FOSL1

Summary

FOSL1 (FOS like 1, AP-1 transcription factor subunit, HGNC:13718) is a protein-coding gene on chromosome 11q13.1, encoding Fos-related antigen 1 (P15407). It is a selective cancer dependency (DepMap: 29.9% of cell lines).

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

Source: NCBI Gene 8061 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 55 total
• Cancer dependency (DepMap): dependent in 29.9% of screened cell lines
• Transcription factor: yes — 54 downstream targets (CollecTRI)
• MANE Select transcript: NM_005438

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13718
Approved symbol	FOSL1
Name	FOS like 1, AP-1 transcription factor subunit
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	fra-1
Ensembl gene	ENSG00000175592
Ensembl biotype	protein_coding
OMIM	136515
Entrez	8061

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000312562, ENST00000448083, ENST00000531493, ENST00000532401, ENST00000534222, ENST00000913991, ENST00000913992, ENST00000950881

RefSeq mRNA: 5 — MANE Select: NM_005438 NM_001300844, NM_001300855, NM_001300856, NM_001300857, NM_005438

CCDS: CCDS73324, CCDS76436, CCDS76437, CCDS8121

Canonical transcript exons

ENST00000312562 — 4 exons

Exon	Start	End
ENSE00001190318	65896809	65897006
ENSE00001190326	65900241	65900388
ENSE00002175025	65892049	65893296
ENSE00003673255	65894014	65894121

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 93.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.3856 / max 827.8208, expressed in 1632 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120729	37.3934	1610
120730	5.3998	1129
120731	0.5925	274

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	93.80	gold quality
stromal cell of endometrium	CL:0002255	87.18	gold quality
gall bladder	UBERON:0002110	86.76	gold quality
vena cava	UBERON:0004087	86.65	gold quality
mucosa of urinary bladder	UBERON:0001259	83.04	gold quality
esophagus mucosa	UBERON:0002469	82.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.22	gold quality
islet of Langerhans	UBERON:0000006	81.19	gold quality
omental fat pad	UBERON:0010414	81.18	gold quality
peritoneum	UBERON:0002358	81.07	gold quality
ascending aorta	UBERON:0001496	80.50	gold quality
thoracic aorta	UBERON:0001515	80.15	gold quality
cervix epithelium	UBERON:0004801	80.14	gold quality
left uterine tube	UBERON:0001303	79.42	gold quality
adipose tissue of abdominal region	UBERON:0007808	79.01	gold quality
lower esophagus mucosa	UBERON:0035834	78.64	gold quality
skin of abdomen	UBERON:0001416	78.41	gold quality
buccal mucosa cell	CL:0002336	77.78	gold quality
descending thoracic aorta	UBERON:0002345	77.74	gold quality
tongue squamous epithelium	UBERON:0006919	77.64	gold quality
upper lobe of left lung	UBERON:0008952	77.23	gold quality
esophagus	UBERON:0001043	76.34	gold quality
left adrenal gland	UBERON:0001234	76.33	gold quality
left coronary artery	UBERON:0001626	76.27	gold quality
cervix squamous epithelium	UBERON:0006922	76.22	silver quality
left adrenal gland cortex	UBERON:0035825	75.60	gold quality
right coronary artery	UBERON:0001625	75.55	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	75.51	gold quality
aorta	UBERON:0000947	75.29	gold quality
upper lobe of lung	UBERON:0008948	75.28	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	124.66
E-ENAD-17	no	55.88
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

54 targets.

Target	Regulation
AP1
CCL2
CCNA2	Unknown
CCND1	Activation
CDKN2A	Unknown
CEBPA
CHUK
CLU	Unknown
CXCL8	Unknown
DCN
EGF
EGFR
ELN	Unknown
ESR1
EZH2	Unknown
FGF2	Unknown
FN1
FOSL1
GABRB3
GCLC	Unknown
GCM1
IKBKB
IL11	Activation
IL2	Unknown
IL6	Activation
ITGAV	Repression
ITGB3	Repression
IVL	Unknown
JUNB
KAT2B

JASPAR motifs

Motif	Name	Family
MA0477.1	FOSL1	Fos-related
MA0477.2	FOSL1	Fos-related
MA0477.3	FOSL1	Fos-related
MA1128.1	FOSL1::JUN	Fos-related::Jun-related
MA1128.2	FOSL1::JUN	Fos-related::Jun-related
MA1129.1	FOSL1::JUN	Fos-related::Jun-related
MA1137.1	FOSL1::JUNB	Fos-related::Jun-related
MA1137.2	FOSL1::JUNB	Fos-related::Jun-related
MA1142.1	FOSL1::JUND	Fos-related::Jun-related
MA1142.2	FOSL1::JUND	Fos-related::Jun-related
MA1143.1	FOSL1::JUND	Fos-related::Jun-related
MA1143.2	FOSL1::JUND	Fos-related::Jun-related

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

Upstream regulators (CollecTRI, top): AP1, ATF1, CREB1, CTNNB1, EGR1, ELK1, ESR1, ETS1, ETS2, F2R, F2RL1, FOS, FOSL1, FOSL2, HMGA2, JUN, JUND, MYC, NR1I2, PGR, RBMX, RELA, RUNX2, SP1, SRF, SRY, TP53, TP73

miRNA regulators (miRDB)

77 targeting FOSL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-646	99.68	67.84	1645

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 29.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Molecular mechanism of transforming growth factor (TGF)-beta1-induced glutathione depletion in alveolar epithelial cells. Involvement of AP-1/ARE and Fra-1. (PMID:11912197)
• upregulation of cyclin D1 and Fra-1 in human colorectal adenocarcinomas is driven by abnormally expressed beta-catenin (PMID:12209953)
• The regulation by Akt3 was found to be due to two specific regions in the Fra-1 regulatory sequence which match Sp1 consensus sites (PMID:12692267)
• cooperative interactions between factors binding to multiple cis-elements of the -379/-283 promoter region appear to regulate TPA-induced fra-1 transcription in human cells (PMID:13679379)
• Fra-1 expression is associated with a more malignant cell phenotype and suggest that Fra-1 could have a pivotal role in breast cancer progression. (PMID:15608675)
• Delayed recruitment of Fra-1 to the IL-8 promoter provides an example how AP-1 subunits may dampen excessive chemokine synthesis. (PMID:15615716)
• Fra-1 may likely play an important role in the maintenance/progression of malignant gliomas (PMID:15831677)
• PI3K through p21-activated kinase 1 regulates FRA-1 proto-oncogene induction by cigarette smoke and the subsequent activation of the Elk1 and cAMP-response element-binding protein transcription factors (PMID:16490785)
• Overexpression of Fra-1, leading to a persistent high cytoplasmic accumulation, may play a role in the process of breast carcinogenesis. (PMID:17192200)
• Data report that the intrinsic instability of Fra-1 depends on a single destabilizer contained within the C-terminal 30 to 40 amino acids. (PMID:17371847)
• The activation of MMP-9 promoter is dependent upon interactions of Fra-1/c-Jun with Stat3. (PMID:17572495)
• FRA-1 can promote motility, invasion, and anchorage-independent growth of lung epithelial cells in vitro, but is insufficient for tumor formation (PMID:17616677)
• Data suggest that HGF-induced effects in some mesothelioma cells are mediated via activation of a novel PI3K/ERK5/Fra-1 feedback pathway (PMID:17872495)
• a large multiprotein complex, which includes Fra-1, p300, P/CAF, junD, junB, and Sp1 acts at the AP1-5 site to produce a synergistic increase in hINV gene expression (PMID:17882273)
• Fra-1 is associated with cell migration in human MMs and that Fra-1 modulation of CD44 may govern migration of selected MMs. (PMID:18096084)
• In colon cells, the induction of epithelial mesenchymal transition by oncogenic Ha-RAS could occur through the overexpression of proteins like FRA-1 and vimentin. (PMID:18098284)
• IL-13R alpha 2, EphA2, and Fra-1 are attractive therapeutic targets representing molecular denominators of high-grade astrocytomas. One hundred percent of GBM tumors overexpress at least one of these proteins. (PMID:18172271)
• Data suggest that Fra-1 enhances lung cancer epithelial cell motility and invasion by inducing the activity of matrix metalloproteinases, in particular MMP-2 and MMP-9, and EGFR-activated signaling. (PMID:18288638)
• A prominent role for ERK1/2 was shown in the TPA-induced activation of c-Jun regulating the Fra1 promoter. (PMID:18435914)
• Fra-1 might play a role in the progression and prognosis of NSCLC. (PMID:19160107)
• study found surface parameters for Fra-1 are similar in general to those of c-Fos and c-Jun; differences were found in the interactions of the three proteins with phospholipids (PMID:19384981)
• Chromatin immunoprecipitation assays confirmed that JunB/Fra-1 proteins interact in vivo with the beta4-integrin promoter and that JunB/Fra-1 promoter occupancy is reduced during keratinocyte differentiation as well as in HPV8 E2 positive keratinocytes (PMID:19923172)
• Expression of the FOSL1 gene proved to substantially increase in both psoriatic lesions of the skin and atherosclerotic lesions of vessels as compared with nonlesion samples. (PMID:20198886)
• AP-1 (Fra-1/c-Jun)-mediated induction of expression of matrix metalloproteinase-2 is required for 15S-hydroxyeicosatetraenoic acid-induced angiogenesis (PMID:20353950)
• in tumor tissue derived from highly metastatic basal-like MDA-MB231 cells, high levels of c-Jun/Fra1 complexes were detected (PMID:20511396)
• High FOSL1 is associated with melanoma. (PMID:20663135)
• FRA1 takes part in a control of architecture and migratory nature of GBM cells. It is a phosphorylated factor that transactivates JunB with which it makes effectively AP-1 pairs. (PMID:21088499)
• A high frequency of Fra-1 in DCIS tumours may be associated with early events in breast carcinogenesis. Although Fra-1 expression correlated with features of a more aggressive phenotype in IDC, no relationship with overall survival was found. (PMID:21371080)
• Fra-1 is an important mediator of interstitial lung disease following gefitinib treatment (PMID:21460858)
• Activated nuclear factor kappaB and Fos-related antigen 1 are elevated in epithelial cells in lung tissues of patients with acute respiratory distress syndrome. (PMID:21526963)
• RT-PCR showed that FOSL1 from osteoblasts from Pfeiffer syndrome grown on PLPG acid plates were upregulated after 30 days. (PMID:21558934)
• Two AP-1 components, c-Jun and Fra-1, were phosphorylated, and bound to the AP-1 binding site of the MMP-1 promoter in 143B cells. (PMID:21640141)
• study shows that YAP could promote cell proliferation by activating transcription factor Fra-1 in oral squamous cell carcinoma. (PMID:21708480)
• study reports Fra-1 is highly expressed in the muscle-invasive form of bladder cancer and to a lesser extent in superficial bladder cancer; gene coding for AXL tyrosine kinase is directly upregulated by Fra-1 in bladder cancer and other cell lines; data demonstrate that AXL mediates the effect of Fra-1 on tumour cell motility but not on cell proliferation (PMID:21822309)
• data suggest the involvement of an injury-induced Fra-1 transcription factor as a regulator of keratinocyte gene expression, which might act as an antagonistic player to restrict epithelial-driven angiogenic responses during normal skin flap integration. (PMID:21840727)
• Molecular characterization of the microRNA-138-Fos-like antigen 1 (FOSL1) regulatory module in squamous cell carcinoma. (PMID:21969367)
• This study demonstrated ESCC patients positive for Fra-1 to be associated with poor prognosis. The findings also suggest that Fra-1 regulation may play an important role in the progression of ESCC. (PMID:22028113)
• identified Fra-1 as a new target of miR-34a and demonstrated that miR-34a inhibits Fra-1 expression at both protein and messenger RNA levels; p53 indirectly regulates Fra-1 expression via a miR-34a-dependant manner in colon cancer cells (PMID:22198213)
• Enhanced FOSL1 expression significantly correlated with high psoriasis area and severity index. High level of FOSL1 gene expression was proposed to be a marker of pathological process activity in psoriasis. (PMID:22235402)
• PKCtheta signalling as an important regulator of Fra-1 accumulation in estrogen receptor positive breast cancer cells. (PMID:22286759)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fosl1a	ENSDARG00000015355
danio_rerio	fosl1b	ENSDARG00000079373
mus_musculus	Fosl1	ENSMUSG00000024912
rattus_norvegicus	Fosl1	ENSRNOG00000072086
drosophila_melanogaster	Atf3	FBGN0028550

Paralogs (8): FOSL2 (ENSG00000075426), BATF3 (ENSG00000123685), FOSB (ENSG00000125740), JDP2 (ENSG00000140044), BATF (ENSG00000156127), ATF3 (ENSG00000162772), BATF2 (ENSG00000168062), FOS (ENSG00000170345)

Protein

Protein identifiers

Fos-related antigen 1 — P15407 (reviewed: P15407)

All UniProt accessions (5): P15407, A0A0S2Z595, E9PKL5, E9PPX2, E9PQT6

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Heterodimer. Interacts with the BAF multiprotein chromatin-remodeling complex subunits SMARCB1 and SMARCD1. Interacts with ARID1A and JUN.

Subcellular location. Nucleus.

Similarity. Belongs to the bZIP family. Fos subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P15407-1	1	yes
P15407-2	2

RefSeq proteins (5): NP_001287773, NP_001287784, NP_001287785, NP_001287786, NP_005429* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00170

UniProt features (11 total): region of interest 6, chain 1, domain 1, splice variant 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15407-F1	67.32	0.26

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): 265

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9031628	NGF-stimulated transcription

MSigDB gene sets: 403 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, AP1_01, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, MORF_FLT1, MORF_MSH3, AMIT_DELAYED_EARLY_GENES, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, TTTGTAG_MIR520D, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, MORF_BRCA1, MORF_ATRX, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP

GO Biological Process (17): in utero embryonic development (GO:0001701), toll-like receptor signaling pathway (GO:0002224), regulation of transcription by RNA polymerase II (GO:0006357), chemotaxis (GO:0006935), inflammatory response (GO:0006954), cellular defense response (GO:0006968), vitellogenesis (GO:0007296), positive regulation of cell population proliferation (GO:0008284), response to wounding (GO:0009611), response to virus (GO:0009615), gene expression (GO:0010467), cytokine-mediated signaling pathway (GO:0019221), placenta blood vessel development (GO:0060674), integrated stress response signaling (GO:0140467), positive regulation of miRNA transcription (GO:1902895), positive regulation of DNA-templated transcription initiation (GO:2000144), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (8): 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 factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837), promoter-specific chromatin binding (GO:1990841), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Nuclear Events (kinase and transcription factor activation)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
defense response	2
positive regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription cis-regulatory region binding	2
cellular anatomical structure	2
chordate embryonic development	1
pattern recognition receptor signaling pathway	1
transcription by RNA polymerase II	1
response to chemical	1
taxis	1
cytoplasm organization	1
female gamete generation	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to stress	1
response to other organism	1
macromolecule biosynthetic process	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
blood vessel development	1
placenta development	1
cellular response to stress	1
intracellular signaling cassette	1
miRNA transcription	1
regulation of miRNA transcription	1
positive regulation of miRNA metabolic process	1
DNA-templated transcription initiation	1
regulation of DNA-templated transcription initiation	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transcription regulator activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1

Protein interactions and networks

STRING

2984 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOSL1	JUND	P17535	998
FOSL1	JUNB	P17275	996
FOSL1	JUN	P05412	996
FOSL1	FOSB	P53539	985
FOSL1	FOSL2	P15408	985
FOSL1	FOS	P01100	984
FOSL1	RELA	Q04206	862
FOSL1	ATF3	P18847	853
FOSL1	MAP3K11	Q16584	802
FOSL1	CEBPB	P17676	785
FOSL1	FTH1	P02794	778
FOSL1	MARK2	Q7KZI7	775
FOSL1	FKBP2	P26885	769
FOSL1	AHNAK	Q09666	769
FOSL1	COX8A	P10176	766
FOSL1	PLCB3	Q01970	766

IntAct

119 interactions, top by confidence:

A	B	Type	Score
JUN	FOS	psi-mi:“MI:0914”(association)	0.980
FOSL1	JUNB	psi-mi:“MI:0915”(physical association)	0.890
JUNB	FOSL1	psi-mi:“MI:0407”(direct interaction)	0.890
JUNB	FOSL1	psi-mi:“MI:0915”(physical association)	0.890
JUN	FOSL1	psi-mi:“MI:2364”(proximity)	0.850
FOSL1	JUN	psi-mi:“MI:0914”(association)	0.850
FOSL1	JUN	psi-mi:“MI:0407”(direct interaction)	0.850
JUN	FOSL1	psi-mi:“MI:0407”(direct interaction)	0.850
FOSL1	JUN	psi-mi:“MI:2364”(proximity)	0.850
FOSL1	USF1	psi-mi:“MI:0915”(physical association)	0.780
FOSL1	NME7	psi-mi:“MI:0915”(physical association)	0.780
NME7	FOSL1	psi-mi:“MI:0915”(physical association)	0.780
JUND	FOSL1	psi-mi:“MI:0914”(association)	0.730
CREB5	FOSL1	psi-mi:“MI:0915”(physical association)	0.720
FOSL1	CREB5	psi-mi:“MI:0915”(physical association)	0.720
ATF2	FOSL1	psi-mi:“MI:0407”(direct interaction)	0.690
FOSL1	TAB2	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (99): FOSL1 (Two-hybrid), CREB5 (Two-hybrid), NME7 (Two-hybrid), LDOC1 (Two-hybrid), CALCOCO1 (Two-hybrid), FOSL1 (Two-hybrid), FOSL1 (Two-hybrid), FOSL1 (Reconstituted Complex), TICAM1 (Affinity Capture-Western), TRAF3 (Affinity Capture-Western), FOSL1 (Affinity Capture-Western), FOSL1 (Affinity Capture-MS), FOSL1 (Affinity Capture-MS), FOSL1 (Two-hybrid), FOSL1 (Two-hybrid)

ESM2 similar proteins: A6NKD9, A7YY54, D3ZLB7, E9Q1P8, E9Q6B2, O00287, O35779, O77627, O77628, O97676, P03966, P04198, P05411, P05412, P05627, P09450, P10158, P11939, P12981, P13346, P15066, P15407, P17275, P17325, P17535, P18870, P23050, P24898, P26014, P27921, P48755, P52909, P53539, P54864, P56432, Q0VBZ5, Q2VPU4, Q61127, Q61976, Q63379

Diamond homologs: A8MPH9, B3MTI9, B3P5D2, B4G652, B4HZE8, B4JYN3, B4K617, B4M5T7, B4NBL5, B4PPK2, B4R090, O02761, O77628, O88479, O97930, P01100, P01101, P01102, P10158, P11939, P12841, P13346, P15407, P18847, P21525, P23050, P29176, P53450, Q29AP1, Q2KII1, Q56TN0, Q56TT7, Q8HZP6, Q91496, Q9Z2Q8, P48755, P53539, P29596, Q60765, Q6DGM8

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
F2RL1	“up-regulates quantity by expression”	FOSL1	“transcriptional regulation”
F2R	“up-regulates quantity by expression”	FOSL1	“transcriptional regulation”
PRKCQ	“up-regulates activity”	FOSL1	phosphorylation
“Integrator complex”	“down-regulates quantity by repression”	FOSL1	“transcriptional regulation”
FOSL2	“up-regulates quantity by expression”	FOSL1	“transcriptional regulation”
JUND	“up-regulates quantity by expression”	FOSL1	“transcriptional regulation”
JUN	“up-regulates quantity by expression”	FOSL1	“transcriptional regulation”
USF1	“down-regulates activity”	FOSL1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 48 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Cellular response to starvation	5	21.8×	2e-04
Response of EIF2AK4 (GCN2) to amino acid deficiency	6	17.5×	2e-04
Regulation of PD-L1(CD274) transcription	6	17.2×	2e-04
Estrogen-dependent gene expression	6	11.9×	4e-04
Signaling by Interleukins	5	8.4×	6e-03
Signaling by Receptor Tyrosine Kinases	6	8.2×	3e-03
Cellular responses to stress	8	7.8×	4e-04
Cellular responses to stimuli	9	7.5×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
integrated stress response signaling	10	149.4×	1e-17
response to endoplasmic reticulum stress	6	21.3×	4e-05
cellular response to hypoxia	5	12.9×	2e-03
regulation of cell cycle	8	12.7×	3e-05
transcription by RNA polymerase II	7	10.5×	3e-04
positive regulation of gene expression	10	8.2×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

522 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65893292:GTCTC:G	acceptor_gain	1.0000
11:65893294:CTC:C	acceptor_gain	1.0000
11:65893295:TC:T	acceptor_gain	1.0000
11:65893296:CCTG:C	acceptor_gain	1.0000
11:65893296:CCTGT:C	acceptor_loss	1.0000
11:65893297:C:CC	acceptor_gain	1.0000
11:65893299:G:C	acceptor_gain	1.0000
11:65893299:G:GC	acceptor_gain	1.0000
11:65893308:C:CT	acceptor_gain	1.0000
11:65893309:A:T	acceptor_gain	1.0000
11:65894008:GCTCA:G	donor_loss	1.0000
11:65894010:TCACC:T	donor_loss	1.0000
11:65894011:CA:C	donor_loss	1.0000
11:65894012:A:AC	donor_gain	1.0000
11:65894013:C:CC	donor_gain	1.0000
11:65894013:C:CG	donor_loss	1.0000
11:65894013:CCG:C	donor_gain	1.0000
11:65894040:T:TA	donor_gain	1.0000
11:65894117:CTGAT:C	acceptor_gain	1.0000
11:65894118:TGAT:T	acceptor_gain	1.0000
11:65894122:C:CC	acceptor_gain	1.0000
11:65894122:CTGG:C	acceptor_loss	1.0000
11:65897004:CTT:C	acceptor_gain	1.0000
11:65900236:CTCA:C	donor_loss	1.0000
11:65900237:TCA:T	donor_loss	1.0000
11:65900238:CACC:C	donor_loss	1.0000
11:65900239:A:C	donor_loss	1.0000
11:65900240:CCTG:C	donor_gain	1.0000
11:65893297:C:T	acceptor_gain	0.9900
11:65894012:ACCG:A	donor_gain	0.9900

AlphaMissense

1744 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65893220:A:G	L161P	1.000
11:65893241:A:G	L154P	1.000
11:65893283:A:G	L140P	1.000
11:65894021:A:G	L133P	1.000
11:65894021:A:T	L133Q	1.000
11:65894033:A:G	L129P	1.000
11:65894041:C:A	R126S	1.000
11:65894041:C:G	R126S	1.000
11:65894042:C:A	R126M	1.000
11:65894042:C:G	R126T	1.000
11:65894045:C:G	R125P	1.000
11:65894050:C:A	R123S	1.000
11:65894050:C:G	R123S	1.000
11:65894051:C:A	R123M	1.000
11:65894051:C:G	R123T	1.000
11:65894052:T:C	R123G	1.000
11:65894053:G:C	C122W	1.000
11:65894055:A:G	C122R	1.000
11:65894061:C:G	A120P	1.000
11:65894063:G:T	A119E	1.000
11:65894066:G:T	A118D	1.000
11:65894071:C:A	K116N	1.000
11:65894071:C:G	K116N	1.000
11:65894073:T:C	K116E	1.000
11:65894074:G:C	N115K	1.000
11:65894074:G:T	N115K	1.000
11:65894075:T:A	N115I	1.000
11:65894076:T:C	N115D	1.000
11:65894085:G:T	R112S	1.000
11:65893187:C:T	C172Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000088891 (11:65893986 A>T), RS1000469488 (11:65899188 C>G,T), RS1000784638 (11:65893516 G>A), RS1001062319 (11:65893831 C>T), RS1001235039 (11:65899526 G>A), RS1001442226 (11:65899784 C>A,T), RS1002153122 (11:65894838 G>A,T), RS1002184175 (11:65894573 C>T), RS1002296696 (11:65900710 A>G), RS1002483683 (11:65896252 T>C), RS1002821459 (11:65900496 T>A), RS1002948107 (11:65896757 C>T), RS1003688900 (11:65895742 T>A), RS1003755310 (11:65895483 A>C), RS1004090720 (11:65896344 T>A)

Disease associations

OMIM: gene MIM:136515 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001725_13	Inflammatory bowel disease	3.000000e-10
GCST002481_8	Acne (severe)	3.000000e-11
GCST004346_52	Psoriasis	7.000000e-09
GCST004600_97	Eosinophil percentage of white cells	3.000000e-17
GCST004606_204	Eosinophil count	7.000000e-24
GCST004624_189	Sum eosinophil basophil counts	4.000000e-22
GCST009798_25	Asthma	2.000000e-09
GCST012227_664	Hip circumference adjusted for BMI	2.000000e-08
GCST90002381_514	Eosinophil count	5.000000e-47
GCST90002382_387	Eosinophil percentage of white cells	4.000000e-38

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0005090	basophil count
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases activity, affects binding, increases expression, increases phosphorylation (+6 more)	10
Tetrachlorodibenzodioxin	decreases reaction, increases expression, affects expression	8
Benzo(a)pyrene	increases expression, increases methylation, decreases methylation	7
Cadmium Chloride	affects cotreatment, increases expression, increases abundance	7
Cyclosporine	affects cotreatment, increases expression	6
Cisplatin	decreases expression, increases reaction, increases expression, affects response to substance	5
Estradiol	affects cotreatment, increases expression	5
Silicon Dioxide	increases expression, decreases expression	5
Aflatoxin B1	affects expression, increases expression	5
Particulate Matter	increases abundance, increases expression, affects cotreatment	5
bisphenol A	affects cotreatment, affects expression, decreases expression	4
(+)-JQ1 compound	affects binding, decreases reaction, decreases expression	4
Asbestos, Crocidolite	affects expression, increases expression, increases reaction	4
Cadmium	increases abundance, increases expression	3
Lipopolysaccharides	affects cotreatment, increases expression, affects expression, affects response to substance	3
lasiocarpine	increases expression	2
methyleugenol	increases expression	2
lead acetate	increases expression, affects cotreatment	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	affects cotreatment, increases expression	2
Decitabine	affects methylation, increases expression	2
Arsenic Trioxide	increases expression	2
Arsenic	increases abundance, increases expression, affects cotreatment	2
Aspirin	affects binding, increases reaction, decreases expression	2
Dust	decreases expression	2
Methylnitronitrosoguanidine	increases expression, decreases expression, affects binding, increases reaction	2
N-Nitrosopyrrolidine	increases expression	2
Oxygen	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Polycyclic Aromatic Hydrocarbons	increases expression, affects cotreatment, increases abundance	2

Cellosaurus cell lines

14 cell lines: 9 cancer cell line, 3 embryonic stem cell, 1 telomerase immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1V6	SEES3-1V human FOSL1, clone1	Embryonic stem cell	Male
CVCL_A1V7	SEES3-1V human FOSL1, clone2	Embryonic stem cell	Male
CVCL_A1V8	SEES3-1V human FOSL1, clone3	Embryonic stem cell	Male
CVCL_B8GA	Abcam HCT 116 FOSL1 KO	Cancer cell line	Male
CVCL_B8W1	Abcam MCF-7 FOSL1 KO	Cancer cell line	Female
CVCL_B9IJ	Abcam A-549 FOSL1 KO	Cancer cell line	Male
CVCL_C3K6	N/Tert-1 FOSL1	Telomerase immortalized cell line	Male
CVCL_D7Q4	Ubigene A-549 FOSL1 KO	Cancer cell line	Male
CVCL_D8LK	Ubigene HCT 116 FOSL1 KO	Cancer cell line	Male
CVCL_D9F1	Ubigene HEK293 FOSL1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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