EID1

Summary

EID1 (EP300 interacting inhibitor of differentiation 1, HGNC:1191) is a protein-coding gene on chromosome 15q21.1, encoding EP300-interacting inhibitor of differentiation 1 (Q9Y6B2). Interacts with RB1 and EP300 and acts as a repressor of MYOD1 transactivation.

Enables histone acetyltransferase binding activity. Involved in cell differentiation and negative regulation of DNA-templated transcription. Acts upstream of or within negative regulation of transcription by RNA polymerase II. Located in cytoplasmic ribonucleoprotein granule and nucleoplasm.

Source: NCBI Gene 23741 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_014335

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1191
Approved symbol	EID1
Name	EP300 interacting inhibitor of differentiation 1
Location	15q21.1
Locus type	gene with protein product
Status	Approved
Aliases	EID-1
Ensembl gene	ENSG00000255302
Ensembl biotype	protein_coding
OMIM	605894
Entrez	23741

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000530028, ENST00000560490

RefSeq mRNA: 1 — MANE Select: NM_014335 NM_014335

CCDS: CCDS53941

Canonical transcript exons

ENST00000530028 — 1 exons

Exon	Start	End
ENSE00002189743	48878134	48880173

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 267.3343 / max 4053.4639, expressed in 1825 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146555	263.1397	1825
207508	1.1416	649
207507	0.9816	506
207511	0.8391	482
207510	0.5629	249
207509	0.3100	87
207504	0.1308	36
146553	0.1116	33
146554	0.0702	23
146552	0.0468	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.76	gold quality
tendon	UBERON:0000043	99.56	gold quality
calcaneal tendon	UBERON:0003701	99.50	gold quality
germinal epithelium of ovary	UBERON:0001304	99.47	gold quality
heart right ventricle	UBERON:0002080	99.46	gold quality
medial globus pallidus	UBERON:0002477	99.20	gold quality
cortical plate	UBERON:0005343	99.16	gold quality
seminal vesicle	UBERON:0000998	99.08	gold quality
superficial temporal artery	UBERON:0001614	99.07	gold quality
ganglionic eminence	UBERON:0004023	99.03	gold quality
pigmented layer of retina	UBERON:0001782	99.02	gold quality
myocardium	UBERON:0002349	99.02	gold quality
prefrontal cortex	UBERON:0000451	98.96	gold quality
embryo	UBERON:0000922	98.93	gold quality
cauda epididymis	UBERON:0004360	98.93	gold quality
right coronary artery	UBERON:0001625	98.92	gold quality
biceps brachii	UBERON:0001507	98.90	gold quality
globus pallidus	UBERON:0001875	98.90	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.90	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.89	gold quality
stromal cell of endometrium	CL:0002255	98.87	gold quality
bronchial epithelial cell	CL:0002328	98.82	gold quality
mucosa of stomach	UBERON:0001199	98.80	gold quality
popliteal artery	UBERON:0002250	98.80	gold quality
ventricular zone	UBERON:0003053	98.80	gold quality
tibial artery	UBERON:0007610	98.80	gold quality
adrenal tissue	UBERON:0018303	98.80	gold quality
descending thoracic aorta	UBERON:0002345	98.79	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.78	gold quality
left coronary artery	UBERON:0001626	98.77	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	79.53
E-HCAD-4	yes	66.82
E-MTAB-8410	yes	59.04
E-HCAD-10	yes	35.01
E-MTAB-8142	yes	13.15
E-CURD-46	yes	10.81
E-MTAB-10042	yes	7.90
E-GEOD-125970	yes	6.86
E-GEOD-130148	yes	4.28
E-GEOD-81547	no	5.29
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
EGR1	Unknown

Upstream regulators (CollecTRI, top): NR0B2

miRNA regulators (miRDB)

94 targeting EID1, 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-5193	100.00	67.26	1744
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
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-1250-3P	99.96	70.04	4038
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4446-5P	99.72	69.19	2544

Literature-anchored findings (GeneRIF, showing 9)

• The role of EID1 in fibroblast biology and fibrosis is reported. (PMID:17559085)
• Repression of E6 and E7 oncogenes results in restoration of pRb suppressor pathways and induced apoptosis in HPV16-positive oropharyngeal squamous cell cancer cell lines. (PMID:19276448)
• miR-138 inhibited adipogenesis through targeting the nuclear receptor coregulator EID-1 (PMID:20486779)
• This study demonstrated that overexpression of EID1 reduced hippocampal long-term potentiation and impaired spatial learning and memory function in the transgenic mice (PMID:22186421)
• Pcid2 is present in the CBP/p300-EID1 complex to control the switch balance of mouse and human embryonic stem cells through modulation of EID1 degradation. (PMID:24167073)
• An unexpected EID1-binding site on SHP is located at the N terminus of the receptor, where EID1 mimics helix H1 of the nuclear receptor ligand-binding domain. (PMID:24379397)
• The results suggest that EID1 is a bona fide substrate of FBXO21 and that the control of EID1 abundance by SCF(FBXO)(21) might affect the transcriptional repression activity of EID1. (PMID:26085330)
• SCF(FBXO21) polyubiquitylates EID1 both in vitro and in vivo and is required for the efficient degradation of EID1 in both cycling and quiescent cells. (PMID:26631746)
• EID1 can modulate adipose mesenchymal stem cells, inducing a brown/beige lineage. (PMID:26643909)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Eid1	ENSMUSG00000091337
rattus_norvegicus	Eid1	ENSRNOG00000008452

Paralogs (2): EID2 (ENSG00000176396), EID2B (ENSG00000176401)

Protein

Protein identifiers

EP300-interacting inhibitor of differentiation 1 — Q9Y6B2 (reviewed: Q9Y6B2)

Alternative names: 21 kDa pRb-associated protein, CREBBP/EP300 inhibitory protein 1, E1A-like inhibitor of differentiation 1

All UniProt accessions (2): Q9Y6B2, H0YN68

UniProt curated annotations — full annotation on UniProt →

Function. Interacts with RB1 and EP300 and acts as a repressor of MYOD1 transactivation. Inhibits EP300 and CBP histone acetyltransferase activity. May be involved in coupling cell cycle exit to the transcriptional activation of genes required for cellular differentiation. May act as a candidate coinhibitory factor for NR0B2 that can be directly linked to transcription inhibitory mechanisms.

Subunit / interactions. Interacts via its LXCXE motif with the entire pocket region of RB1. Interacts with EP300, NR0B2 and TRIM27.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Widely expressed. Most abundantly expressed in heart, skeletal muscle, pancreas, brain and testis. Expressed at much lower levels in placenta and peripheral blood leukocyte. Barely detectable in lung. Also weakly expressed in lung carcinoma A-549 and various leukemia cell lines.

Post-translational modifications. Ubiquitinated in U2OS osteosarcoma cells and is rapidly degraded by proteasome as cells exit the cell cycle exit.

Induction. Down-regulated in differentiating U-937 leukemia cells.

Miscellaneous. Inhibition of MYOD1 may be partly due to the ability of EID1 to bind and inhibit EP300 histone acetyltransferase activity.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y6B2-1	1	yes
Q9Y6B2-2	2

RefSeq proteins (1): NP_055150* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033258	EID	Family

UniProt features (10 total): mutagenesis site 3, region of interest 2, compositionally biased region 2, chain 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7SMD	X-RAY DIFFRACTION	2.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6B2-F1	56.72	0.00

Functional residue map

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

Mutagenesis-validated functional residues (3):

Position	Phenotype
178	abolishes rb1 binding.
180	abolishes rb1 binding.
182	abolishes rb1 binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 220 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MORF_HDAC1, CACCAGC_MIR138, MODULE_503, PAPASPYRIDONOS_UNSTABLE_ATEROSCLEROTIC_PLAQUE_DN, MODULE_195, SCHLOSSER_SERUM_RESPONSE_DN, MODULE_147, GREENBAUM_E2A_TARGETS_DN, TIEN_INTESTINE_PROBIOTICS_24HR_UP, ZHANG_BREAST_CANCER_PROGENITORS_UP, RGAGGAARY_PU1_Q6

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), cell differentiation (GO:0030154), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (3): transcription corepressor activity (GO:0003714), histone acetyltransferase binding (GO:0035035), protein binding (GO:0005515)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasmic ribonucleoprotein granule (GO:0036464), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of DNA-templated transcription	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
cellular developmental process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
transcription coregulator activity	1
enzyme binding	1
binding	1
nuclear lumen	1
cytoplasm	1
ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

400 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EID1	EID3	Q8N140	855
EID1	NR0B2	Q15466	672
EID1	MYOD1	P15172	619
EID1	NDN	Q99608	586
EID1	EP300	Q09472	560
EID1	ACAN	P16112	548
EID1	MAPRE2	Q15555	547
EID1	FBXO21	O94952	447
EID1	BRCC3	P46736	446
EID1	ACTC1	P04270	428
EID1	EID2	Q8N6I1	426
EID1	CREBBP	Q92793	424
EID1	MDM2	Q00987	408
EID1	CDK4	P11802	393
EID1	TBX22	Q9Y458	390
EID1	TXNRD1	Q16881	390

IntAct

34 interactions, top by confidence:

A	B	Type	Score
FBXO21	SKP1	psi-mi:“MI:0914”(association)	0.770
NDN	EID1	psi-mi:“MI:0915”(physical association)	0.690
EID1	NDN	psi-mi:“MI:0915”(physical association)	0.690
EID1	FBXO21	psi-mi:“MI:0915”(physical association)	0.650
FBXO21	EID1	psi-mi:“MI:0403”(colocalization)	0.650
EID1	FBXO21	psi-mi:“MI:0914”(association)	0.650
	EID1	psi-mi:“MI:0915”(physical association)	0.600
Ndn	EID1	psi-mi:“MI:0915”(physical association)	0.580
EID1	Ndn	psi-mi:“MI:0915”(physical association)	0.580
EID1		psi-mi:“MI:0915”(physical association)	0.490
	EID1	psi-mi:“MI:0915”(physical association)	0.490
EID1	MAGEA1	psi-mi:“MI:0915”(physical association)	0.400
EID1	MAGEF1	psi-mi:“MI:0915”(physical association)	0.400
PCNA	EID1	psi-mi:“MI:0915”(physical association)	0.370
EID1	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
PSEN2	EID1	psi-mi:“MI:0915”(physical association)	0.370
EID1	UBE3A	psi-mi:“MI:0915”(physical association)	0.370
XRCC6	EID1	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
EID1	MYO1D	psi-mi:“MI:0914”(association)	0.350
FBXO21	CEP43	psi-mi:“MI:0914”(association)	0.350
SCCPDH	IPO5	psi-mi:“MI:0914”(association)	0.350

BioGRID (92): EID1 (Affinity Capture-Western), EID1 (Reconstituted Complex), EID1 (Affinity Capture-Western), EID1 (Biochemical Activity), EID1 (Affinity Capture-MS), JAK1 (Affinity Capture-MS), IQGAP1 (Affinity Capture-MS), CAMSAP3 (Affinity Capture-MS), DNAJA1 (Affinity Capture-MS), TESK2 (Affinity Capture-MS), PFKP (Affinity Capture-MS), SCAF11 (Affinity Capture-MS), SLIRP (Affinity Capture-MS), DMBT1 (Affinity Capture-MS), FBXO21 (Affinity Capture-MS)

ESM2 similar proteins: A0L486, A1A0T8, A1L3P1, A4VVZ9, A4W2A7, A5VPI8, A6NMA1, A6U7A2, A6X296, A7HX41, A7IM18, A9MA26, B0CKX7, B2IIA1, B2SAC9, B6IN07, B7GUQ0, B8DTW7, C0HK64, C0RHZ3, F5HGI9, K4JY29, O13619, O94688, P08804, P16792, P85800, Q17684, Q2RT88, Q2W519, Q2YN12, Q32PD7, Q3U898, Q55GR4, Q57E91, Q5RDL6, Q6DDA3, Q6FM20, Q6G465, Q6NVV0

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

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
FBXO21	“down-regulates quantity by destabilization”	EID1	binding
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	EID1	polyubiquitination
MDM2	“down-regulates quantity by destabilization”	EID1	polyubiquitination
NDN	“up-regulates activity”	EID1	binding
EID1	“down-regulates activity”	EP300	binding
EID1	down-regulates	MYOD1
EID1	“down-regulates activity”	CREBBP	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

176 predictions. Top by Δscore:

Variant	Effect	Δscore
15:48879298:A:AC	donor_gain	0.9700
15:48878708:CTCGG:C	acceptor_gain	0.9000
15:48878713:C:CC	acceptor_gain	0.8100
15:48878710:CGG:C	acceptor_gain	0.7700
15:48878724:T:TC	acceptor_gain	0.6400
15:48878776:G:GT	donor_gain	0.6300
15:48878709:TCGG:T	acceptor_gain	0.5700
15:48878710:CGGC:C	acceptor_gain	0.5700
15:48878650:G:GG	donor_gain	0.5300
15:48879291:A:C	donor_gain	0.5300
15:48878649:A:AG	donor_gain	0.4900
15:48878760:G:GT	donor_gain	0.4600
15:48878711:GG:G	acceptor_gain	0.4500
15:48878718:A:AG	donor_gain	0.4500
15:48878717:G:A	acceptor_gain	0.4400
15:48878719:T:A	acceptor_gain	0.4300
15:48878712:G:GC	acceptor_gain	0.4100
15:48878734:A:T	donor_gain	0.4100
15:48878777:A:T	donor_gain	0.4100
15:48878454:T:TA	donor_gain	0.4000
15:48878735:GA:G	donor_gain	0.4000
15:48878764:A:T	donor_gain	0.4000
15:48878866:GAATA:G	acceptor_gain	0.4000
15:48878651:T:G	donor_gain	0.3900
15:48878710:CGGCT:C	acceptor_loss	0.3900
15:48878711:GGCT:G	acceptor_loss	0.3900
15:48878712:GC:G	acceptor_loss	0.3900
15:48878713:CT:C	acceptor_loss	0.3900
15:48878714:T:TC	acceptor_loss	0.3900
15:48878723:A:C	acceptor_loss	0.3900

AlphaMissense

1249 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:48878672:T:C	F166L	0.971
15:48878674:T:A	F166L	0.971
15:48878674:T:G	F166L	0.971
15:48878652:T:C	L159S	0.970
15:48878657:T:C	F161L	0.969
15:48878659:T:A	F161L	0.969
15:48878659:T:G	F161L	0.969
15:48878642:T:C	F156L	0.963
15:48878644:T:A	F156L	0.963
15:48878644:T:G	F156L	0.963
15:48878615:T:C	F147L	0.953
15:48878617:T:A	F147L	0.953
15:48878617:T:G	F147L	0.953
15:48878697:T:C	L174P	0.947
15:48878579:T:C	F135L	0.939
15:48878581:T:A	F135L	0.939
15:48878581:T:G	F135L	0.939
15:48878658:T:C	F161S	0.935
15:48878661:T:A	I162N	0.932
15:48878700:C:T	T175I	0.928
15:48878694:G:C	R173P	0.919
15:48878673:T:C	F166S	0.918
15:48878489:T:A	W105R	0.917
15:48878489:T:C	W105R	0.917
15:48878697:T:A	L174Q	0.914
15:48878665:A:C	E163D	0.913
15:48878665:A:T	E163D	0.913
15:48878709:T:A	L178H	0.910
15:48878709:T:C	L178P	0.906
15:48878692:T:A	N172K	0.905

dbSNP variants (sampled 300 via entrez): RS1000064678 (15:48880044 G>A), RS1001776741 (15:48876982 G>A), RS1003180580 (15:48880303 G>A), RS1003586647 (15:48878042 G>A,C), RS1003784840 (15:48880033 T>A,G), RS1004072357 (15:48877681 A>T), RS1005387556 (15:48877459 G>A), RS1006783777 (15:48878084 A>C,T), RS1007272595 (15:48878940 T>C), RS1007371175 (15:48880384 G>A,C), RS1007966946 (15:48878818 A>C), RS1008768638 (15:48880645 A>C), RS1008851388 (15:48879271 T>A), RS1009698731 (15:48878078 T>A,C), RS1010145111 (15:48879997 A>G)

Disease associations

OMIM: gene MIM:605894 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	3
bisphenol A	decreases expression, increases expression	2
cobaltous chloride	decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
nickel chloride	decreases expression	1
torcetrapib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Arbutin	increases expression	1
Bilirubin	decreases expression	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Diuron	decreases expression	1
Doxorubicin	increases expression	1
Piroxicam	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Sarin	decreases expression, increases expression	1
Smoke	increases abundance, decreases expression	1
Thiram	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Acrylamide	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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