ATF3

Summary

ATF3 (activating transcription factor 3, HGNC:785) is a protein-coding gene on chromosome 1q32.3, encoding Cyclic AMP-dependent transcription factor ATF-3 (P18847). This protein binds the cAMP response element (CRE) (consensus: 5’-GTGACGT[AC][AG]-3’), a sequence present in many viral and cellular promoters.

This gene encodes a member of the mammalian activation transcription factor/cAMP responsive element-binding (CREB) protein family of transcription factors. This gene is induced by a variety of signals, including many of those encountered by cancer cells, and is involved in the complex process of cellular stress response. Multiple transcript variants encoding different isoforms have been found for this gene. It is possible that alternative splicing of this gene may be physiologically important in the regulation of target genes.

Source: NCBI Gene 467 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 29 total
• Transcription factor: yes — 119 downstream targets (CollecTRI)
• MANE Select transcript: NM_001674

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:785
Approved symbol	ATF3
Name	activating transcription factor 3
Location	1q32.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000162772
Ensembl biotype	protein_coding
OMIM	603148
Entrez	467

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000336937, ENST00000341491, ENST00000366981, ENST00000366983, ENST00000366985, ENST00000366987, ENST00000464547, ENST00000465155, ENST00000492118, ENST00000613104, ENST00000872903

RefSeq mRNA: 6 — MANE Select: NM_001674 NM_001030287, NM_001040619, NM_001206484, NM_001206486, NM_001206488, NM_001674

CCDS: CCDS1506, CCDS41464, CCDS55688, CCDS58059

Canonical transcript exons

ENST00000341491 — 4 exons

Exon	Start	End
ENSE00001196790	212618127	212618234
ENSE00003597462	212615018	212615261
ENSE00003627503	212619358	212620775
ENSE00003849383	212608761	212608930

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 113.2517 / max 7451.7684, expressed in 1781 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8479	113.1479	1781
8480	0.1038	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vena cava	UBERON:0004087	99.79	gold quality
mucosa of stomach	UBERON:0001199	99.34	gold quality
gall bladder	UBERON:0002110	98.82	gold quality
saphenous vein	UBERON:0007318	98.78	gold quality
trachea	UBERON:0003126	98.58	gold quality
urethra	UBERON:0000057	98.25	gold quality
pericardium	UBERON:0002407	97.87	gold quality
upper leg skin	UBERON:0004262	97.67	gold quality
left uterine tube	UBERON:0001303	97.60	gold quality
cardia of stomach	UBERON:0001162	97.47	gold quality
mucosa of urinary bladder	UBERON:0001259	97.42	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.42	gold quality
omental fat pad	UBERON:0010414	97.36	gold quality
peritoneum	UBERON:0002358	97.30	gold quality
cauda epididymis	UBERON:0004360	96.92	gold quality
nipple	UBERON:0002030	96.50	gold quality
seminal vesicle	UBERON:0000998	96.21	gold quality
parotid gland	UBERON:0001831	96.05	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.48	gold quality
rectum	UBERON:0001052	95.34	gold quality
skin of abdomen	UBERON:0001416	94.73	gold quality
ascending aorta	UBERON:0001496	94.64	gold quality
thoracic aorta	UBERON:0001515	94.09	gold quality
cervix squamous epithelium	UBERON:0006922	94.07	gold quality
epithelium of mammary gland	UBERON:0003244	94.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.86	gold quality
amniotic fluid	UBERON:0000173	93.77	gold quality
upper lobe of left lung	UBERON:0008952	93.77	gold quality
islet of Langerhans	UBERON:0000006	93.69	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.64	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	3191.48
E-MTAB-9841	yes	2240.91
E-GEOD-130473	yes	1006.77
E-GEOD-100618	yes	385.63
E-MTAB-10287	yes	64.61
E-CURD-122	yes	28.10
E-GEOD-135922	yes	26.29
E-HCAD-10	yes	25.87
E-MTAB-10553	yes	22.57
E-GEOD-93593	yes	7.35
E-GEOD-125970	yes	6.85
E-MTAB-6678	yes	6.61
E-GEOD-137537	yes	6.25
E-MTAB-8060	no	1594.84
E-ENAD-17	no	354.16

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

119 targets.

Target	Regulation
ABCC1	Repression
ADIPOQ	Repression
ADIPOR1	Repression
ADIPOR2	Repression
AGRP
AK4	Unknown
AP1
APOB
AQP1
ASNS	Activation
ATF3	Unknown
ATF4
BAX
BECN1
CALCA
CAV1
CCL2	Activation
CCL3	Repression
CCL4	Repression
CCL5	Unknown
CCNA1	Activation
CCNA2	Repression
CCND1	Unknown
CCND3	Activation
CD82	Unknown
CDC25A	Unknown
CDKN1A	Unknown
CEBPA	Unknown
CH25H
CLDN1

JASPAR motifs

Motif	Name	Family
MA0605.2	ATF3	Fos-related
MA0605.3	ATF3	Fos-related

JASPAR matrix evidence (PMIDs): PMID:12815047

Upstream regulators (CollecTRI, top): ATF2, ATF3, ATF4, CEBPB, CEBPG, CREB1, EGR1, EIF2AK3, EIF2AK4, ESR1, FOXL2, HSF1, JDP2, JUN, KLF4, KLF6, MEF2A, MEF2D, MYC, NANOG, NFATC3, NFE2L2, NFKB1, SMAD2, SP3, TP53

miRNA regulators (miRDB)

56 targeting ATF3, 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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-6761-5P	98.71	68.03	1504

Literature-anchored findings (GeneRIF, showing 40)

• role of JNK-ATF3 pathway in apoptosis of vascular endothelial cells associated with hyperhomocysteinemia (PMID:11726207)
• represses 72-kDa type IV collagenase expression by antagonizing p53-dependent trans-activation of the collagenase promoter (PMID:11792711)
• An alternatively spliced isoform of transcriptional repressor ATF3 and its induction by stress stimuli. (PMID:12034827)
• These results demonstrate that overexpression of Activating transcription factor 3 (ATF3) suppresses tumor necrosis factor-alpha-induced cell death of HUVECs, at least in part, through down-regulating the transcription of p53 gene. (PMID:12161427)
• human ATF3 gene is one of the target genes directly activated by p53 (PMID:12372430)
• induction of ATF3 protein, a member of the ATF/CREB family of transcription factors, by ionizing radiation requires normal cellular p53 function (PMID:12386811)
• ATF3 may function as a cytoprotective transcription factor in DOX-treated cardiac myocytes, at least in part, owing to downregulation of p53 (PMID:12392999)
• ATF-2 and ATF3 seem to play an important role in the protective response of human cells to ionizing radiation (PMID:12833146)
• ATF3 isoforms have a role in the transcriptional regulation of the ASNS gene in response to nutrient deprivation (PMID:12881527)
• Demonstrate the critical role of tyrosine phosphorylated ATF3 in IL-10 suppression of MMP-2 gene expression in primary human prostate tumor cells. (PMID:15280448)
• ATF3-FL and C/EBPbeta act as transcriptional suppressors for the ASNS gene to counterbalance the transcription rate activated by ATF4 following amino acid deprivation (PMID:15385533)
• The results suggest that I3C represses cell proliferation through up-regulation of NAG-1 and that ATF3 may play a pivotal role in DIM-induced NAG-1 expression in human colorectal cancer cells. (PMID:15670751)
• this is a novel first report demonstrating that the expression of ATF3 occurs via early growth response gene-1 downstream of extracellular signal-regulated kinase1/2 (PMID:16079301)
• coordinated regulation of mRNA stability by HuR and AUF1 proteins contributes to the observed increase in ATF3 expression following amino acid limitation (PMID:16109718)
• high expression of ATF3 is found in nearly all cases of cHL and is almost exclusively restricted to it (PMID:16263788)
• t10,c12-CLA stimulates ATF3/NAG-1 expression and subsequently induces apoptosis in an isomer specific manner (PMID:16286461)
• ATF3 is up-regulated in the penile skin tissues of boys with hypospadias, which suggests a role for this transcription factor in the development of this abnormality. (PMID:16306208)
• gene mapped to chromosome 1. (PMID:16484797)
• role in a novel mechanism used by interferon-induced serine/threonine protein kinase (PKR) to induce apoptosis (PMID:16613840)
• Transcription factor Wilms’ tumor 1 and ATF3 Transcription Factor are activated in Wilms’ tumor and accelerate tumorigenesis. (PMID:16912181)
• Initial increase in RNA pol II (RNA polymerase II) binding to the promoter and in the transcription rate from the ATF3 gene. (PMID:16989641)
• results indicate that a major signalling pathway, the p38 pathway, plays a critical role in the induction of ATF3 by stress signals, and that ATF3 is functionally important to mediate the pro-apoptotic effects of p38 (PMID:17014422)
• expression of ATF-3 in hypoxic cells represses Id-1 and prevents their loss (PMID:17102133)
• The tumor metastasis suppressor gene Drg-1 suppresses metastasis of prostate tumor cells by inhibiting the invasive ability of the cells via down-regulation of the expression of the ATF3 gene. (PMID:17178897)
• ATF3 may have oncogenic properties in epithelial cells (PMID:17295236)
• We found significant differences in gene expression, specifically with a group of genes, including ATF3, known to be responsive to estrogen or to interact with estrogen receptor. (PMID:17437852)
• Coxsackievirus B3 (CVB3) infection markedly reduced ATF3 expression at mRNA and protein levels in parallel with p53 degradation, and preservation of p53 expression rescued CVB3 infection-induced ATF3 downregulation. (PMID:17599613)
• ATF3 has a dichotomous role in cancer development. (PMID:17952119)
• 17-alpha ethinyl estradiol upregulates ATF3 expression in human foreskin fibroblasts in vitro. (PMID:18001166)
• Sp1 recruits ATF3, c-Jun, and STAT3 to obtain the requisite synergistic effect in neuronal injury through DINE neuronal injury-inducible gene (PMID:18192274)
• ATF3 plays a protective role in renal ischemia-reperfusion injury and the mechanism of the protection may involve suppression of p53 and induction of p21 (PMID:18235102)
• ATF3 gene variants influence the risk of hypospadias (PMID:18426833)
• Alterations in ATF3 gene expression resemble the response to mechanical and ischemic stress reported in other tissues. (PMID:18692824)
• ATF3 is a key mediator of KLF6-induced apoptosis in prostate cancer cells (PMID:18755691)
• IFN-gamma inhibits matrix metalloproteinase expression by inducing expression of transcriptional repressor ATF-3, which then participates in feedback inhibition of Toll-like receptor-induced gene expression in primary human macrophages. (PMID:18802113)
• both ATF3 and Smad were crucially and synergistically involved in down-regulation of Id-1, which regulated JNK phosphorylation in REIC/Dkk-3-induced apoptosis. (PMID:18922905)
• Chk1 affects Cdc25A via rapid phosphorylation and protein turnover, inhibition of Cdc25A transcription by p53-ATF3 is required for the maintenance of cell cycle arrest. (PMID:19060337)
• In human prostate and Hodgkin Reed-Sternberg cancer cells with elevated expression of ATF3, the P1 promoter was constitutively activated and its chromatin structure was modified into active configuration. (PMID:19136462)
• Activating Transcription Factor 3 regulates the PCNA-associated factor p15(PAF) protein and required DNA repair of damaged cells. (PMID:19219066)
• TGF-beta1 stimulates expression of activating transcription factor 3 (ATF3) in human breast cancer cells (MDA-MB231). (PMID:19582787)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	atf3	ENSDARG00000007823
mus_musculus	Atf3	ENSMUSG00000026628
rattus_norvegicus	Atf3	ENSRNOG00000003745
drosophila_melanogaster	Atf3	FBGN0028550

Paralogs (8): FOSL2 (ENSG00000075426), BATF3 (ENSG00000123685), FOSB (ENSG00000125740), JDP2 (ENSG00000140044), BATF (ENSG00000156127), BATF2 (ENSG00000168062), FOS (ENSG00000170345), FOSL1 (ENSG00000175592)

Protein

Protein identifiers

Cyclic AMP-dependent transcription factor ATF-3 — P18847 (reviewed: P18847)

Alternative names: Activating transcription factor 3

All UniProt accessions (3): A0A0A0MRJ2, P18847, Q5VTZ4

UniProt curated annotations — full annotation on UniProt →

Function. This protein binds the cAMP response element (CRE) (consensus: 5’-GTGACGT[AC][AG]-3’), a sequence present in many viral and cellular promoters. Represses transcription from promoters with ATF sites. It may repress transcription by stabilizing the binding of inhibitory cofactors at the promoter. Activates transcription presumably by sequestering inhibitory cofactors away from the promoters. Stress-induced isoform, counteracts the transcriptional repression of isoform 1.

Subunit / interactions. Binds DNA as a homodimer or a heterodimer. Interacts with KAT5; promoting KAT5 autoacetylation and KAT5 deubiquitination by USP7.

Subcellular location. Nucleus.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the bZIP family. ATF subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
P18847-1	1, ATF3	yes
P18847-2	2, ATF3-delta-Zip
P18847-3	3, ATF3-delta-Zip2a/TF3-delta-Zip2b
P18847-4	4, ATF3-delta-Zip2c
P18847-5	5

RefSeq proteins (6): NP_001025458, NP_001035709, NP_001193413, NP_001193415, NP_001193417, NP_001665* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000837	AP-1	Family
IPR004827	bZIP	Domain
IPR046347	bZIP_sf	Homologous_superfamily

Pfam: PF00170

UniProt features (14 total): splice variant 4, sequence variant 2, region of interest 2, cross-link 2, chain 1, domain 1, sequence conflict 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18847-F1	77.45	0.39

Functional residue map

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

Post-translational modifications (3): 162, 78, 175

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-380994	ATF4 activates genes in response to endoplasmic reticulum stress
R-HSA-9633012	Response of EIF2AK4 (GCN2) to amino acid deficiency
R-HSA-9648895	Response of EIF2AK1 (HRI) to heme deficiency
R-HSA-9909649	Regulation of PD-L1(CD274) transcription
R-HSA-2262752	Cellular responses to stress
R-HSA-381042	PERK regulates gene expression
R-HSA-381119	Unfolded Protein Response (UPR)
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9711097	Cellular response to starvation

MSigDB gene sets: 652 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, AMIT_DELAYED_EARLY_GENES, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, ENK_UV_RESPONSE_KERATINOCYTE_UP, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS

GO Biological Process (16): negative regulation of transcription by RNA polymerase II (GO:0000122), gluconeogenesis (GO:0006094), regulation of transcription by RNA polymerase II (GO:0006357), transforming growth factor beta receptor signaling pathway (GO:0007179), positive regulation of cell population proliferation (GO:0008284), positive regulation of gene expression (GO:0010628), endoplasmic reticulum unfolded protein response (GO:0030968), cellular response to amino acid starvation (GO:0034198), response to type II interferon (GO:0034341), response to endoplasmic reticulum stress (GO:0034976), skeletal muscle cell differentiation (GO:0035914), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of ERK1 and ERK2 cascade (GO:0070373), positive regulation of TRAIL-activated apoptotic signaling pathway (GO:1903984), regulation of DNA-templated transcription (GO:0006355), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (13): 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 repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (10): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), Golgi apparatus (GO:0005794), centrosome (GO:0005813), nuclear body (GO:0016604), ciliary basal body (GO:0036064), RNA polymerase II transcription regulator complex (GO:0090575), CHOP-ATF3 complex (GO:1990622)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Cellular responses to stress	3
PERK regulates gene expression	1
Cellular response to starvation	1
Regulation of PD-L1(CD274) expression	1
Cellular responses to stimuli	1
Unfolded Protein Response (UPR)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
regulation of gene expression	2
DNA-templated transcription	2
transcription cis-regulatory region binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
protein dimerization activity	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
intracellular membraneless organelle	2
microtubule organizing center	2
transcription regulator complex	2
nuclear protein-containing complex	2
negative regulation of DNA-templated transcription	1
glucose metabolic process	1
hexose biosynthetic process	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
cellular response to unfolded protein	1
response to endoplasmic reticulum stress	1
intracellular signal transduction	1
cellular response to starvation	1
response to amino acid starvation	1
response to cytokine	1
innate immune response	1
cellular response to stress	1
skeletal muscle tissue development	1
cell differentiation	1
positive regulation of DNA-templated transcription	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1

Protein interactions and networks

STRING

3976 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATF3	JUN	P05412	996
ATF3	FOS	P01100	984
ATF3	JUND	P17535	981
ATF3	SMAD3	P84022	977
ATF3	TP53	P04637	933
ATF3	FOSB	P53539	895
ATF3	FOSL1	P15407	853
ATF3	CREB1	P16220	838
ATF3	SMARCA4	P51532	810
ATF3	PPP1R15A	O75807	803
ATF3	EGR1	P18146	799
ATF3	XBP1	P17861	798
ATF3	CEBPB	P17676	783
ATF3	ATF6	P18850	777
ATF3	HDAC1	Q13547	773

IntAct

193 interactions, top by confidence:

A	B	Type	Score
DDIT3	ATF3	psi-mi:“MI:0407”(direct interaction)	0.960
ATF3	DDIT3	psi-mi:“MI:0407”(direct interaction)	0.960
ATF3	DDIT3	psi-mi:“MI:0915”(physical association)	0.960
DDIT3	ATF3	psi-mi:“MI:0915”(physical association)	0.960
ATF3	DDIT3	psi-mi:“MI:2364”(proximity)	0.960
DDIT3	ATF3	psi-mi:“MI:2364”(proximity)	0.960

BioGRID (191): ATF3 (Biochemical Activity), ATF3 (Two-hybrid), ATF3 (Two-hybrid), ATF3 (Two-hybrid), ATF3 (Two-hybrid), ATF3 (Two-hybrid), ATF3 (Proximity Label-MS), ATF3 (Affinity Capture-MS), ATF3 (Affinity Capture-MS), ATF3 (Affinity Capture-MS), ATF3 (Affinity Capture-MS), ATF3 (Affinity Capture-MS), KAT5 (Affinity Capture-Western), ATF3 (Affinity Capture-Western), KAT5 (Reconstituted Complex)

ESM2 similar proteins: A4IGK3, B7ZAP0, O08609, O54941, O55047, O60519, P18847, P26801, P28574, P29596, P37285, P52161, P52162, P52164, P60762, P61244, P61245, P97875, Q07016, Q07866, Q08CW1, Q08DJ0, Q0VCP9, Q0VD32, Q13330, Q28772, Q2KII1, Q32KT0, Q32M00, Q3T0B9, Q56A18, Q5BJU6, Q5R581, Q5ZIL4, Q60765, Q62599, Q642H2, Q6PH81, Q78E65, Q7TMY4

Diamond homologs: A1L2X1, D4A7E1, E1BD44, F1QW76, F7EMX9, O02761, O35284, O77628, O88479, O97930, P01100, P01101, P01102, P11939, P12841, P18847, P23050, P29176, P29596, P53450, Q16520, Q2KII1, Q56TN0, Q56TT7, Q60765, Q6DGM8, Q8HZP6, Q8N1L9, Q8WYK2, Q91496, Q9Z2Q8, A8MPH9, B3MTI9, B3P5D2, B4G652, B4HZE8, B4JYN3, B4K617, B4M5T7, B4NBL5

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ATF3	“up-regulates quantity by expression”	PCLAF	“transcriptional regulation”
ATF3	“up-regulates quantity by expression”	GDF15	“transcriptional regulation”
ATF3	“up-regulates quantity by expression”	ASNS	“transcriptional regulation”
KLF6	“up-regulates quantity by expression”	ATF3	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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
NGF-stimulated transcription	6	26.8×	4e-05
Signaling by ALK fusions and activated point mutants	7	16.4×	5e-05
Signaling by NTRK1 (TRKA)	5	15.4×	1e-03
Signaling by NTRKs	5	14.2×	1e-03
Regulation of PD-L1(CD274) transcription	6	10.2×	1e-03
Response of EIF2AK4 (GCN2) to amino acid deficiency	5	8.7×	9e-03
Signaling by Interleukins	7	7.0×	2e-03
Cytokine Signaling in Immune system	9	5.7×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
integrated stress response signaling	15	140.4×	2e-27
positive regulation of miRNA transcription	5	19.4×	6e-04
cellular response to xenobiotic stimulus	5	16.1×	1e-03
DNA-templated transcription	5	15.0×	1e-03
liver development	5	14.8×	1e-03
cellular response to calcium ion	5	13.4×	2e-03
response to endoplasmic reticulum stress	6	13.3×	6e-04
transforming growth factor beta receptor signaling pathway	6	12.7×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1180 predictions. Top by Δscore:

Variant	Effect	Δscore
1:212565484:G:GG	donor_gain	1.0000
1:212618115:T:TA	acceptor_gain	1.0000
1:212618116:G:A	acceptor_gain	1.0000
1:212618123:A:AG	acceptor_gain	1.0000
1:212618123:ACAG:A	acceptor_gain	1.0000
1:212618124:C:G	acceptor_gain	1.0000
1:212618125:A:AG	acceptor_gain	1.0000
1:212618125:AG:A	acceptor_gain	1.0000
1:212618126:G:GT	acceptor_gain	1.0000
1:212618126:GG:G	acceptor_gain	1.0000
1:212618126:GGT:G	acceptor_gain	1.0000
1:212618126:GGTA:G	acceptor_gain	1.0000
1:212618230:AGAAA:A	donor_gain	1.0000
1:212618231:GAAA:G	donor_gain	1.0000
1:212618231:GAAAG:G	donor_gain	1.0000
1:212618232:AAA:A	donor_gain	1.0000
1:212618232:AAAG:A	donor_loss	1.0000
1:212618233:AA:A	donor_gain	1.0000
1:212618233:AAG:A	donor_loss	1.0000
1:212618234:AG:A	donor_loss	1.0000
1:212618235:G:GG	donor_gain	1.0000
1:212618235:GTG:G	donor_loss	1.0000
1:212619357:GGA:G	acceptor_gain	1.0000
1:212619552:C:G	donor_gain	1.0000
1:212565479:AAAAT:A	donor_gain	0.9900
1:212565480:AAAT:A	donor_gain	0.9900
1:212565480:AAATG:A	donor_loss	0.9900
1:212565481:AAT:A	donor_gain	0.9900
1:212565482:AT:A	donor_gain	0.9900
1:212565482:ATGT:A	donor_loss	0.9900

AlphaMissense

1186 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:212618172:A:G	N96D	1.000
1:212618185:C:A	A100D	1.000
1:212618187:G:C	A101P	1.000
1:212618193:T:C	C103R	1.000
1:212618196:C:G	R104G	1.000
1:212618197:G:C	R104P	1.000
1:212618227:T:C	L114P	1.000
1:212619361:T:C	S118P	1.000
1:212619371:T:C	L121P	1.000
1:212619392:T:C	L128P	1.000
1:212619413:T:C	L135P	1.000
1:212619446:T:C	L146P	1.000
1:212619454:C:A	H149N	1.000
1:212619454:C:G	H149D	1.000
1:212619455:A:G	H149R	1.000
1:212619456:T:A	H149Q	1.000
1:212619456:T:G	H149Q	1.000
1:212619466:T:C	C153R	1.000
1:212619467:G:A	C153Y	1.000
1:212619468:T:G	C153W	1.000
1:212618161:G:C	R92P	0.999
1:212618164:G:C	R93P	0.999
1:212618171:A:C	R95S	0.999
1:212618171:A:T	R95S	0.999
1:212618173:A:C	N96T	0.999
1:212618173:A:T	N96I	0.999
1:212618174:T:A	N96K	0.999
1:212618174:T:G	N96K	0.999
1:212618175:A:G	K97E	0.999
1:212618177:G:C	K97N	0.999

dbSNP variants (sampled 300 via entrez): RS1000007038 (1:212615933 G>A), RS1000014351 (1:212593132 C>A), RS1000073434 (1:212606402 C>T), RS1000087672 (1:212566721 G>A), RS1000171183 (1:212596739 A>G), RS1000271601 (1:212603200 G>A), RS1000402429 (1:212596474 G>A), RS1000408783 (1:212574516 GT>G), RS1000432174 (1:212596784 A>G), RS1000464584 (1:212616279 A>G), RS1000606579 (1:212597017 G>T), RS1000675107 (1:212591546 G>A,T), RS1000679232 (1:212604657 C>G), RS1000681865 (1:212590587 T>A), RS1000706193 (1:212591268 G>T)

Disease associations

OMIM: gene MIM:603148 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003073_1	Cerebral amyloid deposition (PET imaging)	9.000000e-06
GCST003073_11	Cerebral amyloid deposition (PET imaging)	8.000000e-07
GCST005196_193	Coronary artery disease	8.000000e-06
GCST006202_1	Thiopurine-induced leukopenia in inflammatory bowel disease (conditioned on rs116855232)	1.000000e-06
GCST008337_2	Blood cell traits (multivariate analysis)	1.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007707	cerebral amyloid deposition measurement
EFO:0004305	erythrocyte count
EFO:0004309	platelet count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0005090	basophil count
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11811628	ATF3		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases reaction, increases expression, affects reaction, increases abundance, increases cleavage (+6 more)	14
Cisplatin	affects response to substance, affects expression, decreases expression, decreases reaction, increases reaction (+1 more)	10
Benzo(a)pyrene	affects cotreatment, affects expression, increases expression, affects methylation	9
Resveratrol	affects reaction, increases expression, affects response to substance, increases activity, increases reaction (+2 more)	7
Thapsigargin	increases expression, increases reaction, affects cotreatment	7
deoxynivalenol	affects phosphorylation, increases response to substance, decreases reaction, affects binding, increases activity (+7 more)	6
sulindac sulfide	increases reaction, increases phosphorylation, decreases reaction, increases expression	6
Tobacco Smoke Pollution	increases expression	6
Valproic Acid	affects expression, affects reaction, increases expression	6
Aflatoxin B1	affects expression, increases expression, increases methylation	6
Particulate Matter	increases abundance, increases expression, affects reaction, affects cotreatment, affects binding (+1 more)	6
bisphenol A	affects expression, affects cotreatment, decreases methylation, decreases expression, increases expression	5
Cadmium	increases abundance, increases expression, decreases expression	5
Estradiol	decreases expression, increases expression	5
Fluorouracil	affects expression, increases expression, affects reaction	5
Tunicamycin	increases expression	5
Cyclosporine	increases expression	5
Cadmium Chloride	increases expression, decreases expression, increases abundance	5
Bortezomib	increases expression, increases reaction, increases response to substance	4
Arsenic Trioxide	decreases expression, decreases methylation, increases expression, increases reaction	4
Troglitazone	increases phosphorylation, decreases reaction, increases expression, increases reaction, affects cotreatment (+1 more)	4
Copper	increases expression, affects binding, decreases expression	4
Silicon Dioxide	increases expression	4
Smoke	increases expression, increases reaction, affects reaction, decreases expression	4
Genistein	decreases expression, increases expression	4
methylmercuric chloride	decreases expression, increases expression	3
4-phenylenediamine	increases expression	3
15-acetyldeoxynivalenol	increases expression, affects binding, increases activity, increases reaction	3
SB 203580	decreases reaction, increases expression, decreases degradation, increases abundance	3
Acetaminophen	affects cotreatment, increases expression	3

Cellosaurus cell lines

13 cell lines: 10 cancer cell line, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A0E5	SEES3-1V human ATF3, clone1	Embryonic stem cell	Male
CVCL_A0E6	SEES3-1V human ATF3, clone2	Embryonic stem cell	Male
CVCL_A0E7	SEES3-1V human ATF3, clone3	Embryonic stem cell	Male
CVCL_B1D8	Abcam HCT 116 ATF3 KO	Cancer cell line	Male
CVCL_B1EL	Abcam A-549 ATF3 KO	Cancer cell line	Male
CVCL_B1K9	Abcam HeLa ATF3 KO	Cancer cell line	Female
CVCL_D7KN	Ubigene A-549 ATF3 KO	Cancer cell line	Male
CVCL_D8HL	Ubigene HCT 116 ATF3 KO	Cancer cell line	Male
CVCL_GZ76	K562 eGFP-ATF3	Cancer cell line	Female
CVCL_SD83	HAP1 ATF3 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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