ELF3

Summary

ELF3 (E74 like ETS transcription factor 3, HGNC:3318) is a protein-coding gene on chromosome 1q32.1, encoding ETS-related transcription factor Elf-3 (P78545). Transcriptional activator that binds and transactivates ETS sequences containing the consensus nucleotide core sequence GGA[AT].

Enables DNA-binding transcription activator activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in inflammatory response; negative regulation of DNA-templated transcription; and positive regulation of transcription by RNA polymerase II. Located in Golgi apparatus; cytosol; and nucleoplasm.

Source: NCBI Gene 1999 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 35 total
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• Transcription factor: yes — 35 downstream targets (CollecTRI)
• MANE Select transcript: NM_004433

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3318
Approved symbol	ELF3
Name	E74 like ETS transcription factor 3
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	EPR-1, ESE-1, ERT
Ensembl gene	ENSG00000163435
Ensembl biotype	protein_coding
OMIM	602191
Entrez	1999

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding_CDS_not_defined, 4 protein_coding

ENST00000359651, ENST00000367283, ENST00000367284, ENST00000446188, ENST00000470384, ENST00000475698, ENST00000479874, ENST00000490203, ENST00000495848, ENST00000498017

RefSeq mRNA: 2 — MANE Select: NM_004433 NM_001114309, NM_004433

CCDS: CCDS1419

Canonical transcript exons

ENST00000367284 — 9 exons

Exon	Start	End
ENSE00001074488	202013182	202013298
ENSE00001074490	202011957	202012178
ENSE00001074493	202012344	202012436
ENSE00001074503	202013829	202014024
ENSE00001700333	202015209	202017183
ENSE00001708160	202010587	202010706
ENSE00003461023	202012947	202013036
ENSE00003493687	202011129	202011299
ENSE00003639455	202012640	202012759

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 99.64.

FANTOM5 (CAGE): breadth broad, TPM avg 20.5917 / max 580.2913, expressed in 683 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7774	13.1501	570
7773	7.3974	630
7775	0.0441	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.64	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.60	gold quality
mucosa of transverse colon	UBERON:0004991	99.56	gold quality
rectum	UBERON:0001052	99.37	gold quality
pancreatic ductal cell	CL:0002079	99.03	gold quality
metanephros cortex	UBERON:0010533	98.95	gold quality
gall bladder	UBERON:0002110	98.77	gold quality
body of pancreas	UBERON:0001150	98.75	gold quality
minor salivary gland	UBERON:0001830	98.71	gold quality
esophagus mucosa	UBERON:0002469	98.55	gold quality
islet of Langerhans	UBERON:0000006	98.05	gold quality
pancreas	UBERON:0001264	97.75	gold quality
right uterine tube	UBERON:0001302	97.34	gold quality
palpebral conjunctiva	UBERON:0001812	96.89	gold quality
right lung	UBERON:0002167	96.86	gold quality
nasal cavity epithelium	UBERON:0005384	96.79	gold quality
upper lobe of left lung	UBERON:0008952	96.50	gold quality
oviduct epithelium	UBERON:0004804	96.37	gold quality
epithelial cell of pancreas	CL:0000083	96.29	gold quality
right lobe of liver	UBERON:0001114	95.93	gold quality
saliva-secreting gland	UBERON:0001044	95.80	gold quality
fallopian tube	UBERON:0003889	95.31	gold quality
left uterine tube	UBERON:0001303	95.30	gold quality
mouth mucosa	UBERON:0003729	95.23	gold quality
mucosa of stomach	UBERON:0001199	94.92	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.80	gold quality
upper lobe of lung	UBERON:0008948	94.56	gold quality
transverse colon	UBERON:0001157	94.33	gold quality
vagina	UBERON:0000996	93.61	gold quality
nasal cavity mucosa	UBERON:0001826	93.25	gold quality

Single-cell (SCXA)

Detected in 31 experiment(s), a significant marker in 29.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	5498.68
E-ANND-2	yes	4651.82
E-GEOD-81547	yes	3981.70
E-CURD-122	yes	3036.51
E-MTAB-8221	yes	2703.94
E-MTAB-9906	yes	2569.91
E-MTAB-8530	yes	2566.05
E-GEOD-124472	yes	2348.57
E-CURD-88	yes	2261.36
E-MTAB-8410	yes	2068.15
E-GEOD-114530	yes	1919.80
E-HCAD-10	yes	1802.01
E-HCAD-15	yes	1314.14
E-MTAB-6308	yes	1268.94
E-MTAB-10287	yes	1163.77

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

35 targets.

Target	Regulation
ANGPT1
AR
CCL20	Unknown
CCND3
CLDN7	Unknown
COL2A1
EGR1	Unknown
EHF	Activation
ERBB2
FOLH1
FOXC1
GADD45GIP1
HP
IL1B
KLK3
KRT4	Repression
KRT8
LYZ	Activation
MED23
MMP13	Unknown
MMP9	Repression
NOS2
NOTCH3
POU5F1	Unknown
PRR9	Unknown
PTGS2	Unknown
SPRR1A	Unknown
SPRR1B	Activation
SPRR2A	Activation
SPRR3	Unknown

JASPAR motifs

Motif	Name	Family
MA0640.1	ELF3	Ets-related
MA0640.2	ELF3	Ets-related
MA0640.3	ELF3	Ets-related

JASPAR matrix evidence (PMIDs): PMID:20517297, PMID:9234700

Upstream regulators (CollecTRI, top): AR, FOXA1, KDM5B, NFKB1, NFKB, RELA

miRNA regulators (miRDB)

84 targeting ELF3, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6764-5P	99.75	67.89	2304

Literature-anchored findings (GeneRIF, showing 40)

• ErbB2 activation of ESX gene expression (PMID:12032832)
• ESX regulates HER2 expression by binding to DRIP130 (PMID:12242338)
• co-ordinate activation and binding of ESE-1, Sp1, and NF-kappaB to the MIP-3alpha promoter is required for maximal gene expression by cytokine-stimulated Caco-2 human intestinal epithelial cells. (PMID:12414801)
• Ese-1 binds with Skn-1a in human cells (PMID:12624109)
• ERT mediates the expression of TGF-beta RII, and the transcriptional inhibition of ets-related transcription factor could be a one of the mechanisms of colonic carcinogenesis (PMID:14582709)
• results support a role for the ETS factor ESE-1 as a novel transcriptional regulator of angiopoietin-1 gene regulation in the setting of inflammation (PMID:14715662)
• ESX expression alone confers a transformed and in vitro metastatic phenotype to otherwise normal MCF-12A cells (PMID:14767472)
• activity of ESE-1 is positively and negatively modulated by other interacting proteins including Ku70, Ku86, p300, and CBP. (PMID:15075319)
• stably expressed green fluorescent protein-ESE-1 transforms MCF-12A human mammary epithelial cells; and the ESE-1 SAR domain, acting in the cytoplasm, is necessary and sufficient to mediate this transformation (PMID:15169914)
• the induction of claudin7 expression by ELF3 appears critical to the formation of the epithelial structures in biphasic synovial sarcoma (PMID:17060315)
• AT-hook domain, as well as serine- and aspartic acid-rich domain but not the pointed domain, is necessary for Elf3 activation of promoter activity. (PMID:17148437)
• ESE-1 functions are coordinately regulated by Pak1 phosphorylation and beta-TrCP-dependent ubiquitin-proteasome pathways. (PMID:17491012)
• Intracellular ESE-1 staining in chondrocytes in cartilage from patients with osteoarthritis, but not in normal cartilage, further suggests a fundamental role for ESE-1 in cartilage degeneration and suppression of repair. (PMID:18044710)
• ESE-1 negatively regulates the invasion of oral squamous cell carcinoma via transcriptional suppression of MMP-9. (PMID:18302674)
• ESE-1 and ESE-3 play an important role in airway inflammation. (PMID:18475289)
• activation of ESE-1 via enhanced nuclear translocation mediates tolfenamic acid-induced EGR-1 expression, which plays a critical role in the activation of apoptosis (PMID:19074849)
• ESE-1 contains signal sequences that play a critical role in regulating its subcellular localization and function, and that an intact SAR domain mediates mammary epithelial cell transformation exclusively in the cytoplasm (PMID:21871131)
• a novel role for ELF3 as a procatabolic factor that may contribute to cartilage remodeling and degradation by regulating MMP13 gene transcription. (PMID:22158614)
• ELF3 and CEA expression showed statistically significant differences among four lymph node groups: lymph nodes from patients with colorectal cancer categorized into three Dukes’ stages and LNs from patients with ulcerative colitis. (PMID:22993316)
• Frequent copy number gains at 1q21 and 1q32 are associated with overexpression of the ETS transcription factors ETV3 and ELF3 in breast cancer irrespective of molecular subtypes. (PMID:23329352)
• The physical interaction between ELF3 and androgen receptor (AR) inhibits the recruitment of AR to specific androgen response elements within target gene promoters. (PMID:23435425)
• The concordant upregulation of ESE1/ELF3 and NF-kappaB in human prostate tumors. (PMID:23687337)
• ELF3 is a candidate transcriptional regulator involved in human urothelial cytodifferentiation. (PMID:24374157)
• data suggest that polyomavirus enhancer activator 3 and epithelium-specific transcription factor-1 may play important roles in pluri potent and tumorigenic embryonic carcinoma cells. (PMID:24694612)
• data identify Elf3 as a pivotal driver for beta-catenin signaling in CRC, and highlight potential prognostic and therapeutic significance of Elf3 in CRC. (PMID:24874735)
• ESE-1 actS as an upstream effector to regulate OCT4 transcription in NCCIT pluripotent embryonic carcinoma cells. (PMID:24971534)
• our data suggested that ESE1/ELF3 may promote the UC progression via accelerating NF-kappaB activation and thus facilitating IEC apoptosis. (PMID:25926267)
• suggest that ESE-1 may play a role in regulating airway inflammation by regulating ICAM-1 expression (PMID:26185364)
• ELF3 is a frequently mutated tumor suppressor gene of periampullary tumors. (PMID:26804919)
• ELF3 is a novel transcriptional repressor of estrogen receptor alpha in breast cancer cells. (PMID:26920025)
• data suggest that interactions between ESE1 and beta-/alpha-catenins might be a mechanism by which the ESE1 protein determines the beta-catenin function and tumorigenesis (PMID:27272778)
• ELF3 interacts directly with the HMG domain of Sox9. Importantly, overexpression of ELF3 significantly decreased Sox9/CBP-dependent HAT activity. (PMID:27310669)
• These findings position RIPK4 upstream of a hierarchal IRF6-GRHL3-ELF3 transcription factor pathway in keratinocytes. (PMID:27667567)
• Survival analysis showed that the non-small cell lung carcinoma patients with enhanced expression of CK7, ELF3, EGFR, and EphB4 mRNA in peripheral blood leukocytes had poorer disease-free survival and overall survival than those without. (PMID:27827952)
• Data indicate that the transcription factor E74-like factor 3 (ELF3) was one of the genes whose expression was upregulated in microdissected ovarian cancer cells of long-term survivors. (PMID:28199976)
• Epithelium-specific ETS transcription factor 1 (ESE1), a member of the Ets transcription factor family. (PMID:28247944)
• Data suggest ESE-1 silencing as a mean to treat HER2(+) patients who show resistance to anti-HER2 therapy. (PMID:29187433)
• Data suggest that ELF3 is up-regulated at mRNA and protein levels in NSCLC (non-small cell lung cancer) tissues compared to corresponding control lung tissue; expression level of ELF3 is correlated with overall survival of patients with NSCLC. (PMID:29208568)
• ELF3 knockdown reversed epithelial-mesenchymal transition via repressing ZEB1 expression through miR-141-3p upregulation. (PMID:29523781)
• Leptin synergizes with IL-1beta in inducing ELF3 expression in chondrocytes. (PMID:29550824)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	elf3	ENSDARG00000077982
mus_musculus	Elf3	ENSMUSG00000003051
rattus_norvegicus	Elf3	ENSRNOG00000006330

Paralogs (28): ETV1 (ENSG00000006468), ETV7 (ENSG00000010030), SPI1 (ENSG00000066336), ELF4 (ENSG00000102034), ETV2 (ENSG00000105672), ERF (ENSG00000105722), ELF2 (ENSG00000109381), ELK3 (ENSG00000111145), ETV3 (ENSG00000117036), ELF1 (ENSG00000120690), SPDEF (ENSG00000124664), ELK1 (ENSG00000126767), ETS1 (ENSG00000134954), EHF (ENSG00000135373), ELF5 (ENSG00000135374), ETV6 (ENSG00000139083), FLI1 (ENSG00000151702), GABPA (ENSG00000154727), ERG (ENSG00000157554), ETS2 (ENSG00000157557), ELK4 (ENSG00000158711), FEV (ENSG00000163497), SPIC (ENSG00000166211), ETV4 (ENSG00000175832), ETV5 (ENSG00000244405), ETV3L (ENSG00000253831), ERFL (ENSG00000268041), SPIB (ENSG00000269404)

Protein

Protein identifiers

ETS-related transcription factor Elf-3 — P78545 (reviewed: P78545)

Alternative names: E74-like factor 3, Epithelial-restricted with serine box, Epithelium-restricted Ets protein ESX, Epithelium-specific Ets transcription factor 1

All UniProt accessions (2): P78545, Q5SR36

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator that binds and transactivates ETS sequences containing the consensus nucleotide core sequence GGA[AT]. Acts synergistically with POU2F3 to transactivate the SPRR2A promoter and with RUNX1 to transactivate the ANGPT1 promoter. Also transactivates collagenase, CCL20, CLND7, FLG, KRT8, NOS2, PTGS2, SPRR2B, TGFBR2 and TGM3 promoters. Represses KRT4 promoter activity. Involved in mediating vascular inflammation. May play an important role in epithelial cell differentiation and tumorigenesis. May be a critical downstream effector of the ERBB2 signaling pathway. May be associated with mammary gland development and involution. Plays an important role in the regulation of transcription with TATA-less promoters in preimplantation embryos, which is essential in preimplantation development.

Subunit / interactions. Interacts with TBP. Interacts with CREBBP and EP300; these act as transcriptional coactivators of ELF3 and positively modulate its function. Interacts with XRCC5/KU86 and XRCC6/KU70; these inhibit the ability of ELF3 to bind DNA and negatively modulate its transcriptional activity. Associated with CLND7 and POU2F3. Interacts with ZNF768.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed exclusively in tissues containing a high content of terminally differentiated epithelial cells including mammary gland, colon, trachea, kidney, prostate, uterus, stomach and skin.

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Induction. Transcriptionally regulated by ERBB2 receptor signaling in breast cancer epithelial cells. Up-regulated by phorbol 12-myristate 13-acetate (PMA) in bronchial epithelial cells. By retinoic acid in MCF-7 mammary epithelial cells (at protein level).

Similarity. Belongs to the ETS family.

Isoforms (2)

UniProt ID	Names	Canonical?
P78545-1	1, ESE-1b	yes
P78545-2	2, ESE-1a

RefSeq proteins (2): NP_001107781, NP_004424* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000418	Ets_dom	Domain
IPR003118	Pointed_dom	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR042693	Elf-3_PNT	Domain
IPR046328	ETS_fam	Family

Pfam: PF00178, PF02198

UniProt features (33 total): sequence conflict 11, helix 6, mutagenesis site 4, compositionally biased region 3, chain 1, domain 1, DNA-binding region 1, strand 1, turn 1, region of interest 1, short sequence motif 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2E8P	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78545-F1	66.32	0.20

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 (4):

Position	Phenotype
247–250	no effect on transcriptional repression on krt4 promoter.
315	partially abrogates repressive effect on the krt4 promoter; when associated with a-319.
319	partially abrogates repressive effect on the krt4 promoter; when associated with a-315.
334–337	partially abrogates repressive effect on the krt4 promoter.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1912408	Pre-NOTCH Transcription and Translation

MSigDB gene sets: 220 (showing top): REACTOME_SIGNALING_BY_NOTCH, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_MAMMARY_GLAND_MORPHOGENESIS, GOBP_GLAND_MORPHOGENESIS, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_INFLAMMATORY_RESPONSE, SCHWAB_TARGETS_OF_BMYB_POLYMORPHIC_VARIANTS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, TGACCTY_ERR1_Q2, HATADA_METHYLATED_IN_LUNG_CANCER_DN, MODULE_66, BORLAK_LIVER_CANCER_EGF_UP, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (10): blastocyst development (GO:0001824), regulation of transcription by RNA polymerase II (GO:0006357), inflammatory response (GO:0006954), cell differentiation (GO:0030154), extracellular matrix organization (GO:0030198), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), mammary gland involution (GO:0060056), regulation of DNA-templated transcription (GO:0006355), anatomical structure morphogenesis (GO:0009653)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Pre-NOTCH Expression and Processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
anatomical structure development	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
intracellular membrane-bounded organelle	2
cytoplasm	2
in utero embryonic development	1
defense response	1
cellular developmental process	1
extracellular structure organization	1
external encapsulating structure organization	1
negative regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
tissue remodeling	1
mammary gland morphogenesis	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
developmental process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
DNA binding	1
chromosome	1
nuclear lumen	1
endomembrane system	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1386 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELF3	ELF4	Q99607	979
ELF3	SPRR2A	P35326	817
ELF3	ESX1	Q8N693	771
ELF3	POU2F3	Q9UKI9	734
ELF3	MED23	Q9ULK4	722
ELF3	CCL20	P78556	658
ELF3	TBP	P20226	620
ELF3	SPTBN1	Q01082	587
ELF3	PRR9	Q5T870	511
ELF3	KLF8	O95600	500
ELF3	KRT7	P08729	485
ELF3	KMT5A	Q9NQR1	472
ELF3	PI3	P19957	455
ELF3	CEACAM5	P06731	448
ELF3	POU2F2	P09086	447

IntAct

61 interactions, top by confidence:

A	B	Type	Score
NFE2L2	ELF3	psi-mi:“MI:0915”(physical association)	0.580
ELF3	RELA	psi-mi:“MI:0915”(physical association)	0.460
ELF3	RELA	psi-mi:“MI:0403”(colocalization)	0.460
PRKCI	ELF3	psi-mi:“MI:0915”(physical association)	0.400
APBA3	ELF3	psi-mi:“MI:0915”(physical association)	0.370
	ELF3	psi-mi:“MI:0915”(physical association)	0.370
UBE2D1	ELF3	psi-mi:“MI:0915”(physical association)	0.370
ELF3	UBE2D2	psi-mi:“MI:0915”(physical association)	0.370
CCL2	ELF3	psi-mi:“MI:0915”(physical association)	0.370
CCL24	ELF3	psi-mi:“MI:0915”(physical association)	0.370
IL23A	ELF3	psi-mi:“MI:0915”(physical association)	0.370
IL36A	ELF3	psi-mi:“MI:0915”(physical association)	0.370
NOTCH3	ELF3	psi-mi:“MI:0914”(association)	0.350
	DENND11	psi-mi:“MI:0914”(association)	0.350
ELF3	RSL1D1	psi-mi:“MI:0914”(association)	0.350
ELF3	TRIM24	psi-mi:“MI:2364”(proximity)	0.270
AKT1	ELF3	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	ELF3	psi-mi:“MI:2364”(proximity)	0.270
SMARCA4	ELF3	psi-mi:“MI:2364”(proximity)	0.270
ELF3	SMARCA4	psi-mi:“MI:2364”(proximity)	0.270
SPOP	ELF3	psi-mi:“MI:2364”(proximity)	0.270
ELF3	TP53	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (66): EP300 (Affinity Capture-MS), XRCC6 (Affinity Capture-MS), XRCC5 (Affinity Capture-MS), RPL6 (Affinity Capture-MS), CBR3 (Affinity Capture-MS), XRCC6 (Reconstituted Complex), XRCC5 (Reconstituted Complex), MED23 (Reconstituted Complex), MED23 (Phenotypic Suppression), ELF3 (Affinity Capture-Western), NFKB1 (Affinity Capture-Western), RELA (Affinity Capture-Western), ELF3 (Reconstituted Complex), ELF3 (Affinity Capture-Western), AR (Reconstituted Complex)

ESM2 similar proteins: A1A4L6, F1QDF8, O35914, O75113, O95238, P01105, P10157, P13474, P14921, P15036, P15037, P15062, P15375, P18755, P18756, P19102, P19335, P27577, P40649, P41156, P78545, Q28EW4, Q28F43, Q32NH9, Q3MHT3, Q3UM89, Q3UPW2, Q3YFL6, Q4G112, Q4V7E1, Q5M7N6, Q5SW75, Q66IG8, Q6IE24, Q6NRK3, Q6PUR7, Q708W1, Q708W2, Q76I76, Q7M6U3

Diamond homologs: A0A1W2PQ73, A0JN51, A1A4L6, A1YF15, A1YG61, A1YG91, A2D4Z7, A2T737, A2T762, A3FEM2, A4GTP4, A8WFJ9, O00321, O01519, O70132, O70273, O95238, P01105, P10157, P11308, P11536, P13474, P14921, P15036, P15037, P15062, P18755, P18756, P19102, P19419, P20105, P26323, P27577, P28322, P28324, P29773, P29774, P29775, P29776, P32519

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PAK1	up-regulates	ELF3	phosphorylation
ELF3	“down-regulates quantity by repression”	KRT4	“transcriptional regulation”
ELF3	“up-regulates quantity by expression”	SPRR2A	“transcriptional regulation”
ELF3	“up-regulates quantity by expression”	SPRR1B	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 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
KEAP1-NFE2L2 pathway	6	17.6×	5e-04
Cellular response to chemical stress	5	17.4×	2e-03
Downstream TCR signaling	5	15.7×	3e-03
Interleukin-4 and Interleukin-13 signaling	5	12.6×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	7	8.1×	5e-03
positive regulation of gene expression	8	6.9×	5e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — BLCA, CHOL, COADREAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1467 predictions. Top by Δscore:

Variant	Effect	Δscore
1:202011121:A:AG	acceptor_gain	1.0000
1:202011126:CA:C	acceptor_loss	1.0000
1:202011127:A:AG	acceptor_gain	1.0000
1:202011128:G:GG	acceptor_gain	1.0000
1:202011128:G:GT	acceptor_loss	1.0000
1:202011128:GGT:G	acceptor_gain	1.0000
1:202011128:GGTA:G	acceptor_gain	1.0000
1:202011295:TACAG:T	donor_loss	1.0000
1:202011298:AG:A	donor_loss	1.0000
1:202011301:T:A	donor_loss	1.0000
1:202011945:T:A	acceptor_gain	1.0000
1:202011955:AGAG:A	acceptor_loss	1.0000
1:202011956:GA:G	acceptor_gain	1.0000
1:202011956:GAGAA:G	acceptor_gain	1.0000
1:202012118:GAGC:G	donor_gain	1.0000
1:202012121:C:G	donor_gain	1.0000
1:202012166:C:G	donor_gain	1.0000
1:202012174:CCTCA:C	donor_gain	1.0000
1:202012175:CTCA:C	donor_gain	1.0000
1:202012175:CTCAG:C	donor_loss	1.0000
1:202012176:TCA:T	donor_gain	1.0000
1:202012176:TCAGT:T	donor_loss	1.0000
1:202012178:AGT:A	donor_loss	1.0000
1:202012179:G:GG	donor_gain	1.0000
1:202012179:GT:G	donor_loss	1.0000
1:202012225:C:G	donor_gain	1.0000
1:202012342:A:AG	acceptor_gain	1.0000
1:202012343:G:GG	acceptor_gain	1.0000
1:202012343:GC:G	acceptor_gain	1.0000
1:202012412:G:GT	donor_gain	1.0000

AlphaMissense

2454 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:202013843:C:G	H274D	1.000
1:202013847:T:A	L275Q	1.000
1:202013847:T:C	L275P	1.000
1:202013849:T:A	W276R	1.000
1:202013849:T:C	W276R	1.000
1:202013851:G:C	W276C	1.000
1:202013851:G:T	W276C	1.000
1:202013855:T:C	F278L	1.000
1:202013856:T:C	F278S	1.000
1:202013857:C:A	F278L	1.000
1:202013857:C:G	F278L	1.000
1:202013859:T:A	I279N	1.000
1:202013862:G:C	R280P	1.000
1:202013871:T:A	L283H	1.000
1:202013871:T:C	L283P	1.000
1:202013906:T:A	W295R	1.000
1:202013906:T:C	W295R	1.000
1:202013907:G:C	W295S	1.000
1:202013908:G:C	W295C	1.000
1:202013908:G:T	W295C	1.000
1:202013930:T:C	F303L	1.000
1:202013931:T:C	F303S	1.000
1:202013932:C:A	F303L	1.000
1:202013932:C:G	F303L	1.000
1:202013937:T:C	F305S	1.000
1:202013946:C:T	S308F	1.000
1:202013955:T:A	V311E	1.000
1:202013958:C:A	A312D	1.000
1:202013958:C:T	A312V	1.000
1:202013964:T:C	L314P	1.000

dbSNP variants (sampled 300 via entrez): RS1000111564 (1:202016069 G>A), RS1000353414 (1:202013450 C>G,T), RS1000617976 (1:202009961 C>T), RS1001788426 (1:202014670 C>CA), RS1001890802 (1:202008686 G>T), RS1001945303 (1:202014440 C>T), RS1002555941 (1:202008891 G>A), RS1002581332 (1:202012058 G>A), RS1003063113 (1:202011903 T>A,C), RS1003231444 (1:202016051 G>A), RS1003460706 (1:202013357 C>T), RS1003703290 (1:202016460 A>G), RS1003784538 (1:202010499 G>A), RS1004329330 (1:202010523 C>A,G), RS1005507741 (1:202013402 C>G,T)

Disease associations

OMIM: gene MIM:602191 | 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
GCST011956_60	Systemic lupus erythematosus	4.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2111426 (PROTEIN-PROTEIN INTERACTION)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.23	Kd	590	nM	CHEMBL1077445
6.21	Kd	620	nM	CHEMBL1077474
6.00	Kd	1000	nM	CHEMBL1077454
5.23	Kd	5900	nM	CHEMBL1077475

PubChem BioAssay actives

4 with measured affinity, of 14 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[[(3S,5R)-3-(2-hydroxyethyl)-3-(2-methylpropyl)-2-[[4-(trifluoromethyl)phenyl]methyl]-1,2-oxazolidin-5-yl]methylcarbamothioylamino]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	469608: Inhibition of ESX-Med23 interaction in human BT474 cells assessed as down regulation of ErbB2 expression by Western blotting	kd	0.5900	uM
5-[[(3S,5R)-3-(2-hydroxyethyl)-3-(2-methylpropyl)-2-[(4-phenylphenyl)methyl]-1,2-oxazolidin-5-yl]methylcarbamothioylamino]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	469608: Inhibition of ESX-Med23 interaction in human BT474 cells assessed as down regulation of ErbB2 expression by Western blotting	kd	0.6200	uM
5-[[(3S,5R)-3-(2-hydroxyethyl)-3-(2-methylpropyl)-2-(naphthalen-2-ylmethyl)-1,2-oxazolidin-5-yl]methylcarbamothioylamino]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	469608: Inhibition of ESX-Med23 interaction in human BT474 cells assessed as down regulation of ErbB2 expression by Western blotting	kd	1.0000	uM
5-[[(3S,5R)-2-benzyl-3-(2-hydroxyethyl)-3-(2-methylpropyl)-1,2-oxazolidin-5-yl]methylcarbamothioylamino]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	469608: Inhibition of ESX-Med23 interaction in human BT474 cells assessed as down regulation of ErbB2 expression by Western blotting	kd	5.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, increases methylation	6
sodium arsenite	decreases expression, affects cotreatment, increases abundance	4
Air Pollutants	decreases expression, increases abundance, increases expression	4
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	4
Estradiol	affects cotreatment, decreases expression, affects expression, increases reaction	4
Tetrachlorodibenzodioxin	increases expression	4
trichostatin A	affects cotreatment, increases expression	3
perfluorooctane sulfonic acid	decreases expression, increases expression	3
Calcitriol	increases expression, affects cotreatment, decreases expression	3
Smoke	decreases expression, increases abundance, increases expression	3
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression	3
methylselenic acid	affects expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Microplastics	decreases expression, increases abundance	2
Ethanol	affects cotreatment, increases expression, increases abundance	2
Cisplatin	increases expression, affects expression, affects cotreatment	2
Formaldehyde	increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Testosterone	affects cotreatment, increases expression, decreases expression	2
Tretinoin	increases expression	2
Fenretinide	increases expression	2
Raloxifene Hydrochloride	increases expression, affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
Glupearl 19S	increases expression	1
TAK-243	increases sumoylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
lead acetate	decreases expression	1
arsenite	decreases expression, increases abundance	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1099983	Binding	Inhibition of ESX-Med23 interaction in human BT474 cells assessed as down regulation of ErbB2 expression up to 50 uM by Western blotting	Inhibition of ErbB2(Her2) expression with small molecule transcription factor mimics. — Bioorg Med Chem Lett

Cellosaurus cell lines

6 cell lines: 3 embryonic stem cell, 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1H2	SEES3-1V human ELF3, clone1	Embryonic stem cell	Male
CVCL_A1H3	SEES3-1V human ELF3, clone2	Embryonic stem cell	Male
CVCL_A1H4	SEES3-1V human ELF3, clone3	Embryonic stem cell	Male
CVCL_D7PB	Ubigene A-549 ELF3 KO	Cancer cell line	Male
CVCL_D9E8	Ubigene HEK293 ELF3 KO	Transformed cell line	Female
CVCL_E0CK	Ubigene HeLa ELF3 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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