FOSB
gene geneOn this page
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
| 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: 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
| Exon | Start | End |
|---|---|---|
| ENSE00000858216 | 45471194 | 45471301 |
| ENSE00002785923 | 45467996 | 45468712 |
| ENSE00003534885 | 45470629 | 45470949 |
| ENSE00004787042 | 45472551 | 45475179 |
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:
| Tissue | QTL | q-value | Slope | Lead variant |
|---|---|---|---|---|
| Brain Cortex | eqtl | 2.5e-03 | +2.10 | 19:46336995:T:A |
| Skin Sun Exposed Lower leg | eqtl | 2.2e-02 | -0.66 | 19:46347744:G:T |
| Whole Blood | eqtl | 2.2e-02 | -0.25 | 19:45985160:C:T |
| Esophagus Gastroesophageal Junction | sqtl | 4.3e-02 | -1.50 | 19:44488416:C:T |
FANTOM5 promoters
showing 10 of 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
showing 100 of 285 tissues 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 |
| lower lobe of lung | UBERON:0008949 | 89.55 | silver quality |
| cardiac muscle of right atrium | UBERON:0003379 | 89.45 | gold quality |
| monocyte | CL:0000576 | 89.32 | gold quality |
| parotid gland | UBERON:0001831 | 88.99 | gold quality |
| omental fat pad | UBERON:0010414 | 88.77 | gold quality |
| peritoneum | UBERON:0002358 | 88.71 | gold quality |
| sperm | CL:0000019 | 88.60 | silver quality |
| mononuclear cell | CL:0000842 | 88.59 | gold quality |
| male germ cell | CL:0000015 | 88.47 | silver quality |
| rectum | UBERON:0001052 | 88.29 | gold quality |
| leukocyte | CL:0000738 | 88.17 | gold quality |
| layer of synovial tissue | UBERON:0007616 | 87.48 | gold quality |
| sural nerve | UBERON:0015488 | 87.41 | gold quality |
| adipose tissue of abdominal region | UBERON:0007808 | 87.36 | gold quality |
| hindlimb stylopod muscle | UBERON:0004252 | 87.17 | gold quality |
| secondary oocyte | CL:0000655 | 86.72 | gold quality |
| ascending aorta | UBERON:0001496 | 86.52 | gold quality |
| thoracic aorta | UBERON:0001515 | 86.43 | gold quality |
| lymph node | UBERON:0000029 | 85.94 | gold quality |
| buccal mucosa cell | CL:0002336 | 85.89 | gold quality |
| left ovary | UBERON:0002119 | 85.80 | gold quality |
| lung | UBERON:0002048 | 85.64 | gold quality |
| epithelial cell of pancreas | CL:0000083 | 85.62 | gold quality |
| right coronary artery | UBERON:0001625 | 85.58 | gold quality |
| ovary | UBERON:0000992 | 85.30 | gold quality |
| nephron tubule | UBERON:0001231 | 85.22 | gold quality |
| gingival epithelium | UBERON:0001949 | 84.44 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 84.40 | gold quality |
| oocyte | CL:0000023 | 84.27 | gold quality |
| kidney epithelium | UBERON:0004819 | 84.07 | gold quality |
| skin of hip | UBERON:0001554 | 83.95 | gold quality |
| zone of skin | UBERON:0000014 | 83.91 | gold quality |
| superficial temporal artery | UBERON:0001614 | 83.82 | gold quality |
| metanephric glomerulus | UBERON:0004736 | 83.66 | gold quality |
| cartilage tissue | UBERON:0002418 | 83.56 | gold quality |
| pancreatic ductal cell | CL:0002079 | 83.53 | silver quality |
| renal glomerulus | UBERON:0000074 | 83.50 | gold quality |
| upper lobe of lung | UBERON:0008948 | 83.41 | gold quality |
| cardiac atrium | UBERON:0002081 | 83.39 | gold quality |
| pharyngeal mucosa | UBERON:0000355 | 83.20 | gold quality |
| right atrium auricular region | UBERON:0006631 | 82.54 | gold quality |
| fundus of stomach | UBERON:0001160 | 82.52 | gold quality |
| skin of leg | UBERON:0001511 | 82.48 | gold quality |
| dorsal root ganglion | UBERON:0000044 | 82.20 | gold quality |
| pleura | UBERON:0000977 | 82.16 | gold quality |
| coronary artery | UBERON:0001621 | 82.05 | gold quality |
| body of stomach | UBERON:0001161 | 81.84 | gold quality |
| visceral pleura | UBERON:0002401 | 81.77 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 81.60 | gold quality |
| pylorus | UBERON:0001166 | 81.37 | gold quality |
| parietal pleura | UBERON:0002400 | 81.36 | gold quality |
| stomach | UBERON:0000945 | 81.17 | gold quality |
| renal medulla | UBERON:0000362 | 80.90 | gold quality |
| left coronary artery | UBERON:0001626 | 80.76 | gold quality |
| palpebral conjunctiva | UBERON:0001812 | 80.72 | gold quality |
| gingiva | UBERON:0001828 | 80.36 | gold quality |
| urinary bladder | UBERON:0001255 | 80.19 | gold quality |
| body of tongue | UBERON:0011876 | 80.07 | gold quality |
| aorta | UBERON:0000947 | 79.94 | gold quality |
| olfactory segment of nasal mucosa | UBERON:0005386 | 79.93 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 79.73 | gold quality |
| periodontal ligament | UBERON:0008266 | 79.52 | silver quality |
| adenohypophysis | UBERON:0002196 | 79.24 | gold quality |
| placenta | UBERON:0001987 | 78.92 | gold quality |
| amniotic fluid | UBERON:0000173 | 78.91 | gold quality |
| cortex of kidney | UBERON:0001225 | 78.70 | gold quality |
| bone marrow | UBERON:0002371 | 78.44 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 78.27 | gold quality |
| esophagogastric junction muscularis propria | UBERON:0035841 | 78.21 | gold quality |
| mammalian vulva | UBERON:0000997 | 77.50 | 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 |
HPA expression
RNA tissue specificity: Low tissue specificity
showing 60 of 79 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM | Protein (IHC) |
|---|---|---|---|
| Bone marrow | tissue | 409.7 | not detected |
| Adipose tissue | tissue | 369.6 | medium |
| Smooth muscle | tissue | 330.5 | not detected |
| Gallbladder | tissue | 324.8 | low |
| Thyroid gland | tissue | 296.7 | medium |
| Urinary bladder | tissue | 199.2 | high |
| Ovary | tissue | 197.2 | medium |
| Esophagus | tissue | 176.8 | low |
| Fallopian tube | tissue | 150.3 | low |
| Thymus | tissue | 142.7 | |
| Cervix | tissue | 140.8 | low |
| Pancreas | tissue | 119.1 | not detected |
| Adrenal gland | tissue | 114.8 | not detected |
| Appendix | tissue | 111.8 | low |
| Prostate | tissue | 111.1 | not detected |
| Lung | tissue | 106.9 | not detected |
| Breast | tissue | 86.1 | not detected |
| Liver | tissue | 79.9 | not detected |
| Tongue | tissue | 76.0 | |
| Rectum | tissue | 73.8 | low |
| Salivary gland | tissue | 72.5 | medium |
| Lymph node | tissue | 63.3 | medium |
| Small intestine | tissue | 59.3 | not detected |
| Placenta | tissue | 54.2 | high |
| Stomach 1 | tissue | 43.7 | not detected |
| Endometrium 1 | tissue | 43.6 | not detected |
| Parathyroid gland | tissue | 43.4 | not detected |
| Heart muscle | tissue | 42.6 | not detected |
| Colon | tissue | 35.2 | not detected |
| Kidney | tissue | 32.5 | low |
| Seminal vesicle | tissue | 27.9 | not detected |
| Pituitary gland | tissue | 25.3 | |
| Duodenum | tissue | 23.3 | not detected |
| Spinal cord | tissue | 23.1 | |
| Spleen | tissue | 20.6 | medium |
| Choroid plexus | tissue | 13.5 | |
| Olfactory bulb | tissue | 12.6 | |
| Nucleus accumbens | tissue | 12.3 | |
| Cerebellum | tissue | 11.2 | not detected |
| Postcentral gyrus | tissue | 10.7 | |
| Retina | tissue | 10.0 | |
| Testis | tissue | 8.3 | not detected |
| Vagina | tissue | 8.3 | low |
| Hippocampus | tissue | 6.5 | not detected |
| Cerebral cortex | tissue | 6.2 | not detected |
| Retrosplenial cortex | tissue | 6.2 | |
| Hippocampal formation | tissue | 5.6 | |
| Entorhinal cortex | tissue | 5.6 | |
| Occipital cortex | tissue | 5.5 | |
| Prefrontal cortex | tissue | 5.3 | |
| Retrosplenial and cingulate cortex | tissue | 5.2 | |
| Insular cortex | tissue | 5.2 | |
| Basal ganglia | tissue | 4.9 | not detected |
| Somatosensory cortex | tissue | 4.9 | |
| Locus coeruleus | tissue | 4.8 | |
| Frontal cortex | tissue | 4.7 | |
| Temporal cortex | tissue | 4.5 | |
| Motor cortex | tissue | 4.0 | |
| Ventral forebrain | tissue | 4.0 | |
| Superior colliculi | tissue | 3.9 |
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:
| 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 |
| UN0122.1 | FOSB | Fos-related |
| UN0122.2 | FOSB | Fos-related |
| UN1112.1 | CEBPB::FOSB | CEBP-related,Fos-related |
| UN1124.1 | CEBPE::FOSB | CEBP-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:
| 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 |
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 / exp | o/e | Constrained |
|---|---|---|---|
| 19:45,468,587–45,470,949 | 193 / 207.1 | 0.93 | no |
| 19:45,471,194–45,472,635 | 35 / 83.5 | 0.42 | no |
| 19:45,472,636–45,473,009 | 148 / 170.0 | 0.87 | no |
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)
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 density | 1 |
| decreased body length | 1 |
| decreased body size | 1 |
| increased anxiety-related response | 1 |
| decreased anxiety-related response | 1 |
| abnormal nursing | 1 |
| abnormal pup retrieval | 1 |
| abnormal maternal nurturing | 1 |
| increased exploration in new environment | 1 |
| abnormal seizure response to electrical stimulation | 1 |
| reduced NMDA-mediated synaptic currents | 1 |
| abnormal skin morphology | 1 |
| abnormal learning/memory/conditioning | 1 |
| abnormal parental behavior | 1 |
| abnormal kidney morphology | 1 |
| abnormal emotion/affect behavior | 1 |
| decreased mean corpuscular volume | 1 |
| enlarged kidney | 1 |
| abnormal frequency of paradoxical sleep | 1 |
| abnormal locomotor activation | 1 |
| abnormal depression-related behavior | 1 |
| tonic-clonic seizures | 1 |
| impaired spatial learning | 1 |
| increased locomotor activity | 1 |
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 |
| 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 erecta | B3P5D2 | 83.3% | 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 |
|---|---|---|
| PPP1R13L | protein-coding | 10848 |
| POLR1G | protein-coding | 10849 |
| ERCC1 | protein-coding | 2067 |
| TRU-TCA1-1 | tRNA | 7234 |
| MIR6088 | ncRNA | 102464836 |
| KLC3 | protein-coding | 147700 |
| ERCC2 | protein-coding | 2068 |
| RTN2 | protein-coding | 6253 |
| OPA3-RTN2 | protein-coding | 144667540 |
| PPM1N | protein-coding | 147699 |
| VASP | protein-coding | 7408 |
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 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 by resolution:
| PDB | Title | Method | Resolution (Å) |
|---|---|---|---|
| 9OC3 | Transcription factor DeltaFOSB/JUND bZIP domain in complex with an effector molecule | X-RAY DIFFRACTION | 1.73 |
| 7UCC | Transcription factor FosB/JunD bZIP domain in the reduced form | X-RAY DIFFRACTION | 1.94 |
| 5VPE | Transcription factor FosB/JunD bZIP domain in complex with cognate DNA, type-I crystal | X-RAY DIFFRACTION | 2.05 |
| 6UCI | Transcription factor DeltaFosB bZIP domain self-assembly, oxidized form | X-RAY DIFFRACTION | 2.09 |
| 6UCL | Transcription factor deltaFosB bZIP domain self-assembly, type-I crystal | X-RAY DIFFRACTION | 2.21 |
| 6UCM | Transcription factor DeltaFosB bZIP domain self-assembly, type-II crystal | X-RAY DIFFRACTION | 2.42 |
| 5VPC | Transcription factor FosB/JunD bZIP domain in its oxidized form, type-II crystal | X-RAY DIFFRACTION | 2.5 |
| 5VPB | Transcription factor FosB/JunD bZIP domain in its oxidized form, type-I crystal | X-RAY DIFFRACTION | 2.69 |
| 5VPF | Transcription factor FosB/JunD bZIP domain in complex with cognate DNA, type-II crystal | X-RAY DIFFRACTION | 2.69 |
| 5VPD | Transcription factor FosB/JunD bZIP domain in its oxidized form, type-III crystal | X-RAY DIFFRACTION | 2.79 |
| 5VPA | Transcription factor FosB/JunD bZIP domain | X-RAY DIFFRACTION | 2.83 |
| 7UCD | Transcription factor FosB/JunD bZIP domain covalently modified with the … | X-RAY DIFFRACTION | 3.21 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P53539-F1 | 60.79 | 0.21 |
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)
| Type | Positions |
|---|---|
| Phosphoserine | 27 |
Disulfide bonds (1)
| Type | Positions |
|---|---|
| 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:
| ID | Pathway | Evidence |
|---|---|---|
| R-HSA-9018519 | Estrogen-dependent gene expression | curated |
| R-HSA-9909649 | Regulation of PD-L1(CD274) transcription | curated |
| R-HSA-8939211 | ESR-mediated signaling | — |
| R-HSA-9031628 | NGF-stimulated transcription | electronic |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | — |
| R-HSA-162582 | Signal Transduction | — |
| 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-9938024 | Somatic hypermutation of immunoglobulin genes | electronic |
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:
| Category | Pathways |
|---|---|
| Signal Transduction | 2 |
| ESR-mediated signaling | 1 |
| Nuclear Events (kinase and transcription factor activation) | 1 |
| Regulation of PD-L1(CD274) expression | 1 |
| Affinity selection of immunoglobulins | 1 |
| Signaling by Receptor Tyrosine Kinases | 1 |
| Signaling by NTRKs | 1 |
| Signaling by NTRK1 (TRKA) | 1 |
| Signaling by Nuclear Receptors | 1 |
GO top-level categories
48 GO namespaces:
| 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 |
| 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 |
| nucleic acid binding | 1 |
| double-stranded DNA binding | 1 |
| sequence-specific DNA binding | 1 |
| transcription cis-regulatory region binding | 1 |
| transcription regulator activity | 1 |
| binding | 1 |
| chromosome | 1 |
| intracellular membrane-bounded organelle | 1 |
| nuclear lumen | 1 |
| cytoplasm | 1 |
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 term | NS | Evidence |
|---|---|---|
| nucleoplasm | CC | direct assay |
| nucleus | CC | direct assay |
| sequence-specific double-stranded DNA binding | MF | direct assay |
Protein interactions and networks
STRING
showing 15 of 2,250 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| FOSB | JUND | P17535 | 896 |
| FOSB | JUN | P05412 | 863 |
| FOSB | EGR1 | P18146 | 835 |
| FOSB | FOSL1 | P15407 | 800 |
| FOSB | FOSL2 | P15408 | 792 |
| FOSB | EGR3 | Q06889 | 764 |
| FOSB | FOS | P01100 | 725 |
| FOSB | EGR2 | P11161 | 721 |
| FOSB | NR4A1 | P22736 | 666 |
| FOSB | EHMT2 | Q96KQ7 | 664 |
| FOSB | SYT14 | Q8NB59 | 660 |
| FOSB | NPAS4 | Q8IUM7 | 648 |
| FOSB | SYT16 | Q17RD7 | 637 |
| FOSB | CDK5 | Q00535 | 591 |
| FOSB | DUSP12 | Q9UNI6 | 588 |
IntAct
Human interaction partners of FOSB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).
25 partners by confidence:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| JUNB | physical association | 0.740 | 5 |
| JUN | association | 0.690 | 2 |
| ATF2 | physical association | 0.670 | 3 |
| NFE2L2 | physical association | 0.630 | 6 |
| POU6F2 | physical association | 0.560 | 5 |
| TENT5B | physical association | 0.560 | 5 |
| AGXT | physical association | 0.560 | 3 |
| CENPO | physical association | 0.560 | 3 |
| CREB5 | physical association | 0.560 | 3 |
| CYTH4 | physical association | 0.560 | 3 |
| ENKD1 | physical association | 0.560 | 3 |
| FAM222B | physical association | 0.560 | 3 |
| FAM90A1 | physical association | 0.560 | 3 |
| FOXP3 | physical association | 0.560 | 3 |
| GLIS2 | physical association | 0.560 | 3 |
| NCK2 | physical association | 0.560 | 3 |
| NEDD9 | physical association | 0.560 | 3 |
| PHC2 | physical association | 0.560 | 3 |
| PHF1 | physical association | 0.560 | 3 |
| POGZ | physical association | 0.560 | 3 |
| ROR2 | physical association | 0.560 | 3 |
| TLE5 | physical association | 0.560 | 3 |
| TLX3 | physical association | 0.560 | 3 |
| VEZF1 | physical association | 0.560 | 3 |
| ZC3H10 | physical association | 0.560 | 3 |
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:
| A | Effect | B | Mechanism |
|---|---|---|---|
| CSNK2A1 | up-regulates | FOSB | phosphorylation |
| (-)-anisomycin | up-regulates | FOSB | “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:
| Complex | Subunits | Members |
|---|---|---|
| FOSB-JUND-SMAD3-SMAD4 complex | 4 | FOSB, 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):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 37 |
| Likely benign | 2 |
| Benign | 1 |
SpliceAI
Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 332):
| Position(s) | Effect | Δscore | Sites |
|---|---|---|---|
| 19:45470950 | donor_loss | 1.0000 | 2 |
| 19:45471186 | acceptor_gain | 1.0000 | |
| 19:45471192–45471193 | acceptor_loss | 1.0000 | 5 |
| 19:45471302–45471303 | donor_loss | 1.0000 | 3 |
| 19:45472526 | acceptor_gain | 1.0000 | |
| 19:45472533–45472534 | acceptor_gain | 1.0000 | 2 |
| 19:45472542–45472543 | acceptor_gain | 1.0000 | 2 |
| 19:45468713–45468714 | donor_loss | 0.9900 | 3 |
| 19:45470950–45470951 | donor_loss | 0.9900 | 3 |
| 19:45471193 | acceptor_loss | 0.9900 |
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:
| Residue | Likely-pathogenic substitutions | Mean am_pathogenicity | Max am_pathogenicity |
|---|---|---|---|
| N165 | 8 | 1.000 | 1.000 |
| H218 | 8 | 0.997 | 1.000 |
| F54 | 8 | 0.984 | 0.999 |
| D66 | 8 | 0.969 | 0.996 |
| D188 | 8 | 0.938 | 0.990 |
| D181 | 8 | 0.921 | 0.991 |
| N174 | 8 | 0.885 | 0.992 |
| S64 | 8 | 0.875 | 0.998 |
| D95 | 8 | 0.847 | 0.941 |
| C172 | 7 | 1.000 | 1.000 |
| R173 | 7 | 1.000 | 1.000 |
| C222 | 7 | 0.998 | 0.999 |
| W69 | 7 | 0.995 | 1.000 |
| E163 | 7 | 0.993 | 0.999 |
| F213 | 7 | 0.969 | 0.990 |
| E154 | 7 | 0.968 | 0.998 |
| E191 | 7 | 0.962 | 0.991 |
| K166 | 7 | 0.958 | 1.000 |
| F2 | 7 | 0.955 | 0.986 |
| R159 | 7 | 0.953 | 0.997 |
HPA cancer prognostics
RNA cancer specificity: Low cancer specificity
Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.
3 prognostic cancer types:
| Cancer | Prognostic | p-value |
|---|---|---|
| Kidney Renal Clear Cell Carcinoma (validation) | favorable | 1.07e-07 |
| Kidney Renal Clear Cell Carcinoma (TCGA) | favorable | 0.000368 |
| Breast Invasive Carcinoma (validation) | favorable | 0.000637 |
Disease associations
OMIM: gene MIM:164772 | disease phenotypes:
GWAS associations
5 associations:
| Study | Trait | p-value |
|---|---|---|
| GCST007827_3 | Alzheimer’s disease or HDL levels (pleiotropy) | 1e-97 |
| GCST006979_504 | Heel bone mineral density | 2e-16 |
| GCST006288_575 | Heel bone mineral density | 3e-12 |
| GCST006979_503 | Heel bone mineral density | 5e-12 |
| GCST006288_291 | Heel bone mineral density | 3e-6 |
EFO canonical traits (from GWAS)
2 canonical traits:
| 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)
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.
| Ligand | Measure | Value |
|---|---|---|
| CHEMBL4640716 | IC50 | 58000 nM |
CTD chemical–gene interactions
111 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| sodium arsenite | increases activity, increases expression, decreases expression, decreases methylation, affects cotreatment (+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 expression, decreases reaction, increases expression | 4 |
| Air Pollutants | increases abundance, increases expression, affects expression | 3 |
| 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 |
| Estradiol | affects cotreatment, decreases expression, increases expression | 2 |
| Hydrogen Peroxide | affects expression, increases expression | 2 |
| Ozone | increases expression, affects expression, increases abundance | 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 | affects expression, increases 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 |
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)
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.
Related Atlas pages
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): epithelioid hemangioma, osteoblastoma, pseudomyogenic hemangioendothelioma