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FOSB

gene
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Also known as G0S3GOSBGOS3AP-1MGC42291DKFZp686C0818

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
  • GTEx eGene: eQTL in 3 tissues, sQTL in 1 (q < 0.05)
  • Constraint (gnomAD): pLI 0.95 (loss-of-function intolerant), LOEUF 0.53 (moderately constrained)
  • Transcription factor: yes — 43 downstream targets (CollecTRI)
  • MANE Select transcript: NM_006732
  • Interaction hub: 2,250 STRING partners (top 5% of genes corpus-wide)

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:3797
Approved symbolFOSB
NameFosB proto-oncogene, AP-1 transcription factor subunit
Location19q13.32
Locus typegene with protein product
StatusApproved
AliasesG0S3, GOSB, GOS3, AP-1, MGC42291, DKFZp686C0818
Ensembl geneENSG00000125740
Ensembl biotypeprotein_coding
OMIM164772
Entrez2354

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 retained_intron

MANE Select: ENST00000353609

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 8, TSL 2: 1, TSL 5: 2

ENST00000353609, ENST00000417353, ENST00000443841, ENST00000585836, ENST00000586113, ENST00000586615, ENST00000587358, ENST00000589593, ENST00000590335, ENST00000591858, ENST00000592436, ENST00000592811, ENST00001135595

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

CCDS: CCDS12664, CCDS46113, CCDS92643

Canonical transcript exons

ENST00000353609 — 4 exons

ExonStartEnd
ENSE000008582164547119445471301
ENSE000027859234546799645468712
ENSE000035348854547062945470949
ENSE000047870424547255145475179

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.

Highest expression (Bgee): mucosa of stomach, upper leg skin, gall bladder, saphenous vein, nipple.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FOSB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 3 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

4 significant tissue × QTL associations:

TissueQTLq-valueSlopeLead variant
Brain Cortexeqtl2.5e-03+2.1019:46336995:T:A
Skin Sun Exposed Lower legeqtl2.2e-02-0.6619:46347744:G:T
Whole Bloodeqtl2.2e-02-0.2519:45985160:C:T
Esophagus Gastroesophageal Junctionsqtl4.3e-02-1.5019:44488416:C:T

FANTOM5 promoters

showing 10 of 24 alternative TSS:

Promoter IDTPM avgSamples expressed
176431144.56261485
1764381.2051382
1764770.194185
1764560.146065
1764470.139054
1764520.108934
1764530.097938
1764760.095046
1764390.067418
1764540.064413

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
mucosa of stomachUBERON:000119999.67gold quality
upper leg skinUBERON:000426299.29gold quality
gall bladderUBERON:000211099.21gold quality
saphenous veinUBERON:000731899.14gold quality
nippleUBERON:000203099.00gold quality
vena cavaUBERON:000408798.91gold quality
granulocyteCL:000009498.68gold quality
mucosa of urinary bladderUBERON:000125998.31gold quality
mucosa of paranasal sinusUBERON:000503097.16gold quality
bone marrow cellCL:000209296.62gold quality
penisUBERON:000098996.12gold quality
tracheaUBERON:000312695.99gold quality
left uterine tubeUBERON:000130395.41gold quality
urethraUBERON:000005795.07gold quality
smooth muscle tissueUBERON:000113594.89gold quality
epithelium of mammary glandUBERON:000324494.63gold quality
mammary ductUBERON:000176594.29gold quality
cervix epitheliumUBERON:000480193.85gold quality
skin of abdomenUBERON:000141693.71gold quality
cervix squamous epitheliumUBERON:000692293.53gold quality
cardia of stomachUBERON:000116293.36gold quality
vermiform appendixUBERON:000115492.58gold quality
right ovaryUBERON:000211891.01gold quality
trigeminal ganglionUBERON:000167590.92gold quality
synovial jointUBERON:000221790.58gold quality
oviduct epitheliumUBERON:000480490.58gold quality
seminal vesicleUBERON:000099890.57gold quality
blood vessel layerUBERON:000479790.17gold quality
caecumUBERON:000115389.87gold quality
fallopian tubeUBERON:000388989.82gold quality
lower lobe of lungUBERON:000894989.55silver quality
cardiac muscle of right atriumUBERON:000337989.45gold quality
monocyteCL:000057689.32gold quality
parotid glandUBERON:000183188.99gold quality
omental fat padUBERON:001041488.77gold quality
peritoneumUBERON:000235888.71gold quality
spermCL:000001988.60silver quality
mononuclear cellCL:000084288.59gold quality
male germ cellCL:000001588.47silver quality
rectumUBERON:000105288.29gold quality
leukocyteCL:000073888.17gold quality
layer of synovial tissueUBERON:000761687.48gold quality
sural nerveUBERON:001548887.41gold quality
adipose tissue of abdominal regionUBERON:000780887.36gold quality
hindlimb stylopod muscleUBERON:000425287.17gold quality
secondary oocyteCL:000065586.72gold quality
ascending aortaUBERON:000149686.52gold quality
thoracic aortaUBERON:000151586.43gold quality
lymph nodeUBERON:000002985.94gold quality
buccal mucosa cellCL:000233685.89gold quality
left ovaryUBERON:000211985.80gold quality
lungUBERON:000204885.64gold quality
epithelial cell of pancreasCL:000008385.62gold quality
right coronary arteryUBERON:000162585.58gold quality
ovaryUBERON:000099285.30gold quality
nephron tubuleUBERON:000123185.22gold quality
gingival epitheliumUBERON:000194984.44gold quality
upper lobe of left lungUBERON:000895284.40gold quality
oocyteCL:000002384.27gold quality
kidney epitheliumUBERON:000481984.07gold quality
skin of hipUBERON:000155483.95gold quality
zone of skinUBERON:000001483.91gold quality
superficial temporal arteryUBERON:000161483.82gold quality
metanephric glomerulusUBERON:000473683.66gold quality
cartilage tissueUBERON:000241883.56gold quality
pancreatic ductal cellCL:000207983.53silver quality
renal glomerulusUBERON:000007483.50gold quality
upper lobe of lungUBERON:000894883.41gold quality
cardiac atriumUBERON:000208183.39gold quality
pharyngeal mucosaUBERON:000035583.20gold quality
right atrium auricular regionUBERON:000663182.54gold quality
fundus of stomachUBERON:000116082.52gold quality
skin of legUBERON:000151182.48gold quality
dorsal root ganglionUBERON:000004482.20gold quality
pleuraUBERON:000097782.16gold quality
coronary arteryUBERON:000162182.05gold quality
body of stomachUBERON:000116181.84gold quality
visceral pleuraUBERON:000240181.77gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099181.60gold quality
pylorusUBERON:000116681.37gold quality
parietal pleuraUBERON:000240081.36gold quality
stomachUBERON:000094581.17gold quality
renal medullaUBERON:000036280.90gold quality
left coronary arteryUBERON:000162680.76gold quality
palpebral conjunctivaUBERON:000181280.72gold quality
gingivaUBERON:000182880.36gold quality
urinary bladderUBERON:000125580.19gold quality
body of tongueUBERON:001187680.07gold quality
aortaUBERON:000094779.94gold quality
olfactory segment of nasal mucosaUBERON:000538679.93gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047379.73gold quality
periodontal ligamentUBERON:000826679.52silver quality
adenohypophysisUBERON:000219679.24gold quality
placentaUBERON:000198778.92gold quality
amniotic fluidUBERON:000017378.91gold quality
cortex of kidneyUBERON:000122578.70gold quality
bone marrowUBERON:000237178.44gold quality
descending thoracic aortaUBERON:000234578.27gold quality
esophagogastric junction muscularis propriaUBERON:003584178.21gold quality
mammalian vulvaUBERON:000099777.50gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-CURD-122yes1861.51
E-GEOD-134144yes1603.55
E-GEOD-114530yes1543.01
E-MTAB-11011yes1334.47
E-GEOD-130473yes1063.34
E-MTAB-8530yes950.87
E-CURD-6yes343.62
E-MTAB-7052yes160.02
E-HCAD-1yes55.25
E-CURD-88yes45.46
E-GEOD-135922yes30.41
E-MTAB-8410yes24.91
E-HCAD-4yes22.93
E-MTAB-10553yes19.22
E-CURD-46yes18.66

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cellAxisnTPMProtein (IHC)
Bone marrowtissue409.7not detected
Adipose tissuetissue369.6medium
Smooth muscletissue330.5not detected
Gallbladdertissue324.8low
Thyroid glandtissue296.7medium
Urinary bladdertissue199.2high
Ovarytissue197.2medium
Esophagustissue176.8low
Fallopian tubetissue150.3low
Thymustissue142.7
Cervixtissue140.8low
Pancreastissue119.1not detected
Adrenal glandtissue114.8not detected
Appendixtissue111.8low
Prostatetissue111.1not detected
Lungtissue106.9not detected
Breasttissue86.1not detected
Livertissue79.9not detected
Tonguetissue76.0
Rectumtissue73.8low
Salivary glandtissue72.5medium
Lymph nodetissue63.3medium
Small intestinetissue59.3not detected
Placentatissue54.2high
Stomach 1tissue43.7not detected
Endometrium 1tissue43.6not detected
Parathyroid glandtissue43.4not detected
Heart muscletissue42.6not detected
Colontissue35.2not detected
Kidneytissue32.5low
Seminal vesicletissue27.9not detected
Pituitary glandtissue25.3
Duodenumtissue23.3not detected
Spinal cordtissue23.1
Spleentissue20.6medium
Choroid plexustissue13.5
Olfactory bulbtissue12.6
Nucleus accumbenstissue12.3
Cerebellumtissue11.2not detected
Postcentral gyrustissue10.7
Retinatissue10.0
Testistissue8.3not detected
Vaginatissue8.3low
Hippocampustissue6.5not detected
Cerebral cortextissue6.2not detected
Retrosplenial cortextissue6.2
Hippocampal formationtissue5.6
Entorhinal cortextissue5.6
Occipital cortextissue5.5
Prefrontal cortextissue5.3
Retrosplenial and cingulate cortextissue5.2
Insular cortextissue5.2
Basal gangliatissue4.9not detected
Somatosensory cortextissue4.9
Locus coeruleustissue4.8
Frontal cortextissue4.7
Temporal cortextissue4.5
Motor cortextissue4.0
Ventral forebraintissue4.0
Superior colliculitissue3.9

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Blood vessel (80.5), Flocculonodular lobe (69.6), Hippocampus, CA1 (26.9), Dorsal spinal cord (23.1), Parietal operculum (22.7).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

showing 30 of 43 targets:

TargetRegulation
ADAM2
ALBRepression
AP1Unknown
BGLAPActivation
CCKActivation
CCN2Activation
CCND1Activation
CCNE1Unknown
CD14Activation
CD9Activation
CDK2Unknown
CDK5Activation
COL3A1Activation
CREB1Activation
CXCL8Activation
DNAJB4
DRD2Activation
FASLGActivation
FOSUnknown
FOSBUnknown
GFAPActivation
GRIN1Activation
GRIN2AActivation
IL11Activation
IL2Activation
ITGA2BActivation
LGALS1Activation
MAP2Repression
MMP2Activation
MYCActivation

JASPAR motifs

MotifNameFamily
MA1127.1FOSB::JUNFos-related,Jun-related
MA1135.1FOSB::JUNBFos-related,Jun-related
MA1135.2FOSB::JUNBFos-related,Jun-related
MA1136.1FOSB::JUNBFos-related,Jun-related
UN0122.1FOSBFos-related
UN0122.2FOSBFos-related
UN1112.1CEBPB::FOSBCEBP-related,Fos-related
UN1124.1CEBPE::FOSBCEBP-related,Fos-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)

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

showing 30 of 87 miRNAs:

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-5193100.0067.261744
HSA-MIR-5692B100.0071.322622
HSA-MIR-5692C100.0071.322622
HSA-MIR-1277-5P100.0073.955056
HSA-MIR-7110-3P100.0073.182486
HSA-MIR-34A-5P99.9971.211784
HSA-MIR-449A99.9971.051776
HSA-MIR-806899.9873.852376
HSA-MIR-27A-3P99.9872.132955
HSA-MIR-27B-3P99.9872.132955
HSA-MIR-998599.9872.112939
HSA-MIR-1468-3P99.9672.743797
HSA-MIR-23A-3P99.9574.243163
HSA-MIR-23B-3P99.9574.243163
HSA-MIR-23C99.9573.923192
HSA-MIR-1-3P99.9372.351914
HSA-MIR-20699.9372.501893
HSA-MIR-61399.9171.501710
HSA-MIR-464899.9167.00710
HSA-MIR-4731-5P99.8967.232537
HSA-MIR-4728-5P99.8569.394718
HSA-MIR-6756-5P99.8267.972466
HSA-MIR-6785-5P99.8268.684428
HSA-MIR-6842-5P99.8067.541587
HSA-MIR-7110-5P99.8067.841712
HSA-MIR-204-5P99.7971.622439
HSA-MIR-211-5P99.7971.652440
HSA-MIR-6817-3P99.7968.352126
HSA-MIR-430699.7270.503630
HSA-MIR-149-3P99.7268.223963

Functional genomics

gnomAD constraint: pLI 0.951, LOEUF 0.534, missense Z 1.19 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000353609 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)Missense obs / expo/eConstrained
19:45,468,587–45,470,949193 / 207.10.93no
19:45,471,194–45,472,63535 / 83.50.42no
19:45,472,636–45,473,009148 / 170.00.87no

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

OrganismSymbolGene ID
danio_reriofosbENSDARG00000055751
mus_musculusFosbENSMUSG00000003545
rattus_norvegicusFosbENSRNOG00000046667
drosophila_melanogasterAtf3FBGN0028550

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:95575) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 24 distinct phenotype terms.

Mouse phenotype (MP)Records
decreased bone mineral density1
decreased body length1
decreased body size1
increased anxiety-related response1
decreased anxiety-related response1
abnormal nursing1
abnormal pup retrieval1
abnormal maternal nurturing1
increased exploration in new environment1
abnormal seizure response to electrical stimulation1
reduced NMDA-mediated synaptic currents1
abnormal skin morphology1
abnormal learning/memory/conditioning1
abnormal parental behavior1
abnormal kidney morphology1
abnormal emotion/affect behavior1
decreased mean corpuscular volume1
enlarged kidney1
abnormal frequency of paradoxical sleep1
abnormal locomotor activation1
abnormal depression-related behavior1
tonic-clonic seizures1
impaired spatial learning1
increased locomotor activity1

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.

OrganismUniProtIdentityMethod
Gallus gallusP11939100.0%Diamond
Ovis ariesO0276199.0%Diamond
Mesocricetus auratusO8847997.6%Diamond
Cricetiscus campbelliQ56TT797.6%Diamond
Phodopus roborovskiiQ56TN097.4%Diamond
Bos taurusO7762897.1%Diamond
Felis catusQ8HZP697.1%Diamond
Cricetulus griseusQ9Z2Q896.9%Diamond
Sus scrofaO9793096.8%Diamond
Canis lupus familiarisQ9TUB390.8%Diamond
Drosophila yakubaB4PPK288.0%Diamond
Takifugu rubripesP5345087.2%Diamond
Dichotomyctere fluviatilisQ9149687.2%Diamond
Drosophila simulansB4R09085.7%Diamond
Drosophila erectaB3P5D283.3%Diamond
Cyprinus carpioP7970255.9%Diamond
Avian retrovirus NK24P23050100.0%Diamond
FBJ murine osteosarcoma virusP0110298.5%Diamond
Finkel-Biskis-Jinkins murine sarcoma virusP2917689.5%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).

SymbolTypeEntrez
PPP1R13Lprotein-coding10848
POLR1Gprotein-coding10849
ERCC1protein-coding2067
TRU-TCA1-1tRNA7234
MIR6088ncRNA102464836
KLC3protein-coding147700
ERCC2protein-coding2068
RTN2protein-coding6253
OPA3-RTN2protein-coding144667540
PPM1Nprotein-coding147699
VASPprotein-coding7408

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): K7EJ89, K7EKA0, K7ERZ8, P53539

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 IDNamesCanonical?
P53539-11, FosB-Lyes
P53539-22
P53539-33
P53539-44
P53539-55
P53539-66
P53539-77
P53539-88
P53539-99
P53539-1010
P53539-1111, deltaFosB

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

Domains & families (InterPro)

IDNameType
IPR000837AP-1Family
IPR004827bZIPDomain
IPR046347bZIP_sfHomologous_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 by resolution:

PDBTitleMethodResolution (Å)
9OC3Transcription factor DeltaFOSB/JUND bZIP domain in complex with an effector moleculeX-RAY DIFFRACTION1.73
7UCCTranscription factor FosB/JunD bZIP domain in the reduced formX-RAY DIFFRACTION1.94
5VPETranscription factor FosB/JunD bZIP domain in complex with cognate DNA, type-I crystalX-RAY DIFFRACTION2.05
6UCITranscription factor DeltaFosB bZIP domain self-assembly, oxidized formX-RAY DIFFRACTION2.09
6UCLTranscription factor deltaFosB bZIP domain self-assembly, type-I crystalX-RAY DIFFRACTION2.21
6UCMTranscription factor DeltaFosB bZIP domain self-assembly, type-II crystalX-RAY DIFFRACTION2.42
5VPCTranscription factor FosB/JunD bZIP domain in its oxidized form, type-II crystalX-RAY DIFFRACTION2.5
5VPBTranscription factor FosB/JunD bZIP domain in its oxidized form, type-I crystalX-RAY DIFFRACTION2.69
5VPFTranscription factor FosB/JunD bZIP domain in complex with cognate DNA, type-II crystalX-RAY DIFFRACTION2.69
5VPDTranscription factor FosB/JunD bZIP domain in its oxidized form, type-III crystalX-RAY DIFFRACTION2.79
5VPATranscription factor FosB/JunD bZIP domainX-RAY DIFFRACTION2.83
7UCDTranscription factor FosB/JunD bZIP domain covalently modified with the …X-RAY DIFFRACTION3.21

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P53539-F160.790.21

Human Protein Atlas

Protein class: Predicted intracellular proteins, Transcription factors, Basic domains

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; vesicles

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 (1)

TypePositions
Phosphoserine27

Disulfide bonds (1)

TypePositions
Interchain (with c-285 in jund)172

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

IDPathwayEvidence
R-HSA-9018519Estrogen-dependent gene expressioncurated
R-HSA-9909649Regulation of PD-L1(CD274) transcriptioncurated
R-HSA-8939211ESR-mediated signaling—
R-HSA-9031628NGF-stimulated transcriptionelectronic
R-HSA-198725Nuclear Events (kinase and transcription factor activation)—
R-HSA-162582Signal Transduction—
R-HSA-187037Signaling by NTRK1 (TRKA)—
R-HSA-166520Signaling by NTRKs—
R-HSA-9006931Signaling by Nuclear Receptors—
R-HSA-9006934Signaling by Receptor Tyrosine Kinases—
R-HSA-9938024Somatic hypermutation of immunoglobulin geneselectronic

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 (18): 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), 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

9 top-level categories:

CategoryPathways
Signal Transduction2
ESR-mediated signaling1
Nuclear Events (kinase and transcription factor activation)1
Regulation of PD-L1(CD274) expression1
Affinity selection of immunoglobulins1
Signaling by Receptor Tyrosine Kinases1
Signaling by NTRKs1
Signaling by NTRK1 (TRKA)1
Signaling by Nuclear Receptors1

GO top-level categories

48 GO namespaces:

CategoryTerms
regulation of transcription by RNA polymerase II3
transcription by RNA polymerase II3
RNA polymerase II transcription regulatory region sequence-specific DNA binding3
cellular anatomical structure3
regulation of DNA-templated transcription2
DNA-templated transcription2
response to chemical2
response to ketone2
response to alcohol2
response to oxygen-containing compound2
DNA binding2
negative regulation of DNA-templated transcription1
response to amine1
multi-organism reproductive process1
multi-multicellular organism process1
response to external stimulus1
response to abiotic stimulus1
response to steroid hormone1
response to hormone1
cellular response to chemical stimulus1
cellular response to endogenous stimulus1
response to isoquinoline alkaloid1
adult behavior1
response to cocaine1
response to glucocorticoid1
response to mineralocorticoid1
response to purine-containing compound1
response to organophosphorus1
regulation of gene expression1
regulation of RNA biosynthetic process1
response to alkaloid1
positive regulation of DNA-templated transcription1
cis-regulatory region sequence-specific DNA binding1
chromatin1
DNA-binding transcription factor activity1
DNA-binding transcription factor activity, RNA polymerase II-specific1
DNA-binding transcription activator activity1
positive regulation of transcription by RNA polymerase II1
nucleic acid binding1
double-stranded DNA binding1
sequence-specific DNA binding1
transcription cis-regulatory region binding1
transcription regulator activity1
binding1
chromosome1
intracellular membrane-bounded organelle1
nuclear lumen1
cytoplasm1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 31 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO termNSEvidence
nucleoplasmCCdirect assay
nucleusCCdirect assay
sequence-specific double-stranded DNA bindingMFdirect assay

Protein interactions and networks

STRING

showing 15 of 2,250 interactions by confidence (×1000):

Protein AProtein BPartner UniProtScore
FOSBJUNDP17535896
FOSBJUNP05412863
FOSBEGR1P18146835
FOSBFOSL1P15407800
FOSBFOSL2P15408792
FOSBEGR3Q06889764
FOSBFOSP01100725
FOSBEGR2P11161721
FOSBNR4A1P22736666
FOSBEHMT2Q96KQ7664
FOSBSYT14Q8NB59660
FOSBNPAS4Q8IUM7648
FOSBSYT16Q17RD7637
FOSBCDK5Q00535591
FOSBDUSP12Q9UNI6588

IntAct

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

25 partners by confidence:

PartnerInteraction typeMIscoreRecords
JUNBphysical association0.7405
JUNassociation0.6902
ATF2physical association0.6703
NFE2L2physical association0.6306
POU6F2physical association0.5605
TENT5Bphysical association0.5605
AGXTphysical association0.5603
CENPOphysical association0.5603
CREB5physical association0.5603
CYTH4physical association0.5603
ENKD1physical association0.5603
FAM222Bphysical association0.5603
FAM90A1physical association0.5603
FOXP3physical association0.5603
GLIS2physical association0.5603
NCK2physical association0.5603
NEDD9physical association0.5603
PHC2physical association0.5603
PHF1physical association0.5603
POGZphysical association0.5603
ROR2physical association0.5603
TLE5physical association0.5603
TLX3physical association0.5603
VEZF1physical association0.5603
ZC3H10physical association0.5603

BioGRID (74 interactions; top human partners by supporting records): JUN (Affinity Capture-MS; 5 records), JUNB (Affinity Capture-MS; 5 records), NFE2L2 (Two-hybrid; 3 records), ATF2 (Two-hybrid; 2 records), CREB5 (Two-hybrid; 2 records), LINC00963 (Protein-RNA; 2 records), MIDN (Affinity Capture-MS; 2 records), AES (Two-hybrid), AGXT (Two-hybrid), APEX1 (Affinity Capture-RNA), ATF7 (Affinity Capture-MS), AUH (Affinity Capture-MS), BAG3 (Affinity Capture-Luminescence), CBL (Positive Genetic), CEBPE (Negative Genetic)

SIGNOR signaling

3 signaling interactions:

AEffectBMechanism
CSNK2A1up-regulatesFOSBphosphorylation
(-)-anisomycinup-regulatesFOSB“chemical activation”
N“up-regulates quantity by expression”FOSB“transcriptional regulation”

Protein complexes (CORUM) (1)

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

1 complexes by size:

ComplexSubunitsMembers
FOSB-JUND-SMAD3-SMAD4 complex4FOSB, JUND, SMAD3, SMAD4

Disease & clinical

Genetic variants

Variant evidence for FOSB: 44 ClinVar records (0 pathogenic / likely pathogenic); 1 CIViC cancer variant; 5 GWAS associations.

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance37
Likely benign2
Benign1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 332):

Position(s)EffectΔscoreSites
19:45470950donor_loss1.00002
19:45471186acceptor_gain1.0000
19:45471192–45471193acceptor_loss1.00005
19:45471302–45471303donor_loss1.00003
19:45472526acceptor_gain1.0000
19:45472533–45472534acceptor_gain1.00002
19:45472542–45472543acceptor_gain1.00002
19:45468713–45468714donor_loss0.99003
19:45470950–45470951donor_loss0.99003
19:45471193acceptor_loss0.9900

AlphaMissense

796 missense substitutions predicted likely pathogenic (of 2,158 scored), across 188 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:

ResidueLikely-pathogenic substitutionsMean am_pathogenicityMax am_pathogenicity
N16581.0001.000
H21880.9971.000
F5480.9840.999
D6680.9690.996
D18880.9380.990
D18180.9210.991
N17480.8850.992
S6480.8750.998
D9580.8470.941
C17271.0001.000
R17371.0001.000
C22270.9980.999
W6970.9951.000
E16370.9930.999
F21370.9690.990
E15470.9680.998
E19170.9620.991
K16670.9581.000
F270.9550.986
R15970.9530.997

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

CancerPrognosticp-value
Kidney Renal Clear Cell Carcinoma (validation)favorable1.07e-07
Kidney Renal Clear Cell Carcinoma (TCGA)favorable0.000368
Breast Invasive Carcinoma (validation)favorable0.000637

Disease associations

OMIM: gene MIM:164772 | disease phenotypes:

GWAS associations

5 associations:

StudyTraitp-value
GCST007827_3Alzheimer’s disease or HDL levels (pleiotropy)1e-97
GCST006979_504Heel bone mineral density2e-16
GCST006288_575Heel bone mineral density3e-12
GCST006979_503Heel bone mineral density5e-12
GCST006288_291Heel bone mineral density3e-6

EFO canonical traits (from GWAS)

2 canonical traits:

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

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

CIViC curated variants (1)

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

Rearrangement.

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 12 human assays (13 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
CHEMBL4640716IC5058000 nM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
sodium arseniteincreases activity, increases expression, decreases expression, decreases methylation, affects cotreatment (+1 more)8
Cadmium Chlorideaffects cotreatment, increases expression5
Benzo(a)pyreneaffects methylation, increases expression, increases methylation4
Silicon Dioxideincreases expression4
Dronabinoldecreases expression, decreases reaction, increases expression4
Air Pollutantsincreases abundance, increases expression, affects expression3
Benzenedecreases expression3
Cadmiumdecreases expression, increases expression3
Formaldehydeincreases expression3
Nickelincreases expression3
Tetrachlorodibenzodioxindecreases reaction, increases expression, affects expression3
Asbestos, Crocidoliteaffects expression, increases expression3
Particulate Matterincreases abundance, increases expression3
cylindrospermopsinincreases expression2
Estradiolaffects cotreatment, decreases expression, increases expression2
Hydrogen Peroxideaffects expression, increases expression2
Ozoneincreases expression, affects expression, increases abundance2
Silverdecreases expression, increases expression2
Tetradecanoylphorbol Acetateincreases expression2
Tobacco Smoke Pollutionincreases expression2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxideaffects expression, increases expression2
Thapsigarginincreases expression2
aristolochic acid Iincreases expression1
bisphenol Fincreases expression1
methylmercuric chlorideincreases expression1
triphenyl phosphateaffects expression1
deoxynivalenolaffects cotreatment, increases expression1
2-methyl-4-isothiazolin-3-oneincreases expression1
hydroxyhydroquinoneincreases expression1
beta-lapachoneincreases expression1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4625230BindingInhibition 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 poDiscovery 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):

CellosaurusNameCategorySex
CVCL_A1V3SEES3-1V human FOSB, clone1Embryonic stem cellMale
CVCL_A1V4SEES3-1V human FOSB, clone2Embryonic stem cellMale
CVCL_A1V5SEES3-1V human FOSB, clone3Embryonic stem cellMale
CVCL_D1MKAbcam K-562 FOSB KOCancer cell lineFemale
CVCL_D2J5Abcam Raji FOSB KOCancer cell lineMale
CVCL_E1XNHAP1 FOSB (-) 1Cancer cell lineMale
CVCL_E1XPHAP1 FOSB (-) 2Cancer cell lineMale
CVCL_E1XQHAP1 FOSB (-) 3Cancer cell lineMale
CVCL_UQ52Abcam Jurkat FOSB KOCancer cell lineMale

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

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