EGR1

Summary

EGR1 (early growth response 1, HGNC:3238) is a protein-coding gene on chromosome 5q31.2, encoding Early growth response protein 1 (P18146). Transcriptional regulator.

The protein encoded by this gene belongs to the EGR family of C2H2-type zinc-finger proteins. It is a nuclear protein and functions as a transcriptional regulator. The products of target genes it activates are required for differentitation and mitogenesis. Studies suggest this is a cancer suppressor gene.

Source: NCBI Gene 1958 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 49 total
• Druggable target: yes
• Transcription factor: yes — 398 downstream targets (CollecTRI)
• MANE Select transcript: NM_001964

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3238
Approved symbol	EGR1
Name	early growth response 1
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	225, TIS8, AT225, G0S30, NGFI-A, ZIF268, KROX-24, ZIF-268
Ensembl gene	ENSG00000120738
Ensembl biotype	protein_coding
OMIM	128990
Entrez	1958

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000239938

RefSeq mRNA: 1 — MANE Select: NM_001964 NM_001964

CCDS: CCDS4206

Canonical transcript exons

ENST00000239938 — 2 exons

Exon	Start	End
ENSE00000817461	138466757	138469303
ENSE00001955206	138465479	138466068

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 245.9271 / max 8677.1634, expressed in 1801 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58770	233.7994	1795
58796	8.5856	1263
58795	1.0619	399
58794	0.8158	378
58793	0.5373	273
58767	0.5301	275
58768	0.4078	212
58769	0.1891	71

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	99.75	gold quality
left uterine tube	UBERON:0001303	99.70	gold quality
gall bladder	UBERON:0002110	99.42	gold quality
saphenous vein	UBERON:0007318	99.40	gold quality
vena cava	UBERON:0004087	99.26	gold quality
upper leg skin	UBERON:0004262	99.19	gold quality
nipple	UBERON:0002030	99.15	gold quality
periodontal ligament	UBERON:0008266	99.00	gold quality
seminal vesicle	UBERON:0000998	98.99	gold quality
renal medulla	UBERON:0000362	98.87	gold quality
cardia of stomach	UBERON:0001162	98.84	gold quality
epithelium of mammary gland	UBERON:0003244	98.82	gold quality
descending thoracic aorta	UBERON:0002345	98.81	gold quality
mammary duct	UBERON:0001765	98.72	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.50	gold quality
urethra	UBERON:0000057	98.42	gold quality
olfactory bulb	UBERON:0002264	98.42	gold quality
granulocyte	CL:0000094	98.40	gold quality
omental fat pad	UBERON:0010414	98.37	gold quality
peritoneum	UBERON:0002358	98.36	gold quality
parotid gland	UBERON:0001831	98.27	gold quality
penis	UBERON:0000989	98.18	gold quality
tendon of biceps brachii	UBERON:0008188	98.17	gold quality
pancreatic ductal cell	CL:0002079	98.15	gold quality
thoracic aorta	UBERON:0001515	97.94	gold quality
ascending aorta	UBERON:0001496	97.93	gold quality
skin of abdomen	UBERON:0001416	97.80	gold quality
adenohypophysis	UBERON:0002196	97.63	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.61	gold quality
blood vessel layer	UBERON:0004797	97.60	gold quality

Single-cell (SCXA)

Detected in 31 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	2868.04
E-MTAB-8322	yes	2578.36
E-MTAB-7052	yes	2444.31
E-MTAB-6678	yes	2195.19
E-GEOD-134144	yes	1747.27
E-MTAB-6701	yes	1543.49
E-MTAB-10283	yes	1000.17
E-GEOD-130473	yes	642.81
E-CURD-88	yes	30.63
E-MTAB-10553	yes	25.27
E-HCAD-4	yes	22.83
E-HCAD-10	yes	19.58
E-MTAB-9543	yes	16.27
E-CURD-46	yes	11.00
E-CURD-119	yes	8.93

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

398 targets.

Target	Regulation
ABCA2	Unknown
ABCB1	Activation
ABL1
ACE	Activation
ACHE	Unknown
ACKR3
ACTA2	Unknown
ACVR1
ADAM2
ADAMTS13	Unknown
ADAMTS16	Activation
ADRB1	Repression
AGER
AKR1B1	Unknown
AKT1
ALAS1
ALDOC
ALOX5	Activation
ALOX5AP	Activation
ANGPTL4	Unknown
APC
APEX1	Activation
APOA1	Activation
APP
AR	Repression
ARC	Activation
AREG	Activation
ATF3	Activation
ATG4B	Activation
ATP2A2	Repression

JASPAR motifs

Motif	Name	Family
MA0162.2	EGR1	Three-zinc finger Kruppel-related
MA0162.3	EGR1	Three-zinc finger Kruppel-related
MA0162.4	EGR1	Three-zinc finger Kruppel-related
MA0162.5	EGR1	Three-zinc finger Kruppel-related

JASPAR matrix evidence (PMIDs): PMID:16041365

Upstream regulators (CollecTRI, top): AP1, APP, ARX, ASCL2, ATF1, ATF2, ATF3, ATF5, BCAR1, BMAL1, BRCA1, CREB1, DKK1, DMTF1, E2F1, EGR1, EGR2, EGR3, EID1, ELF3, ELK1, ELK3, ELK4, ESR1, ETS1, ETS2, FOXC1, FOXO1, FOXO3, GAST, GNRH1, HDAC1, HLX, HNF4A, ID3, IRF6, IRX1, JUN, KLF5, MAML1

miRNA regulators (miRDB)

110 targeting EGR1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-124-3P	99.89	73.74	3043

Literature-anchored findings (GeneRIF, showing 40)

• Egr-1 in the cancer tissue shows down-regulated expression that supports the inhibited function of Egr-1 in cancer growth and suggests Egr-1 may have an important role in gene therapy of esophageal carcinoma. (PMID:11819815)
• Early Growth Response-1 gene mediates up-regulation of epidermal growth factor receptor expression during hypoxia (PMID:11830539)
• HIV Tat binds Egr proteins and enhances Egr-dependent transactivation of the Fas ligand promoter (PMID:11909874)
• Egr-1 gene of transfected HHCC and ECa109 cells showed obvious suppression of the cell growth and malignant phenotypes, but no suppression in SMMC7721 (HCC cell line) cells. (PMID:11925592)
• Activation of human monoamine oxidase B gene expression by a protein kinase C MAPK signal transduction pathway involves c-Jun and Egr-1. (PMID:11956220)
• role in mediating tissue factor expression in endothelial cells induced by CD40 ligand (PMID:11978801)
• Egr-1 is necessary and sufficient to activate human PPARgamma1 gene expression in VSMC (PMID:12011097)
• Egr1 has multiple roles in prostate tumor cell growth and survival, cell differentiation, tumor progression, angiogenesis, and apoptosis. (PMID:12065847)
• Egr1 translates developmental signals into appropriate changes in gene expression at multiple stages of thymocyte development. (PMID:12165491)
• Egr1 is the oncostatin M-induced transcription factor that binds to the SIRE sequence of the LDL receptor promoter (PMID:12235180)
• transactivation of the EGF receptor as well as stimulation of the mitogen activated/extracellular signal-regulated protein kinase (ERK) are essential for substance P/NK-1 receptor-induced activation of Egr-1 biosynthesis (PMID:12384223)
• The proximal serum response element in the Egr-1 promoter mediates response to thrombin in primary human endothelial cells. Thrombin does this by a MAPK-dependent mechanism that involves an interaction between SRF & SRE-1. (PMID:12393577)
• Egr-1 expression and cell apoptosis may have an important biological significance in esophageal carcinogenesis. (PMID:12439908)
• studies for the first time identify Egr-1 as a nuclear target of gastrin and show that functional interplay of Egr-1, Sp1, and CREB is indispensable for gastrin-dependent CgA transactivation in gastric epithelial cells (PMID:12456801)
• Data demonstrate that Egr-1, AP1 and Smad are part components of the transforming growth factor beta signal transduction pathway that regulates PPAR gamma expression. (PMID:12457461)
• Keratinocytes of chronic psoriatic plaques were characterized by enhanced p16, p14(ARF), and p12 expression accompanied by elevated Egr-1 levels (PMID:12507899)
• Overexpression of EGR1 via generation of superoxide anions inhibits the basolateral Na+/K+-ATPase activity of kidney proximal tubule cells. (PMID:12517959)
• role of Egr-1 in lipopolysaccharide (LPS) induction of TF and inflammatory mediators in vivo was evaluated using Egr-1(+/+) and Egr-1(-/-) mice (PMID:12543866)
• Egr-1 has a significant role in carcinogenesis and in cancer progression, especially metastasis. (PMID:12553019)
• upregulation of Egr-1 might contribute to fibrosis observed in rheumatoid arthritis synovium by activation of genes encoding the alpha1 and alpha2 chains of type I collagen (PMID:12553721)
• PI3K/ERK signaling by the EP(4) receptors induces the functional expression of early growth response factor-1 (EGR-1) (PMID:12566441)
• The enhanced expression of Egr-1 may regulate the activity of matrix metalloproteinases in synovial fibroblasts by enhancing the expression of the TIMP-1, -2, and -3 genes. (PMID:12571843)
• data demonstrates that eukaryotic translation initiation factor 4E binding protein 1 is a new target for early growth response-1 (PMID:12618431)
• Egr-1 represses COL2A1 by preventing interactions between Sp1 and the general transcriptional machinery (PMID:12637574)
• Egr1 controls p21Cip1 expression by directly interacting with a specific sequence on its gene promoter. (PMID:12690110)
• These results suggest that induction of egr-1 may be needed to regulate genes involved in DNA repair, cell survival, and apoptosis. (PMID:12706485)
• stimulation by ATP via a protein kinase C-dependent pathway in the human osteoblastic HOBIT cell line (PMID:12729460)
• study provides the first evidence of the crucial role of Egr-1 in microvascular endothelial cell growth, neovascularization, tumor angiogenesis and tumor growth (PMID:12872165)
• EGR1 binds to the androgen receptor (AR) in prostate carcinoma cells, and an EGR1-AR complex can be detected (PMID:12890669)
• study provides strong evidence that early growth response 1 regulates low density lipoprotein receptor transcription via a novel mechanism of protein-protein interaction with CCAAT enhancer-binding protein beta (PMID:12947119)
• activation of JNK and expression of Egr-1 gene in B lymphoblasts mediate a cellular response to genotoxic agents that may be induced by Fanconi anemia proteins (PMID:12958075)
• early growth response 1 regulates inducible heparanase gene transcription in activated T cells (PMID:14522979)
• EGR-1 is required for expression of NAG-1 by troglitazone (PMID:14662774)
• expression of Egr-1, c-fos and cyclin D1 varies in esophageal precancerous lesions and cancer tissues, suggesting an involvement of these genes in the development of esophageal carcinoma. (PMID:14966901)
• microtubules regulate EGR-1 localization in benign prostate cells but not in malignant prostate cells (PMID:14985468)
• Although EGR-1 is induced by PDGF in human airway smooth muscle cells in cell culture, the role of EGR-1 in airway remodeling and asthma remains to be established. (PMID:15003938)
• mPGES-1 and Egr-1 are novel targets of PPARgamma (PMID:15023995)
• Helicobacter pylori induced expression of Egr-1 in gastric epithelial cell lines in a dose-dependent manner, suggesting a role, in part, in Helicobacter pathology (PMID:15155664)
• Review examines emerging evidence that ERG-1 orchestrates transcriptional response to vascular injury. (PMID:15211096)
• Cells induced with serum to increase endogenous Egr1 increase the transcription of p300/CBP only when Egr1 binding sites in the promoter are not mutated, causing the expression of downstream targets of Egr1. (PMID:15225550)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Egr1	ENSMUSG00000038418
rattus_norvegicus	Egr1	ENSRNOG00000019422
caenorhabditis_elegans		WBGENE00044651

Paralogs (4): EGR2 (ENSG00000122877), EGR4 (ENSG00000135625), EGR3 (ENSG00000179388), WT1 (ENSG00000184937)

Protein

Protein identifiers

Early growth response protein 1 — P18146 (reviewed: P18146)

Alternative names: AT225, Nerve growth factor-induced protein A, Transcription factor ETR103, Transcription factor Zif268, Zinc finger protein 225, Zinc finger protein Krox-24

All UniProt accessions (2): P18146, Q546S1

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator. Recognizes and binds to the DNA sequence 5’-GCG(T/G)GGGCG-3’(EGR-site) in the promoter region of target genes. Binds double-stranded target DNA, irrespective of the cytosine methylation status. Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia. Plays a role in the regulation of cell survival, proliferation and cell death. Activates expression of p53/TP53 and TGFB1, and thereby helps prevent tumor formation. Required for normal progress through mitosis and normal proliferation of hepatocytes after partial hepatectomy. Mediates responses to ischemia and hypoxia; regulates the expression of proteins such as IL1B and CXCL2 that are involved in inflammatory processes and development of tissue damage after ischemia. Regulates biosynthesis of luteinizing hormone (LHB) in the pituitary. Regulates the amplitude of the expression rhythms of clock genes: BMAL1, PER2 and NR1D1 in the liver via the activation of PER1 (clock repressor) transcription. Regulates the rhythmic expression of core-clock gene BMAL1 in the suprachiasmatic nucleus (SCN).

Subunit / interactions. Interacts with SNAI1 and SP1 upon 12-O-tetradecanoylphorbol-13-acetate (TPA) induction.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Detected in neutrophils (at protein level).

Domain organisation. Binds to DNA motifs with the sequence 5’-GCG(T/G)GGGCG-3’ via its C2H2-type zinc fingers. The first, most N-terminal zinc finger binds to the 3’-GCG motif, the middle zinc finger interacts with the central TGG motif, and the C-terminal zinc finger binds to the 5’-GCG motif. Binds double-stranded target DNA, irrespective of the cytosine methylation status. Has reduced affinity for target DNA where the cytosines have been oxidized to 5-hydroxymethylcytosine. Does not bind target DNA where the cytosines have been oxidized to 5-formylcytosine or 5-carboxylcytosine.

Induction. By growth factors.

Similarity. Belongs to the EGR C2H2-type zinc-finger protein family.

RefSeq proteins (1): NP_001955* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR021839	EGR1_C	Repeat
IPR021849	EGR_N	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF11914, PF11928

UniProt features (37 total): site 9, compositionally biased region 5, region of interest 5, sequence variant 4, helix 4, zinc finger region 3, strand 3, turn 2, chain 1, cross-link 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4X9J	X-RAY DIFFRACTION	1.41
4R2A	X-RAY DIFFRACTION	1.59
4R2C	X-RAY DIFFRACTION	1.89
4R2D	X-RAY DIFFRACTION	2.09
5N14	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18146-F1	50.63	0.04

Functional residue map

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

Catalytic / active sites (9): 336 (interaction with dna); 347 (interaction with dna); 351 (interaction with dna); 357 (interaction with dna); 375 (interaction with dna); 379 (interaction with dna); 403 (interaction with dna); 407 (interaction with dna); 413 (interaction with dna)

Post-translational modifications (1): 305

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9031628	NGF-stimulated transcription
R-HSA-909733	Interferon alpha/beta signaling

MSigDB gene sets: 752 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_CIRCADIAN_RHYTHM, GOBP_MEMORY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_RESPONSE_TO_IONIZING_RADIATION, MODY_HIPPOCAMPUS_POSTNATAL, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_METANEPHROS_DEVELOPMENT, LU_IL4_SIGNALING, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM

GO Biological Process (37): negative regulation of transcription by RNA polymerase II (GO:0000122), response to hypoxia (GO:0001666), response to ischemia (GO:0002931), regulation of transcription by RNA polymerase II (GO:0006357), response to glucose (GO:0009749), positive regulation of gene expression (GO:0010628), T cell differentiation (GO:0030217), BMP signaling pathway (GO:0030509), positive regulation of chemokine production (GO:0032722), positive regulation of interleukin-1 beta production (GO:0032731), response to insulin (GO:0032868), circadian regulation of gene expression (GO:0032922), regulation of protein sumoylation (GO:0033233), skeletal muscle cell differentiation (GO:0035914), regulation of neuron apoptotic process (GO:0043523), positive regulation of gene expression via chromosomal CpG island demethylation (GO:0044029), estrous cycle (GO:0044849), locomotor rhythm (GO:0045475), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of hormone biosynthetic process (GO:0046886), circadian temperature homeostasis (GO:0060086), interleukin-1-mediated signaling pathway (GO:0070498), cellular response to hypoxia (GO:0071456), cellular response to gamma radiation (GO:0071480), cellular response to heparin (GO:0071504), cellular response to mycophenolic acid (GO:0071506), glomerular mesangial cell proliferation (GO:0072110), positive regulation of glomerular metanephric mesangial cell proliferation (GO:0072303), negative regulation of canonical Wnt signaling pathway (GO:0090090), cellular response to interleukin-8 (GO:0098759), positive regulation of post-translational protein modification (GO:1901875), positive regulation of miRNA transcription (GO:1902895), regulation of progesterone biosynthetic process (GO:2000182), regulation of DNA-templated transcription (GO:0006355), regulation of apoptotic process (GO:0042981), rhythmic process (GO:0048511)

GO Molecular Function (17): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), 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 (GO:0003677), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), double-stranded methylated DNA binding (GO:0010385), histone acetyltransferase binding (GO:0035035), sequence-specific DNA binding (GO:0043565), hemi-methylated DNA-binding (GO:0044729), sequence-specific double-stranded DNA binding (GO:1990837), promoter-specific chromatin binding (GO:1990841), protein binding (GO:0005515), enzyme binding (GO:0019899), metal ion binding (GO:0046872)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
PTEN Regulation	1
Nuclear Events (kinase and transcription factor activation)	1
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
double-stranded DNA binding	3
cellular anatomical structure	3
response to stress	2
regulation of gene expression	2
transcription cis-regulatory region binding	2
negative regulation of DNA-templated transcription	1
response to decreased oxygen levels	1
response to hexose	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
lymphocyte differentiation	1
T cell activation	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
positive regulation of cytokine production	1
chemokine production	1
regulation of chemokine production	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
positive regulation of interleukin-1 production	1
response to peptide hormone	1
circadian rhythm	1
protein sumoylation	1
regulation of protein modification by small protein conjugation or removal	1
skeletal muscle tissue development	1
cell differentiation	1
regulation of apoptotic process	1
neuron apoptotic process	1
transcription initiation-coupled chromatin remodeling	1
ovulation cycle	1
locomotory behavior	1
circadian behavior	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
transcription regulatory region nucleic acid binding	1

Protein interactions and networks

STRING

5088 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EGR1	NAB2	Q15742	965
EGR1	FOS	P01100	951
EGR1	NAB1	Q13506	941
EGR1	JUN	P05412	915
EGR1	FOSB	P53539	881
EGR1	PPARG	P37231	870
EGR1	MYC	P01106	867
EGR1	AKT1	P31749	828
EGR1	CREB1	P16220	807
EGR1	ATF3	P18847	799
EGR1	PITX1	P78337	794
EGR1	JUND	P17535	787
EGR1	NR3C1	P04150	775
EGR1	ELK4	P28323	775
EGR1	TP53	P04637	765

IntAct

31 interactions, top by confidence:

A	B	Type	Score
CTNNB1	TCF4	psi-mi:“MI:0914”(association)	0.940
EP300	VDR	psi-mi:“MI:0914”(association)	0.550
EGR1	CDKN2A	psi-mi:“MI:0915”(physical association)	0.520
CDKN2A	EGR1	psi-mi:“MI:0915”(physical association)	0.520
EGR1	CTNNB1	psi-mi:“MI:0915”(physical association)	0.500
CTNNB1	EGR1	psi-mi:“MI:0915”(physical association)	0.500
NEDD4	EGR1	psi-mi:“MI:0407”(direct interaction)	0.440
SNAI1	EGR1	psi-mi:“MI:0915”(physical association)	0.400
EGR1	SP1	psi-mi:“MI:0915”(physical association)	0.400
SUMO1	EGR1	psi-mi:“MI:0915”(physical association)	0.400
EGR1	bipA	psi-mi:“MI:0915”(physical association)	0.370
	EGR1	psi-mi:“MI:0915”(physical association)	0.370
EGR1	rep	psi-mi:“MI:0915”(physical association)	0.370
EGR1	MAGEB2	psi-mi:“MI:0914”(association)	0.350
EGR1	NES	psi-mi:“MI:0914”(association)	0.350
EGR1	NAB1	psi-mi:“MI:0914”(association)	0.350
LEF1	TCF4	psi-mi:“MI:0914”(association)	0.350
TCF4	EGR1	psi-mi:“MI:0914”(association)	0.350
EGR1	TP53	psi-mi:“MI:0403”(colocalization)	0.350
VDR	EGR1	psi-mi:“MI:0914”(association)	0.350
EGR1	VDR	psi-mi:“MI:0914”(association)	0.350
EGR1		psi-mi:“MI:0915”(physical association)	0.000
EGR1	astD	psi-mi:“MI:0915”(physical association)	0.000
SREBF2	EGR1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (90): EP300 (Affinity Capture-Western), EP300 (Reconstituted Complex), EGR1 (Reconstituted Complex), FOSL2 (Affinity Capture-MS), JUNB (Affinity Capture-MS), JUND (Affinity Capture-MS), MAGEB2 (Affinity Capture-MS), PSMD2 (Affinity Capture-MS), MED6 (Affinity Capture-MS), POP1 (Affinity Capture-MS), DNAJC8 (Affinity Capture-MS), PHIP (Affinity Capture-MS), ARID2 (Affinity Capture-MS), EGR1 (Reconstituted Complex), EGR1 (Affinity Capture-Western)

ESM2 similar proteins: A1XSY8, O08656, O43474, P08046, P08151, P08152, P08154, P09022, P09027, P10070, P11161, P13360, P15976, P17679, P18146, P19544, P22561, P26632, P26633, P31249, P40656, P43300, P43301, P43429, P46153, P47806, P49639, P49952, P50476, P51774, Q05159, Q06889, Q07424, Q08427, Q0VGT2, Q29W20, Q60793, Q61169, Q6NW96, Q6P0J3

Diamond homologs: A1C6L9, A1DH89, A2QCJ9, A4II20, B0XSK6, B8NGC8, O14335, O59958, O94130, O94131, O94166, P08046, P08154, P18146, P26632, P27705, P39943, P50898, P52288, P53035, P78871, Q00453, Q01800, Q01981, Q02026, Q02027, Q05620, Q18250, Q29W20, Q4X0Z3, Q5AMH6, Q6GQH4, Q6NTY6, Q9HFS2, Q9P7D9, Q9P889, Q9Y7G2, A1XSY8, O73691, O73692

SIGNOR signaling

46 interactions.

A	Effect	B	Mechanism
NfKb-p65/p50	up-regulates	EGR1	binding
EGR1	“up-regulates quantity by expression”	COL4A1	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	COL4A2	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	COL11A1	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	COL7A1	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	COL10A1	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	ABCB1	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	CYP2B6	“transcriptional regulation”
EGR1	“down-regulates quantity by repression”	HSD11B2	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	HYAL1	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	NAB2	“transcriptional regulation”
NAB2	“down-regulates quantity by repression”	EGR1	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	BCAR1	“transcriptional regulation”
BCAR1	“up-regulates quantity by expression”	EGR1	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	PCSK2	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	SOD1	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	FAP	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	PTGES	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	SLC4A2	“transcriptional regulation”
GAST	“up-regulates quantity by expression”	EGR1	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	TBXA2R	“transcriptional regulation”
HDAC1	“down-regulates quantity by repression”	EGR1	“transcriptional regulation”
NfKb-p65/p50	“down-regulates quantity by repression”	EGR1	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	CHGA	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	GDF15	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	HPSE	“transcriptional regulation”
EGR1	“down-regulates quantity by repression”	FCER2	“transcriptional regulation”
EGR1	“down-regulates quantity by repression”	FAS	“transcriptional regulation”
EGR1	up-regulates	Monocyte_differentiation
HLX	“down-regulates quantity by repression”	EGR1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 18 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
Transcriptional Regulation by VENTX	5	102.2×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
canonical Wnt signaling pathway	5	51.1×	4e-06
positive regulation of gene expression	5	12.9×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

121 predictions. Top by Δscore:

Variant	Effect	Δscore
5:138466066:CAGG:C	donor_loss	1.0000
5:138466067:AGGT:A	donor_loss	1.0000
5:138466068:GGT:G	donor_loss	1.0000
5:138466069:GTAAG:G	donor_loss	1.0000
5:138466070:T:A	donor_loss	1.0000
5:138466756:GA:G	acceptor_gain	1.0000
5:138466065:GCAG:G	donor_gain	0.9900
5:138466069:G:GG	donor_gain	0.9900
5:138466751:T:A	acceptor_gain	0.9900
5:138466751:TGCCA:T	acceptor_loss	0.9900
5:138466753:CCA:C	acceptor_loss	0.9900
5:138466754:CAGA:C	acceptor_loss	0.9900
5:138466755:A:AG	acceptor_gain	0.9900
5:138466756:G:A	acceptor_loss	0.9900
5:138466756:G:GG	acceptor_gain	0.9900
5:138466756:GAGT:G	acceptor_gain	0.9900
5:138466756:GAGTC:G	acceptor_gain	0.9800
5:138466066:CAG:C	donor_gain	0.9400
5:138466064:CGCAG:C	donor_gain	0.9100
5:138466065:GCAGG:G	donor_gain	0.9100
5:138466067:AG:A	donor_gain	0.9000
5:138466068:GG:G	donor_gain	0.9000
5:138466753:CCAG:C	acceptor_gain	0.9000
5:138466756:G:C	acceptor_gain	0.8900
5:138466754:CAG:C	acceptor_gain	0.8800
5:138466755:AGA:A	acceptor_gain	0.8800
5:138466785:CGAGA:C	acceptor_gain	0.8300
5:138466648:G:GT	donor_gain	0.8000
5:138466659:T:TA	donor_gain	0.7700
5:138466660:A:AA	donor_gain	0.7700

AlphaMissense

3549 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:138467467:T:A	C340S	1.000
5:138467467:T:C	C340R	1.000
5:138467468:G:C	C340S	1.000
5:138467469:C:G	C340W	1.000
5:138467482:T:A	C345S	1.000
5:138467482:T:C	C345R	1.000
5:138467483:G:A	C345Y	1.000
5:138467483:G:C	C345S	1.000
5:138467484:T:G	C345W	1.000
5:138467494:T:C	F349L	1.000
5:138467495:T:C	F349S	1.000
5:138467495:T:G	F349C	1.000
5:138467496:C:A	F349L	1.000
5:138467496:C:G	F349L	1.000
5:138467513:T:C	L355P	1.000
5:138467518:C:A	R357S	1.000
5:138467519:G:C	R357P	1.000
5:138467521:C:A	H358N	1.000
5:138467521:C:G	H358D	1.000
5:138467522:A:C	H358P	1.000
5:138467522:A:G	H358R	1.000
5:138467523:C:A	H358Q	1.000
5:138467523:C:G	H358Q	1.000
5:138467527:C:A	R360S	1.000
5:138467528:G:C	R360P	1.000
5:138467533:C:G	H362D	1.000
5:138467535:C:A	H362Q	1.000
5:138467535:C:G	H362Q	1.000
5:138467551:T:C	F368L	1.000
5:138467552:T:C	F368S	1.000

dbSNP variants (sampled 300 via entrez): RS1000738349 (5:138464067 C>T), RS1001030752 (5:138465031 G>A,C), RS1001138967 (5:138464225 A>G), RS1001386200 (5:138464933 G>A), RS1002341171 (5:138464336 A>G), RS1002699503 (5:138466661 G>A), RS1003758725 (5:138468273 C>A), RS1004424241 (5:138465599 G>C,T), RS1004476491 (5:138468808 GT>G), RS1005045445 (5:138467667 C>A,G,T), RS1005688130 (5:138464622 A>G), RS1006278463 (5:138465627 C>A), RS1006546668 (5:138464253 G>A), RS1006671194 (5:138466497 C>T), RS1007008096 (5:138464076 G>A)

Disease associations

OMIM: gene MIM:128990 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): squamous cell carcinoma (MONDO:0005096)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002539_60	Schizophrenia	5.000000e-09
GCST004521_139	Autism spectrum disorder or schizophrenia	2.000000e-09
GCST004521_66	Autism spectrum disorder or schizophrenia	1.000000e-08
GCST004791_2	Amyotrophic lateral sclerosis (C9orf72 mutation interaction)	2.000000e-06
GCST004946_112	Schizophrenia	1.000000e-09
GCST006990_3	Cerebrospinal AB1-42 levels in Alzheimer’s disease dementia	7.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3616355 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects methylation, decreases expression, increases stability, decreases reaction (+3 more)	18
Estradiol	decreases expression, increases reaction, affects expression, affects cotreatment, increases expression	10
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	10
Tetrachlorodibenzodioxin	affects expression, decreases degradation, decreases expression, increases expression	9
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases activity, decreases expression, decreases reaction, increases expression	8
Benzo(a)pyrene	affects activity, decreases expression, increases expression	8
bisphenol A	affects reaction, affects cotreatment, affects expression, increases expression, increases methylation	7
Arsenic Trioxide	affects expression, affects methylation, decreases expression, increases expression, affects cotreatment	7
Troglitazone	increases reaction, decreases expression, increases activity, increases stability, decreases reaction (+3 more)	7
Silicon Dioxide	decreases expression, increases expression, affects localization, increases activity, decreases reaction	7
Tobacco Smoke Pollution	increases localization, decreases expression, increases expression	7
Particulate Matter	affects cotreatment, decreases expression, increases abundance, increases expression, affects reaction (+2 more)	7
Resveratrol	decreases reaction, increases activity, affects reaction, increases reaction, increases expression (+3 more)	6
Quercetin	increases expression, decreases expression	6
Tetradecanoylphorbol Acetate	decreases reaction, increases expression, affects reaction, increases reaction	6
deoxynivalenol	affects reaction, increases expression, increases phosphorylation, increases reaction	5
U 0126	decreases expression, decreases reaction, increases expression	5
Cadmium	affects expression, decreases expression, increases abundance, increases expression	5
Aflatoxin B1	affects expression, decreases methylation, increases expression	5
Cadmium Chloride	decreases expression, increases abundance, increases expression	5
methylmercuric chloride	increases expression, affects cotreatment	4
sulindac sulfide	affects reaction, increases expression, increases reaction, decreases reaction	4
Acetaminophen	decreases expression, affects localization, increases expression, affects reaction, decreases reaction	4
Arsenic	decreases expression, affects expression, decreases methylation, increases abundance, increases expression (+2 more)	4
Cisplatin	decreases expression, increases expression, increases activity, increases reaction, increases response to substance (+2 more)	4
Fluorouracil	affects binding, increases reaction, decreases expression, affects reaction, decreases reaction (+3 more)	4
Hydrogen Peroxide	affects expression, increases expression	4
Silver	increases expression, decreases expression	4
Dronabinol	affects cotreatment, increases expression, decreases expression	4
Tretinoin	decreases reaction, increases expression	4

ChEMBL screening assays

35 unique, capped per target: 35 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3619311	Binding	Activation of Egr1 in human AGS cells assessed as increase in cleaved caspase-3 level at 100 uM by Western blot analysis in presence of caspase-3 inhibitor Ac-DEVD-CHO	Induction of apoptosis by genipin inhibits cell proliferation in AGS human gastric cancer cells via Egr1/p21 signaling pathway. — Bioorg Med Chem Lett

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1F4	SEES3-1V human EGR1, clone1	Embryonic stem cell	Male
CVCL_A1F5	SEES3-1V human EGR1, clone2	Embryonic stem cell	Male
CVCL_A1F6	SEES3-1V human EGR1, clone3	Embryonic stem cell	Male
CVCL_B8F5	Abcam HCT 116 EGR1 KO	Cancer cell line	Male
CVCL_B9HD	Abcam A-549 EGR1 KO	Cancer cell line	Male
CVCL_D2EY	Abcam MCF-7 EGR1 KO	Cancer cell line	Female
CVCL_E1CV	Ubigene THP-1 EGR1 KO	Cancer cell line	Male
CVCL_E1FZ	Abcam HeLa EGR1 KO	Cancer cell line	Female
CVCL_XN38	HAP1 EGR1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00868088	PHASE4	COMPLETED	Photodynamic Therapy to Treat Actinic Damage in Patients With Squamous Cell Carcinoma (SCC) of the Lip
NCT02088515	PHASE4	COMPLETED	Nedaplatin (Jiebaishu®) Combined With Docetaxel for Advanced Lung Squamous Cell Carcinoma
NCT02151149	PHASE4	COMPLETED	Safety and Efficacy Study of Abraxane in Combination With Carboplatin to Treat Advanced NSCL Cancer in the Elderly
NCT03388931	PHASE4	WITHDRAWN	Radiotherapy Dose Escalation in Locally Advanced Squamous Cell Carcinoma of the Larynx or Hypopharynx
NCT00101582	PHASE3	COMPLETED	Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer
NCT00201279	PHASE3	COMPLETED	Chemoprevention Study of Oral Cavity Squamous Cell Carcinoma
NCT00201383	PHASE3	COMPLETED	Post-Operative Adjuvant Concurrent Chemoradiotherapy For High Risk Oral Cavity Squamous Cell Carcinoma Patients
NCT00382031	PHASE3	COMPLETED	Zalutumumab in Patients With Non-curable Head and Neck Cancer
NCT00472459	PHASE3	COMPLETED	Photodynamic Therapy (PDT) With Metvix® 160 Milligrams/Gram Cream in Organ Transplant Participants With Non-melanoma Skin Cancer
NCT00559351	PHASE3	TERMINATED	RCT on the Combined Modality Treatment of Squamous Cell Carcinoma of the Esophagus
NCT01161498	PHASE3	TERMINATED	Study of Safety and Efficacy of Talimogene Laherparepvec With Cisplatin and Radiotherapy for Treatment of Locally Advanced Head and Neck Cancer
NCT01363466	PHASE3	TERMINATED	Evaluation of Hysterectomy After Chemoradiation Therapy for Stage IB2/II Cervical Cancer
NCT01532453	PHASE3	TERMINATED	Prevention of UV-induced Carcinogenic Skin Alterations in Immunosuppressed Solid Organ Transplanted Patients
NCT01706939	PHASE3	ACTIVE_NOT_RECRUITING	The Quarterback Trial: Reduced Dose Radiotherapy for HPV+ Oropharynx Cancer
NCT03115476	PHASE3	TERMINATED	A Trial to Compare the Incidence of Squamous Cell Carcinoma (SCC) and Other Skin Neoplasia on Skin Areas Treated With Ingenol Disoxate Gel or Vehicle Gel for Actinic Keratosis on Face and Chest or Scalp
NCT03257267	PHASE3	COMPLETED	Study of Cemiplimab in Adults With Cervical Cancer
NCT00139230	PHASE2	COMPLETED	Combination Chemotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck
NCT00176254	PHASE2	COMPLETED	Paclitaxel, Carboplatin and Radiotherapy as Induction Therapy in Locally Advanced Head and Neck Cancer
NCT00176267	PHASE2	COMPLETED	Paclitaxel, Carboplatin And Low Dose Radiation As Induction Therapy In Locally Advanced Head And Neck Cancer
NCT00197444	PHASE2	COMPLETED	Low-Dose Nedaplatin (CDGP:Cis-Diammine-Glycolatoplatinum)/5-FU Combined With Radiation for Esophageal Cancer
NCT00255476	PHASE2	COMPLETED	The IRESSA Novel Head and Neck Chemotherapy Evaluation Study
NCT00400205	PHASE2	TERMINATED	Study of Induction Docetaxel, Cisplatin and 5-Fluorouracil
NCT00409565	PHASE2	COMPLETED	A Phase II Trial of Cetuximab and Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer
NCT00446446	PHASE2	COMPLETED	PRISM (Panitumumab Regimen In Second-line Monotherapy of Head and Neck Cancer)
NCT00476476	PHASE2	COMPLETED	Erlotinib in Women With Squamous Cell Carcinoma of the Vulvar
NCT00485485	PHASE2	COMPLETED	Imatinib Mesylate (Gleevec) and Docetaxel in Patients With Head and Neck Squamous Cell Cancer
NCT00500760	PHASE2	COMPLETED	Study of Addition of Panitumumab to Chemoradiation Therapy in Patients With Locally Advanced Head and Neck Cancer
NCT00542308	PHASE2	COMPLETED	Zalutumumab in Non-curable Patients With SCCHN
NCT00547157	PHASE2	COMPLETED	Radiotherapy Plus Panitumumab Compared to Chemoradiotherapy With Unresected, Locally Advanced Squamous Cell Carcinoma of the Head and Neck
NCT00573131	PHASE2	TERMINATED	Efficacy and Safety of OncoGel™ Added to Chemotherapy and Radiation Before Surgery in Subjects With Esophageal Cancer
NCT00586040	PHASE2	COMPLETED	Photochemical Tissue Bonding
NCT00605709	PHASE2	WITHDRAWN	Dose-Ranging Safety and Efficacy Study of Topical Creams Containing API 31510 for the Treatment of in Situ Cutaneous Squamous Cell Carcinoma
NCT00661427	PHASE2	COMPLETED	Cetuximab at Either 500 or 750 mg/m2 Every Other Week for Recurrent or Metastatic Head and Neck Squamous Cell Cancer
NCT01009203	PHASE2	TERMINATED	Temsirolimus (Torisel®) and Erlotinib (Tarceva®) in Platinum-Refractory/Ineligible, Advanced, Squamous Cell Carcinoma
NCT01077999	PHASE2	COMPLETED	Chemoradiation and Panitumumab for Esophageal Cancer
NCT01133665	PHASE2	COMPLETED	Cetuximab and Lenalidomide in Head and Neck
NCT01232374	PHASE2	UNKNOWN	Nimotuzumab in Combination With Chemoradiation for Local Advanced Esophageal Squamous Cell Carcinoma
NCT01333852	PHASE2	TERMINATED	Metformin Plus Paclitaxel for Metastatic or Recurrent Head and Neck Cancer
NCT01561456	PHASE2	COMPLETED	Study of AXL1717 Compared to Docetaxel to Treat Squamous Cell Carcinoma or Adenocarcinoma of the Lung
NCT01666431	PHASE2	TERMINATED	Single-center Investigator Initiated Pilot Study Investigating the Tumor Response of Squamous Cell Carcinoma Lesions in Patients Under Lapatinib Treatment