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

• GWAS associations: 4
• Clinical variants (ClinVar): 51 total — 1 likely-pathogenic
• GTEx eGene: eQTL in 5 tissues, sQTL in 3 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Constraint (gnomAD): pLI 0.87 (intermediate), LOEUF 0.58 (moderately constrained)
• Transcription factor: yes — 380 downstream targets (CollecTRI)
• MANE Select transcript: NM_005252
• Interaction hub: 6,961 STRING partners (top 1% of genes corpus-wide)

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: 16 — 14 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000303562

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 6, TSL 3: 1, TSL 4: 1, TSL 5: 1

ENST00000303562, ENST00000535987, ENST00000554212, ENST00000554617, ENST00000555242, ENST00000555347, ENST00000555672, ENST00000555686, ENST00000556324, ENST00000557139, ENST00000871987, ENST00000944924, ENST00000988368, ENST00001119055, ENST00001119056, ENST00001136861

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.

Highest expression (Bgee): mucosa of stomach, upper leg skin, gall bladder, uterine tube, monocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FOS is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 5 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

8 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	sqtl	1.6e-04	+0.66	14:75280555:T:C
Pituitary	eqtl	4.8e-03	+0.26	14:76059770:A:G
Cells EBV-transformed lymphocytes	eqtl	1.0e-02	+0.38	14:75297911:A:C
Brain Putamen basal ganglia	eqtl	1.4e-02	-0.26	14:75632310:C:T
Testis	eqtl	1.5e-02	+0.70	14:75490856:A:G
Pancreas	eqtl	1.5e-02	+0.22	14:74555835:A:G
Stomach	sqtl	2.1e-02	-1.89	14:74375798:C:T
Esophagus Muscularis	sqtl	2.9e-02	-0.88	14:75342363:C:T

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

showing 100 of 305 tissues 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
skin of leg	UBERON:0001511	98.65	gold quality
thoracic aorta	UBERON:0001515	98.64	gold quality
descending thoracic aorta	UBERON:0002345	98.64	gold quality
cardiac atrium	UBERON:0002081	98.62	gold quality
ascending aorta	UBERON:0001496	98.58	gold quality
adenohypophysis	UBERON:0002196	98.57	gold quality
aorta	UBERON:0000947	98.53	gold quality
upper lobe of left lung	UBERON:0008952	98.52	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.50	gold quality
tibial artery	UBERON:0007610	98.48	gold quality
popliteal artery	UBERON:0002250	98.47	gold quality
caecum	UBERON:0001153	98.42	gold quality
left coronary artery	UBERON:0001626	98.40	gold quality
pituitary gland	UBERON:0000007	98.36	gold quality
lymph node	UBERON:0000029	98.31	gold quality
pericardium	UBERON:0002407	98.31	gold quality
cauda epididymis	UBERON:0004360	98.31	gold quality
pylorus	UBERON:0001166	98.30	gold quality
coronary artery	UBERON:0001621	98.30	gold quality
synovial joint	UBERON:0002217	98.28	gold quality
periodontal ligament	UBERON:0008266	98.26	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.22	gold quality
body of stomach	UBERON:0001161	98.16	gold quality
olfactory bulb	UBERON:0002264	98.11	gold quality
renal medulla	UBERON:0000362	98.09	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.08	gold quality
spinal cord	UBERON:0002240	98.03	gold quality
upper lobe of lung	UBERON:0008948	98.03	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.00	gold quality
transverse colon	UBERON:0001157	97.98	gold quality
stomach	UBERON:0000945	97.77	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.69	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.69	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.65	gold quality
right adrenal gland cortex	UBERON:0035827	97.37	gold quality
fundus of stomach	UBERON:0001160	97.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.24	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.24	gold quality
ectocervix	UBERON:0012249	97.05	gold quality
trigeminal ganglion	UBERON:0001675	96.97	gold quality
minor salivary gland	UBERON:0001830	96.92	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.92	gold quality
blood vessel layer	UBERON:0004797	96.91	gold quality
lower esophagus	UBERON:0013473	96.91	gold quality
adrenal cortex	UBERON:0001235	96.90	gold quality
dorsal root ganglion	UBERON:0000044	96.85	gold quality
lung	UBERON:0002048	96.83	gold quality
right lobe of liver	UBERON:0001114	96.82	gold quality
small intestine	UBERON:0002108	96.78	gold quality
mucosa of transverse colon	UBERON:0004991	96.77	gold quality
mammary duct	UBERON:0001765	96.76	gold quality
sural nerve	UBERON:0015488	96.75	gold quality
left adrenal gland cortex	UBERON:0035825	96.71	gold quality
spleen	UBERON:0002106	96.66	gold quality
saliva-secreting gland	UBERON:0001044	96.65	gold quality
thyroid gland	UBERON:0002046	96.63	gold quality
zone of skin	UBERON:0000014	96.61	gold quality
adrenal gland	UBERON:0002369	96.49	gold quality
body of pancreas	UBERON:0001150	96.48	gold quality
esophagus	UBERON:0001043	96.46	gold quality
ovary	UBERON:0000992	96.42	gold quality
right adrenal gland	UBERON:0001233	96.39	gold quality
middle frontal gyrus	UBERON:0002702	96.36	gold quality
pharyngeal mucosa	UBERON:0000355	96.35	gold quality
epithelium of mammary gland	UBERON:0003244	96.35	gold quality
adult organism	UBERON:0007023	96.33	gold quality
left lobe of thyroid gland	UBERON:0001120	96.24	gold quality
left adrenal gland	UBERON:0001234	96.22	gold quality
colonic epithelium	UBERON:0000397	96.21	gold quality
esophagus mucosa	UBERON:0002469	95.94	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	2146.4	medium
Esophagus	tissue	1177.9	medium
Ovary	tissue	1090.9	medium
Gallbladder	tissue	1088.4	high
Fallopian tube	tissue	1083.7	not detected
Adipose tissue	tissue	1038.1	low
Tongue	tissue	947.0
Thyroid gland	tissue	946.2	high
Smooth muscle	tissue	900.6	medium
Urinary bladder	tissue	882.4	high
Prostate	tissue	742.1	low
Adrenal gland	tissue	694.8	high
Cervix	tissue	656.3	high
Rectum	tissue	590.1	medium
Small intestine	tissue	549.8	low
Appendix	tissue	543.8	medium
Salivary gland	tissue	523.7	low
Lung	tissue	459.2	low
Breast	tissue	448.0	not detected
Seminal vesicle	tissue	435.1	not detected
Pituitary gland	tissue	424.2
Lymph node	tissue	420.9	not detected
Thymus	tissue	397.3
Placenta	tissue	391.7	high
Endometrium 1	tissue	384.4	low
Stomach 1	tissue	337.2	medium
Spinal cord	tissue	324.5
Vagina	tissue	314.6	high
Colon	tissue	276.9	medium
Liver	tissue	270.8	medium
Parathyroid gland	tissue	249.0	high
Kidney	tissue	248.6	medium
Duodenum	tissue	220.9	medium
Retina	tissue	216.5
Heart muscle	tissue	195.1	medium
Choroid plexus	tissue	194.6
Pancreas	tissue	154.0	medium
Spleen	tissue	135.5	low
Cerebellum	tissue	114.4	medium
Locus coeruleus	tissue	108.9
Testis	tissue	81.5	low
Hippocampus	tissue	76.6	low
Superior colliculi	tissue	58.5
Epididymis	tissue	55.2	low
Nucleus accumbens	tissue	52.6
Cerebral cortex	tissue	51.8	low
Occipital cortex	tissue	51.8
Substantia nigra	tissue	48.0
Skin 1	tissue	41.4	medium
Medulla oblongata	tissue	40.9
Hippocampal formation	tissue	40.4
Entorhinal cortex	tissue	40.4
Retrosplenial cortex	tissue	40.3
Pons	tissue	38.5
Retrosplenial and cingulate cortex	tissue	36.9
Somatosensory cortex	tissue	36.8
Postcentral gyrus	tissue	33.8
Insular cortex	tissue	33.0
Prefrontal cortex	tissue	32.0
Hypothalamus	tissue	32.0

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (725.5), Supraoptic nucleus (366.9), Flocculonodular lobe (332.8), Dorsal spinal cord (324.5), Area postrema (263.5).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

showing 30 of 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)

Targeting FOS by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 102 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.868, LOEUF 0.581, missense Z 1.44 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000303562 — one region, missense o/e 0.84.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:95574) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 113 distinct phenotype terms.

Mouse phenotype (MP)	Records
failure of tooth eruption	3
decreased body size	3
absent teeth	3
abnormal bone marrow cavity morphology	2
osteopetrosis	2
short snout	2
abnormal spatial learning	2
premature death	2
decreased osteoclast cell number	2
increased bone trabecula number	2
abnormal long bone epiphysis morphology	1
abnormal long bone metaphysis morphology	1
abnormal compact bone thickness	1
abnormal long bone hypertrophic chondrocyte zone	1
increased granulocyte number	1
decreased cell proliferation	1
absent hair follicles	1
alopecia	1
domed cranium	1
short limbs	1
kinked tail	1
abnormal spleen morphology	1
decreased thymocyte number	1
impaired ovarian folliculogenesis	1
abnormal spermatogenesis	1

+88 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	P11939	100.0%	Diamond
Ovis aries	O02761	99.0%	Diamond
Mesocricetus auratus	O88479	97.6%	Diamond
Cricetiscus campbelli	Q56TT7	97.6%	Diamond
Phodopus roborovskii	Q56TN0	97.4%	Diamond
Bos taurus	O77628	97.1%	Diamond
Felis catus	Q8HZP6	97.1%	Diamond
Cricetulus griseus	Q9Z2Q8	96.9%	Diamond
Sus scrofa	O97930	96.8%	Diamond
Drosophila persimilis	B4G652	93.1%	Diamond
Canis lupus familiaris	Q9TUB3	90.8%	Diamond
Drosophila yakuba	B4PPK2	88.0%	Diamond
Takifugu rubripes	P53450	87.2%	Diamond
Dichotomyctere fluviatilis	Q91496	87.2%	Diamond
Drosophila simulans	B4R090	85.7%	Diamond
Drosophila sechellia	B4HZE8	84.5%	Diamond
Drosophila erecta	B3P5D2	83.3%	Diamond
Xenopus laevis	A1L2X1	80.0%	Diamond
Xenopus tropicalis	F7EMX9	80.0%	Diamond
Drosophila mojavensis	B4K617	74.2%	Diamond
Drosophila virilis	B4M5T7	74.2%	Diamond
Drosophila grimshawi	B4JYN3	66.7%	Diamond
Drosophila ananassae	B3MTI9	63.5%	Diamond
Cyprinus carpio	P79702	55.9%	Diamond
Avian retrovirus NK24	P23050	100.0%	Diamond
FBJ murine osteosarcoma virus	P01102	98.5%	Diamond
Finkel-Biskis-Jinkins murine sarcoma virus	P29176	89.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TMED10	protein-coding	10972
NEK9	protein-coding	91754
LINC01220	ncRNA	731223
JDP2-AS1	ncRNA	101928377
JDP2	protein-coding	122953

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 by resolution:

PDB	Title	Method	Resolution (Å)
1A02	STRUCTURE OF THE DNA BINDING DOMAINS OF NFAT, FOS AND JUN BOUND TO DNA	X-RAY DIFFRACTION	2.7
1FOS	TWO HUMAN C-FOS:C-JUN:DNA COMPLEXES	X-RAY DIFFRACTION	3.05
1S9K	Crystal Structure of Human NFAT1 and Fos-Jun on the IL-2 ARRE1 Site	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Transcription factors, Basic domains, Cancer-related genes, Candidate cancer biomarkers

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

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)

Type	Positions
Phosphothreonine	325, 331, 232
Phosphoserine	362, 374
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	113, 128, 265
Phosphotyrosine	10, 30

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 quiescent cells …
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 quiescent cells …
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 when heterodimerized …
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 associated with …
374	no change in sumoylation levels. loss of protein stability. reduced mos/mapk-mediated transforming ability; when associated with a-362.
374	increased protein stability. increased mos/mapk-mediated transforming ability and no change in sumoylation levels; when associated with …

Function

Pathways and Gene Ontology

Reactome pathways

9 curated (TAS) of 52; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

52 pathways:

ID	Pathway	Evidence
R-HSA-450341	Activation of the AP-1 family of transcription factors	curated
R-HSA-9018519	Estrogen-dependent gene expression	curated
R-HSA-9634638	Estrogen-dependent nuclear events downstream of ESR-membrane signaling	curated
R-HSA-2871796	FCERI mediated MAPK activation	curated
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling	curated
R-HSA-2559580	Oxidative Stress Induced Senescence	curated
R-HSA-9909649	Regulation of PD-L1(CD274) transcription	curated
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)	curated
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes	curated
R-HSA-2559583	Cellular Senescence	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	electronic
R-HSA-8939211	ESR-mediated signaling	—
R-HSA-9009391	Extra-nuclear estrogen signaling	—
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-448424	Interleukin-17 signaling	—
R-HSA-450294	MAP kinase activation	—
R-HSA-450282	MAPK targets/ Nuclear events mediated by MAP kinases	—
R-HSA-975871	MyD88 cascade initiated on plasma membrane	—
R-HSA-975155	MyD88 dependent cascade initiated on endosome	—
R-HSA-166166	MyD88-independent TLR4 cascade	—
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane	—
R-HSA-9031628	NGF-stimulated transcription	electronic
R-HSA-9768919	NPAS4 regulates expression of target genes	electronic
R-HSA-198725	Nuclear Events (kinase and transcription factor activation)	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-162582	Signal Transduction	—
R-HSA-449147	Signaling by Interleukins	—
R-HSA-187037	Signaling by NTRK1 (TRKA)	—
R-HSA-166520	Signaling by NTRKs	—
R-HSA-9006931	Signaling by Nuclear Receptors	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—
R-HSA-975138	TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	—
R-HSA-937061	TRIF (TICAM1)-mediated TLR4 signaling	—
R-HSA-168142	Toll Like Receptor 10 (TLR10) Cascade	—
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade	—
R-HSA-168164	Toll Like Receptor 3 (TLR3) Cascade	—
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade	—
R-HSA-168176	Toll Like Receptor 5 (TLR5) Cascade	—
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade	—
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade	—
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade	—
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade	—
R-HSA-168898	Toll-like Receptor Cascades	—
R-HSA-9634815	Transcriptional Regulation by NPAS4	—
R-HSA-3700989	Transcriptional Regulation by TP53	—

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 (45): 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 mechanical stimulus (GO:0009612), 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), 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), response to ethanol (GO:0045471), 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 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), mononuclear cell differentiation (GO:1903131), response to forskolin (GO:1904321), cellular response to phorbol 13-acetate 12-myristate (GO:1904628), cellular response to prolactin (GO:1990646), regulation of DNA-templated transcription (GO:0006355), cellular response to hormone stimulus (GO:0032870), response to cytokine (GO:0034097), response to steroid hormone (GO:0048545), cellular response to transforming growth factor beta stimulus (GO:0071560)

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 (10): 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), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737)

Reactome top-level categories

17 top-level categories:

Category	Pathways
Toll-like Receptor Cascades	3
Cellular Senescence	2
Toll Like Receptor 4 (TLR4) Cascade	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
Immune System	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Signaling by Receptor Tyrosine Kinases	1

GO top-level categories

showing 60 of 61 GO namespaces:

Category	Terms
cellular anatomical structure	5
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
binding	3
animal gross anatomical part developmental process	2
regulation of DNA-templated transcription	2
response to chemical	2
response to abiotic stimulus	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 external stimulus	1
response to stimulus	1
striated muscle cell proliferation	1
pallium development	1
cell differentiation	1
generation of neurons	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
core promoter sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transcription factor binding	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
protein binding	1
DNA-binding transcription factor binding	1
SMAD binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
chromatin binding	1
nucleic acid binding	1
chromosome	1
endomembrane system	1
RNA polymerase II transcription regulator complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 21 of 73 annotations. The rest are phylogenetic / computational / electronic (IEA).

21 experimentally-supported GO terms:

GO term	NS	Evidence
SMAD protein signal transduction	BP	direct assay
cellular response to reactive oxygen species	BP	direct assay
positive regulation of DNA-templated transcription	BP	direct assay
positive regulation of miRNA transcription	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	direct assay
regulation of transcription by RNA polymerase II	BP	direct assay
transforming growth factor beta receptor signaling pathway	BP	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
protein-DNA complex	CC	mutant phenotype
transcription factor AP-1 complex	CC	direct assay
DNA-binding transcription activator activity, RNA polymerase II-specific	MF	direct assay
DNA-binding transcription factor activity	MF	direct assay
R-SMAD binding	MF	physical interaction
RNA polymerase II cis-regulatory region sequence-specific DNA binding	MF	direct assay
RNA polymerase II core promoter sequence-specific DNA binding	MF	mutant phenotype
RNA polymerase II-specific DNA-binding transcription factor binding	MF	physical interaction
identical protein binding	MF	physical interaction
sequence-specific double-stranded DNA binding	MF	direct assay
transcription cis-regulatory region binding	MF	direct assay
transcription coregulator binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 6,961 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOS	JUN	P05412	981
FOS	EGR1	P18146	920
FOS	JUND	P17535	915
FOS	MYC	P01106	864
FOS	NFATC1	O95644	861
FOS	CREB1	P16220	859
FOS	TNFSF11	O14788	844
FOS	POMC	P01189	815
FOS	ACP5	P13686	806
FOS	SRF	P11831	805
FOS	HCRT	O43612	777
FOS	STAT3	P40763	776
FOS	NR4A1	P22736	776
FOS	CRH	P06850	771
FOS	EGR2	P11161	764

IntAct

Human interaction partners of FOS in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 165 partners by confidence:

Partner	Interaction type	MIscore	Records
JUN	proximity	0.980	39
JUNB	direct interaction	0.950	9
ATF2	direct interaction	0.940	11
JUND	direct interaction	0.930	5
DDIT3	direct interaction	0.880	11
ATF4	direct interaction	0.710	4
ATF7	direct interaction	0.690	2
STAT1	physical association	0.650	6
MAFB	direct interaction	0.620	2
RPUSD4	physical association	0.610	4
ATF3	direct interaction	0.590	2
CEBPG	physical association	0.590	2
PHB1	colocalization	0.590	1
ADAMTSL4	physical association	0.560	3
ARHGDIB	physical association	0.560	3
ASCL4	physical association	0.560	3
BECN1	physical association	0.560	3
C19orf25	physical association	0.560	3
CCDC120	physical association	0.560	3
CCDC26	physical association	0.560	3
COMMD10	physical association	0.560	3
CREB5	physical association	0.560	3
EIF2B4	physical association	0.560	3
ENKD1	physical association	0.560	3
GPBP1L1	physical association	0.560	3
GRB10	physical association	0.560	3
ITGB3BP	physical association	0.560	3
JADE2	physical association	0.560	3
KLF15	physical association	0.560	3
KRTAP19-5	physical association	0.560	3

BioGRID (441 interactions; top human partners by supporting records): JUN (Reconstituted Complex; 52 records), ATF2 (Two-hybrid; 10 records), JUNB (Two-hybrid; 9 records), JUND (Affinity Capture-MS; 9 records), DDIT3 (FRET; 6 records), RFWD2 (Affinity Capture-MS; 6 records), CREB5 (Two-hybrid; 5 records), NCOA1 (Reconstituted Complex; 5 records), RUNX2 (Reconstituted Complex; 5 records), STK40 (Affinity Capture-MS; 5 records), ATF7 (Affinity Capture-MS; 4 records), CREBBP (Two-hybrid; 4 records), DET1 (Affinity Capture-MS; 4 records), KDM2B (Affinity Capture-Western; 4 records), VARS (Affinity Capture-MS; 4 records)

SIGNOR signaling

showing 30 of 54 signaling 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”
Gbeta	up-regulates	FOS	phosphorylation
MAPK3	up-regulates	FOS	phosphorylation
RPS6KA1	“up-regulates activity”	FOS	phosphorylation
FOS	“up-regulates activity”	JUN	binding
CSDE1	“down-regulates quantity”	FOS	“post transcriptional regulation”
MIR9-1HG	“up-regulates quantity by expression”	FOS	“transcriptional regulation”
PRKACA	“up-regulates activity”	FOS	phosphorylation
N	“up-regulates quantity by expression”	FOS	“transcriptional regulation”
GTF2I	“up-regulates quantity by expression”	FOS	“transcriptional regulation”

Protein complexes (CORUM) (9)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

9 complexes by size:

Complex	Subunits	Members
★ MegaTrans complex	10	ESR1, FOS, GATA3, STAT1, XRCC5, XRCC6, FOXA1, PRKDC, RARA, TFAP2C
★ MegaTrans complex	10	FOS, FOXA1, STAT1, XRCC5, XRCC6, ESR1, GATA3, PRKDC, RARG, TFAP2C
SMAD3-SMAD4-cJun-cFos complex	4	FOS, JUN, SMAD3, SMAD4
NFAT-JUN-FOS DNA-protein complex	3	FOS, JUN, NFATC2
ERG-JUN-FOS DNA-protein complex	3	ERG, FOS, JUN
ETS2-FOS-JUN complex	3	ETS2, FOS, JUN
c-Fos-c-Jun-SAF-1 complex	3	FOS, JUN, MAZ
★ FOS-JUN-THRA complex	3	FOS, JUN, THRA
★ AR-FOS complex	2	AR, FOS

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 165 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
Response of EIF2AK1 (HRI) to heme deficiency	5	31.9×	3e-04
RNA Polymerase III Transcription Termination	5	22.2×	1e-03
RNA Polymerase III Abortive And Retractive Initiation	5	12.4×	6e-03
Cellular response to starvation	7	10.3×	1e-03
Signaling by ALK fusions and activated point mutants	7	9.4×	2e-03
Response of EIF2AK4 (GCN2) to amino acid deficiency	8	7.9×	2e-03
rRNA processing	6	7.8×	1e-02
Estrogen-dependent gene expression	9	6.1×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
integrated stress response signaling	8	37.0×	2e-08
negative regulation of type II interferon production	5	12.6×	6e-03
liver development	6	8.8×	7e-03
response to endoplasmic reticulum stress	7	7.7×	5e-03
regulation of cell cycle	10	4.9×	5e-03

Disease & clinical

Genetic variants

Variant evidence for FOS: 51 ClinVar records (1 pathogenic / likely pathogenic); 2 CIViC cancer variants; 4 GWAS associations. Per-variant detail is on Sugi Variant.

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)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4526463	NM_005252.4(FOS):c.463C>T (p.Arg155Cys)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore FOS’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 22 predictions of 157):

Position(s)	Effect	Δscore	Sites
14:75279124	donor_loss	1.0000
14:75279869	acceptor_gain	1.0000
14:75279875–75279876	acceptor_loss	1.0000	5
14:75280129	donor_loss	1.0000	2
14:75280546	acceptor_gain	1.0000
14:75280554	acceptor_gain	1.0000
14:75280558–75280559	acceptor_loss	1.0000	5
14:75280668–75280669	donor_loss	1.0000	4
14:75280768	acceptor_gain	1.0000
14:75280774	acceptor_gain	1.0000

AlphaMissense

906 missense substitutions predicted likely pathogenic (of 2,468 scored), across 218 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
N147	8	1.000	1.000
H200	8	0.998	1.000
F343	8	0.972	0.997
D170	8	0.954	0.995
D163	8	0.940	0.995
F60	8	0.923	0.993
N156	8	0.906	0.995
F341	8	0.884	0.970
D370	8	0.827	0.946
D72	8	0.825	0.937
C154	7	1.000	1.000
R158	7	0.999	1.000
R144	7	0.998	1.000
C204	7	0.998	0.999
R146	7	0.997	1.000
E145	7	0.988	0.997
E173	7	0.985	0.994
W75	7	0.983	0.999
F195	7	0.972	0.997
K148	7	0.963	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:164810 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): osteopetrosis (MONDO:0017198)

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

GWAS associations

4 associations:

Study	Trait	p-value
GCST005537_131	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	2e-9
GCST001725_26	Inflammatory bowel disease	3e-8
GCST004132_15	Crohn’s disease	1e-7
GCST001588_6	Periodontal microbiota	9e-7

MeSH disease descriptors

1 disease descriptors:

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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 95,185 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL140	CURCUMIN	3	95,185

Clinical evidence (CIViC)

Drug × variant × indication, from 1 curated evidence items; also 2 diagnostic. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

1 predictive associations by evidence level:

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

Clinical-actionability assertions (CIViC AMP/ASCO/CAP)

Curated AMP/ASCO/CAP tier assertions — the clinical-actionability classification (Tier I highest) for this gene’s variants, distilling the CIViC evidence above into a tiered call.

1 CIViC assertions:

Molecular profile	Disease	Therapy	Type	AMP tier	Significance
FOS Rearrangement	Osteoblastoma		Diagnostic	Tier I - Level A	Positive

CIViC curated variants (2)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

Rearrangement, Overexpression.

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

54 measured of 71 human assays (71 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
ethyl 4-(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)-2-(thiophen-2-yl)pyrimidine-5-carboxylate	IC50	20 nM
ethyl 4-(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)-2-(thiophen-3-yl)pyrimidine-5-carboxylate	IC50	100 nM
4-(3-Methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-2-phenyl-pyrimidine-5-carboxylic acid ethyl ester	IC50	100 nM
1-[5-(4,5-Dihydro-oxazol-2-yl)-2-thiophen-2-yl-pyrimidin-4-ylamino]-3-methyl-pyrrole-2,5-dione	IC50	200 nM
4-(3-Methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-2-(5-methyl-thiophen-2-yl)-pyrimidine-5-carboxylic acid ethyl ester	IC50	200 nM
3-methyl-1-(5-(4-methyloxazol-2-yl)-2-(thiophen-2-yl)pyrimidin-4-ylamino)-1H-pyrrole-2,5-dione	IC50	200 nM
3-methyl-1-(5-(2-methyl-2H-tetrazol-5-yl)-2-(thiophen-2-yl)pyrimidin-4-ylamino)-1H-pyrrole-2,5-dione	IC50	200 nM
4-(3-Methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester	IC50	200 nM
ethyl 2-(3,5-dichlorophenyl)-4-(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)pyrimidine-5-carboxylate	IC50	300 nM
ethyl 2-(5-chlorothiophen-2-yl)-4-(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)pyrimidine-5-carboxylate	IC50	300 nM
3-methyl-1-(5-(3-methylisoxazol-5-yl)-2-(thiophen-2-yl)pyrimidin-4-ylamino)-1H-pyrrole-2,5-dione	IC50	300 nM
ethyl 2-(4-chlorophenyl)-4-(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)pyrimidine-5-carboxylate	IC50	300 nM
3-methyl-1-(5-(5-methyl-1,3,4-oxadiazol-2-yl)-2-(thiophen-2-yl)pyrimidin-4-ylamino)-1H-pyrrole-2,5-dione	IC50	300 nM
4-(3-Methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-2-(4-trifluoromethyl-phenyl)-pyrimidine-5-carboxylic acid ethyl ester	IC50	400 nM
ethyl 2-(furan-2-carbonyl)-4-(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)pyrimidine-5-carboxylate	IC50	700 nM
ethyl 2-(4-fluorophenyl)-4-(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)pyrimidine-5-carboxylate	IC50	700 nM
2-(3-Bromo-phenyl)-4-(3-methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-pyrimidine-5-carboxylic acid ethyl ester	IC50	700 nM
2-(4-Methoxy-phenyl)-4-(3-methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-pyrimidine-5-carboxylic acid ethyl ester	IC50	900 nM
4-(3-Methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-2-trifluoromethyl-pyrimidine-5-carboxylic acid ethyl ester	IC50	1000 nM
ethyl 4-(methyl(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-yl)amino)-2-(thiophen-2-yl)pyrimidine-5-carboxylate	IC50	1000 nM
ethyl 4-(3-methyl-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-ylamino)-2-(phenylthio)pyrimidine-5-carboxylate	IC50	1000 nM
2-Cyclopropyl-4-(3-methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-pyrimidine-5-carboxylic acid ethyl ester	IC50	1000 nM
ethyl 2-tert-butyl-4-(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)pyrimidine-5-carboxylate	IC50	1000 nM
ethyl 2-(2,6-dichloropyridin-4-yl)-4-(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)pyrimidine-5-carboxylate	IC50	2000 nM
ethyl 4-(methyl(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-yl)amino)-2-phenylpyrimidine-5-carboxylate	IC50	2000 nM
2-Cyclohex-1-enylmethyl-4-(3-methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-pyrimidine-5-carboxylic acid ethyl ester	IC50	2000 nM
2-(4-Fluoro-phenyl)-4-[methyl-(3-methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-amino]-pyrimidine-5-carboxylic acid ethyl ester	IC50	3000 nM
4-[Acetyl-(3-methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-amino]-2-phenyl-pyrimidine-5-carboxylic acid ethyl ester	IC50	4000 nM
2-Benzo[b]thiophen-2-yl-4-(3-methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-pyrimidine-5-carboxylic acid ethyl ester	IC50	4000 nM
ethyl 2-(3-methoxyphenyl)-4-(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)pyrimidine-5-carboxylate	IC50	5000 nM
4-(3-Methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-2-thiophen-2-yl-pyrimidine-5-carbonitrile	IC50	5000 nM
3-[2-isobutoxy-5-(4-isobutoxybenzoyl)phenyl]propionic acid	IC50	5000 nM
3-[2-isobutoxy-5-(3-isobutoxybenzoyl)phenyl]propionic acid	IC50	5800 nM
ethyl 4-(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)-2-(quinolin-3-yl)pyrimidine-5-carboxylate	IC50	6000 nM
ethyl 4-(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)-2-(pyridin-4-yl)pyrimidine-5-carboxylate	IC50	6000 nM
ethyl 2-benzyl-4-(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)pyrimidine-5-carboxylate	IC50	7000 nM
4-(3-Methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-2-(3-nitro-phenyl)-pyrimidine-5-carboxylic acid ethyl ester	IC50	7000 nM
4-(3-Methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-2-(2-methyl-thiazol-4-yl)-pyrimidine-5-carboxylic acid ethyl ester	IC50	8000 nM
(S)-3-{(S)-2-[(S)-2-((S)-2-{(S)-2-[(S)-2-(2-Amino-acetylamino)-4-carbamoyl-butyrylamino]-4-methyl-pentanoylamino}-3-carboxy-propionylamino)-4-methyl-pentanoylamino]-propionylamino}-N-carboxymethyl-succinamic acid	IC50	8000 nM
ethyl 2-ethyl-4-(methyl(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-yl)amino)pyrimidine-5-carboxylate	IC50	10000 nM
2-Ethyl-4-(3-methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-pyrimidine-5-carboxylic acid ethyl ester	IC50	10000 nM
ethyl 4-(2,5-dioxo-2H-pyrrol-1(5H)-ylamino)-2-(trifluoromethyl)pyrimidine-5-carboxylate	IC50	10000 nM
2-Benzenesulfonyl-4-(3-methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-pyrimidine-5-carboxylic acid ethyl ester	IC50	10000 nM
ethyl 4-(3,4-dimethyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)-2-(trifluoromethyl)pyrimidine-5-carboxylate	IC50	10000 nM
ethyl 2-(3,5-dimethyl-1H-pyrazol-1-yl)-4-(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)pyrimidine-5-carboxylate	IC50	10000 nM
(R)-4-(4-methylpentanoyl)-8-(4-methylpentylidene)-1-thia-4-azaspiro[4.5]decane-3-carboxylic acid	IC50	11800 nM
(R)-8-(3-methylbutylidene)-4-(5-methylhexanoyl)-1-thia-4-aza-spiro[4.5]decane-3-carboxylic acid	IC50	13300 nM
ethyl 4-(3-methyl-2,5-dioxo-2H-pyrrol-1(5H)-ylamino)-2-phenoxypyrimidine-5-carboxylate	IC50	15000 nM
2-Methyl-4-(3-methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-pyrimidine-5-carboxylic acid ethyl ester	IC50	16000 nM
4-(2,5-Dioxo-3-phenyl-2,5-dihydro-pyrrol-1-ylamino)-2-trifluoromethyl-pyrimidine-5-carboxylic acid ethyl ester	IC50	20000 nM

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

52 with measured affinity, of 122 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
Curcumin	1178344: Inhibition of Fos-Jun dimer formation (unknown origin)	ic50	0.0069	uM
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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, increases reaction, affects expression, affects cotreatment, decreases expression (+3 more)	31
Tetradecanoylphorbol Acetate	affects localization, decreases reaction, increases expression, increases activity, affects cotreatment (+2 more)	25
sodium arsenite	increases expression, affects activity, affects binding, decreases expression, increases abundance (+7 more)	18
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	affects cotreatment, affects localization, decreases reaction, increases phosphorylation, increases expression (+1 more)	18
Cadmium Chloride	increases abundance, increases reaction, decreases reaction, increases expression, increases phosphorylation (+1 more)	16
Resveratrol	increases expression, affects localization, decreases activity, affects cotreatment, decreases reaction (+3 more)	15
Arsenic Trioxide	affects binding, increases expression, decreases expression, increases phosphorylation, increases activity (+3 more)	14
Cadmium	increases phosphorylation, affects cotreatment, increases abundance, increases reaction, decreases expression (+3 more)	14
U 0126	affects cotreatment, decreases reaction, increases abundance, increases expression, increases phosphorylation (+2 more)	11
Particulate Matter	decreases reaction, affects reaction, affects cotreatment, affects expression, increases abundance (+3 more)	10
bisphenol A	increases expression, affects expression, affects reaction, decreases expression, increases reaction (+1 more)	9
Fulvestrant	decreases reaction, increases expression, decreases expression	9
Quercetin	increases reaction, affects reaction, affects binding, decreases reaction, increases expression (+2 more)	9
Tetrachlorodibenzodioxin	affects localization, increases phosphorylation, affects cotreatment, affects expression, affects binding (+4 more)	9
SB 203580	increases reaction, decreases reaction, increases expression, increases phosphorylation	7
Benzo(a)pyrene	affects activity, increases expression	7
Copper	affects binding, increases expression, increases activity, increases reaction, decreases expression	7
Lipopolysaccharides	increases reaction, increases phosphorylation, affects response to substance, affects localization, decreases reaction (+5 more)	7
Tobacco Smoke Pollution	increases expression, affects expression	7
(+)-JQ1 compound	decreases expression, increases expression	6
Acetylcysteine	decreases reaction, increases expression, increases activity, decreases activity	6
Air Pollutants	affects cotreatment, affects expression, increases abundance, increases expression, decreases expression	6
Hydrogen Peroxide	decreases reaction, increases activity, increases expression, decreases expression	6
Valproic Acid	decreases expression, decreases methylation, increases expression	6
Cisplatin	affects response to substance, affects cotreatment, increases expression, increases reaction	5
Doxorubicin	decreases expression, decreases reaction, increases expression, affects expression, affects reaction	5
Nicotine	decreases reaction, affects cotreatment, decreases activity, increases expression, increases phosphorylation	5
Plant Extracts	decreases expression, decreases reaction, increases expression, increases activity	5
Silicon Dioxide	decreases expression, increases expression, increases methylation	5
Arachidonic Acid	decreases phosphorylation, affects reaction, affects cotreatment, decreases expression, decreases reaction (+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

42 cell lines: 27 transformed cell line, 10 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)

Via MONDO — disease-level, not drug-specific.

19 trials:

NCT	Phase	Status	Title
NCT00004402	Phase 3	COMPLETED	Phase III Randomized Study of Interferon Gamma in Children With Severe, Congenital Osteopetrosis
NCT00638820	Phase 2	TERMINATED	Reduced Intensity AlloTransplant For Osteopetrosis
NCT00968864	Phase 2	TERMINATED	T-cell Depleted Alternative Donor Transplantation
NCT02171104	Phase 2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT02666768	Phase 2	COMPLETED	ACTIMMUNE in Intermediate Osteopetrosis
NCT00145886	Phase 1	TERMINATED	rhPTH Therapy for Low Turnover Bone Fragility
NCT00775931	Phase 2/3	COMPLETED	Allogeneic Transplantation For Severe Osteopetrosis
NCT01019876	Phase 2/3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT01087398	Phase 2/3	UNKNOWN	Hematopoietic Stem Cell Transplantation for Malignant Infantile Osteopetrosis
NCT00730314	Phase 1/2	COMPLETED	Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells
NCT02065869	Phase 1/2	TERMINATED	Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant
NCT03301168	Phase 1/2	ACTIVE_NOT_RECRUITING	Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant
NCT07665021	Phase 1/2	RECRUITING	Gene-Modified Stem Cell Therapy for Children With Autosomal Recessive Osteopetrosis (ARO)
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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for FOS across ~30M SureChEMBL compounds — explore on Sugi Predict.