FOSB

Summary

FOSB (FosB proto-oncogene, AP-1 transcription factor subunit, HGNC:3797) is a protein-coding gene on chromosome 19q13.32, encoding Protein FosB (P53539). Heterodimerizes with proteins of the JUN family to form an AP-1 transcription factor complex, thereby enhancing their DNA binding activity to gene promoters containing an AP-1 consensus sequence 5’-TGA[GC]TCA-3’ and enhancing their transcriptional activity.

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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2354 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 44 total
• Druggable target: yes
• Transcription factor: yes — 43 downstream targets (CollecTRI)
• MANE Select transcript: NM_006732

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3797
Approved symbol	FOSB
Name	FosB proto-oncogene, AP-1 transcription factor subunit
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	G0S3, GOSB, GOS3, AP-1, MGC42291, DKFZp686C0818
Ensembl gene	ENSG00000125740
Ensembl biotype	protein_coding
OMIM	164772
Entrez	2354

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 2 retained_intron

ENST00000353609, ENST00000417353, ENST00000443841, ENST00000585836, ENST00000586113, ENST00000586615, ENST00000587358, ENST00000589593, ENST00000590335, ENST00000591858, ENST00000592436, ENST00000592811

RefSeq mRNA: 3 — MANE Select: NM_006732 NM_001114171, NM_001411069, NM_006732

CCDS: CCDS12664, CCDS46113, CCDS92643

Canonical transcript exons

ENST00000353609 — 4 exons

Exon	Start	End
ENSE00000858216	45471194	45471301
ENSE00002785923	45467996	45468712
ENSE00002892216	45472551	45475179
ENSE00003534885	45470629	45470949

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 99.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 147.2039 / max 19108.8961, expressed in 1523 samples.

FANTOM5 promoters (24 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176431	144.5626	1485
176438	1.2051	382
176477	0.1941	85
176456	0.1460	65
176447	0.1390	54
176452	0.1089	34
176453	0.0979	38
176476	0.0950	46
176439	0.0674	18
176454	0.0644	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	99.67	gold quality
upper leg skin	UBERON:0004262	99.29	gold quality
gall bladder	UBERON:0002110	99.21	gold quality
saphenous vein	UBERON:0007318	99.14	gold quality
nipple	UBERON:0002030	99.00	gold quality
vena cava	UBERON:0004087	98.91	gold quality
granulocyte	CL:0000094	98.68	gold quality
mucosa of urinary bladder	UBERON:0001259	98.31	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.16	gold quality
bone marrow cell	CL:0002092	96.62	gold quality
penis	UBERON:0000989	96.12	gold quality
trachea	UBERON:0003126	95.99	gold quality
left uterine tube	UBERON:0001303	95.41	gold quality
urethra	UBERON:0000057	95.07	gold quality
smooth muscle tissue	UBERON:0001135	94.89	gold quality
epithelium of mammary gland	UBERON:0003244	94.63	gold quality
mammary duct	UBERON:0001765	94.29	gold quality
cervix epithelium	UBERON:0004801	93.85	gold quality
skin of abdomen	UBERON:0001416	93.71	gold quality
cervix squamous epithelium	UBERON:0006922	93.53	gold quality
cardia of stomach	UBERON:0001162	93.36	gold quality
vermiform appendix	UBERON:0001154	92.58	gold quality
right ovary	UBERON:0002118	91.01	gold quality
trigeminal ganglion	UBERON:0001675	90.92	gold quality
synovial joint	UBERON:0002217	90.58	gold quality
oviduct epithelium	UBERON:0004804	90.58	gold quality
seminal vesicle	UBERON:0000998	90.57	gold quality
blood vessel layer	UBERON:0004797	90.17	gold quality
caecum	UBERON:0001153	89.87	gold quality
fallopian tube	UBERON:0003889	89.82	gold quality

Single-cell (SCXA)

Detected in 32 experiment(s), a significant marker in 24.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	1861.51
E-GEOD-134144	yes	1603.55
E-GEOD-114530	yes	1543.01
E-MTAB-11011	yes	1334.47
E-GEOD-130473	yes	1063.34
E-MTAB-8530	yes	950.87
E-CURD-6	yes	343.62
E-MTAB-7052	yes	160.02
E-HCAD-1	yes	55.25
E-CURD-88	yes	45.46
E-GEOD-135922	yes	30.41
E-MTAB-8410	yes	24.91
E-HCAD-4	yes	22.93
E-MTAB-10553	yes	19.22
E-CURD-46	yes	18.66

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

43 targets.

Target	Regulation
ADAM2
ALB	Repression
AP1	Unknown
BGLAP	Activation
CCK	Activation
CCN2	Activation
CCND1	Activation
CCNE1	Unknown
CD14	Activation
CD9	Activation
CDK2	Unknown
CDK5	Activation
COL3A1	Activation
CREB1	Activation
CXCL8	Activation
DNAJB4
DRD2	Activation
FASLG	Activation
FOS	Unknown
FOSB	Unknown
GFAP	Activation
GRIN1	Activation
GRIN2A	Activation
IL11	Activation
IL2	Activation
ITGA2B	Activation
LGALS1	Activation
MAP2	Repression
MMP2	Activation
MYC	Activation

JASPAR motifs

Motif	Name	Family
MA1127.1	FOSB::JUN	Fos-related::Jun-related
MA1135.1	FOSB::JUNB	Fos-related::Jun-related
MA1135.2	FOSB::JUNB	Fos-related::Jun-related
MA1136.1	FOSB::JUNB	Fos-related::Jun-related

JASPAR matrix evidence (PMIDs): PMID:11988758

Upstream regulators (CollecTRI, top): AP1, CEBPA, CREB1, ESR1, FOS, FOSB, FOXC1, RELA, SP1, SRF, STAT6

miRNA regulators (miRDB)

87 targeting FOSB, 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-5193	100.00	67.26	1744
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963

Literature-anchored findings (GeneRIF, showing 40)

• demonstrated that a functional AP-1 site mediates MMP-2 transcription in cardiac cells through the binding of distinctive Fra1-JunB and FosB-JunB heterodimers. The synthesis of MMP-2 is considered to be independent of the AP-1 transcriptional complex (PMID:12371906)
• AP-1 (c-Jun & FosB) binds to a site in the 5’ untranslated region of the CD95L gene. Transdominant negative Jun mutants reduce CD95L promoter activity. FosB dimerized with c-Jun has an important role in TCR/CD3-mediated activation-induced cell death. (PMID:12618758)
• VEGF and PlGF induced expression of both full-length FosB mRNA and an alternatively spliced variant. (PMID:14741347)
• In hepatoma-associated anorexia-cachexia FpsB was induced in several brain areas of thes forebrain. (PMID:15926923)
• Coordinated down- and up-regulation of the various AP-1 subunits in the course of epidermal wound healing is important for its undisturbed progress, putatively by influencing inflammation and cell-cell communication. (PMID:17495958)
• activation of protein kinase A elicits an immediate response through induction of genes such as ID2 and FosB, followed by sustained secretion of bone-related cytokines such as BMP-2, IGF-1, and IL-11 (PMID:18490653)
• DeltaFosB was able to trigger partial Pref-1-mediated de-differentiation of adipocytes, which also retained their adipocytic cell phenotype. (PMID:18491952)
• An IFN-gamma-mediated homeostatic loop limits the potential for tissue damage associated with inflammation and identifies transcriptional factor AP-1 that regulates matrix metalloproteinase expression in myeloid cells in inflammatory settings. (PMID:18802113)
• MicroRNA-101, which is aberrantly expressed in hepatocellular carcinoma, could repress the expression of the FOS oncogene. (PMID:19133651)
• FosB is induced in PMA treated K562 cells in a sustained manner and forms an active AP-1 protein-DNA complex. Down-regulation of FosB with specific shRNAs inhibited the induction of CD41, a specific cell surface marker of megakaryocytes. (PMID:19381435)
• Results suggest that in addition to clinically prognostic factors, FOS-B expression has a debatable impact on patient survival. (PMID:19795327)
• RGS16 and FosB are underexpressed in pancreatic cancer with lymph node metastasis and associated with reduced survival (PMID:20571966)
• transcription factor FosB/activating protein-1 (AP-1) activation is a prominent downstream signal of the extracellular nucleotide receptor P2RX7 in monocytic and osteoblastic cells (PMID:20813842)
• Findings indicate that neurobehavioral stress leads to FosB-driven increases in IL8, which is associated with increased tumor growth and metastases. (PMID:20826776)
• AP-1 protein induction during monopoiesis favors C/EBP: AP-1 heterodimers over C/EBP homodimerization and stimulates FosB transcription. (PMID:21543584)
• Induction of a DeltaFOSB mediated transcriptional pattern in the prefrontal cortex is opposite to the down-regulation observed in the nucleus accumbens in patients with major depressive disorder (PMID:21616539)
• Report Fos-B expression in skin keratinocytes/fibroblasts and keloid fibroblasts exposed to genistein. (PMID:23614275)
• Data indicate a significant correlation in miR-181b, FOS and miR-21 expression glioma tissues. (PMID:23810250)
• This study describing the expres-sion pattern of FosB/ FosB immunoreactivity inpost mortem basal ganglia sections from Parkinson disease patients. (PMID:23933656)
• Pseudomyogenic haemangioendothelioma consistently displays a SERPINE1-FOSB fusion gene, resulting from a translocation between chromosomes 7 and 19. (PMID:24374978)
• The abnormalities were screened by FISH in 44 epithelioid hemangioma (EH) from different locations with seven additional EH revealing FOSB gene rearrangements, all except one being fused to ZFP36. (PMID:25043949)
• studies of FosB are providing new insight into the molecular basis of depression and antidepressant action. (PMID:25446562)
• our findings show that DeltaFosB increases the expression of MMP-9 and exhibits a significantly high survival and proliferation in MCF-7 cells. (PMID:26608367)
• These results suggest that SETDB1- mediated FosB expression is a common molecular phenomenon, and might be a novel pathway responsible for the increase in cell proliferation that frequently occurs during anticancer drug therapy. (PMID:26949019)
• FOSB overexpression results in TNBC cell death, whereas inhibition of calcium signaling eliminates FOSB induction and blocks TP4-induced TNBC cell death (PMID:27248170)
• FosB expression in the prefrontal cortex and hippocampus of the cocaine addicted and depression patients (PMID:27494187)
• Diffuse and strong FOSB expression was specific for pseudomyogenic hemangioendothelioma in the current series and FOSB immunohistochemistry is an effective tool for differentiating between PHE and its histological mimics. (PMID:27515856)
• Our results using a number of approaches, such as promoter reporter assay, FosB knock down and Chip assay, suggest that the expression of miR-22 is regulated transcriptionally by FosB. (PMID:27889568)
• FOSB is a highly sensitive and diagnostically useful marker for pseudomyogenic hemangioendothelioma. (PMID:28009608)
• results shows the involvement of Spry2 in regulation of FosB and Runx2 genes, MAPK signaling and proliferation of mesenchymal stem cells. (PMID:28387432)
• The NFATc3 first induced the expression of its interaction partner FosB before forming the heterodimeric NFATc3-FosB transcription factor complex, which bound the proximal AP-1 site in the TF gene promoter and activated TF expression. (PMID:28724635)
• the mechanism underlying redox-regulation of AP-1 Fos/Jun transcription factors and provide structural insight for therapeutic interventions targeting AP-1 proteins. (PMID:28981703)
• FOSB immunohistochemistry is sensitive in the diagnosis of angiolymphoid hyperplasia with eosinophilia, and allows differentiation from its histological mimics (PMID:29527734)
• Findings iindicate a human bone tumour defined by mutations of FOS and FOSB. (PMID:29858576)
• Recurrent ACTB-FOSB fusions are found in pseudomyogenic hemangioendothelioma. (PMID:30256258)
• Recurrent ACTB-FOSB fusion occurs in pseudomyogenic hemangioendothelioma. (PMID:30459475)
• We identified increased level of Fos-B mRNA, the binding target of FUS, in FUS-mutant MNs. While Fos-B reduction using si-RNA or an inhibitor ameliorated the observed aberrant axon branching, Fos-B overexpression resulted in aberrant axon branching even in vivo. The commonality of those phenotypes was further confirmed with other amyotrophic lateral sclerosis (ALS) causative mutation than FUS (PMID:31262712)
• Poly(ADP-ribose) Polymerases (PARP) cleavage and positive annexin V level are increased during piperlongumine (PL) treatment with FosB overexpression in MCF7 breast cancer cells, whereas PARP cleavage and positive annexin V level were decreased during PL treatment with siFosB transfection, implying that FosB is a pro-apoptotic protein for induction of cell death in PL-treated MCF7 breast cancer cells. (PMID:31735020)
• Association of FOSB exon 4 unmethylation with poor prognosis in patients with latestage nonsmall cell lung cancer. (PMID:31894310)
• Clinicopathologic study of 6 cases of epithelioid osteoblastoma of the jaws with immunoexpression analysis of FOS and FOSB. (PMID:32482537)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fosb	ENSDARG00000055751
mus_musculus	Fosb	ENSMUSG00000003545
rattus_norvegicus	Fosb	ENSRNOG00000046667
drosophila_melanogaster	Atf3	FBGN0028550

Paralogs (8): FOSL2 (ENSG00000075426), BATF3 (ENSG00000123685), JDP2 (ENSG00000140044), BATF (ENSG00000156127), ATF3 (ENSG00000162772), BATF2 (ENSG00000168062), FOS (ENSG00000170345), FOSL1 (ENSG00000175592)

Protein

Protein identifiers

Protein FosB — P53539 (reviewed: P53539)

Alternative names: FosB proto-oncogene, AP-1 transcription factor subunit, G0/G1 switch regulatory protein 3, Transcription factor AP-1 subunit FosB

All UniProt accessions (4): P53539, K7EJ89, K7EKA0, K7ERZ8

UniProt curated annotations — full annotation on UniProt →

Function. Heterodimerizes with proteins of the JUN family to form an AP-1 transcription factor complex, thereby enhancing their DNA binding activity to gene promoters containing an AP-1 consensus sequence 5’-TGA[GC]TCA-3’ and enhancing their transcriptional activity. As part of the AP-1 complex, facilitates enhancer selection together with cell-type-specific transcription factors by collaboratively binding to nucleosomal enhancers and recruiting the SWI/SNF (BAF) chromatin remodeling complex to establish accessible chromatin. Together with JUN, plays a role in activation-induced cell death of T cells by binding to the AP-1 promoter site of FASLG/CD95L, and inducing its transcription in response to activation of the TCR/CD3 signaling pathway. Exhibits transactivation activity in vitro. Involved in the display of nurturing behavior towards newborns. May play a role in neurogenesis in the hippocampus and in learning and memory-related tasks by regulating the expression of various genes involved in neurogenesis, depression and epilepsy. Implicated in behavioral responses related to morphine reward and spatial memory. Exhibits lower transactivation activity than isoform 1 in vitro. The heterodimer with JUN does not display any transcriptional activity, and may thereby act as an transcriptional inhibitor. May be involved in the regulation of neurogenesis in the hippocampus. May play a role in synaptic modifications in nucleus accumbens medium spiny neurons and thereby play a role in adaptive and pathological reward-dependent learning, including maladaptive responses involved in drug addiction. Seems to be more stably expressed with a half-life of ~9.5 hours in cell culture as compared to 1.5 hours half-life of isoform 1.

Subunit / interactions. Heterodimer; binds to DNA as heterodimer. Component of an AP-1 transcription factor complex; composed of FOS-JUN heterodimers. As part of the AP-1 transcription factor complex, forms heterodimers with JUN, JUNB or JUND, thereby binding to the AP-1 consensus sequence and stimulating transcription. Interacts with the BAF multiprotein chromatin-remodeling complex subunits SMARCB1 and SMARCD1. Interacts with ARID1A and JUN. Homodimer under oxidizing conditions and monomer under reducing conditions (in vitro). Heterodimer; binds to DNA as heterodimer. Forms heterodimers with JUNB, JUN or JUND; thereby binding to the AP-1 consensus sequence but does not stimulate transcription. Forms heterodimers with JUND under oxidizing conditions.

Subcellular location. Nucleus.

Tissue specificity. Expressed in the nucleus accumbens of the striatum (at protein level).

Post-translational modifications. Phosphorylated. Phosphorylated at Ser-27 by CSNK2A1; phosphorylation increases protein stability and transactivation potential.

Domain organisation. Binds DNA via bZIP domain; DNA-binding is under control of cellular redox homeostasis (in vitro). To enable DNA binding, the bZIP domain must undergo a conformational rearrangement which requires the reduction of the interchain disulfide bond between FosB and JunD (in vitro). The bZIP domain is able to form homomeric oligomers via formation of interchain disulfide bonds under non-reducing conditions (in vitro). Under reducing conditions, the disulfide-bonded homomeric species dissociates into monomers (in vitro).

Similarity. Belongs to the bZIP family. Fos subfamily.

Isoforms (11)

UniProt ID	Names	Canonical?
P53539-1	1, FosB-L	yes
P53539-2	2
P53539-3	3
P53539-4	4
P53539-5	5
P53539-6	6
P53539-7	7
P53539-8	8
P53539-9	9
P53539-10	10
P53539-11	11, deltaFosB

RefSeq proteins (3): NP_001107643, NP_001397998, NP_006723* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00170

UniProt features (26 total): compositionally biased region 7, splice variant 6, region of interest 6, chain 1, domain 1, modified residue 1, disulfide bond 1, sequence variant 1, sequence conflict 1, helix 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
9OC3	X-RAY DIFFRACTION	1.73
7UCC	X-RAY DIFFRACTION	1.94
5VPE	X-RAY DIFFRACTION	2.05
6UCI	X-RAY DIFFRACTION	2.09
6UCL	X-RAY DIFFRACTION	2.21
6UCM	X-RAY DIFFRACTION	2.42
5VPC	X-RAY DIFFRACTION	2.5
5VPB	X-RAY DIFFRACTION	2.69
5VPF	X-RAY DIFFRACTION	2.69
5VPD	X-RAY DIFFRACTION	2.79
5VPA	X-RAY DIFFRACTION	2.83
7UCD	X-RAY DIFFRACTION	3.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53539-F1	60.79	0.21

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 (1): 27

Disulfide bonds (1): 172

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-9031628	NGF-stimulated transcription
R-HSA-9909649	Regulation of PD-L1(CD274) transcription

MSigDB gene sets: 398 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE45365_NK_CELL_VS_BCELL_UP, ATF_B, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, KANG_DOXORUBICIN_RESISTANCE_UP, CHIBA_RESPONSE_TO_TSA_UP, GGTGTGT_MIR329, GOBP_BEHAVIOR, TGCGCANK_UNKNOWN, GOBP_RESPONSE_TO_COCAINE, GOBP_RESPONSE_TO_AMINE, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, FISCHER_G1_S_CELL_CYCLE, GOBP_RESPONSE_TO_CORTICOSTEROID

GO Biological Process (19): negative regulation of transcription by RNA polymerase II (GO:0000122), response to amphetamine (GO:0001975), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), female pregnancy (GO:0007565), response to xenobiotic stimulus (GO:0009410), response to mechanical stimulus (GO:0009612), response to progesterone (GO:0032570), cellular response to hormone stimulus (GO:0032870), response to nicotine (GO:0035094), response to morphine (GO:0043278), response to ethanol (GO:0045471), behavioral response to cocaine (GO:0048148), response to corticosterone (GO:0051412), response to cAMP (GO:0051591), cellular response to calcium ion (GO:0071277), regulation of DNA-templated transcription (GO:0006355), response to cocaine (GO:0042220), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), sequence-specific double-stranded DNA binding (GO:1990837), double-stranded DNA binding (GO:0003690), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
ESR-mediated signaling	1
Nuclear Events (kinase and transcription factor activation)	1
Regulation of PD-L1(CD274) expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
DNA-templated transcription	2
response to chemical	2
response to ketone	2
response to alcohol	2
response to oxygen-containing compound	2
DNA binding	2
negative regulation of DNA-templated transcription	1
response to amine	1
multi-organism reproductive process	1
multi-multicellular organism process	1
response to external stimulus	1
response to abiotic stimulus	1
response to steroid hormone	1
response to hormone	1
cellular response to chemical stimulus	1
cellular response to endogenous stimulus	1
response to isoquinoline alkaloid	1
adult behavior	1
response to cocaine	1
response to glucocorticoid	1
response to mineralocorticoid	1
response to purine-containing compound	1
response to organophosphorus	1
response to calcium ion	1
cellular response to metal ion	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
response to alkaloid	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1

Protein interactions and networks

STRING

2622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOSB	JUN	P05412	998
FOSB	JUND	P17535	998
FOSB	JUNB	P17275	996
FOSB	FOSL1	P15407	985
FOSB	FOS	P01100	984
FOSB	FOSL2	P15408	984
FOSB	ATF3	P18847	895
FOSB	EGR1	P18146	881
FOSB	EGR3	Q06889	845
FOSB	CREB1	P16220	808
FOSB	MAF	O75444	774
FOSB	NR4A1	P22736	751
FOSB	DUSP12	Q9UNI6	708
FOSB	DUSP1	P28562	702
FOSB	EGR2	P11161	698

IntAct

94 interactions, top by confidence:

A	B	Type	Score
JUN	ATF2	psi-mi:“MI:0914”(association)	0.950
JUNB	FOSB	psi-mi:“MI:0915”(physical association)	0.740
FOSB	JUN	psi-mi:“MI:0914”(association)	0.690
ATF2	FOSB	psi-mi:“MI:0915”(physical association)	0.670
NFE2L2	FOSB	psi-mi:“MI:0915”(physical association)	0.630
JUN	NFATC1	psi-mi:“MI:0914”(association)	0.610
FOSB	ZC3H10	psi-mi:“MI:0915”(physical association)	0.560
FOSB	TLE5	psi-mi:“MI:0915”(physical association)	0.560
FOSB	FOXP3	psi-mi:“MI:0915”(physical association)	0.560
FOSB	POU6F2	psi-mi:“MI:0915”(physical association)	0.560
FOSB	CENPO	psi-mi:“MI:0915”(physical association)	0.560
FOSB	VEZF1	psi-mi:“MI:0915”(physical association)	0.560
NCK2	FOSB	psi-mi:“MI:0915”(physical association)	0.560
PHC2	FOSB	psi-mi:“MI:0915”(physical association)	0.560
FOSB	NEDD9	psi-mi:“MI:0915”(physical association)	0.560
FOSB	ENKD1	psi-mi:“MI:0915”(physical association)	0.560
PHF1	FOSB	psi-mi:“MI:0915”(physical association)	0.560
FOSB	CREB5	psi-mi:“MI:0915”(physical association)	0.560
FOSB	TENT5B	psi-mi:“MI:0915”(physical association)	0.560
FOSB	CYTH4	psi-mi:“MI:0915”(physical association)	0.560
FOSB	FAM90A1	psi-mi:“MI:0915”(physical association)	0.560
FOSB	ROR2	psi-mi:“MI:0915”(physical association)	0.560
POGZ	FOSB	psi-mi:“MI:0915”(physical association)	0.560
TLX3	FOSB	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (57): FOSB (Affinity Capture-MS), FOSB (Affinity Capture-MS), FOSB (Reconstituted Complex), FOSB (Affinity Capture-MS), FOSB (PCA), FOSB (Affinity Capture-RNA), FOSB (Two-hybrid), FOSB (Two-hybrid), FOSB (Two-hybrid), FOSB (Two-hybrid), FOSB (Two-hybrid), FOSB (Two-hybrid), FOSB (Two-hybrid), FOSB (Two-hybrid), FOSB (Two-hybrid)

ESM2 similar proteins: A3KNX5, A6NI15, A7YWL5, B0BN13, D3ZLB7, E9Q9M8, O02761, O35906, O70240, O94983, O97930, P01102, P11939, P13346, P23050, P53539, P70298, P70595, P70660, P97303, Q15742, Q28C89, Q3U1J1, Q5EBA3, Q61122, Q61127, Q62722, Q62912, Q62985, Q6NW59, Q80Y50, Q86UZ6, Q8CD60, Q8HZP6, Q90ZL1, Q91ZM2, Q92886, Q96JB3, Q99NA2, Q9BE45

Diamond homologs: A8MPH9, B3MTI9, B3P5D2, B4G652, B4HZE8, B4JYN3, B4K617, B4M5T7, B4NBL5, B4PPK2, B4R090, O02761, O77628, O88479, O97930, P01100, P01101, P01102, P10158, P11939, P12841, P13346, P15407, P18847, P21525, P23050, P29176, P48755, P53450, P53539, Q29AP1, Q2KII1, Q56TN0, Q56TT7, Q8HZP6, Q91496, Q9Z2Q8, Q6DGM8, D3ZLB7, P15408

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CSNK2A1	up-regulates	FOSB	phosphorylation
(-)-anisomycin	up-regulates	FOSB	“chemical activation”
N	“up-regulates quantity by expression”	FOSB	“transcriptional regulation”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

672 predictions. Top by Δscore:

Variant	Effect	Δscore
19:45470946:GACG:G	donor_gain	1.0000
19:45470947:ACGG:A	donor_loss	1.0000
19:45470950:GTGA:G	donor_gain	1.0000
19:45470954:G:GG	donor_gain	1.0000
19:45471186:T:A	acceptor_gain	1.0000
19:45471192:A:AG	acceptor_gain	1.0000
19:45471193:G:GG	acceptor_gain	1.0000
19:45471193:GC:G	acceptor_gain	1.0000
19:45471193:GCT:G	acceptor_gain	1.0000
19:45471193:GCTC:G	acceptor_gain	1.0000
19:45471193:GCTCA:G	acceptor_gain	1.0000
19:45471299:GCG:G	donor_gain	1.0000
19:45471300:CGGTG:C	donor_loss	1.0000
19:45471302:G:C	donor_loss	1.0000
19:45471303:T:G	donor_loss	1.0000
19:45472526:T:A	acceptor_gain	1.0000
19:45472528:T:TA	acceptor_gain	1.0000
19:45472533:T:TA	acceptor_gain	1.0000
19:45472534:G:A	acceptor_gain	1.0000
19:45472542:T:TA	acceptor_gain	1.0000
19:45472543:G:A	acceptor_gain	1.0000
19:45472546:CTCAG:C	acceptor_loss	1.0000
19:45472547:TCAGG:T	acceptor_loss	1.0000
19:45472548:CAG:C	acceptor_loss	1.0000
19:45472550:GGAG:G	acceptor_loss	1.0000
19:45468708:CCCAG:C	donor_gain	0.9900
19:45468711:AGGT:A	donor_loss	0.9900
19:45468712:GGTA:G	donor_loss	0.9900
19:45468713:G:C	donor_loss	0.9900
19:45468713:G:GG	donor_gain	0.9900

AlphaMissense

2158 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:45470669:C:A	P56H	1.000
19:45470675:T:A	V58D	1.000
19:45470684:T:A	I61N	1.000
19:45470707:T:A	W69R	1.000
19:45470707:T:C	W69R	1.000
19:45470709:G:C	W69C	1.000
19:45470709:G:T	W69C	1.000
19:45471227:C:A	R161S	1.000
19:45471227:C:T	R161C	1.000
19:45471231:G:C	R162P	1.000
19:45471237:G:C	R164P	1.000
19:45471239:A:C	N165H	1.000
19:45471239:A:G	N165D	1.000
19:45471240:A:C	N165T	1.000
19:45471240:A:G	N165S	1.000
19:45471240:A:T	N165I	1.000
19:45471241:T:A	N165K	1.000
19:45471241:T:G	N165K	1.000
19:45471242:A:G	K166E	1.000
19:45471243:A:T	K166I	1.000
19:45471244:A:C	K166N	1.000
19:45471244:A:T	K166N	1.000
19:45471246:T:C	L167P	1.000
19:45471248:G:A	A168T	1.000
19:45471248:G:C	A168P	1.000
19:45471249:C:A	A168E	1.000
19:45471249:C:T	A168V	1.000
19:45471251:G:A	A169T	1.000
19:45471251:G:C	A169P	1.000
19:45471252:C:A	A169E	1.000

dbSNP variants (sampled 300 via entrez): RS1000056837 (19:45472387 A>G), RS1000394319 (19:45475348 G>T), RS1000405841 (19:45475563 A>G), RS1001139911 (19:45466044 C>T), RS1001145355 (19:45467579 G>A), RS1001477555 (19:45466735 C>T), RS1001531474 (19:45467043 A>G), RS1001550921 (19:45466478 C>A,T), RS1002039909 (19:45472436 C>T), RS1002064648 (19:45473931 T>C,G), RS1002531847 (19:45475575 G>C), RS1002689339 (19:45469551 C>T), RS1002833692 (19:45471446 G>C), RS1003151394 (19:45469744 G>A), RS1003739347 (19:45472517 T>C)

Disease associations

OMIM: gene MIM:164772 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST006288_675	Heel bone mineral density	3.000000e-12
GCST006288_75	Heel bone mineral density	3.000000e-06
GCST006979_683	Heel bone mineral density	5.000000e-12
GCST006979_684	Heel bone mineral density	2.000000e-16
GCST007827_3	Alzheimer’s disease or HDL levels (pleiotropy)	1.000000e-97

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4630755 (PROTEIN COMPLEX), CHEMBL4630821 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, decreases methylation, affects cotreatment, increases abundance, increases activity (+1 more)	8
Cadmium Chloride	affects cotreatment, increases expression	5
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	4
Silicon Dioxide	increases expression	4
Dronabinol	decreases reaction, increases expression, decreases expression	4
Benzene	decreases expression	3
Cadmium	decreases expression, increases expression	3
Formaldehyde	increases expression	3
Nickel	increases expression	3
Tetrachlorodibenzodioxin	decreases reaction, increases expression, affects expression	3
Asbestos, Crocidolite	affects expression, increases expression	3
Particulate Matter	increases abundance, increases expression	3
cylindrospermopsin	increases expression	2
Air Pollutants	increases expression, affects expression, increases abundance	2
Estradiol	increases expression, affects cotreatment, decreases expression	2
Hydrogen Peroxide	affects expression, increases expression	2
Silver	decreases expression, increases expression	2
Tetradecanoylphorbol Acetate	increases expression	2
Tobacco Smoke Pollution	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression, affects expression	2
Thapsigargin	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	affects cotreatment, increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
hydroxyhydroquinone	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4625230	Binding	Inhibition of recombinant Hi6-tagged deltaFOSB (unknown origin)/His6-tagged JUND (unknown origin) expressed in insect cells interaction with TAMRA labeled 5’-GTCGGTGACTCAAAACA-3’ AP1 oligonucleotide measured after 15 mins by fluorescence po	Discovery of phenanthridine analogues as novel chemical probes disrupting the binding of DNA to ΔFosB homodimers and ΔFosB/JunD heterodimers. — Bioorg Med Chem Lett

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_A1V3	SEES3-1V human FOSB, clone1	Embryonic stem cell	Male
CVCL_A1V4	SEES3-1V human FOSB, clone2	Embryonic stem cell	Male
CVCL_A1V5	SEES3-1V human FOSB, clone3	Embryonic stem cell	Male
CVCL_D1MK	Abcam K-562 FOSB KO	Cancer cell line	Female
CVCL_D2J5	Abcam Raji FOSB KO	Cancer cell line	Male
CVCL_E1XN	HAP1 FOSB (-) 1	Cancer cell line	Male
CVCL_E1XP	HAP1 FOSB (-) 2	Cancer cell line	Male
CVCL_E1XQ	HAP1 FOSB (-) 3	Cancer cell line	Male
CVCL_UQ52	Abcam Jurkat FOSB KO	Cancer cell line	Male

Clinical trials (associated diseases)

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