013913
ENSE00001309890	132006112	132006302
ENSE00001310250	132025646	132025804
ENSE00001311924	132069495	132069641
ENSE00001312430	131991407	131991456
ENSE00001312813	132018210	132018376
ENSE00001314074	132062110	132062323
ENSE00001315315	132064668	132064886
ENSE00001316186	132053146	132053224
ENSE00001316695	132011498	132011634
ENSE00001317637	132054974	132055019
ENSE00001318812	131982093	131982478
ENSE00001318929	131994867	131994956
ENSE00001322634	131987705	131987890
ENSE00001324276	132067362	132067486
ENSE00001325093	131979694	131979793
ENSE00001325986	132020049	132020218
ENSE00001328035	132028017	132028288
ENSE00001328756	132013490	132013664
ENSE00001379608	132076516	132076593
ENSE00001471225	131990636	131990714
ENSE00001506215	131989964	131990104
ENSE00003464180	132044671	132044715
ENSE00003489068	132044800	132044953
ENSE00003497946	132044177	132044311
ENSE00003531824	132037953	132038096
ENSE00003534798	132031953	132032149
ENSE00003555102	132043304	132043462
ENSE00003598755	132043645	132043728
ENSE00003603503	132029989	132030158
ENSE00003623736	132045727	132045900
ENSE00003633600	132045319	132045560
ENSE00003633996	132050323	132050459
ENSE00003664503	132037682	132037793
ENSE00003724513	131949942	131950036
ENSE00003747068	132077401	132080460

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.7301 / max 276.5269, expressed in 1810 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128773	29.4879	1810
128772	0.2422	130

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.10	gold quality
sural nerve	UBERON:0015488	94.03	gold quality
secondary oocyte	CL:0000655	92.75	gold quality
ventricular zone	UBERON:0003053	92.30	gold quality
medial globus pallidus	UBERON:0002477	91.51	gold quality
right uterine tube	UBERON:0001302	91.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.06	gold quality
cerebellar hemisphere	UBERON:0002245	90.31	gold quality
left ovary	UBERON:0002119	90.25	gold quality
cerebellar cortex	UBERON:0002129	90.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.16	gold quality
right ovary	UBERON:0002118	89.77	gold quality
globus pallidus	UBERON:0001875	89.57	gold quality
ganglionic eminence	UBERON:0004023	89.56	gold quality
ovary	UBERON:0000992	89.37	gold quality
cerebellum	UBERON:0002037	89.33	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.22	gold quality
body of uterus	UBERON:0009853	88.93	gold quality
endothelial cell	CL:0000115	88.91	gold quality
nipple	UBERON:0002030	88.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.70	gold quality
pituitary gland	UBERON:0000007	88.66	gold quality
embryo	UBERON:0000922	88.60	gold quality
endocervix	UBERON:0000458	88.53	gold quality
adenohypophysis	UBERON:0002196	88.41	gold quality
middle temporal gyrus	UBERON:0002771	88.26	gold quality
cortical plate	UBERON:0005343	88.17	gold quality
ectocervix	UBERON:0012249	88.16	gold quality
skin of leg	UBERON:0001511	88.12	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXN1, KAT5, KAT7, KDM5C, MBD2

miRNA regulators (miRDB)

88 targeting EP400, 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-4668-3P	100.00	68.74	2635
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-6739-5P	99.80	67.87	2806

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 94.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 18)

• p400 is a component of the p53-p21(WAF1/CIP1/sid1) pathway, regulating the p21 transcription and cell senescence induction program. (PMID:15655109)
• p400 is a regulator of the ARF-p53 pathway and a component of the cellular machinery that couples proliferation to cell death (PMID:15741165)
• Tip60 and p400 play distinct roles in DNA damage-induced apoptosis and underline the importance of the Tip60 complex and its regulation in the proper control of cell fate. (PMID:16601686)
• These findings establish that Myc, via p400, is an essential downstream target of adenovirus E1A. (PMID:18413597)
• Myc recruits the Tip60/p400 complex to achieve a coordinated histone acetylation/exchange reaction at activated promoters. (PMID:18985155)
• p400/Tip60 ratio is critical for colon cancer cells proliferation and response to therapeutic drugs through the control of stress-response pathways. (PMID:19169279)
• Results suggest that p400 represses basal p21 gene expression through dual mechanisms that include direct inhibition of TIP60 and ATP-dependent positioning of H2A.Z at the promoter. (PMID:20351180)
• Depletion of p400 indeed increases intracellular reactive oxygen species levels and causes the appearance of DNA damage (PMID:20548951)
• p400 is a novel DNA damage response protein and p400-mediated alterations in nucleosome and chromatin structure promote both chromatin ubiquitination and the accumulation of brca1 and 53BP1 at sites of DNA damage. (PMID:20876283)
• incorporation of the histone variant H2A.Z at the promoter regions of PPARgamma target genes by p400/Brd8 is essential to allow fat cell differentiation (PMID:23064015)
• age-dependent p400 downregulation and loss of H2A.Z localisation may contribute to the onset of replicative senescence through a sustained high rate of p21 transcription (PMID:23146670)
• The p400 ATPase is required for DNA repair by homologous recombination. (PMID:23266955)
• Our data suggest that the highly proliferative, decreased-p400 subgroup of renal cell carcinomas represents tumors that are characterized by a loss of the tumor-suppressive mechanism of senescence. (PMID:23982490)
• Data indicate that three genes, namely Chemokine (C-X-C motif) receptor 2 (CXCR2), C-C chemokine receptor type 2 (CCR2) and E1A-Binding Protein P400 (EP400), were able to identify HCC individually with accuracies of 82.4%, 78.4% and 65%, respectively. (PMID:24332572)
• All together these results show that p400 acts as a brake to prevent alternative End Joining-dependent genetic instability and underline its potential value as a clinical marker. (PMID:26578561)
• EP400 deposits H3.3 into chromatin alongside H2AZ and contributes to gene regulation after Pol II pre-initiation complex assembly. (PMID:26669263)
• Taken together, the findings suggest that a protein-protein interaction between ATM and p400 ATPase occurs independently of DNA damage and contributes to efficient DNA damage response and repair. (PMID:27814680)
• TIP60/P400/H4K12ac Plays a Role as a Heterochromatin Back-up Skeleton in Breast Cancer. (PMID:33099470)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ep400	ENSDARG00000100965
mus_musculus	Ep400	ENSMUSG00000029505
rattus_norvegicus	Ep400	ENSRNOG00000037483

Paralogs (30): HLTF (ENSG00000071794), SMARCA2 (ENSG00000080503), SRCAP (ENSG00000080603), ATRX (ENSG00000085224), RAD54L (ENSG00000085999), BTAF1 (ENSG00000095564), CHD8 (ENSG00000100888), SMARCA1 (ENSG00000102038), CHD4 (ENSG00000111642), CHD5 (ENSG00000116254), TTF2 (ENSG00000116830), HELLS (ENSG00000119969), ZRANB3 (ENSG00000121988), CHD6 (ENSG00000124177), SMARCA4 (ENSG00000127616), INO80 (ENSG00000128908), CHD1L (ENSG00000131778), SMARCAL1 (ENSG00000138375), SHPRH (ENSG00000146414), SMARCA5 (ENSG00000153147), CHD1 (ENSG00000153922), SMARCAD1 (ENSG00000163104), RAD54L2 (ENSG00000164080), CHD3 (ENSG00000170004), CHD7 (ENSG00000171316), CHD2 (ENSG00000173575), CHD9 (ENSG00000177200), ERCC6L (ENSG00000186871), RAD54B (ENSG00000197275), ERCC6 (ENSG00000225830)

Protein

Protein identifiers

E1A-binding protein p400 — Q96L91 (reviewed: Q96L91)

Alternative names: CAG repeat protein 32, Domino homolog, Trinucleotide repeat-containing gene 12 protein, p400 kDa SWI2/SNF2-related protein

All UniProt accessions (5): A0A0A0MR70, A0A0A0MR72, A0A0A0MR80, A0A8V8TRJ5, Q96L91

UniProt curated annotations — full annotation on UniProt →

Function. Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. May be required for transcriptional activation of E2F1 and MYC target genes during cellular proliferation. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. May regulate ZNF42 transcription activity. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome.

Subunit / interactions. Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. May also participate in the formation of NuA4 related complexes which lack the KAT5/TIP60 catalytic subunit, but which include the SWI/SNF related protein SRCAP. The NuA4 complex interacts with MYC and the adenovirus E1A protein. EP400 interacts with TRRAP, RUVBL1 and RUVBL2. Component of a SWR1-like complex. Interacts with ZNF42. Interacts with PHF5A. Interacts with human cytomegalovirus UL27. Interacts with human adenovirus 5 E1A protein; this interaction stabilizes MYC.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed.

Similarity. Belongs to the SNF2/RAD54 helicase family. SWR1 subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
Q96L91-1	1	yes
Q96L91-2	2
Q96L91-3	3
Q96L91-4	4
Q96L91-5	5

RefSeq proteins (1): NP_056224* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000330	SNF2_N	Domain
IPR001005	SANT/Myb	Domain
IPR001650	Helicase_C-like	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR014012	HSA_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR031575	EP400_N	Domain
IPR038718	SNF2-like_sf	Homologous_superfamily
IPR049730	SNF2/RAD54-like_C	Domain

Pfam: PF00176, PF00271, PF07529, PF15790

UniProt features (176 total): helix 51, strand 31, compositionally biased region 26, region of interest 19, modified residue 18, sequence conflict 10, turn 9, domain 4, splice variant 4, chain 1, short sequence motif 1, binding site 1, sequence variant 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
9CAF	ELECTRON MICROSCOPY	2.35
8QR1	ELECTRON MICROSCOPY	2.4
9C57	ELECTRON MICROSCOPY	2.75
9CAD	ELECTRON MICROSCOPY	3.05
9CAE	ELECTRON MICROSCOPY	3.07
8XVT	ELECTRON MICROSCOPY	3.2
8XVV	ELECTRON MICROSCOPY	3.2
9C6N	ELECTRON MICROSCOPY	3.29
9C47	ELECTRON MICROSCOPY	3.4
9CAC	ELECTRON MICROSCOPY	3.43
8QRI	ELECTRON MICROSCOPY	3.5
9C62	ELECTRON MICROSCOPY	5.28
8XVG	ELECTRON MICROSCOPY	9.4

Predicted structure (AlphaFold)

No AlphaFold model available for Q96L91 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Ligand- & substrate-binding residues (1): 1116–1123

Post-translational modifications (18): 53, 135, 315, 321, 736, 755, 928, 941, 945, 1011, 1472, 1547, 1728, 1732, 2349, 2356, 2686, 2813

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2559584	Formation of Senescence-Associated Heterochromatin Foci (SAHF)
R-HSA-2559586	DNA Damage/Telomere Stress Induced Senescence
R-HSA-3214847	HATs acetylate histones

MSigDB gene sets: 152 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_DNA_RECOMBINATION, MORF_MSH3, MORF_BRCA1, MORF_ATRX, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, MORF_ESR1, GOBP_REGULATION_OF_DNA_REPAIR, BROWNE_HCMV_INFECTION_48HR_DN, MORF_PPP5C, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_RESPONSE_TO_STRESS

GO Biological Process (7): DNA repair (GO:0006281), chromatin organization (GO:0006325), 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)

GO Molecular Function (8): DNA binding (GO:0003677), chromatin binding (GO:0003682), helicase activity (GO:0004386), ATP binding (GO:0005524), hydrolase activity (GO:0016787), protein antigen binding (GO:1990405), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (6): nucleosome (GO:0000786), Swr1 complex (GO:0000812), nucleoplasm (GO:0005654), nuclear speck (GO:0016607), NuA4 histone acetyltransferase complex (GO:0035267), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
DNA Damage/Telomere Stress Induced Senescence	1
Cellular Senescence	1
Chromatin modifying enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
DNA metabolic process	1
DNA damage response	1
cellular component organization	1
apoptotic process	1
regulation of programmed cell death	1
DNA-templated transcription	1
regulation of 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
nucleic acid binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
ATP-dependent activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
catalytic activity	1
antigen binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
chromatin	1
protein-DNA complex	1
histone deacetylase complex	1
nuclear chromosome	1
INO80-type complex	1
nuclear lumen	1
cellular anatomical structure	1
nuclear ribonucleoprotein granule	1
H4/H2A histone acetyltransferase complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3351 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EP400	KAT5	Q92993	998
EP400	TRRAP	Q9Y4A5	994
EP400	RUVBL2	Q9Y230	993
EP400	RUVBL1	P82276	988
EP400	BRD8	Q9H0E9	949
EP400	ACTL6A	O96019	937
EP400	DMAP1	Q9NPF5	935
EP400	ANP32E	Q9BTT0	891
EP400	MYC	P01106	859
EP400	H2AZ1	P0C0S5	850
EP400	YEATS4	O95619	845
EP400	MYCL	P12524	829
EP400	H2AC20	Q16777	817
EP400	H2AC19	P20670	817
EP400	H2AZ2	Q71UI9	796

IntAct

202 interactions, top by confidence:

A	B	Type	Score
MYC	MAX	psi-mi:“MI:0914”(association)	0.980
STAT2	STAT1	psi-mi:“MI:0914”(association)	0.930
ANKRD40	AHCY	psi-mi:“MI:0914”(association)	0.900
RUVBL1	ZNHIT1	psi-mi:“MI:0914”(association)	0.860
MRGBP	YEATS4	psi-mi:“MI:0914”(association)	0.840
YEATS4	ZNHIT1	psi-mi:“MI:0914”(association)	0.790
MED23	MED19	psi-mi:“MI:2364”(proximity)	0.770
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
MYC	EP400	psi-mi:“MI:0915”(physical association)	0.760
TRRAP	ATXN7	psi-mi:“MI:0914”(association)	0.740
MBTD1	YEATS4	psi-mi:“MI:0914”(association)	0.730
MBTD1	MORF4L2	psi-mi:“MI:0914”(association)	0.730
MORF4L1	SIN3B	psi-mi:“MI:0914”(association)	0.730
ACTL6A	ZNHIT1	psi-mi:“MI:0914”(association)	0.720
VPS72	ZNHIT1	psi-mi:“MI:0914”(association)	0.690
ALAS1	EP400	psi-mi:“MI:0915”(physical association)	0.670
EP400	ALAS1	psi-mi:“MI:0915”(physical association)	0.670
BRD8	MORF4L2	psi-mi:“MI:0915”(physical association)	0.670
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
RUVBL2	POLR3A	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
MORF4L2	YEATS4	psi-mi:“MI:0914”(association)	0.640
FOXR1	YEATS4	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640

BioGRID (350): EP400 (Two-hybrid), EP400 (Affinity Capture-MS), EP400 (Affinity Capture-MS), EP400 (Affinity Capture-MS), EP400 (Reconstituted Complex), EP400 (Affinity Capture-MS), EP400 (Affinity Capture-MS), EP400 (Affinity Capture-MS), EP400 (Affinity Capture-MS), EP400 (Affinity Capture-MS), EP400 (Affinity Capture-MS), EP400 (Affinity Capture-MS), EP400 (Co-fractionation), EP400 (Co-fractionation), EP400 (Co-fractionation)

ESM2 similar proteins: A0A060D764, A2WM14, A2WV68, A2XMN1, A2XYN9, A2YFT9, A2YXQ1, B8AX53, O23875, O64647, P48000, Q01KM7, Q0DAE8, Q0E342, Q0J6N4, Q0J995, Q0JNI9, Q10CE8, Q10EC6, Q10ED2, Q17308, Q53PH2, Q5NAN5, Q5R7N4, Q5VRW2, Q5Z5I4, Q652B0, Q688U3, Q6ER21, Q6YXH5, Q6YZE8, Q6Z869, Q6ZBH6, Q7EXZ2, Q7LFL8, Q7X7N3, Q7XPY1, Q8IVW6, Q8LN68, Q8LT05

Diamond homologs: A0A0P0WGX7, A1C9W6, A1CZE5, A2BGR3, A2R9H9, A4H7G5, A4HVU6, A4IHD2, A4PBL4, A4R227, A5E0W5, A6ZL17, A6ZU34, A7EQA8, A7TJI3, B2ZFP3, B3LN76, B3MMA5, B4F769, B4KHL5, B5VE38, B6EU02, C0H4W3, C7GQI8, F4I8S3, F4K493, O13682, O14148, P0CO16, P0CO17, P0CO18, P0CO19, P32863, P36607, P38086, P46100, P47264, P53115, P75093, Q05471

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EP400	“form complex”	“NuA4 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 195 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
HATs acetylate histones	22	12.7×	1e-15
NS1 Mediated Effects on Host Pathways	5	10.4×	5e-03
DNA Damage Recognition in GG-NER	5	10.4×	5e-03
Deactivation of the beta-catenin transactivating complex	6	10.2×	2e-03
Chromatin organization	16	9.5×	4e-09
Formation of the beta-catenin:TCF transactivating complex	10	8.8×	4e-05
Antimicrobial mechanism of IFN-stimulated genes	6	8.6×	4e-03
Chromatin modifying enzymes	16	8.4×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
regulation of double-strand break repair	17	55.5×	4e-24
positive regulation of double-strand break repair via homologous recombination	18	38.7×	4e-22
positive regulation of transcription by RNA polymerase III	5	26.3×	9e-05
regulation of DNA replication	8	16.5×	3e-06
response to cAMP	5	14.3×	1e-03
regulation of DNA repair	8	12.4×	2e-05
positive regulation of myoblast differentiation	6	12.3×	7e-04
cellular response to estradiol stimulus	5	11.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	459
Likely benign	113
Benign	43

Top pathogenic / likely-pathogenic (0)

SpliceAI

9203 predictions. Top by Δscore:

Variant	Effect	Δscore
12:131950032:CCAGG:C	donor_gain	1.0000
12:131950033:CAGG:C	donor_gain	1.0000
12:131950034:AGG:A	donor_gain	1.0000
12:131950035:GG:G	donor_gain	1.0000
12:131950035:GGG:G	donor_gain	1.0000
12:131950036:GG:G	donor_gain	1.0000
12:131950037:G:GA	donor_loss	1.0000
12:131950037:G:GG	donor_gain	1.0000
12:131964107:GATAT:G	donor_gain	1.0000
12:131979692:A:AG	acceptor_gain	1.0000
12:131979693:G:GG	acceptor_gain	1.0000
12:131979693:GC:G	acceptor_gain	1.0000
12:131979693:GCA:G	acceptor_gain	1.0000
12:131979693:GCAGC:G	acceptor_gain	1.0000
12:131981488:GAGCA:G	acceptor_gain	1.0000
12:131987703:A:AG	acceptor_gain	1.0000
12:131987704:G:GG	acceptor_gain	1.0000
12:131987863:G:GT	donor_gain	1.0000
12:131987867:TGGA:T	donor_gain	1.0000
12:131987887:GAAG:G	donor_gain	1.0000
12:131987888:AAG:A	donor_loss	1.0000
12:131987891:G:C	donor_loss	1.0000
12:131987892:T:A	donor_loss	1.0000
12:131989963:GCTC:G	acceptor_gain	1.0000
12:131991310:ACGT:A	acceptor_gain	1.0000
12:131991310:ACGTG:A	acceptor_gain	1.0000
12:132005181:G:GT	donor_gain	1.0000
12:132005182:A:T	donor_gain	1.0000
12:132005214:GGT:G	donor_gain	1.0000
12:132005253:A:AG	donor_gain	1.0000

AlphaMissense

20215 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000030149 (12:131950962 C>A,T), RS1000068485 (12:132000240 T>A), RS1000089825 (12:132038373 G>C), RS1000100705 (12:132066399 G>A), RS1000118723 (12:132079920 A>G), RS1000132351 (12:132055958 A>G,T), RS1000153094 (12:131969577 C>T), RS1000156476 (12:131991244 G>GT), RS1000179970 (12:132009464 C>T), RS1000211053 (12:131963313 C>T), RS1000238287 (12:131969684 G>A,C), RS1000247510 (12:132040471 C>G,T), RS1000290422 (12:132002426 A>G), RS1000300057 (12:132040729 C>T), RS1000300259 (12:132046286 A>G)

Disease associations

OMIM: gene MIM:606265 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with or without early-onset generalized epilepsy	Strong	Autosomal recessive
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (2): neurodevelopmental disorder (MONDO:0700092), neurodevelopmental disorder with or without early-onset generalized epilepsy (MONDO:0030930)

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004621_60	Red cell distribution width	4.000000e-13
GCST005951_3	Body mass index	6.000000e-09
GCST006804_44	Red cell distribution width	1.000000e-13
GCST90002390_178	Mean corpuscular hemoglobin	4.000000e-10
GCST90002392_399	Mean corpuscular volume	2.000000e-15
GCST90002396_542	Mean reticulocyte volume	7.000000e-19
GCST90002397_51	Mean spheric corpuscular volume	3.000000e-19
GCST90002403_465	Red blood cell count	7.000000e-10
GCST90002404_149	Red cell distribution width	2.000000e-34

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0004340	body mass index
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, affects cotreatment, decreases expression	2
sodium arsenite	increases expression, affects expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	increases abundance, increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Ozone	increases expression, increases abundance, affects cotreatment	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
chloroacetaldehyde	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases expression, increases abundance, affects cotreatment	1
sodium arsenate	decreases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	affects expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
coumarin	affects phosphorylation	1
torcetrapib	increases expression	1
bisphenol S	decreases expression, affects cotreatment	1
Sunitinib	increases expression	1
Zoledronic Acid	decreases expression	1
Vorinostat	decreases expression	1
Cidofovir	decreases expression	1
Cadmium	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E1W3	HAP1 EP400 (-) 2	Cancer cell line	Male
CVCL_XN47	HAP1 EP400 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice