FSTL1

Summary

FSTL1 (follistatin like 1, HGNC:3972) is a protein-coding gene on chromosome 3q13.33, encoding Follistatin-related protein 1 (Q12841). Secreted glycoprotein that is involved in various physiological processes, such as angiogenesis, regulation of the immune response, cell proliferation and differentiation.

This gene encodes a protein with similarity to follistatin, an activin-binding protein. It contains an FS module, a follistatin-like sequence containing 10 conserved cysteine residues. This gene product is thought to be an autoantigen associated with rheumatoid arthritis.

Source: NCBI Gene 11167 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_007085

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3972
Approved symbol	FSTL1
Name	follistatin like 1
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	FRP, FSL1, OCC1, OCC-1, tsc36
Ensembl gene	ENSG00000163430
Ensembl biotype	protein_coding
OMIM	605547
Entrez	11167

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 12 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000295633, ENST00000424703, ENST00000464690, ENST00000467994, ENST00000468098, ENST00000469005, ENST00000472536, ENST00000480823, ENST00000485968, ENST00000488318, ENST00000710954, ENST00000875453, ENST00000875454, ENST00000875455, ENST00000936490, ENST00000955572, ENST00000955573, ENST00000955574, ENST00000955575

RefSeq mRNA: 1 — MANE Select: NM_007085 NM_007085

CCDS: CCDS2998

Canonical transcript exons

ENST00000295633 — 11 exons

Exon	Start	End
ENSE00001074451	120410952	120410984
ENSE00001873188	120450897	120450992
ENSE00001940161	120409532	120409662
ENSE00003491862	120450684	120450746
ENSE00003512862	120415923	120416027
ENSE00003540743	120411854	120411983
ENSE00004014190	120399883	120399959
ENSE00004014191	120403242	120403354
ENSE00004014192	120392293	120396996
ENSE00004014195	120402808	120402918
ENSE00004014196	120404853	120404971

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 99.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 247.1482 / max 3142.6245, expressed in 1409 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44078	245.5009	1409
44063	0.9789	464
44062	0.6684	329

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.84	gold quality
calcaneal tendon	UBERON:0003701	99.68	gold quality
smooth muscle tissue	UBERON:0001135	99.40	gold quality
gall bladder	UBERON:0002110	99.26	gold quality
colonic epithelium	UBERON:0000397	99.19	gold quality
ascending aorta	UBERON:0001496	99.11	gold quality
thoracic aorta	UBERON:0001515	99.11	gold quality
right coronary artery	UBERON:0001625	99.07	gold quality
descending thoracic aorta	UBERON:0002345	99.05	gold quality
left coronary artery	UBERON:0001626	99.04	gold quality
left uterine tube	UBERON:0001303	98.94	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.82	gold quality
aorta	UBERON:0000947	98.80	gold quality
right atrium auricular region	UBERON:0006631	98.80	gold quality
ventricular zone	UBERON:0003053	98.79	gold quality
lower esophagus	UBERON:0013473	98.78	gold quality
sural nerve	UBERON:0015488	98.77	gold quality
nerve	UBERON:0001021	98.73	gold quality
tibial nerve	UBERON:0001323	98.73	gold quality
popliteal artery	UBERON:0002250	98.73	gold quality
tibial artery	UBERON:0007610	98.73	gold quality
omental fat pad	UBERON:0010414	98.70	gold quality
peritoneum	UBERON:0002358	98.63	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.63	gold quality
mucosa of stomach	UBERON:0001199	98.50	gold quality
artery	UBERON:0001637	98.43	gold quality
endocervix	UBERON:0000458	98.33	gold quality
vermiform appendix	UBERON:0001154	98.31	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.24	gold quality
coronary artery	UBERON:0001621	98.02	gold quality

Single-cell (SCXA)

Detected in 31 experiment(s), a significant marker in 30.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	1619.39
E-CURD-112	yes	1579.32
E-CURD-79	yes	1397.24
E-MTAB-7407	yes	1361.99
E-HCAD-13	yes	420.48
E-MTAB-10018	yes	281.13
E-MTAB-8530	yes	256.47
E-CURD-10	yes	199.18
E-MTAB-8142	yes	108.82
E-MTAB-10287	yes	99.45
E-HCAD-1	yes	93.18
E-MTAB-8410	yes	61.28
E-GEOD-135922	yes	57.89
E-HCAD-10	yes	52.77
E-GEOD-134144	yes	35.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AKT1

miRNA regulators (miRDB)

159 targeting FSTL1, 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-9-5P	100.00	72.28	2361
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753

Literature-anchored findings (GeneRIF, showing 40)

• Whilst follistatin expression is unchanged, follistatin-related gene is down-regulated in endometrial carcinoma. (PMID:15296481)
• FRP mRNA is overexpressed in rheumatoid arthritis synovium, the product of which exerts inhibitory activity on synovial cell growth (PMID:15638044)
• TSC-36 can be induced in VSMCs (vascular smooth muscle cells) and inhibits VSMCs proliferation in vitro and in vivo. (PMID:16256108)
• Elevated myocardial expression of FST-like genes is a feature of heart failure and may be linked to both disease severity and mechanisms underlying recovery. (PMID:18617621)
• Fstl1 is a secreted muscle protein or myokine that can function to promote endothelial cell function and stimulates revascularization in response to ischemic insult through its ability to activate Akt-eNOS signaling (PMID:18718903)
• Cell migration and invasion assays demonstrated a remarkably lower cell migration and invasion capability in FSTL1-transfected cells in relation to downregulation of matrix metallopeptidase-2 (PMID:18796737)
• FSTL-1 is overexpressed by 2-3-fold in synovial tissues of rheumatoid arthritis patients compared with control synovium obtained from subjects undergoing knee arthroscopic anterior cruciate ligament repair. (PMID:19109154)
• DIP2A could be a cell-surface receptor protein and mediate a FOS down-regulation signal of FRP. FRP bound to DIP2A and CD14, and also with proteins of the TGF-beta superfamily (PMID:20860622)
• Elevated FSTL1 levels reflect not only joint diseases but also inflammation and tissue degradation in systemic autoimmune diseases. (PMID:21303509)
• These data suggest that Cx43 inhibits the invasion and metastasis of pulmonary giant cell carcinoma cells by modulating the secretion of FSTL1, which is regulated by histone acetylation. (PMID:21718795)
• Data show that the serum and synovial fluid (SF) FSTL1 levels were markedly higher in female OA patients than in males. (PMID:22117761)
• FRP has the function of evoking innate immune responses as one of the endogenous TLR4 agonists. (PMID:22265692)
• A clear inverse correlation between the expression pattern of FSTL1 (pro-migratory) and miR-198 (anti-migratory) highlights the importance of this regulatory switch in controlling context-specific gene expression to orchestrate wound re-epithelialization. (PMID:23395958)
• results demonstrated that follistatin-like protein 1 (Fstl1) is expressed and secreted by human myotubes and plasma Fstl1 levels are increased after exercise (PMID:23419164)
• FSTL1 is a potential mediator of inflammation and insulin resistance in obesity. (PMID:24347831)
• These results suggest that FSTL-1 may act on the NLRP3 inflammasome to promote IL-1beta secretion from monocytes/macrophages. (PMID:24470197)
• FSTL1 is elevated in various inflammatory conditions and decreased during the course of treatment. FSTL1 may therefore be a valuable biomarker for such diseases. (PMID:24838142)
• Fstl1 is induced in response to lung injury and promotes the accumulation of myofibroblasts and subsequent fibrosis. These data suggest that Fstl1 may serve as a novel therapeutic target for treatment of progressive lung fibrosis. (PMID:25584011)
• FSTL1 is elevated in patients with osteoarthritis and involved in the progression of synovial inflammation. (PMID:25888873)
• administration of Fstl1 induced airway remodeling and increased OSM, whereas administration of an anti-OSM Ab blocked the effect of Fstl1 on inducing airway remodeling, eosinophilic airway inflammation (PMID:26355153)
• provide mechanistic insight into the regulation of erythropoiesis by FSTL1 signaling and lay a foundation for exploring FSTL1 signaling as a therapeutic target for anemia (PMID:26365350)
• data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans (PMID:26375005)
• the knockdown of FSTL1 induces apoptosis through a mitotic arrest and caspase-dependent cell death. FSTL1 plays the important roles in cellular proliferation and apoptosis in lung cancer cells, and thus can be a new target for lung cancer treatment. (PMID:26716515)
• Children with chronic heart failure group had a significantly higher serum level of FSTL1 than the control group. (PMID:26903060)
• Data show that follistatin like-1 (FSTL1) was frequently downregulated in nasopharyngeal carcinoma (NPC) cell lines and primary tumor biopsies by promoter hypermethylation. (PMID:26918942)
• Segmental allergen challenge increases levels of airway follistatin-like 1 in patients with asthma. (PMID:27001159)
• DROMs levels positively associated with Fstl1, Hemoglobin A1c and hsCRP levels. (PMID:27145224)
• results indicate that rs1259293 is associated with an increased risk and unfavorable postoperative prognosis of renal cell carcinoma, possibly by down-regulating FSTL1 expression in renal tissues. (PMID:27225192)
• this study shows that 1) the expression of follistatin-like protein 1 is upregulated in rheumatoid arthritis patients; 2) miR-27a inhibits cell migration of rheumatoid arthritis synoviocytes by targeting follistatin-like protein 1 and restraining the TLR4/NFkappaB pathway (PMID:27498552)
• FSTL1 displays anti-inflammatory effects against oxidized low-density lipoprotein-induced pro-inflammatory cytokine production via a mechanism that involves the TLR4/MyD88/NF-kappaB and MAPK signaling pathways. (PMID:27569284)
• FSTL1 plays a critical role in immune regulation, enhancing the antigen presentation ability of dendritic cells by up-regulating NF-kappab expression and down-regulating JNK expression. (PMID:27859422)
• Results showed that: 1- FSTL-1 expression is localized to the stromal compartment of the pancreas; 2- FSTL-1 expression is reduced in pancreatic cancer, and 3- FSTL-1 inhibited pancreatic cancer cell proliferation. (PMID:27886258)
• FSTL1 mRNA levels increased in castration-resistant prostate cancer in association with predominantly nuclear FSTL1. (PMID:27976415)
• Study suggests that follistatin like 1 plays an important role in lung fibrosis, and may serve as a novel therapeutic target for treatment of silicosis. (PMID:28341862)
• In cultured human pulmonary artery smooth muscle cells, hypoxia-promoted cellular viability, DNA synthesis and migration were suppressed by exogenous FSTL1 but enhanced by small interfering RNA targeting FSTL1 (PMID:28361925)
• knockdown of FSTL1 inhibited ASM cell proliferation and migration induced by PDGF-BB at least partially via inhibiting the activation of ERK and AKT. These results provide novel insight into the pathogenesis of airway remodeling in childhood asthma and FSTL1 may be a possible therapeutic strategy for the treatment of asthma. (PMID:28393245)
• FSTL1 may induce epithelial mesenchymal transition and airway remodeling by activating autophagy. (PMID:28473327)
• Data show that follistatin-like 1 (FSTL1) contributed to unfavorable post-surgical outcome of hepatocellular carcinoma (HCC) patients via inhibiting cell apoptosis. (PMID:28655132)
• current study revealed that low FSTL1, BMP4, and Smad4 expression significantly predict poor prognosis in lung adenocarcinoma but not in squamous cell carcinoma. (PMID:28852126)
• Data provide evidence that FSTL1 modestly affects the proliferation of breast cancer cells and vascular endothelial cells. These findings improve the understanding of the functions of FSTL1 in breast cancer development and angiogenesis. (PMID:28857515)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fstl1a	ENSDARG00000015559
danio_rerio	fstl1b	ENSDARG00000039576
mus_musculus	Fstl1	ENSMUSG00000022816
rattus_norvegicus	Fstl1	ENSRNOG00000002746

Paralogs (6): FSTL4 (ENSG00000053108), FSTL3 (ENSG00000070404), SPINK5 (ENSG00000133710), FST (ENSG00000134363), FSTL5 (ENSG00000168843), SPINK6 (ENSG00000178172)

Protein

Protein identifiers

Follistatin-related protein 1 — Q12841 (reviewed: Q12841)

Alternative names: Follistatin-like protein 1

All UniProt accessions (3): C9J5G4, Q12841, H7C4W4

UniProt curated annotations — full annotation on UniProt →

Function. Secreted glycoprotein that is involved in various physiological processes, such as angiogenesis, regulation of the immune response, cell proliferation and differentiation. Plays a role in the development of the central nervous system, skeletal system, lungs, and ureter. Promotes endothelial cell survival, migration and differentiation into network structures in an AKT-dependent manner. Also promotes survival of cardiac myocytes. Initiates various signaling cascades by activating different receptors on the cell surface such as DIP2A, TLR4 or BMP receptors.

Subunit / interactions. Homodimer. Interacts with SCN10A. Interacts with DIP2A; DIP2A may act as a cell surface receptor for FSTL1. Interacts with BMP4. Interacts with CD14; this interaction promotes TL4-mediated signaling cascade.

Subcellular location. Secreted.

Tissue specificity. Overexpressed in synovial tissues from rheumatoid arthritis.

Isoforms (2)

UniProt ID	Names	Canonical?
Q12841-1	1	yes
Q12841-2	2

RefSeq proteins (1): NP_009016* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR002350	Kazal_dom	Domain
IPR003645	Fol_N	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR015369	Follistatin/Osteonectin_EGF	Domain
IPR036058	Kazal_dom_sf	Homologous_superfamily
IPR050653	Prot_Inhib_GrowthFact_Antg	Family
IPR057020	EF-hand_FSTL1	Domain

Pfam: PF07648, PF09289, PF23244, PF23564

UniProt features (19 total): disulfide bond 5, domain 5, glycosylation site 3, sequence conflict 2, signal peptide 1, chain 1, splice variant 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12841-F1	87.06	0.60

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): 165

Disulfide bonds (5): 31–42, 36–52, 54–84, 58–77, 66–98

Glycosylation sites (3): 180, 144, 175

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-201451	Signaling by BMP
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation

MSigDB gene sets: 315 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, BOYLAN_MULTIPLE_MYELOMA_PCA1_DN, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, PAL_PRMT5_TARGETS_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GNF2_PTX3, TGACCTY_ERR1_Q2, FOXO4_01, FOXO1_01

GO Biological Process (6): cell differentiation (GO:0030154), regulation of BMP signaling pathway (GO:0030510), negative regulation of apoptotic process (GO:0043066), endothelial cell migration (GO:0043542), endothelial cell differentiation (GO:0045446), hematopoietic stem cell homeostasis (GO:0061484)

GO Molecular Function (3): calcium ion binding (GO:0005509), heparin binding (GO:0008201), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by TGFB family members	1
Metabolism of proteins	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular developmental process	1
BMP signaling pathway	1
regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
regulation of cellular response to growth factor stimulus	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cell migration	1
endothelium development	1
epithelial cell differentiation	1
homeostasis of number of cells	1
metal ion binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
binding	1
cellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1
extracellular vesicle	1

Protein interactions and networks

STRING

1226 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FSTL1	TLR2	O60603	963
FSTL1	TLR6	Q9Y2C9	916
FSTL1	DIP2A	Q14689	816
FSTL1	TLR1	Q15399	799
FSTL1	TLR4	O00206	772
FSTL1	TLR5	O60602	723
FSTL1	IL6	P05231	641
FSTL1	FSTL3	O95633	612
FSTL1	TGFB1	P01137	608
FSTL1	SPP1	P10451	607
FSTL1	TLR8	Q9NR97	602
FSTL1	BMP4	P12644	600
FSTL1	THY1	P04216	579
FSTL1	SPARC	P09486	571
FSTL1	TLR3	O15455	525

IntAct

77 interactions, top by confidence:

A	B	Type	Score
FSTL1	APPBP2	psi-mi:“MI:0915”(physical association)	0.790
APPBP2	FSTL1	psi-mi:“MI:0915”(physical association)	0.790
FSTL1	CD14	psi-mi:“MI:0915”(physical association)	0.660
CD14	FSTL1	psi-mi:“MI:0915”(physical association)	0.660
CD14	FSTL1	psi-mi:“MI:0407”(direct interaction)	0.660
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
DIP2A	FSTL1	psi-mi:“MI:0915”(physical association)	0.630
FSTL1	DIP2A	psi-mi:“MI:0915”(physical association)	0.630
FSTL1	DIP2A	psi-mi:“MI:0407”(direct interaction)	0.630
SGTA	FSTL1	psi-mi:“MI:0915”(physical association)	0.560
FSTL1	SGTA	psi-mi:“MI:0915”(physical association)	0.560
FSTL1	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
TGFB1	FSTL1	psi-mi:“MI:0407”(direct interaction)	0.540
FSTL1	INHBA	psi-mi:“MI:0407”(direct interaction)	0.540
FSTL1	BMP2	psi-mi:“MI:0407”(direct interaction)	0.540
FSTL1	INHBA	psi-mi:“MI:0915”(physical association)	0.540
TGFB1	FSTL1	psi-mi:“MI:0915”(physical association)	0.540
FSTL1	BMP2	psi-mi:“MI:0915”(physical association)	0.540
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
INSL6	POTEF	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
LRRC4C	DVL2	psi-mi:“MI:0914”(association)	0.530

BioGRID (75): FSTL1 (Two-hybrid), FSTL1 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), FSTL1 (Two-hybrid), FSTL1 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PUP4, A2AFS3, M0R7X9, O70472, O75882, O95803, P01134, P26012, P52799, P52848, P69849, Q02353, Q05204, Q0VCJ8, Q12841, Q13635, Q15155, Q3UHN9, Q3ZBS2, Q58D84, Q5EA46, Q5JPE7, Q5R9Y1, Q5U4X8, Q5VV63, Q5ZJB7, Q5ZMH6, Q61115, Q62356, Q62632, Q6A051, Q6GQK9, Q6GQT9, Q6P988, Q6UXG2, Q7Z5A7, Q86TD4, Q90693, Q91WE9, Q96CW9

Diamond homologs: A0A1D5PUP4, A0JP86, A2ASQ1, A3KN33, A5YT95, E9Q7X7, G4V4G1, G5ECE3, O00468, O00634, O09118, O15230, O62650, O75094, O75445, O88280, O94813, O95631, O95633, O95980, P02468, P02469, P07942, P0DKM7, P0DKM8, P0DKM9, P10184, P10669, P11046, P11047, P15215, P15800, P16895, P19883, P21674, P25304, P31514, P31515, P31696, P47931

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
FSTL1	“up-regulates activity”	DIP2A	binding
FSTL1	“up-regulates activity”	AKT
AKT1	“up-regulates quantity by expression”	FSTL1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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
TCF dependent signaling in response to WNT	6	12.2×	8e-04
Signaling by TGFB family members	6	11.9×	8e-04
Extracellular matrix organization	6	6.5×	6e-03
Diseases of signal transduction by growth factor receptors and second messengers	6	5.9×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of bone mineralization	6	33.1×	6e-06
positive regulation of SMAD protein signal transduction	6	32.4×	6e-06
cellular response to transforming growth factor beta stimulus	7	27.2×	6e-06
chondrocyte differentiation	6	25.4×	2e-05
odontogenesis of dentin-containing tooth	6	25.4×	2e-05
positive regulation of osteoblast differentiation	7	22.1×	6e-06
epithelial to mesenchymal transition	5	22.0×	3e-04
embryonic digit morphogenesis	5	21.2×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1752 predictions. Top by Δscore:

Variant	Effect	Δscore
3:120399878:CTCA:C	donor_loss	1.0000
3:120399879:TCAC:T	donor_loss	1.0000
3:120399880:CACC:C	donor_loss	1.0000
3:120399881:A:C	donor_loss	1.0000
3:120399882:C:CG	donor_loss	1.0000
3:120402741:T:TA	donor_gain	1.0000
3:120402928:C:CT	acceptor_gain	1.0000
3:120403229:A:AC	donor_gain	1.0000
3:120403240:A:AC	donor_gain	1.0000
3:120403241:C:CC	donor_gain	1.0000
3:120403241:CT:C	donor_gain	1.0000
3:120403241:CTCTT:C	donor_gain	1.0000
3:120403245:T:TA	donor_gain	1.0000
3:120403275:A:AC	donor_gain	1.0000
3:120403276:C:CC	donor_gain	1.0000
3:120403350:GTCCC:G	acceptor_gain	1.0000
3:120403352:CCC:C	acceptor_gain	1.0000
3:120403353:CC:C	acceptor_gain	1.0000
3:120403353:CCC:C	acceptor_gain	1.0000
3:120403354:CC:C	acceptor_gain	1.0000
3:120403355:C:CC	acceptor_gain	1.0000
3:120404849:TCAC:T	donor_loss	1.0000
3:120404850:CA:C	donor_loss	1.0000
3:120404969:GTT:G	acceptor_gain	1.0000
3:120404969:GTTC:G	acceptor_loss	1.0000
3:120404971:TC:T	acceptor_loss	1.0000
3:120404972:C:CA	acceptor_loss	1.0000
3:120404972:C:CC	acceptor_gain	1.0000
3:120404973:T:C	acceptor_loss	1.0000
3:120409660:CAA:C	acceptor_gain	1.0000

AlphaMissense

2054 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:120402833:C:A	W260C	1.000
3:120402833:C:G	W260C	1.000
3:120409657:A:G	C113R	1.000
3:120411901:C:G	C84S	1.000
3:120411901:C:T	C84Y	1.000
3:120411902:A:G	C84R	1.000
3:120411902:A:T	C84S	1.000
3:120411910:C:G	R81P	1.000
3:120411916:A:G	L79P	1.000
3:120411922:C:T	C77Y	1.000
3:120415966:C:G	C42S	1.000
3:120415967:A:T	C42S	1.000
3:120415984:C:G	C36S	1.000
3:120415984:C:T	C36Y	1.000
3:120415985:A:T	C36S	1.000
3:120402827:A:C	C262W	0.999
3:120402828:C:G	C262S	0.999
3:120402828:C:T	C262Y	0.999
3:120402829:A:G	C262R	0.999
3:120402829:A:T	C262S	0.999
3:120402835:A:G	W260R	0.999
3:120402835:A:T	W260R	0.999
3:120402848:A:C	C255W	0.999
3:120402850:A:G	C255R	0.999
3:120402855:C:G	C253S	0.999
3:120402856:A:G	C253R	0.999
3:120402856:A:T	C253S	0.999
3:120402914:A:C	C233W	0.999
3:120402915:C:G	C233S	0.999
3:120402916:A:G	C233R	0.999

dbSNP variants (sampled 300 via entrez): RS1000003817 (3:120419227 G>A), RS1000141661 (3:120395526 G>T), RS1000150206 (3:120424898 G>A), RS1000200869 (3:120439604 G>A), RS1000269990 (3:120404522 G>A), RS1000272362 (3:120449485 A>T), RS1000306925 (3:120433440 G>A,T), RS1000334811 (3:120396732 G>A), RS1000370329 (3:120427400 T>C), RS1000387603 (3:120425721 G>A), RS1000403177 (3:120404797 C>G), RS1000423930 (3:120442789 A>C,G,T), RS1000517972 (3:120443431 G>T), RS1000595796 (3:120437089 T>A,G), RS1000651939 (3:120413630 G>A)

Disease associations

OMIM: gene MIM:605547 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001762_50	Obesity-related traits	7.000000e-06
GCST006585_948	Blood protein levels	1.000000e-26

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005189	respiratory quotient

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	5
bisphenol A	affects cotreatment, increases methylation, decreases expression, increases expression	4
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
entinostat	decreases expression, affects cotreatment	2
bisphenol S	decreases methylation, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
3,4-dichloroaniline	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases secretion	1
perfluorooctanoic acid	decreases expression	1
naphthenic acid	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
seocalcitol	increases expression	1
azoxystrobin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1

Clinical trials (associated diseases)

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