EID2

Summary

EID2 (EP300 interacting inhibitor of differentiation 2, HGNC:28292) is a protein-coding gene on chromosome 19q13.2, encoding EP300-interacting inhibitor of differentiation 2 (Q8N6I1). Interacts with EP300 and acts as a repressor of MYOD-dependent transcription and muscle differentiation.

Enables SMAD binding activity. Involved in several processes, including negative regulation of transcription by RNA polymerase II; negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway; and transforming growth factor beta receptor complex assembly. Located in nucleoplasm.

Source: NCBI Gene 163126 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_153232

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28292
Approved symbol	EID2
Name	EP300 interacting inhibitor of differentiation 2
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	EID-2, MGC20452
Ensembl gene	ENSG00000176396
Ensembl biotype	protein_coding
OMIM	609773
Entrez	163126

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000390658

RefSeq mRNA: 1 — MANE Select: NM_153232 NM_153232

CCDS: CCDS12540

Canonical transcript exons

ENST00000390658 — 1 exons

Exon	Start	End
ENSE00001508568	39538707	39540161

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 92.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.6225 / max 123.4035, expressed in 1798 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180895	6.6713	1720
180896	6.0248	1643
180894	3.4153	1528
180897	0.5111	287

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	92.61	gold quality
pons	UBERON:0000988	92.57	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.98	gold quality
kidney epithelium	UBERON:0004819	91.70	gold quality
cerebellar vermis	UBERON:0004720	91.53	gold quality
prefrontal cortex	UBERON:0000451	90.83	gold quality
ileal mucosa	UBERON:0000331	90.76	gold quality
postcentral gyrus	UBERON:0002581	90.61	gold quality
tibialis anterior	UBERON:0001385	90.02	gold quality
superior frontal gyrus	UBERON:0002661	90.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.95	gold quality
parietal lobe	UBERON:0001872	89.87	gold quality
frontal cortex	UBERON:0001870	89.71	gold quality
placenta	UBERON:0001987	89.28	gold quality
neocortex	UBERON:0001950	89.18	gold quality
Brodmann (1909) area 46	UBERON:0006483	88.99	gold quality
cerebral cortex	UBERON:0000956	88.67	gold quality
cortical plate	UBERON:0005343	88.66	gold quality
upper arm skin	UBERON:0004263	88.50	gold quality
anterior cingulate cortex	UBERON:0009835	88.20	gold quality
hypothalamus	UBERON:0001898	88.11	gold quality
superior vestibular nucleus	UBERON:0007227	87.97	gold quality
right frontal lobe	UBERON:0002810	87.95	gold quality
entorhinal cortex	UBERON:0002728	87.77	gold quality
lateral nuclear group of thalamus	UBERON:0002736	87.75	gold quality
right adrenal gland cortex	UBERON:0035827	87.59	gold quality
right adrenal gland	UBERON:0001233	87.38	gold quality
left adrenal gland	UBERON:0001234	87.26	gold quality
left adrenal gland cortex	UBERON:0035825	87.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.26
E-MTAB-10290	no	86.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting EID2, 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-1277-5P	100.00	73.95	5056
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-3908	98.75	67.31	1160
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-548AY-3P	98.37	65.14	562
HSA-MIR-138-1-3P	98.25	67.89	867
HSA-MIR-5196-3P	97.57	65.98	979

Literature-anchored findings (GeneRIF, showing 1)

• EID-2 may function as an endogenous suppressor of TGF-beta signaling (PMID:14612439)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Eid2	ENSMUSG00000046058
rattus_norvegicus	Eid2	ENSRNOG00000065487

Paralogs (2): EID2B (ENSG00000176401), EID1 (ENSG00000255302)

Protein

Protein identifiers

EP300-interacting inhibitor of differentiation 2 — Q8N6I1 (reviewed: Q8N6I1)

Alternative names: CREBBP/EP300 inhibitor 2, EID-1-like inhibitor of differentiation 2

All UniProt accessions (1): Q8N6I1

UniProt curated annotations — full annotation on UniProt →

Function. Interacts with EP300 and acts as a repressor of MYOD-dependent transcription and muscle differentiation. Inhibits EP300 histone acetyltransferase activity. Acts as a repressor of TGFB/SMAD transcriptional responses. May act as a repressor of the TGFB/SMAD3-dependent signaling by selectively blocking formation of TGFB-induced SMAD3-SMAD4 complex.

Subunit / interactions. Heterodimer with EID2B. Interacts with the C-terminus of EP300. Interacts with HDAC1 and HDAC2. Interacts with SMAD2, SMAD4 and with the MH2 domain of SMAD3.

Subcellular location. Nucleus.

Tissue specificity. Most abundantly expressed in placenta. Highly expressed in liver, brain, heart, skeletal muscle, and kidney.

Domain organisation. The N-terminal portion of EID2 is required for nuclear localization.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N6I1-1	1	yes
Q8N6I1-2	2

RefSeq proteins (1): NP_694964* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033258	EID	Family

UniProt features (11 total): region of interest 2, sequence variant 2, compositionally biased region 2, modified residue 2, chain 1, coiled-coil region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6I1-F1	58.28	0.11

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 (2): 59, 75

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 106 (showing top): GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, WANG_CLIM2_TARGETS_UP, TGCGCANK_UNKNOWN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, KOYAMA_SEMA3B_TARGETS_UP, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA_STIMULUS, KUUSELO_PANCREATIC_CANCER_19Q13_AMPLIFICATION, GOBP_RESPONSE_TO_GROWTH_FACTOR, DING_LUNG_CANCER_EXPRESSION_BY_COPY_NUMBER, GOBP_TRANSFORMING_GROWTH_FACTOR_BETA_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), transforming growth factor beta receptor complex assembly (GO:0007181), muscle organ development (GO:0007517), cell differentiation (GO:0030154), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), regulation of cell population proliferation (GO:0042127), negative regulation of DNA-templated transcription (GO:0045892), negative regulation of SMAD protein signal transduction (GO:0060392)

GO Molecular Function (3): transcription corepressor activity (GO:0003714), SMAD binding (GO:0046332), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of DNA-templated transcription	2
transforming growth factor beta receptor signaling pathway	2
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
protein-containing complex assembly	1
animal organ development	1
muscle structure development	1
cellular developmental process	1
regulation of transforming growth factor beta receptor signaling pathway	1
cell population proliferation	1
regulation of cellular process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
regulation of SMAD protein signal transduction	1
SMAD protein signal transduction	1
negative regulation of intracellular signal transduction	1
transcription coregulator activity	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

376 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EID2	EID3	Q8N140	890
EID2	SMC5	Q8IY18	707
EID2	ZNF324B	Q6AW86	635
EID2	RABEP2	Q9H5N1	575
EID2	RAD17	O75943	468
EID2	LGALS16	A8MUM7	444
EID2	ACTC1	P04270	436
EID2	NSMCE4A	Q9NXX6	435
EID2	EID1	Q9Y6B2	426
EID2	LGALS13	Q9UHV8	420
EID2	ARIH2	O95376	418
EID2	TRIM28	Q13263	393
EID2	NR5A1	Q13285	384
EID2	SMAD4	Q13485	375
EID2	OR1E2	P47887	372

IntAct

18 interactions, top by confidence:

A	B	Type	Score
BCL2L10	BCL2L11	psi-mi:“MI:0914”(association)	0.830
MAGEE1	MCC	psi-mi:“MI:0914”(association)	0.670
EID2	MAGEA1	psi-mi:“MI:0915”(physical association)	0.400
EID2	MAGEF1	psi-mi:“MI:0915”(physical association)	0.400
NDN	EID2	psi-mi:“MI:0915”(physical association)	0.400
EID2B	EID2	psi-mi:“MI:0915”(physical association)	0.400
SPG11	EID2	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
KERA	VWA8	psi-mi:“MI:0914”(association)	0.350
MAGEE1	MCC	psi-mi:“MI:0914”(association)	0.350
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350
MAGEE1	FYN	psi-mi:“MI:0914”(association)	0.350
AURKB	VWA8	psi-mi:“MI:0914”(association)	0.350
C6orf141	ITPRID2	psi-mi:“MI:0914”(association)	0.350
SLC1A3	DDX11L8	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): EID2 (Reconstituted Complex), EID2 (Affinity Capture-Western), EID2 (Affinity Capture-MS), EID2 (Affinity Capture-MS), EID2 (Affinity Capture-MS), EID2 (Affinity Capture-MS), SMAD2 (Affinity Capture-Western), SMAD3 (Affinity Capture-Western), SMAD4 (Affinity Capture-Western), EID2 (Affinity Capture-Western), EID2 (Affinity Capture-Western), EID2 (Affinity Capture-Western), SMAD3 (Reconstituted Complex), EID2 (Protein-RNA), EID2 (Affinity Capture-MS)

ESM2 similar proteins: A9CB87, B3LVF9, B4G325, B4JTS9, B4K843, B4LY66, B4N943, D5LWW7, F5HH39, O55439, P03254, P03255, P03269, P03270, P04499, P0C1P3, P0C677, P0C693, P0C6I3, P0C6J1, P12541, P12977, P12978, P14349, P16755, P21186, P27556, P34675, P48313, Q09230, Q17QW4, Q196V0, Q3KST2, Q3KSV2, Q5R590, Q5SC49, Q64897, Q65947, Q69022, Q69138

Diamond homologs: Q17QW4, Q5RDL6, Q6X7S9, Q8N6I1, Q96D98, Q9Y6B2, Q9DCR4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
EID2	down-regulates	SMAD3	binding
EID2	“down-regulates activity”	SMAD3/SMAD4	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

237 predictions. Top by Δscore:

Variant	Effect	Δscore
19:39540003:T:TA	donor_gain	0.9000
19:39539597:C:CT	acceptor_gain	0.8900
19:39539996:GCCTA:G	donor_loss	0.7800
19:39539997:CCTA:C	donor_loss	0.7800
19:39539998:CTACC:C	donor_loss	0.7800
19:39539999:TACCT:T	donor_loss	0.7800
19:39540001:C:T	donor_loss	0.7800
19:39539569:TT:T	acceptor_gain	0.7600
19:39539995:GGCCT:G	donor_loss	0.7600
19:39539571:C:CC	acceptor_gain	0.7500
19:39539776:C:A	donor_gain	0.7500
19:39540002:C:G	donor_loss	0.7300
19:39539628:ATGCC:A	acceptor_gain	0.6900
19:39539629:TGCCT:T	acceptor_gain	0.6900
19:39539638:CG:C	acceptor_gain	0.6800
19:39539598:A:T	acceptor_gain	0.6700
19:39539603:G:GC	acceptor_gain	0.6000
19:39539631:CCT:C	acceptor_gain	0.5900
19:39539575:C:CT	acceptor_gain	0.5800
19:39539597:C:T	acceptor_gain	0.5800
19:39539600:A:C	acceptor_gain	0.5800
19:39540023:G:GC	donor_gain	0.5800
19:39539568:ATTCT:A	acceptor_loss	0.5700
19:39539569:TTCT:T	acceptor_loss	0.5700
19:39539570:TC:T	acceptor_loss	0.5700
19:39539571:C:T	acceptor_loss	0.5700
19:39539572:T:G	acceptor_loss	0.5700
19:39539641:T:A	acceptor_gain	0.5700
19:39539902:C:A	donor_gain	0.5700
19:39539632:C:A	acceptor_gain	0.5600

AlphaMissense

1513 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:39539433:G:T	A216D	0.999
19:39539439:A:G	L214P	0.999
19:39539517:C:A	R188M	0.999
19:39539537:G:C	F181L	0.999
19:39539537:G:T	F181L	0.999
19:39539538:A:C	F181C	0.999
19:39539538:A:G	F181S	0.999
19:39539539:A:G	F181L	0.999
19:39539434:C:G	A216P	0.998
19:39539568:A:T	I171K	0.998
19:39539400:A:G	L227P	0.997
19:39539409:A:T	I224K	0.997
19:39539412:A:G	L223P	0.997
19:39539421:A:T	I220N	0.997
19:39539431:A:G	S217P	0.997
19:39539445:A:T	I212K	0.997
19:39539526:C:T	C185Y	0.997
19:39539527:A:G	C185R	0.997
19:39539530:C:G	A184P	0.997
19:39539610:A:G	L157P	0.997
19:39539613:A:G	F156S	0.997
19:39539395:A:G	C229R	0.996
19:39539445:A:C	I212R	0.996
19:39539448:G:T	T211K	0.996
19:39539451:A:G	F210S	0.996
19:39539516:C:A	R188S	0.996
19:39539516:C:G	R188S	0.996
19:39539525:G:C	C185W	0.996
19:39539548:G:T	R178S	0.996
19:39539568:A:G	I171T	0.996

dbSNP variants (sampled 300 via entrez): RS1000468934 (19:39539093 T>C), RS1000756579 (19:39538708 T>C), RS1001964458 (19:39539416 G>A), RS1002250028 (19:39539185 A>G), RS1002434028 (19:39539065 T>C), RS1002697335 (19:39540822 A>T), RS1002846894 (19:39540224 T>G), RS1003180965 (19:39540525 C>T), RS1003371789 (19:39540556 G>A,T), RS1004255564 (19:39541331 C>A,T), RS1004479330 (19:39540978 T>A), RS1005004309 (19:39540407 G>A,T), RS1005073913 (19:39542094 T>G), RS1007599005 (19:39538545 A>G), RS1007817743 (19:39538291 A>G)

Disease associations

OMIM: gene MIM:609773 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002935_5	Lead levels	4.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
Air Pollutants	increases abundance, decreases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Smoke	increases abundance, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
deoxynivalenol	increases expression	1
resorcinol	increases expression	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases expression	1
Cannabidiol	decreases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Phenobarbital	affects expression	1
Phthalic Acids	increases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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