FOS

Summary

FOS (Fos proto-oncogene, AP-1 transcription factor subunit, HGNC:3796) is a protein-coding gene on chromosome 14q24.3, encoding Protein c-Fos (P01100). Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. In precision oncology, FOS Overexpression confers sensitivity to Irbesartan in Colon Adenocarcinoma (CIViC Level C).

The Fos gene family consists of 4 members: FOS, FOSB, FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerize with proteins of the JUN family, thereby forming the transcription factor complex AP-1. As such, the FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation. In some cases, expression of the FOS gene has also been associated with apoptotic cell death.

Source: NCBI Gene 2353 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Berardinelli-Seip congenital lipodystrophy (Supportive, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 51 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Transcription factor: yes — 380 downstream targets (CollecTRI)
• MANE Select transcript: NM_005252

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3796
Approved symbol	FOS
Name	Fos proto-oncogene, AP-1 transcription factor subunit
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	c-fos, AP-1
Ensembl gene	ENSG00000170345
Ensembl biotype	protein_coding
OMIM	164810
Entrez	2353

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000303562, ENST00000535987, ENST00000554212, ENST00000554617, ENST00000555242, ENST00000555347, ENST00000555672, ENST00000555686, ENST00000556324, ENST00000557139, ENST00000871987, ENST00000944924

RefSeq mRNA: 1 — MANE Select: NM_005252 NM_005252

CCDS: CCDS9841

Canonical transcript exons

ENST00000303562 — 4 exons

Exon	Start	End
ENSE00001129865	75280783	75282230
ENSE00001152027	75280560	75280667
ENSE00001152033	75279877	75280128
ENSE00003641426	75278828	75279123

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 547.1624 / max 21298.4507, expressed in 1777 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140625	545.3284	1777
140627	0.5870	169
140632	0.2562	84
140628	0.2355	97
140634	0.2285	92
140633	0.1670	77
140630	0.1586	59
140631	0.1193	49
140626	0.0441	14
140629	0.0379	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	99.94	gold quality
upper leg skin	UBERON:0004262	99.86	gold quality
gall bladder	UBERON:0002110	99.85	gold quality
left uterine tube	UBERON:0001303	99.83	gold quality
monocyte	CL:0000576	99.79	gold quality
mononuclear cell	CL:0000842	99.75	gold quality
leukocyte	CL:0000738	99.74	gold quality
granulocyte	CL:0000094	99.70	gold quality
nipple	UBERON:0002030	99.54	gold quality
skin of hip	UBERON:0001554	99.53	gold quality
trachea	UBERON:0003126	99.38	gold quality
omental fat pad	UBERON:0010414	99.38	gold quality
tibial nerve	UBERON:0001323	99.35	gold quality
skin of abdomen	UBERON:0001416	99.34	gold quality
peritoneum	UBERON:0002358	99.29	gold quality
seminal vesicle	UBERON:0000998	99.28	gold quality
cardia of stomach	UBERON:0001162	99.28	gold quality
right ovary	UBERON:0002118	99.20	gold quality
vena cava	UBERON:0004087	99.19	gold quality
urethra	UBERON:0000057	99.16	gold quality
bone marrow cell	CL:0002092	99.09	gold quality
penis	UBERON:0000989	99.07	gold quality
saphenous vein	UBERON:0007318	99.05	gold quality
vermiform appendix	UBERON:0001154	99.01	gold quality
rectum	UBERON:0001052	99.00	gold quality
right coronary artery	UBERON:0001625	98.89	gold quality
left ovary	UBERON:0002119	98.80	gold quality
right lung	UBERON:0002167	98.73	gold quality
mucosa of urinary bladder	UBERON:0001259	98.71	gold quality
right atrium auricular region	UBERON:0006631	98.66	gold quality

Single-cell (SCXA)

Detected in 56 experiment(s), a significant marker in 38.

Experiment	Marker?	Max mean expression
E-CURD-89	yes	12772.83
E-CURD-55	yes	12292.83
E-GEOD-76312	yes	8614.83
E-MTAB-10287	yes	8372.73
E-GEOD-149689	yes	8156.18
E-CURD-122	yes	6305.51
E-MTAB-6308	yes	6200.18
E-GEOD-106540	yes	5066.69
E-GEOD-134144	yes	4500.46
E-MTAB-8911	yes	4305.87
E-CURD-120	yes	3513.43
E-MTAB-8498	yes	3410.67
E-GEOD-150728	yes	3213.89
E-CURD-85	yes	2943.40
E-MTAB-8530	yes	2461.84

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

380 targets.

Target	Regulation
A2M
AANAT	Unknown
ABCB1
ACHE
ACP5	Unknown
ACTA1	Unknown
ACTB
ADAM2
ADCYAP1
AFF2
AFP	Activation
AGTR2
AKR1B15
ALAS2
ALB
ALOX12	Activation
AP1	Repression
APP
AQP5
ARNT	Unknown
AVP
BATF3	Unknown
BCL2	Activation
BCL2L1	Unknown
BCL2L11	Unknown
BGLAP	Unknown
BLOC1S3
BMP2	Activation
BMP4	Activation
BRCA1	Activation

JASPAR motifs

Motif	Name	Family
MA0099.2	FOS::JUN	Fos-related::Jun-related
MA0099.3	FOS::JUN	Fos-related::Jun-related
MA0099.4	FOS::JUN	Fos-related::Jun-related
MA0476.1	FOS	Fos-related
MA0476.2	FOS	Fos-related
MA1126.1	FOS::JUN	Fos-related::Jun-related
MA1126.2	FOS::JUN	Fos-related::Jun-related
MA1134.1	FOS::JUNB	Fos-related::Jun-related
MA1134.2	FOS::JUNB	Fos-related::Jun-related
MA1141.1	FOS::JUND	Fos-related::Jun-related
MA1141.2	FOS::JUND	Fos-related::Jun-related
MA1951.1	FOS	Fos-related
MA1951.2	FOS	Fos-related

JASPAR matrix evidence (PMIDs): PMID:17916232, PMID:11988758, PMID:2511004

Upstream regulators (CollecTRI, top): AHR, AIRE, AP1, APP, AR, ARHGAP35, ARNT, ATF1, ATF2, ATF6, BRCA1, CALCR, CEBPA, CEBPB, CEBPG, CLU, CREB1, CREM, DACH1, DKK1, DNMT1, EGR1, EGR4, ELK1, ELK3, ELK4, EPHB2, ESR1, ESR2, ETS1, ETS2, FLI1, FOS, FOSB, FOXC1, FOXL2, FOXM1, GLI2, GLI3, GTF2I

miRNA regulators (miRDB)

102 targeting FOS, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-95-5P	99.89	72.17	3973

Literature-anchored findings (GeneRIF, showing 40)

• Crystal structure of a ternary SAP-1/SRF/c-fos SRE DNA complex (PMID:11846562)
• Bombesin antagonists inhibit growth of MDA-MB-435 estrogen-independent breast cancers and decrease the expression of the ErbB-2/HER-2 oncoprotein and c-jun and c-fos oncogenes (PMID:11891317)
• Analysis of heterophilic and homophilic interactions of cadherins using the c-Jun/c-Fos dimerization domains (PMID:11909859)
• Effects of fluid shear stress on expression of proto-oncogenes c-fos and c-myc in cultured human umbilical vein endothelial cells. (PMID:12082260)
• candidate genes that may be involved in the origination of ameloblastoma and several genes previously unidentified in relation to human tooth development. (PMID:12147741)
• Review. AP1 plays a crucial role during human papillomavirus (HPV) early gene expression, in particular of the expression of E6 and E7 oncoproteins. (PMID:12183893)
• results suggest that Hic-5 participates in the transcriptional regulation of c-fos as a scaffold in transcriptional complexes (PMID:12445807)
• studies suggest that the cooperative interaction of the estrogen receptor with Fos and Jun proteins helps confer estrogen responsiveness to the endogenous progesterone receptor gene (PMID:12446585)
• Tumor promoter arsenite stimulates histone H3 phosphoacetylation of this and c-jun proto-oncogene chromatin in diploid fibroblasts. (PMID:12547826)
• Expression of c-fos was induced by TPA and Saikosaponin a during 30 min to 6 h of treatment. (PMID:12592382)
• independent and cooperative activation of chromosomal c-fos promoter by STAT3 (PMID:12600988)
• p53 and c-fos are significantly overexpressed in thyroid cancer patients, indicating their role in the genetic mechanisms leading to thyroid tumorigenesis (PMID:12687275)
• data demonstratre that c-Fos physically and functionally interacts with JCV major early regulatory protein large T-Ag and that this interaction modulates JCV transcription and replication in glial cells (PMID:12692226)
• Up-regulation of c-Fos in the lymphocytes of rheumatoid arthritis patients. (PMID:12705898)
• a physical interaction between c-Fos and STAT-1 participates in NOS2 gene transcriptional activation in lung epithelium (PMID:12788789)
• Phosphorylation of the carboxy-terminal transactivation domain of c-FGOS by extracellular signal-related kinase mediates the transcriptional activation of AP-1 and cellular neoplastic transformation by PDGF. (PMID:12972619)
• c-fos and AP-1 are regulated by JNK and p38 MAPK (PMID:14511403)
• c-Fos proto-oncoprotein is degraded by the proteasome independently of its own ubiquitinylation (PMID:14517309)
• The positive c-fos immunoreactivity observed in sudden infant death syndrome suggests that the neurons of the dorsal motor vagal nucleus involved in the regulation of breathing are able to yield an intense, immediate ventilatory response to hypoxia. (PMID:14629301)
• VEGF and PlGF induced expression of both full-length FosB mRNA and an alternatively spliced variant. (PMID:14741347)
• 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)
• FOS is the primary target of up-regulation in Helicobacter pylori infections in human gastric cancer cells. (PMID:15188457)
• AP-1 and JNK have roles in reactive oxygen species activation in tobacco-induced mucin production in lung cells (PMID:15262961)
• c-jun, junD, junB, and c-fos and Notch2 are expressed in splenic marginal zone lymphoma (PMID:15507668)
• loss of Net and constitutive c-fos expression appear to be a key event in the transformation of cervical cancer cells. (PMID:15548518)
• SDF-1/CXCL12 enhanced cell survival in synergy with other cytokines involves activation of CREB and induction of Mcl-1 and c-Fos (PMID:15588513)
• In psoriatic epidermis, c-Jun expression was prominent in both hyperproliferating basal and suprabasal keratinocytes, whereas c-Fos expression was unchanged. (PMID:15654976)
• p38alpha and -beta mediate UV-induced, AP-1-mediated, c-Fos phosphorylation (PMID:15708845)
• TBP affects the NF1 and c-fos promoters in a manner reciprocal to that of TLF, stimulating the c-fos promoter and inhibiting NF1 transcription (PMID:15767669)
• bFGF induces the increased expression of c-fos through PI 3-K/PKB in CNE- I nasopharyngeal carcinoma cell line. (PMID:15835820)
• No statistical significances of p73 or c-fos expressions were observed between involutional hemangioma and normal skin. (PMID:15844599)
• Vasoactive intestinal peptide induces FOS expression in a prostatic neoplasm cell line. (PMID:15921770)
• In hepatoma-associated anorexia-cachexia c-Fos was induced in several brain areas of thes forebrain. (PMID:15926923)
• PGE2 increases the expression and secretion of VEGF in HCC cells by activating the transcription factor c-fos, promotes the angiogenesis of hepatocellular carcinoma and plays an important role in the pathogenesis of liver cancer. (PMID:16038047)
• activity of the AP-1 components c-Jun, ATF2, and c-Fos is altered in renal cystic tissue of patients with autosomal dominant polycystic kidney disease (PMID:16049073)
• c-Fos/c-Jun AP-1 dimer activity is downregulated by SUMO-1, SUMO-2, and SUMO-3 (PMID:16055710)
• c-Fos represents a novel target for the isomerizing activity of Pin1, which has a role in the mechanism by which c-Jun and c-Fos cooperate to regulate AP-1-dependent gene transcription (PMID:16123044)
• INI1/hSNF5/BAF47 could be recruited to the region of c-fos promoter to reduce histone acetylation (PMID:16219292)
• Results showed that certain regulation involved in c-myc, c-fos, and c-jun was present in the apoptosis, and the c-Myc dependent-on and Jun N-terminal kinase (JNK) pathway also play roles. (PMID:16552729)
• c-Fos binding at the TGFbeta1 promoter proximal AP-1 site in human colon carcinoma cells is required for TGFbeta1 production by the tumor cells. (PMID:16637060)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fosab	ENSDARG00000031683
mus_musculus	Fos	ENSMUSG00000021250
rattus_norvegicus	Fos	ENSRNOG00000008015
drosophila_melanogaster	Atf3	FBGN0028550

Paralogs (8): FOSL2 (ENSG00000075426), BATF3 (ENSG00000123685), FOSB (ENSG00000125740), JDP2 (ENSG00000140044), BATF (ENSG00000156127), ATF3 (ENSG00000162772), BATF2 (ENSG00000168062), FOSL1 (ENSG00000175592)

Protein

Protein identifiers

Protein c-Fos — P01100 (reviewed: P01100)

Alternative names: Cellular oncogene fos, Fos proto-oncogene, AP-1 transcription factor subunit, G0/G1 switch regulatory protein 7, Proto-oncogene c-Fos, Transcription factor AP-1 subunit c-Fos

All UniProt accessions (8): P01100, G3V289, G3V2V7, G3V5J9, G3V5N7, G3V5N9, H0YJM3, Q6FG41

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. In the heterodimer, FOS and JUN/AP-1 basic regions each seems to interact with symmetrical DNA half sites. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling. Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation. In growing cells, activates phospholipid synthesis, possibly by activating CDS1 and PI4K2A. This activity requires Tyr-dephosphorylation and association with the endoplasmic reticulum.

Subunit / interactions. Heterodimer; with JUN. Component of the SMAD3/SMAD4/JUN/FOS complex required for synergistic TGF-beta-mediated transcription at the AP1 promoter site. Interacts with SMAD3; the interaction is weak even on TGF-beta activation. Interacts with MAFB. Interacts with TSC22D3 (via N-terminus); this interaction inhibits the binding of active AP1 to its target DNA. Interacts with CDS1 and PI4K2A. Interacts (via bZIP domain and leucine-zipper region) with the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF) subunits SMARCB1, SMARCC2 and SMARCD1. Interacts (via bZIP domain and leucine-zipper region) with ARID1A.

Subcellular location. Nucleus. Endoplasmic reticulum. Cytoplasm. Cytosol.

Post-translational modifications. Phosphorylated in the C-terminal upon stimulation by nerve growth factor (NGF) and epidermal growth factor (EGF). Phosphorylated, in vitro, by MAPK and RSK1. Phosphorylation on both Ser-362 and Ser-374 by MAPK1/2 and RSK1/2 leads to protein stabilization with phosphorylation on Ser-374 being the major site for protein stabilization on NGF stimulation. Phosphorylation on Ser-362 and Ser-374 primes further phosphorylations on Thr-325 and Thr-331 through promoting docking of MAPK to the DEF domain. Phosphorylation on Thr-232, induced by HA-RAS, activates the transcriptional activity and antagonizes sumoylation. Phosphorylation on Ser-362 by RSK2 in osteoblasts contributes to osteoblast transformation. Constitutively sumoylated with SUMO1, SUMO2 and SUMO3. Desumoylated by SENP2. Sumoylation requires heterodimerization with JUN and is enhanced by mitogen stimulation. Sumoylation inhibits the AP-1 transcriptional activity and is, itself, inhibited by Ras-activated phosphorylation on Thr-232. In quiescent cells, the small amount of FOS present is phosphorylated at Tyr-10 and Tyr-30 by SRC. This Tyr-phosphorylated form is cytosolic. In growing cells, dephosphorylated by PTPN2. Dephosphorylation leads to the association with endoplasmic reticulum membranes and activation of phospholipid synthesis.

Similarity. Belongs to the bZIP family. Fos subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P01100-1	1	yes
P01100-2	2
P01100-3	3

RefSeq proteins (1): NP_005243* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00170

UniProt features (37 total): mutagenesis site 16, modified residue 7, region of interest 4, cross-link 3, splice variant 2, chain 1, domain 1, sequence conflict 1, helix 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1A02	X-RAY DIFFRACTION	2.7
1FOS	X-RAY DIFFRACTION	3.05
1S9K	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01100-F1	58.48	0.19

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 (10): 325, 331, 362, 374, 113, 128, 265, 10, 30, 232

Mutagenesis-validated functional residues (16):

Position	Phenotype
10	loss of activation of phospholipid synthesis; when associated with e-30.
10	overall loss of tyr-phosphorylation, including that of y-30 phosphorylation. localizes to the endoplasmic reticulum in q
30	loss of activation of phospholipid synthesis; when associated with e-10.
30	overall loss of tyr-phosphorylation, including that of y-10 phosphorylation. localizes to the endoplasmic reticulum in q
106	no effect on tyr-phosphorylation. loss of endoplasmic reticulum localization in quiescent cells.
128	no change in sumoylation.
192	no change in sumoylation.
232	decreased sumoylation levels.
265	abolishes sumoylation. no change in nuclear location nor on protein stability. increased ap1 transactivation activity wh
325	no change in sumoylation levels.
331	no change in sumoylation levels.
337	no effect on tyr-phosphorylation. loss of endoplasmic reticulum localization in quiescent cells.
362	loss of protein stability. reduced mos/mapk-mediated transforming ability; when associated with a-374.
362	increased protein stability. increased mos/mapk-mediated transforming ability and no change in sumoylation levels; when
374	no change in sumoylation levels. loss of protein stability. reduced mos/mapk-mediated transforming ability; when associa
374	increased protein stability. increased mos/mapk-mediated transforming ability and no change in sumoylation levels; when

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2871796	FCERI mediated MAPK activation
R-HSA-450341	Activation of the AP-1 family of transcription factors
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-9031628	NGF-stimulated transcription
R-HSA-9634638	Estrogen-dependent nuclear events downstream of ESR-membrane signaling
R-HSA-9768919	NPAS4 regulates expression of target genes
R-HSA-9909649	Regulation of PD-L1(CD274) transcription
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)

MSigDB gene sets: 966 (showing top): PID_BCR_5PATHWAY, GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, ATF_B, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_MEMORY, TGGTGCT_MIR29A_MIR29B_MIR29C, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, LEE_NEURAL_CREST_STEM_CELL_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION

GO Biological Process (52): conditioned taste aversion (GO:0001661), neural retina development (GO:0003407), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), inflammatory response (GO:0006954), transforming growth factor beta receptor signaling pathway (GO:0007179), female pregnancy (GO:0007565), response to xenobiotic stimulus (GO:0009410), response to light stimulus (GO:0009416), response to gravity (GO:0009629), response to toxic substance (GO:0009636), response to activity (GO:0014823), skeletal muscle cell proliferation (GO:0014856), cerebral cortex development (GO:0021987), neuron differentiation (GO:0030182), osteoclast differentiation (GO:0030316), response to lipopolysaccharide (GO:0032496), response to progesterone (GO:0032570), response to insulin (GO:0032868), cellular response to zinc ion starvation (GO:0034224), cellular response to reactive oxygen species (GO:0034614), response to immobilization stress (GO:0035902), skeletal muscle cell differentiation (GO:0035914), response to muscle stretch (GO:0035994), response to ethanol (GO:0045471), positive regulation of osteoclast differentiation (GO:0045672), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), response to corticosterone (GO:0051412), myoblast proliferation (GO:0051450), response to cAMP (GO:0051591), SMAD protein signal transduction (GO:0060395), cellular response to calcium ion (GO:0071277), cellular response to tumor necrosis factor (GO:0071356), cellular response to epidermal growth factor stimulus (GO:0071364), cellular response to parathyroid hormone stimulus (GO:0071374), cellular response to hypoxia (GO:0071456), medium-term memory (GO:0072375), integrated stress response signaling (GO:0140467), positive regulation of miRNA transcription (GO:1902895)

GO Molecular Function (18): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), RNA polymerase II core promoter sequence-specific DNA binding (GO:0000979), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coregulator binding (GO:0001221), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), R-SMAD binding (GO:0070412), sequence-specific double-stranded DNA binding (GO:1990837), promoter-specific chromatin binding (GO:1990841), DNA binding (GO:0003677), chromatin binding (GO:0003682), double-stranded DNA binding (GO:0003690), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (11): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), nuclear matrix (GO:0016363), protein-DNA complex (GO:0032993), transcription factor AP-1 complex (GO:0035976), RNA polymerase II transcription regulator complex (GO:0090575), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Cellular Senescence	2
Fc epsilon receptor (FCERI) signaling	1
MAPK targets/ Nuclear events mediated by MAP kinases	1
Signaling by Interleukins	1
Transcriptional Regulation by TP53	1
ESR-mediated signaling	1
Nuclear Events (kinase and transcription factor activation)	1
Extra-nuclear estrogen signaling	1
Transcriptional Regulation by NPAS4	1
Regulation of PD-L1(CD274) expression	1
Differentiation of T cells	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
binding	3
anatomical structure development	2
regulation of DNA-templated transcription	2
response to chemical	2
DNA binding	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
cytoplasm	2
protein-containing complex	2
feeding behavior	1
associative learning	1
retina development in camera-type eye	1
transcription by RNA polymerase II	1
DNA-templated transcription	1
defense response	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
multi-organism reproductive process	1
multi-multicellular organism process	1
response to radiation	1
response to abiotic stimulus	1
response to stimulus	1
striated muscle cell proliferation	1
pallium development	1
cell differentiation	1
generation of neurons	1
myeloid leukocyte differentiation	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
response to steroid hormone	1
response to ketone	1
response to peptide hormone	1
cellular response to starvation	1
response to zinc ion starvation	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1

Protein interactions and networks

STRING

8025 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOS	JUN	P05412	999
FOS	JUND	P17535	998
FOS	CREB1	P16220	996
FOS	JUNB	P17275	995
FOS	MAF	O75444	995
FOS	ESR1	P03372	994
FOS	STAT3	P40763	985
FOS	FOSB	P53539	984
FOS	FOSL2	P15408	984
FOS	FOSL1	P15407	984
FOS	ATF3	P18847	984
FOS	SPI1	P17947	965
FOS	NR3C1	P04150	958
FOS	SMAD3	P84022	955
FOS	MAFB	Q9Y5Q3	955

IntAct

387 interactions, top by confidence:

A	B	Type	Score
JUN	FOS	psi-mi:“MI:2364”(proximity)	0.980
JUN	FOS	psi-mi:“MI:0407”(direct interaction)	0.980
FOS	JUN	psi-mi:“MI:0914”(association)	0.980
FOS	JUN	psi-mi:“MI:0407”(direct interaction)	0.980
FOS	JUN	psi-mi:“MI:2364”(proximity)	0.980
JUN	FOS	psi-mi:“MI:0915”(physical association)	0.980
JUNB	FOS	psi-mi:“MI:0407”(direct interaction)	0.950
ATF2	FOS	psi-mi:“MI:0407”(direct interaction)	0.940
FOS	ATF2	psi-mi:“MI:0915”(physical association)	0.940
JUND	FOS	psi-mi:“MI:0407”(direct interaction)	0.930
DDIT3	FOS	psi-mi:“MI:0407”(direct interaction)	0.880
DDIT3	FOS	psi-mi:“MI:2364”(proximity)	0.880
DDIT3	FOS	psi-mi:“MI:0915”(physical association)	0.880
RARA	NCOR1	psi-mi:“MI:0914”(association)	0.800
ATF4	FOS	psi-mi:“MI:0407”(direct interaction)	0.710
ATF7	FOS	psi-mi:“MI:0407”(direct interaction)	0.690
STAT1	FOS	psi-mi:“MI:0915”(physical association)	0.650
FOS	STAT1	psi-mi:“MI:0915”(physical association)	0.650

BioGRID (441): FOS (Affinity Capture-Western), JUN (Reconstituted Complex), FOS (Reconstituted Complex), NQO1 (Affinity Capture-Western), NQO1 (Co-fractionation), JUN (Affinity Capture-Western), JUN (Co-fractionation), JUN (Co-localization), NQO1 (Co-localization), FOS (Two-hybrid), FOS (Two-hybrid), GNG11 (Two-hybrid), JUNB (Two-hybrid), PRKAA2 (Two-hybrid), PSMC5 (Two-hybrid)

ESM2 similar proteins: A1L224, A2VD01, D3ZLB7, F6VAN0, G3V909, O02761, O35451, O43889, O77628, O88479, O94983, O97930, P01100, P01101, P01102, P0C0N8, P0C0N9, P11939, P12841, P18850, P20389, P38532, Q00613, Q08CW8, Q08DJ8, Q1LYG4, Q3SYZ3, Q502F0, Q56TN0, Q56TT7, Q5FVM5, Q5RCM9, Q5UEM7, Q5UEM8, Q61817, Q64210, Q66HA2, Q68CJ9, Q6QDP7, Q6ZPJ0

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

54 interactions.

A	Effect	B	Mechanism
MAPK3	“up-regulates activity”	FOS	phosphorylation
CREB1	“up-regulates quantity by expression”	FOS	“transcriptional regulation”
(-)-anisomycin	up-regulates	FOS	“chemical activation”
RPS6KA4	“up-regulates activity”	FOS	phosphorylation
MAPK1	“up-regulates activity”	FOS	phosphorylation
ERK1/2	“up-regulates activity”	FOS	phosphorylation
ERK1/2	up-regulates	FOS	phosphorylation
RPS6K	“up-regulates activity”	FOS	phosphorylation
ARNT	“down-regulates quantity by repression”	FOS	“transcriptional regulation”
FOS	“up-regulates quantity by expression”	HSD3B2	“transcriptional regulation”
FOS	“up-regulates quantity by expression”	STAR	“transcriptional regulation”
FOS	“up-regulates quantity by expression”	CYP19A1	“transcriptional regulation”
“arachidonic acid”	up-regulates	FOS
TWIST2	“up-regulates quantity by expression”	FOS	“transcriptional regulation”
TWIST1	“up-regulates quantity by expression”	FOS	“transcriptional regulation”
miR-155	“up-regulates quantity by expression”	FOS	“post transcriptional regulation”
FOS	“form complex”	AP1	binding
ETS1	“up-regulates quantity”	FOS	“transcriptional regulation”
UBE2I	“down-regulates activity”	FOS	sumoylation
“SAE1/SAE2 complex”	“down-regulates activity”	FOS	sumoylation
YY2	“up-regulates quantity by expression”	FOS	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 70 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
Signaling by ALK fusions and activated point mutants	5	15.0×	2e-03
Estrogen-dependent gene expression	7	10.6×	9e-04
Activation of anterior HOX genes in hindbrain development during early embryogenesis	5	9.1×	6e-03
Chromatin organization	5	8.2×	6e-03
PIP3 activates AKT signaling	6	8.0×	4e-03
Chromatin modifying enzymes	5	7.2×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
integrated stress response signaling	6	68.0×	1e-07
liver development	5	17.9×	9e-04
response to endoplasmic reticulum stress	5	13.5×	2e-03
regulation of cell cycle	6	7.2×	7e-03
transcription by RNA polymerase II	6	6.8×	8e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	29
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4526463	NM_005252.4(FOS):c.463C>T (p.Arg155Cys)	Likely pathogenic

SpliceAI

340 predictions. Top by Δscore:

Variant	Effect	Δscore
14:75279120:GCAG:G	donor_gain	1.0000
14:75279121:CAGG:C	donor_loss	1.0000
14:75279122:AGG:A	donor_loss	1.0000
14:75279124:G:GA	donor_loss	1.0000
14:75279124:G:GG	donor_gain	1.0000
14:75279869:T:A	acceptor_gain	1.0000
14:75279872:TCTA:T	acceptor_loss	1.0000
14:75279873:CTAG:C	acceptor_loss	1.0000
14:75279875:A:AC	acceptor_loss	1.0000
14:75279875:A:AG	acceptor_gain	1.0000
14:75279875:AG:A	acceptor_gain	1.0000
14:75279876:G:GA	acceptor_loss	1.0000
14:75279876:G:GG	acceptor_gain	1.0000
14:75279876:GG:G	acceptor_gain	1.0000
14:75279876:GGA:G	acceptor_gain	1.0000
14:75279876:GGAC:G	acceptor_gain	1.0000
14:75279876:GGACT:G	acceptor_gain	1.0000
14:75280110:G:GT	donor_gain	1.0000
14:75280126:CAGGT:C	donor_loss	1.0000
14:75280129:G:C	donor_loss	1.0000
14:75280546:T:TA	acceptor_gain	1.0000
14:75280548:T:TA	acceptor_gain	1.0000
14:75280553:A:AG	acceptor_gain	1.0000
14:75280554:T:G	acceptor_gain	1.0000
14:75280556:CTA:C	acceptor_loss	1.0000
14:75280558:A:AG	acceptor_gain	1.0000
14:75280559:G:GC	acceptor_gain	1.0000
14:75280559:GT:G	acceptor_gain	1.0000
14:75280559:GTT:G	acceptor_gain	1.0000
14:75280559:GTTA:G	acceptor_gain	1.0000

AlphaMissense

2468 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:75280597:G:C	R144T	1.000
14:75280597:G:T	R144M	1.000
14:75280598:G:C	R144S	1.000
14:75280598:G:T	R144S	1.000
14:75280603:G:C	R146T	1.000
14:75280603:G:T	R146M	1.000
14:75280604:G:C	R146S	1.000
14:75280604:G:T	R146S	1.000
14:75280605:A:C	N147H	1.000
14:75280605:A:G	N147D	1.000
14:75280606:A:C	N147T	1.000
14:75280606:A:T	N147I	1.000
14:75280607:T:A	N147K	1.000
14:75280607:T:G	N147K	1.000
14:75280608:A:G	K148E	1.000
14:75280609:A:T	K148M	1.000
14:75280610:G:C	K148N	1.000
14:75280610:G:T	K148N	1.000
14:75280614:G:A	A150T	1.000
14:75280614:G:C	A150P	1.000
14:75280615:C:A	A150D	1.000
14:75280617:G:A	A151T	1.000
14:75280617:G:C	A151P	1.000
14:75280618:C:A	A151E	1.000
14:75280620:G:C	A152P	1.000
14:75280621:C:A	A152D	1.000
14:75280623:A:G	K153E	1.000
14:75280625:A:C	K153N	1.000
14:75280625:A:T	K153N	1.000
14:75280626:T:A	C154S	1.000

dbSNP variants (sampled 300 via entrez): RS1000193997 (14:75279947 C>G,T), RS1000461777 (14:75277316 T>C), RS1000564429 (14:75278471 C>A,G,T), RS1000605600 (14:75278435 T>TC,TCC), RS1000629494 (14:75279651 A>G), RS1001231333 (14:75281609 T>C), RS1001600506 (14:75281906 G>A), RS1004410793 (14:75279281 C>A), RS1004587215 (14:75282199 A>C), RS1004822487 (14:75277878 C>G,T), RS1005141842 (14:75282440 TGGGGAC>T), RS1005760217 (14:75277611 C>T), RS1006059978 (14:75277939 T>A), RS1006877693 (14:75277835 G>A), RS1006930040 (14:75277534 G>T)

Disease associations

OMIM: gene MIM:164810 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Berardinelli-Seip congenital lipodystrophy	Supportive	Autosomal recessive

Mondo (2): osteopetrosis (MONDO:0017198), Berardinelli-Seip congenital lipodystrophy (MONDO:0018883)

Orphanet (1): Osteopetrosis and related disorders (Orphanet:2781)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0011002	Osteopetrosis

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001588_6	Periodontal microbiota	9.000000e-07
GCST001725_26	Inflammatory bowel disease	3.000000e-08
GCST004132_40	Crohn’s disease	1.000000e-07
GCST005537_119	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	2.000000e-09

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010022	Osteopetrosis	C05.116.099.708.702.678

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111421 (PROTEIN COMPLEX), CHEMBL5029 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 93,882 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL140	CURCUMIN	3	93,882

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items; also 2 diagnostic.

Variant	Therapy	Indication	Effect	Level	CIViC
FOS Overexpression	Irbesartan	Colon Adenocarcinoma	Sensitivity/Response	CIViC C	EID1634

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

ChEMBL bioactivities

53 potent at pChembl≥5 of 59 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.16	IC50	6.9	nM	CURCUMIN
8.10	IC50	7.9	nM	NORDIHYDROGUAIARETIC ACID
7.70	IC50	20	nM	CHEMBL43549
7.00	IC50	100	nM	CHEMBL43610
7.00	IC50	100	nM	CHEMBL42952
6.70	IC50	200	nM	CHEMBL44525
6.70	IC50	200	nM	CHEMBL295192
6.70	IC50	200	nM	CHEMBL295508
6.70	IC50	200	nM	CHEMBL42650
6.70	IC50	200	nM	CHEMBL43534
6.68	IC50	210	nM	DIHYDROGUAIARETIC ACID
6.52	IC50	300	nM	CHEMBL296695
6.52	IC50	300	nM	CHEMBL45261
6.52	IC50	300	nM	CHEMBL296202
6.52	IC50	300	nM	CHEMBL43259
6.52	IC50	300	nM	CHEMBL42204
6.40	IC50	400	nM	CHEMBL295050
6.16	IC50	700	nM	CHEMBL43251
6.16	IC50	700	nM	CHEMBL43451
6.16	IC50	700	nM	CHEMBL42079
6.05	IC50	900	nM	CHEMBL297842
6.00	IC50	1000	nM	CHEMBL413028
6.00	IC50	1000	nM	CHEMBL42235
6.00	IC50	1000	nM	CHEMBL42719
6.00	IC50	1000	nM	CHEMBL42547
6.00	IC50	1000	nM	CHEMBL46509
5.70	IC50	2000	nM	CHEMBL43388
5.70	IC50	2000	nM	CHEMBL44089
5.70	IC50	2000	nM	CHEMBL416627
5.52	IC50	3000	nM	CHEMBL43550
5.40	IC50	4000	nM	CHEMBL3341959
5.40	IC50	4000	nM	CHEMBL3341960
5.40	IC50	4000	nM	CHEMBL297420
5.40	IC50	4000	nM	CHEMBL43199
5.30	IC50	5000	nM	CHEMBL200061
5.30	IC50	5000	nM	CHEMBL290202
5.30	IC50	5000	nM	CHEMBL42503
5.27	IC50	5400	nM	CHEMBL492977
5.24	IC50	5800	nM	CHEMBL199325
5.22	IC50	6000	nM	CHEMBL298245
5.22	IC50	6000	nM	CHEMBL42815
5.16	IC50	7000	nM	CHEMBL298418
5.16	IC50	7000	nM	CHEMBL296896
5.10	IC50	8000	nM	CHEMBL3222140
5.10	IC50	8000	nM	CHEMBL186600
5.10	IC50	8000	nM	CHEMBL43158
5.05	IC50	8980	nM	CHEMBL3341958
5.00	IC50	1e+04	nM	CHEMBL47053
5.00	IC50	1e+04	nM	CHEMBL42687
5.00	IC50	1e+04	nM	CHEMBL43606

PubChem BioAssay actives

51 with measured affinity, of 120 total; 50 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
4-[4-(3,4-dihydroxyphenyl)-2,3-dimethylbutyl]benzene-1,2-diol	1178344: Inhibition of Fos-Jun dimer formation (unknown origin)	ic50	0.0079	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-thiophen-2-ylpyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.0200	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-phenylpyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.1000	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-thiophen-3-ylpyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.1000	uM
3-methyl-1-[[5-(4-methyl-1,3-oxazol-2-yl)-2-thiophen-2-ylpyrimidin-4-yl]amino]pyrrole-2,5-dione	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.2000	uM
3-methyl-1-[[5-(2-methyltetrazol-5-yl)-2-thiophen-2-ylpyrimidin-4-yl]amino]pyrrole-2,5-dione	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.2000	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-(5-methylthiophen-2-yl)pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.2000	uM
1-[[5-(4,5-dihydro-1,3-oxazol-2-yl)-2-thiophen-2-ylpyrimidin-4-yl]amino]-3-methylpyrrole-2,5-dione	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.2000	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-methylsulfanylpyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.2000	uM
4-[4-(4-hydroxy-3-methoxyphenyl)-2,3-dimethylbutyl]-2-methoxyphenol	1178344: Inhibition of Fos-Jun dimer formation (unknown origin)	ic50	0.2100	uM
ethyl 2-(5-chlorothiophen-2-yl)-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.3000	uM
ethyl 2-(3,5-dichlorophenyl)-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.3000	uM
3-methyl-1-[[5-(3-methyl-1,2-oxazol-5-yl)-2-thiophen-2-ylpyrimidin-4-yl]amino]pyrrole-2,5-dione	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.3000	uM
3-methyl-1-[[5-(5-methyl-1,3,4-oxadiazol-2-yl)-2-thiophen-2-ylpyrimidin-4-yl]amino]pyrrole-2,5-dione	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.3000	uM
ethyl 2-(4-chlorophenyl)-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.3000	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-[4-(trifluoromethyl)phenyl]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.4000	uM
ethyl 2-(4-fluorophenyl)-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.7000	uM
ethyl 2-(furan-2-carbonyl)-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.7000	uM
ethyl 2-(3-bromophenyl)-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.7000	uM
ethyl 2-(4-methoxyphenyl)-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	0.9000	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-(trifluoromethyl)pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	1.0000	uM
ethyl 2-cyclopropyl-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	1.0000	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-phenylsulfanylpyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	1.0000	uM
ethyl 4-[methyl-(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-thiophen-2-ylpyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	1.0000	uM
ethyl 2-tert-butyl-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	1.0000	uM
ethyl 2-(cyclohexen-1-ylmethyl)-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	2.0000	uM
ethyl 2-(2,6-dichloro-4-pyridinyl)-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	2.0000	uM
ethyl 4-[methyl-(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-phenylpyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	2.0000	uM
ethyl 2-(4-fluorophenyl)-4-[methyl-(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	3.0000	uM
2-[[(1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-(2-carboxybenzoyl)oxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picen-4a-yl]methoxycarbonyl]benzoic acid	1178345: Inhibition of Fos-Jun dimer formation (unknown origin) by EMSA method	ic50	4.0000	uM
disodium;2-[[(1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-(2-carboxylatobenzoyl)oxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picen-4a-yl]methoxycarbonyl]benzoate	1178345: Inhibition of Fos-Jun dimer formation (unknown origin) by EMSA method	ic50	4.0000	uM
ethyl 2-(1-benzothiophen-2-yl)-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	4.0000	uM
ethyl 4-[acetyl-(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-phenylpyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	4.0000	uM
3-[2-(2-methylpropoxy)-5-[4-(2-methylpropoxy)benzoyl]phenyl]propanoic acid	259211: Inhibition of the expression of AP1-luciferase by TPA-stimulated NIH3T3 cells	ic50	5.0000	uM
ethyl 2-(3-methoxyphenyl)-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	5.0000	uM
4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-thiophen-2-ylpyrimidine-5-carbonitrile	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	5.0000	uM
(1E,4Z,6E)-5-hydroxy-1,7-bis(3-methoxyphenyl)hepta-1,4,6-trien-3-one	1178345: Inhibition of Fos-Jun dimer formation (unknown origin) by EMSA method	ic50	5.4000	uM
3-[2-(2-methylpropoxy)-5-[3-(2-methylpropoxy)benzoyl]phenyl]propanoic acid	259211: Inhibition of the expression of AP1-luciferase by TPA-stimulated NIH3T3 cells	ic50	5.8000	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-pyridin-4-ylpyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	6.0000	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-quinolin-3-ylpyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	6.0000	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-(3-nitrophenyl)pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	7.0000	uM
ethyl 2-benzyl-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	7.0000	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-(2-methyl-1,3-thiazol-4-yl)pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	8.0000	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[(2-aminoacetyl)amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-(carboxymethylamino)-4-oxobutanoic acid	241259: Inhibitory activity against transcription activator protein-1 (AP-1)	ic50	8.0000	uM
(1E,4Z,6E)-5-hydroxy-1,7-bis(4-methylphenyl)hepta-1,4,6-trien-3-one	1178345: Inhibition of Fos-Jun dimer formation (unknown origin) by EMSA method	ic50	8.9800	uM
ethyl 2-(3,5-dimethylpyrazol-1-yl)-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	10.0000	uM
ethyl 4-[(2,5-dioxopyrrol-1-yl)amino]-2-(trifluoromethyl)pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	10.0000	uM
ethyl 4-[(3,4-dimethyl-2,5-dioxopyrrol-1-yl)amino]-2-(trifluoromethyl)pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	10.0000	uM
ethyl 2-ethyl-4-[methyl-(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	10.0000	uM
ethyl 2-ethyl-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	95092: Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, increases reaction, affects reaction, decreases reaction, affects expression (+3 more)	31
Tetradecanoylphorbol Acetate	affects cotreatment, affects binding, increases reaction, affects localization, decreases reaction (+2 more)	25
sodium arsenite	increases stability, increases expression, increases reaction, affects binding, decreases expression (+7 more)	18
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases phosphorylation, increases expression, decreases phosphorylation, affects cotreatment, affects localization (+1 more)	18
Cadmium Chloride	decreases reaction, increases expression, increases phosphorylation, decreases expression, increases abundance (+1 more)	16
Resveratrol	decreases reaction, increases expression, affects localization, increases activity, decreases activity (+3 more)	15
Arsenic Trioxide	decreases reaction, increases expression, affects expression, affects binding, increases reaction (+3 more)	14
Cadmium	affects cotreatment, decreases expression, decreases reaction, increases phosphorylation, increases abundance (+3 more)	14
U 0126	affects cotreatment, decreases reaction, increases abundance, increases expression, increases phosphorylation (+2 more)	11
bisphenol A	affects reaction, decreases expression, increases reaction, decreases reaction, increases expression (+1 more)	9
Fulvestrant	decreases reaction, increases expression, decreases expression	9
Quercetin	decreases reaction, increases expression, affects cotreatment, decreases expression, increases reaction (+2 more)	9
Tetrachlorodibenzodioxin	increases reaction, decreases reaction, increases phosphorylation, increases expression, affects cotreatment (+4 more)	9
Particulate Matter	increases phosphorylation, affects reaction, affects cotreatment, decreases expression, increases abundance (+2 more)	9
SB 203580	decreases reaction, increases expression, increases phosphorylation, increases reaction	7
Benzo(a)pyrene	affects activity, increases expression	7
Copper	increases expression, increases activity, increases reaction, decreases expression, affects binding	7
Lipopolysaccharides	decreases expression, affects activity, affects localization, increases phosphorylation, affects response to substance (+5 more)	7
Tobacco Smoke Pollution	affects expression, increases expression	7
(+)-JQ1 compound	decreases expression, increases expression	6
Acetylcysteine	increases expression, increases activity, decreases activity, decreases reaction	6
Hydrogen Peroxide	decreases reaction, increases activity, increases expression, decreases expression	6
Valproic Acid	decreases methylation, increases expression, decreases expression	6
Air Pollutants	decreases expression, increases expression, affects cotreatment, affects expression, increases abundance	5
Cisplatin	affects response to substance, affects cotreatment, increases expression, increases reaction	5
Doxorubicin	affects expression, affects reaction, decreases expression, decreases reaction, increases expression	5
Nicotine	increases expression, increases phosphorylation, decreases reaction, affects cotreatment, decreases activity	5
Plant Extracts	increases activity, decreases expression, decreases reaction, increases expression	5
Silicon Dioxide	decreases expression, increases expression, increases methylation	5
Arachidonic Acid	decreases reaction, increases expression, decreases phosphorylation, affects reaction, affects cotreatment (+1 more)	5

ChEMBL screening assays

11 unique, capped per target: 10 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3223401	Binding	Inhibition of c-FOS/AP1 (unknown origin)	Small-molecule inhibitors of dimeric transcription factors: Antagonism of proteinprotein and proteinDNA interactions — Medchemcomm
CHEMBL705832	Functional	Inhibition of AP-1 (activator protein-1) mediated transcriptional activation in Jurkat T-cells	Novel inhibitors of AP-1 and NF-kappaB mediated gene expression: structure-activity relationship studies of ethyl 4-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-2-(trifluoromethyl)++ +pyrimidi ne-5-carboxylate. — Bioorg Med Chem Lett

Cellosaurus cell lines

40 cell lines: 27 transformed cell line, 8 cancer cell line, 5 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1V0	SEES3-1V human FOS, clone1	Embryonic stem cell	Male
CVCL_A1V1	SEES3-1V human FOS, clone2	Embryonic stem cell	Male
CVCL_A1V2	SEES3-1V human FOS, clone3	Embryonic stem cell	Male
CVCL_AW21	K562 eGFP-FOS	Cancer cell line	Female
CVCL_B6DV	HL3	Transformed cell line	Sex unspecified
CVCL_B6DW	HL7	Transformed cell line	Sex unspecified
CVCL_B6DX	HL8	Transformed cell line	Sex unspecified
CVCL_B6DY	HL9	Transformed cell line	Sex unspecified
CVCL_B6DZ	PL51	Transformed cell line	Sex unspecified
CVCL_B7TU	e-hChon-1	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004402	PHASE3	COMPLETED	Phase III Randomized Study of Interferon Gamma in Children With Severe, Congenital Osteopetrosis
NCT00638820	PHASE2	TERMINATED	Reduced Intensity AlloTransplant For Osteopetrosis
NCT00968864	PHASE2	TERMINATED	T-cell Depleted Alternative Donor Transplantation
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT02666768	PHASE2	COMPLETED	ACTIMMUNE in Intermediate Osteopetrosis
NCT00145886	PHASE1	TERMINATED	rhPTH Therapy for Low Turnover Bone Fragility
NCT00775931	PHASE2/PHASE3	COMPLETED	Allogeneic Transplantation For Severe Osteopetrosis
NCT01019876	PHASE2/PHASE3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT01087398	PHASE2/PHASE3	UNKNOWN	Hematopoietic Stem Cell Transplantation for Malignant Infantile Osteopetrosis
NCT00730314	PHASE1/PHASE2	COMPLETED	Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells
NCT02065869	PHASE1/PHASE2	TERMINATED	Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant
NCT03301168	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant
NCT00043329	Not specified	COMPLETED	Post Marketing Surveillance Study of Actimmune in Patients With Severe, Malignant Osteopetrosis
NCT00145587	Not specified	TERMINATED	Stem Cell Transplantation for Children Affected With Osteopetrosis
NCT01199094	Not specified	COMPLETED	Clinical Assessment of Patients With High Bone Mass Due to Mutation in Lrp5
NCT01200017	Not specified	NO_LONGER_AVAILABLE	Expanded Access Protocol (EAP) Using the CliniMACS® Device for Pediatric Haplocompatible Donor Stem Cell Transplant
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT06521580	Not specified	COMPLETED	Outcomes of Patients With Osteopetrosis Weight-bearing Bone Fractures