IGFBP3

Summary

IGFBP3 (insulin like growth factor binding protein 3, HGNC:5472) is a protein-coding gene on chromosome 7p12.3, encoding Insulin-like growth factor-binding protein 3 (P17936). Multifunctional protein that plays a critical role in regulating the availability of IGFs such as IGF1 and IGF2 to their receptors and thereby regulates IGF-mediated cellular processes including proliferation, differentiation, and apoptosis in a cell-type specific manner.

This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 3486 — RefSeq curated summary.

At a glance

• GWAS associations: 63
• Clinical variants (ClinVar): 42 total
• Druggable target: yes
• MANE Select transcript: NM_000598

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5472
Approved symbol	IGFBP3
Name	insulin like growth factor binding protein 3
Location	7p12.3
Locus type	gene with protein product
Status	Approved
Aliases	IBP3, BP-53
Ensembl gene	ENSG00000146674
Ensembl biotype	protein_coding
OMIM	146732
Entrez	3486

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000381083, ENST00000381086, ENST00000417621, ENST00000428530, ENST00000448817, ENST00000460209, ENST00000460477, ENST00000465642, ENST00000613132, ENST00000908403, ENST00000908404, ENST00000908405, ENST00000908406

RefSeq mRNA: 2 — MANE Select: NM_000598 NM_000598, NM_001013398

CCDS: CCDS34632, CCDS5505

Canonical transcript exons

ENST00000613132 — 5 exons

Exon	Start	End
ENSE00001612524	45916548	45916667
ENSE00001702993	45914805	45914945
ENSE00001888357	45920738	45921272
ENSE00003246105	45912245	45913834
ENSE00003563850	45917213	45917439

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 141.0371 / max 11131.4501, expressed in 1328 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83984	133.1645	1313
83981	2.2759	483
83973	1.4628	358
83979	0.8807	287
83974	0.7945	274
83976	0.6231	35
83955	0.4119	134
83982	0.2644	110
83951	0.1767	67
83980	0.1485	60

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	99.95	gold quality
palpebral conjunctiva	UBERON:0001812	99.83	gold quality
cartilage tissue	UBERON:0002418	99.80	gold quality
placenta	UBERON:0001987	99.77	gold quality
descending thoracic aorta	UBERON:0002345	99.25	gold quality
mucosa of urinary bladder	UBERON:0001259	99.08	gold quality
peritoneum	UBERON:0002358	99.03	gold quality
omental fat pad	UBERON:0010414	99.03	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.99	gold quality
mammalian vulva	UBERON:0000997	98.91	gold quality
pericardium	UBERON:0002407	98.89	gold quality
upper leg skin	UBERON:0004262	98.87	gold quality
skin of hip	UBERON:0001554	98.74	gold quality
thoracic aorta	UBERON:0001515	98.72	gold quality
right lobe of liver	UBERON:0001114	98.69	gold quality
ascending aorta	UBERON:0001496	98.69	gold quality
nasal cavity epithelium	UBERON:0005384	98.58	gold quality
liver	UBERON:0002107	98.56	gold quality
vena cava	UBERON:0004087	98.55	gold quality
myometrium	UBERON:0001296	98.48	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.44	gold quality
aorta	UBERON:0000947	98.43	gold quality
body of uterus	UBERON:0009853	98.39	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.30	gold quality
tibial artery	UBERON:0007610	98.23	gold quality
adipose tissue	UBERON:0001013	98.22	gold quality
popliteal artery	UBERON:0002250	98.22	gold quality
urethra	UBERON:0000057	98.19	gold quality
left ovary	UBERON:0002119	98.19	gold quality
endocervix	UBERON:0000458	98.15	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	26548.09
E-HCAD-23	yes	14719.41
E-MTAB-6308	yes	5941.72
E-CURD-7	yes	5451.49
E-ENAD-21	yes	3081.98
E-GEOD-135922	yes	3006.41
E-MTAB-8142	yes	2998.87
E-MTAB-7407	yes	2906.13
E-HCAD-24	yes	2304.83
E-HCAD-11	yes	2278.33
E-CURD-98	yes	2080.75
E-HCAD-13	yes	1906.55
E-MTAB-9435	yes	1185.86
E-GEOD-86618	yes	980.94
E-ANND-5	yes	665.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CDX2, CXXC1, DLX5, DNMT3A, EP300, ESR1, EWSR1, FLI1, FOXO3, GLI2, HDAC1, HIF1A, HOXC6, HOXD10, ID2, ID4, MECP2, MYB, NCOA3, NCOR1, NKX3-1, NR3C1, RARA, RARB, RUNX1, SND1, SP1, SP3, SPI1, STAT1, TBP, TFAP2A, TFCP2, TP53, TP63, TP73, USF1, VDR

miRNA regulators (miRDB)

85 targeting IGFBP3, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 40)

• This study defines a signaling pathway for IGFBP-3 from a cell surface receptor to nuclear transcriptional activity, requiring TGF-betaRII but not dependent on the nuclear translocation of IGFBP-3 (PMID:11751851)
• Hypothyroidism is associated with significant reductions of IGFBP-3 (PMID:11762714)
• Insulin-like growth factor (IGF)-binding protein-3 mutants that do not bind IGF-I or IGF-II stimulate apoptosis in human prostate cancer cells (PMID:11784719)
• The upstream AP2-binding site of IGFBP3’s promoter is specifically hypermethylated in hepatomas. (PMID:11804742)
• interaction with STAT-1 during chondrogenesis (PMID:11886859)
• Reduced serum insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 levels in adults with inflammatory bowel disease. (PMID:11914023)
• Total and free insulin-like growth factor I, insulin-like growth factor binding protein 3 and acid-labile subunit reflect clinical activity in acromegaly. (PMID:11914026)
• Insulin-like growth factor-binding protein-3 activates a phosphotyrosine phosphatase (PMID:11940579)
• induces early apoptosis and has potential tumor suppressive effects in prostate cancer (PMID:11948969)
• study the changes of plasma insulin-like growth factor -1 (IGF-1) and IGF binding protein 3 (IGFBP3) in patients with acute cerebral infarct (ACI) and acute cerebral hemorrhage (ACH) (PMID:11953210)
• A possible role for insulin-like growth factor-binding protein-3 autocrine/paracrine loops in controlling hepatocellular carcinoma cell proliferation (PMID:11959812)
• IGFBP-3 is essential for TNF-alpha-induced apoptosis in PC-3 cells (PMID:11971816)
• identification of the proteolytic cleavage sites in circulating IGFBP-3 (PMID:11997031)
• determination of blood levels in adult patients with severe liver disease before and after orthotopic liver transplantation (PMID:12006706)
• Insulin-like growth factor I, IGF-binding protein 3, and lung cancer risk in a prospective study of men in China. (PMID:12011225)
• Enhanced expression in gastric cancer cells increases paclitaxel and etoposide-induced growth inhibition (PMID:12051736)
• The amino-terminal region induces apoptosis of MCF-7 breast carcinoma cells. (PMID:12054563)
• Insulin-like growth factor binding protein-3 inhibits the growth of non-small cell lung cancer. (PMID:12068000)
• is inversely associated with benign prostatic hyperplasia risk (PMID:12111701)
• Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer. (PMID:12122101)
• circulating level of IGFBP3 is related to the extent of myocardial injury in patients with hypertrophic cardiomyopathy. (PMID:12135130)
• high levels of IGFBP-3 predicted distant recurrence but not death in postmenopausal breast cancer patients and those with estrogen receptor-positive tumors (PMID:12150454)
• expression increases during immortalization of cervical keratinocytes (PMID:12163384)
• IGFBP-3 promoter is activated by Trichostatin A-upregulated Sp1 (PMID:12200149)
• Variable mid-region is responsible for the specific pro-apoptotic functions of IGFBP-3; phosphorylation may provide a mechanism for regulation of this action (PMID:12210764)
• improves insulin resistance by GH-dependent and independent mechanisms (PMID:12213898)
• HT29 tumor cell proliferation in vitro was due, at least in part, to surgery-related depletion of insulin-like growth factor binding protein 3 in peripheral blood. (PMID:12219010)
• These results provide evidence that a specific intracellular signal is triggered by IGFBP-3 binding to a cell surface receptor. (PMID:12220677)
• role in breast cancer cell growth - review (PMID:12242693)
• Hypermethylation of IGFBP-3 promoter is associated with non-small cell lung cancer (PMID:12473575)
• IGFBP-3 concentration significantly lower in acute ischemic stroke than in controls. (PMID:12508918)
• data demonstrate for the first time that serum levels of IGFs (including free fractions) and IGFBPs are not increased in euthyroid Graves’ patients with active thyroid eye disease (PMID:12519841)
• Follicular fluid IGF-1 and IGFBP-3 levels were not significantly different among the groups; however, follicular fluid IGFBP-1 levels were lower in those patients with moderate/severe endometriosis (PMID:12571183)
• quantities of IGFBP-3 produced in culture by human cartilage are small compared with the amount supplied in the form of “small complexes” from the circulation (PMID:12571851)
• Augmented serum levels of the IGF-I/IGF-binding protein-3 ratio in pre-menopausal patients with type I breast cysts. (PMID:12590636)
• IGFBP-3 supports myoblast differentiation (PMID:12599210)
• IGFBP-3 mRNA and protein are differentially expressed in distinct human brain microvascular endothelial cells populations. (PMID:12725526)
• isolated amino-terminal and carboxyl-terminal domains of IGFBP-3 cooperate in the presence of IGFs to form high-affinity complexes that retain the ability to block IGF activity. (PMID:12810533)
• Divergent influences of sex steroids, IGF-1, and IGFBP3 on age-related changes in lean body mass in healthy elderly men and women. (PMID:12865482)
• endurance training improves glucose disposal and increases insulin-like growth binding protein-1 and -3 in men (PMID:12870155)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	igfbp3	ENSDARG00000099144
mus_musculus	Igfbp3	ENSMUSG00000020427
rattus_norvegicus	Igfbp3	ENSRNOG00000061910

Paralogs (5): IGFBP2 (ENSG00000115457), IGFBP5 (ENSG00000115461), IGFBP4 (ENSG00000141753), IGFBP1 (ENSG00000146678), IGFBP6 (ENSG00000167779)

Protein

Protein identifiers

Insulin-like growth factor-binding protein 3 — P17936 (reviewed: P17936)

All UniProt accessions (6): P17936, A6XND0, B3KWK7, C9JMX4, H0Y485, H0Y5K2

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional protein that plays a critical role in regulating the availability of IGFs such as IGF1 and IGF2 to their receptors and thereby regulates IGF-mediated cellular processes including proliferation, differentiation, and apoptosis in a cell-type specific manner. Also exhibits IGF-independent antiproliferative and apoptotic effects mediated by its receptor TMEM219/IGFBP-3R. Inhibits the positive effect of humanin on insulin sensitivity. Promotes testicular germ cell apoptosis. Acts via LRP-1/alpha2M receptor, also known as TGF-beta type V receptor, to mediate cell growth inhibition independent of IGF1. Mechanistically, induces serine-specific dephosphorylation of IRS1 or IRS2 upon ligation to its receptor, leading to the inhibitory cascade. In the nucleus, interacts with transcription factors such as retinoid X receptor-alpha/RXRA to regulate transcriptional signaling and apoptosis.

Subunit / interactions. Interacts with XLKD1. Binds IGF2 more than IGF1. Forms a ternary complex of about 140 to 150 kDa with IGF1 or IGF2 and a 85 kDa glycoprotein (ALS). Interacts with humanin; humanin competes with importin KPNB1 for binding to IGFBP3, blocking IGFBP3 nuclear import and IGFBP3-mediated apoptosis. Interacts with TMEM219. Interacts with RXRA; this interaction modulates the transcriptional activity of RXRA. Interacts with LRP1; this interaction mediates cell growth inhibition independent of IGF1.

Subcellular location. Secreted. Nucleus.

Tissue specificity. Expressed by most tissues. Present in plasma.

Post-translational modifications. Phosphorylated by FAM20C in the extracellular medium. Phosphorylated by CK2; resulting in decreased nuclear localization.

Domain organisation. The thyroglobulin type-1 domain mediates interaction with HN.

Induction. Up-regulated in the presence of IGF1, insulin and other growth-stimulating factors such as growth hormone, EGF and phorbol esters.

Isoforms (2)

UniProt ID	Names	Canonical?
P17936-1	1	yes
P17936-2	2

RefSeq proteins (2): NP_000589, NP_001013416 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000716	Thyroglobulin_1	Domain
IPR000867	IGFBP-like	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR012211	IGFBP-3	Family
IPR017891	Insulin_GF-bd_Cys-rich_CS	Conserved_site
IPR022321	IGFBP_1-6_chordata	Family
IPR036857	Thyroglobulin_1_sf	Homologous_superfamily

Pfam: PF00086, PF00219

UniProt features (35 total): disulfide bond 9, sequence variant 6, modified residue 4, glycosylation site 3, mutagenesis site 3, region of interest 3, domain 2, compositionally biased region 2, signal peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7WRQ	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17936-F1	67.94	0.28

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 (4): 194, 201, 202, 148

Disulfide bonds (9): 40–67, 43–69, 51–70, 58–73, 81–94, 88–114, 213–240, 251–262, 264–285

Glycosylation sites (3): 116, 136, 199

Mutagenesis-validated functional residues (3):

Position	Phenotype
194	strongly enhanced apoptotic potential.
202	no change in apoptotic potential.
215	completely abolished als binding.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-6803211	TP53 Regulates Transcription of Death Receptors and Ligands
R-HSA-8957275	Post-translational protein phosphorylation

MSigDB gene sets: 403 (showing top): LEE_NEURAL_CREST_STEM_CELL_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, HARRIS_HYPOXIA, GOBP_REGULATION_OF_PHOSPHORYLATION, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, PEREZ_TP63_TARGETS, GCANCTGNY_MYOD_Q6, HALMOS_CEBPA_TARGETS_UP, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_OSTEOBLAST_DIFFERENTIATION, KYNG_DNA_DAMAGE_DN, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_1, IIZUKA_LIVER_CANCER_PROGRESSION_L1_G1_UP

GO Biological Process (18): MAPK cascade (GO:0000165), regulation of cell growth (GO:0001558), osteoblast differentiation (GO:0001649), negative regulation of protein phosphorylation (GO:0001933), protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), negative regulation of cell population proliferation (GO:0008285), negative regulation of signal transduction (GO:0009968), regulation of glucose metabolic process (GO:0010906), negative regulation of smooth muscle cell migration (GO:0014912), positive regulation of apoptotic process (GO:0043065), positive regulation of MAPK cascade (GO:0043410), regulation of insulin-like growth factor receptor signaling pathway (GO:0043567), positive regulation of insulin-like growth factor receptor signaling pathway (GO:0043568), type B pancreatic cell proliferation (GO:0044342), positive regulation of myoblast differentiation (GO:0045663), negative regulation of smooth muscle cell proliferation (GO:0048662), regulation of growth (GO:0040008)

GO Molecular Function (8): fibronectin binding (GO:0001968), insulin-like growth factor binding (GO:0005520), protein tyrosine phosphatase activator activity (GO:0008160), insulin-like growth factor I binding (GO:0031994), insulin-like growth factor II binding (GO:0031995), metal ion binding (GO:0046872), protein binding (GO:0005515), growth factor binding (GO:0019838)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), endoplasmic reticulum lumen (GO:0005788), insulin-like growth factor binding protein complex (GO:0016942), insulin-like growth factor ternary complex (GO:0042567)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of proteins	1
TP53 Regulates Transcription of Cell Death Genes	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of signal transduction	2
insulin-like growth factor receptor signaling pathway	2
protein binding	2
insulin-like growth factor binding	2
intracellular signaling cassette	1
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
ossification	1
cell differentiation	1
regulation of protein phosphorylation	1
protein phosphorylation	1
negative regulation of protein modification process	1
negative regulation of phosphorylation	1
phosphorylation	1
protein modification process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
glucose metabolic process	1
regulation of carbohydrate metabolic process	1
regulation of small molecule metabolic process	1
smooth muscle cell migration	1
regulation of smooth muscle cell migration	1
negative regulation of cell migration	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
positive regulation of signal transduction	1
regulation of insulin-like growth factor receptor signaling pathway	1

Protein interactions and networks

STRING

3056 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGFBP3	IGF1	P01343	999
IGFBP3	IGF2	P01344	999
IGFBP3	INS	P01308	995
IGFBP3	IGFALS	P35858	994
IGFBP3	EGFR	P00533	971
IGFBP3	IGF1R	P08069	946
IGFBP3	FN1	P02751	923
IGFBP3	IGFBP5	P24593	911
IGFBP3	RXRA	P19793	907
IGFBP3	GHR	P10912	897
IGFBP3	VTN	P01141	860
IGFBP3	IGFBP2	P18065	831
IGFBP3	PPARG	P37231	797
IGFBP3	GHRH	P01286	770
IGFBP3	GH1	P01241	764

IntAct

68 interactions, top by confidence:

A	B	Type	Score
STK26	STRN	psi-mi:“MI:0914”(association)	0.860
IGFBP3	TMEM219	psi-mi:“MI:0915”(physical association)	0.660
TMEM219	IGFBP3	psi-mi:“MI:0407”(direct interaction)	0.660
TMEM219	IGFBP3	psi-mi:“MI:0915”(physical association)	0.660
	IGFBP3	psi-mi:“MI:0407”(direct interaction)	0.610
	IGFBP3	psi-mi:“MI:0915”(physical association)	0.610
IGFBP3	MT-RNR2	psi-mi:“MI:0407”(direct interaction)	0.600
IGFBP3	MT-RNR2	psi-mi:“MI:0915”(physical association)	0.600
PRKCA	IGFBP3	psi-mi:“MI:0915”(physical association)	0.560
YWHAG	IGFBP3	psi-mi:“MI:0915”(physical association)	0.560
SETDB1	IGFBP3	psi-mi:“MI:0915”(physical association)	0.560
KAT5	IGFBP3	psi-mi:“MI:0915”(physical association)	0.560
LMO3	IGFBP3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (89): IGFBP3 (Reconstituted Complex), IGFBP3 (Reconstituted Complex), Ltbp1 (Two-hybrid), Igf2 (Two-hybrid), COL1A1 (Co-purification), IGFBP3 (Affinity Capture-Western), IGFBP3 (Reconstituted Complex), POLA2 (Two-hybrid), GTF3C1 (Two-hybrid), IGFBP3 (Affinity Capture-MS), IGF1R (Co-purification), IGFBP3 (Reconstituted Complex), IGFBP3 (Reconstituted Complex), IGFBP3 (Co-purification), SFPQ (Affinity Capture-MS)

ESM2 similar proteins: A4IIA2, A5A8Y8, B3F211, P01186, P08833, P10769, P12843, P13384, P15473, P16042, P16229, P17936, P18065, P19336, P21743, P21744, P24591, P24592, P24593, P24594, P24787, P24853, P35455, P35572, P47876, P47877, P47878, P47879, P47880, P49705, P51693, P97466, Q03157, Q05717, Q05718, Q07079, Q13253, Q28985, Q29400, Q32L50

Diamond homologs: A4IIA2, A5PKD8, B3F211, D3ZKF5, E1BJW1, P08833, P12843, P13384, P15473, P16611, P17936, P18065, P20959, P21743, P21744, P22692, P24591, P24592, P24593, P24594, P24853, P24854, P35572, P42642, P47876, P47877, P47878, P47879, P47880, P49705, Q05716, Q05717, Q05718, Q07079, Q16270, Q28893, Q28985, Q29400, Q5XHC5, Q61581

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CSNK2A1	“up-regulates quantity by stabilization”	IGFBP3	phosphorylation
MECP2	“down-regulates quantity by repression”	IGFBP3	“transcriptional regulation”
SND1	“up-regulates quantity by expression”	IGFBP3	“transcriptional regulation”
IGFBP3	down-regulates	Neuron_maturation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 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
Cell Cycle	7	9.7×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of ERK1 and ERK2 cascade	5	15.2×	2e-03
protein phosphorylation	6	14.6×	1e-03
negative regulation of gene expression	5	12.3×	4e-03
DNA damage response	5	9.6×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

701 predictions. Top by Δscore:

Variant	Effect	Δscore
7:45913831:TTAA:T	acceptor_gain	1.0000
7:45913835:C:CC	acceptor_gain	1.0000
7:45914799:ACT:A	donor_loss	1.0000
7:45914800:CTCA:C	donor_loss	1.0000
7:45914801:TCA:T	donor_loss	1.0000
7:45914802:C:CG	donor_loss	1.0000
7:45914803:AC:A	donor_gain	1.0000
7:45914803:ACCC:A	donor_loss	1.0000
7:45914804:C:CA	donor_loss	1.0000
7:45914804:CC:C	donor_gain	1.0000
7:45914941:CGACA:C	acceptor_gain	1.0000
7:45914942:GACA:G	acceptor_gain	1.0000
7:45914943:ACA:A	acceptor_gain	1.0000
7:45914944:CA:C	acceptor_gain	1.0000
7:45914944:CAC:C	acceptor_gain	1.0000
7:45914946:C:CC	acceptor_gain	1.0000
7:45914947:T:C	acceptor_loss	1.0000
7:45914948:G:C	acceptor_gain	1.0000
7:45916544:TCA:T	donor_loss	1.0000
7:45916545:CA:C	donor_loss	1.0000
7:45916546:A:AG	donor_loss	1.0000
7:45916547:C:CT	donor_loss	1.0000
7:45916547:CCTG:C	donor_gain	1.0000
7:45917211:A:AC	donor_gain	1.0000
7:45917212:C:CC	donor_gain	1.0000
7:45917451:C:CT	acceptor_gain	1.0000
7:45917451:C:T	acceptor_gain	1.0000
7:45917452:A:T	acceptor_gain	1.0000
7:45913830:ATTAA:A	acceptor_gain	0.9900
7:45913832:TAA:T	acceptor_gain	0.9900

AlphaMissense

1751 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:45914907:C:A	W263C	1.000
7:45914907:C:G	W263C	1.000
7:45916579:C:G	C240S	1.000
7:45916580:A:T	C240S	1.000
7:45914944:C:G	C251S	0.999
7:45914945:A:G	C251R	0.999
7:45914945:A:T	C251S	0.999
7:45916548:C:A	Q250H	0.999
7:45916548:C:G	Q250H	0.999
7:45916562:A:C	Y246D	0.999
7:45916567:C:T	G244E	0.999
7:45916568:C:G	G244R	0.999
7:45916568:C:T	G244R	0.999
7:45916578:A:C	C240W	0.999
7:45916579:C:A	C240F	0.999
7:45916579:C:T	C240Y	0.999
7:45916580:A:G	C240R	0.999
7:45916659:G:C	C213W	0.999
7:45916660:C:A	C213F	0.999
7:45916660:C:G	C213S	0.999
7:45916660:C:T	C213Y	0.999
7:45916661:A:G	C213R	0.999
7:45916661:A:T	C213S	0.999
7:45914890:C:A	G269V	0.998
7:45914890:C:T	G269E	0.998
7:45914891:C:A	G269W	0.998
7:45914899:T:A	D266V	0.998
7:45914906:A:G	C264R	0.998
7:45914911:C:G	C262S	0.998
7:45914911:C:T	C262Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000074147 (7:45919101 C>T), RS1000241348 (7:45919926 C>CA,CG,CT), RS1000366084 (7:45913019 T>A,C), RS1000724933 (7:45913898 T>C), RS1000732540 (7:45916136 GTGGTATGACCTCA>G), RS1000759316 (7:45913609 G>A), RS1001185316 (7:45918096 C>T), RS1001276933 (7:45917946 G>A), RS1001698693 (7:45918499 A>G), RS1001802204 (7:45912508 T>C), RS1002293678 (7:45922711 G>A), RS1002393646 (7:45922483 A>G), RS1003264600 (7:45915243 A>G), RS1003367544 (7:45921445 C>G,T), RS1003398476 (7:45921233 A>C,G)

Disease associations

OMIM: gene MIM:146732 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

63 associations (top):

Study	Trait	p-value
GCST000872_10	QRS duration	1.000000e-09
GCST000937_3	Insulin-like growth factors	3.000000e-101
GCST001850_42	Major depressive disorder	9.000000e-06
GCST002563_11	Hypospadias	2.000000e-14
GCST002647_68	Height	9.000000e-10
GCST002843_6	Sitting height ratio	3.000000e-08
GCST002937_11	Molybdenum levels	6.000000e-06
GCST003160_3	Subjective response to lithium treatment in bipolar disorder	5.000000e-07
GCST003274_5	Pulse pressure	2.000000e-14
GCST003377_1	Venous thromboembolism	2.000000e-08
GCST003542_93	Night sleep phenotypes	1.000000e-07
GCST003598_14	QRS duration	2.000000e-09
GCST003598_41	QRS duration	1.000000e-08
GCST003983_36	Male-pattern baldness	3.000000e-09
GCST003995_6	Tonsillectomy	2.000000e-15
GCST004053_4	Poor prognosis in Crohn’s disease	4.000000e-08
GCST004278_78	Pulse pressure	4.000000e-07
GCST004278_92	Pulse pressure	2.000000e-06
GCST004386_14	Diastolic blood pressure	5.000000e-06
GCST004387_8	Pulse pressure	9.000000e-07
GCST004388_7	Blood pressure traits (multi-trait analysis)	7.000000e-16
GCST004775_26	Pulse pressure	5.000000e-10
GCST005014_144	Tonsillectomy	2.000000e-15
GCST005790_5	Rosacea symptom severity	2.000000e-06
GCST006009_5	Pulse pressure	2.000000e-08
GCST006021_24	Systolic blood pressure	4.000000e-08
GCST006228_7	Systolic blood pressure	3.000000e-11
GCST006230_4	Pulse pressure	3.000000e-29
GCST006585_2845	Blood protein levels	2.000000e-09
GCST006976_11	Macular thickness	2.000000e-32

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0004626	IGFBP-3 measurement
EFO:0007118	sitting height ratio
EFO:0005763	pulse pressure measurement
EFO:0007924	tonsillectomy risk measurement
EFO:0007936	disease prognosis measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0009180	rosacea severity measurement
EFO:0004312	vital capacity
EFO:0004314	forced expiratory volume
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0004747	protein measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3997 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2854744	Efficacy	3	fluorouracil	Stomach Neoplasms

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2854744	IGFBP3	3	3.00	1	fluorouracil
rs2854746	IGFBP3		0.00	0
rs3110697	IGFBP3		0.00	0

ChEMBL bioactivities

41 potent at pChembl≥5 of 41 total, top 39 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.25	Ki	5.6	nM	CHEMBL292700
8.12	Ki	7.5	nM	CHEMBL58396
8.10	Ki	8	nM	CHEMBL56978
8.05	Ki	9	nM	CHEMBL292841
8.03	Ki	9.4	nM	CHEMBL56740
7.96	Ki	11	nM	CHEMBL294258
7.96	Ki	11	nM	CHEMBL300828
7.92	Ki	12	nM	CHEMBL292890
7.89	Ki	13	nM	CHEMBL131104
7.75	Ki	18	nM	CHEMBL61192
7.70	Ki	20	nM	CHEMBL57760
7.62	Ki	24	nM	CHEMBL56720
7.60	Ki	25	nM	CHEMBL56721
7.57	Ki	27	nM	CHEMBL128554
7.55	Ki	28	nM	CHEMBL130994
7.54	Ki	29	nM	CHEMBL301887
7.54	Ki	29	nM	CHEMBL336069
7.51	Ki	31	nM	CHEMBL301447
7.50	Ki	32	nM	CHEMBL57564
7.50	Ki	32	nM	CHEMBL291454
7.50	Ki	32	nM	CHEMBL57084
7.50	Ki	32	nM	CHEMBL57742
7.42	Ki	38	nM	CHEMBL57388
7.36	Ki	44	nM	CHEMBL128555
7.29	Ki	51	nM	CHEMBL293339
7.24	Ki	58	nM	CHEMBL128883
7.22	Ki	60	nM	CHEMBL57745
7.21	Ki	62	nM	CHEMBL57769
7.16	Ki	70	nM	CHEMBL292612
7.16	Ki	70	nM	CHEMBL128111
7.14	Ki	72	nM	CHEMBL293379
7.00	Ki	100	nM	CHEMBL416319
6.96	Ki	110	nM	CHEMBL60573
6.96	Ki	110	nM	CHEMBL58431
6.96	Ki	110	nM	CHEMBL57604
6.89	Ki	130	nM	CHEMBL292844
6.85	Ki	140	nM	CHEMBL132276
6.50	Ki	320	nM	CHEMBL339236
6.07	Ki	850	nM	CHEMBL57992

PubChem BioAssay actives

41 with measured affinity, of 46 total; 39 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-(3,4-dihydroxybenzoyl)-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0056	uM
1-[(3,4-dihydroxyphenyl)methyl]-6,7-dihydroxyisoquinoline-3-carboxylic acid	93215: Inhibitory activity against Insulin-like growth factor binding protein 3	ki	0.0075	uM
4-[(3,4-dihydroxyphenyl)methyl]-6,7-dihydroxyquinoline-2-carboxylic acid	93213: Ability of compound to displace Insulin-Like Growth Factor (IGF-I) from its binding to Insulin-like growth factor binding protein 3 (IGFBP-3)	ki	0.0080	uM
1-[4-(3,5-dichlorophenoxy)-3-fluorobenzoyl]-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0090	uM
1-[3-fluoro-4-(4-methylphenoxy)benzoyl]-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0094	uM
6,7-dihydroxy-1-[hydroxy-(2,4,6-trimethylphenyl)methyl]isoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0110	uM
1-[4-(3-chlorophenoxy)-3-fluorobenzoyl]-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0110	uM
1-[4-(3,4-dichlorophenoxy)-3-fluorobenzoyl]-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0120	uM
6,7-dihydroxy-1-(naphthalene-2-carbonyl)isoquinoline-3-carboxylic acid	93215: Inhibitory activity against Insulin-like growth factor binding protein 3	ki	0.0130	uM
6,7-dihydroxy-1-[hydroxy-[4-(trifluoromethyl)phenyl]methyl]isoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0180	uM
1-[4-(4-chlorophenoxy)-3-fluorobenzoyl]-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0200	uM
1-[(3-fluorophenyl)-hydroxymethyl]-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0240	uM
1-[(2-chlorophenyl)-hydroxymethyl]-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0250	uM
6,7-dihydroxy-1-(naphthalene-1-carbonyl)isoquinoline-3-carboxylic acid	93215: Inhibitory activity against Insulin-like growth factor binding protein 3	ki	0.0270	uM
1-(3,4-dihydroxybenzoyl)-6,7-dihydroxy-2H-isoquinolin-3-one	93215: Inhibitory activity against Insulin-like growth factor binding protein 3	ki	0.0280	uM
1-[(3,4-dihydroxyphenyl)methyl]-6,7-dihydroxy-2H-isoquinolin-3-one	93215: Inhibitory activity against Insulin-like growth factor binding protein 3	ki	0.0290	uM
1-(3,4-dichlorobenzoyl)-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0290	uM
1-[4-(4-chlorophenyl)sulfanyl-3-fluorobenzoyl]-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0310	uM
1-[3-fluoro-4-[4-(trifluoromethyl)phenoxy]benzoyl]-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0320	uM
1-[3-fluoro-4-(4-phenylphenoxy)benzoyl]-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0320	uM
6,7-dihydroxy-1-(4-nitrobenzoyl)isoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0320	uM
6,7-dihydroxy-1-[hydroxy-(4-phenoxyphenyl)methyl]isoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0320	uM
6,7-dihydroxy-1-[4-(trifluoromethyl)benzoyl]isoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0380	uM
1-(2,4-dichlorobenzoyl)-6,7-dihydroxyisoquinoline-3-carboxylic acid	93215: Inhibitory activity against Insulin-like growth factor binding protein 3	ki	0.0440	uM
1-(3,4-difluorobenzoyl)-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0510	uM
(6,7-dihydroxyisoquinolin-1-yl)-(3,4-dihydroxyphenyl)methanone	93215: Inhibitory activity against Insulin-like growth factor binding protein 3	ki	0.0580	uM
6-amino-1-(3,4-dihydroxybenzoyl)-7-hydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0600	uM
1-[4-(2-ethylhexylamino)-3-fluorobenzoyl]-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0620	uM
1-(1,3-benzodioxole-5-carbonyl)-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0700	uM
5-bromo-1-(3,4-dihydroxybenzoyl)-6-hydroxy-7-methoxyisoquinoline-3-carboxylic acid	93215: Inhibitory activity against Insulin-like growth factor binding protein 3	ki	0.0700	uM
1-(1,3-benzodioxol-5-ylmethyl)-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.0720	uM
6,7-dihydroxy-1-(2,4,6-trimethylbenzoyl)isoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.1000	uM
6,7-dihydroxy-1-[4-(methanesulfonamido)benzoyl]isoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.1100	uM
1-(3-fluorobenzoyl)-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.1100	uM
1-(2-chlorobenzoyl)-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.1100	uM
1-(4-aminobenzoyl)-6,7-dihydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.1300	uM
8-bromo-1-(3,4-dihydroxybenzoyl)-7-hydroxy-6-methoxyisoquinoline-3-carboxylic acid	93215: Inhibitory activity against Insulin-like growth factor binding protein 3	ki	0.1400	uM
7-hydroxy-1-(3-hydroxy-4-methoxybenzoyl)-6-methoxyisoquinoline-3-carboxylic acid	93215: Inhibitory activity against Insulin-like growth factor binding protein 3	ki	0.3200	uM
6-amino-1-(1,3-benzodioxole-5-carbonyl)-7-hydroxyisoquinoline-3-carboxylic acid	93214: Ability to displace Insulin-Like Growth Factor (IGF-I) from its binding to human insulin-like growth factor binding protein 3 (hIGFBP-3)	ki	0.8500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression, decreases expression, decreases secretion	14
Benzo(a)pyrene	affects methylation, affects cotreatment, increases expression, decreases expression, decreases reaction (+1 more)	9
Particulate Matter	decreases expression, increases abundance, increases expression, affects expression	9
sodium arsenite	decreases expression, decreases methylation, affects cotreatment, increases abundance, increases expression	8
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, affects expression, decreases expression	6
Tretinoin	increases expression	6
Progesterone	affects expression, affects cotreatment, decreases expression, decreases secretion, affects activity	5
Decitabine	affects acetylation, affects expression, increases expression	4
Air Pollutants	increases expression, decreases expression, increases abundance	4
Cisplatin	affects cotreatment, decreases expression, increases expression	4
Curcumin	affects cotreatment, increases expression, decreases expression, increases secretion	4
Ethinyl Estradiol	affects expression, decreases expression	4
Tunicamycin	decreases reaction, increases N-linked glycosylation, decreases N-linked glycosylation, increases expression	4
Cyclosporine	decreases reaction, increases secretion, decreases expression, increases expression	4
Aflatoxin B1	affects expression, decreases expression, decreases methylation, increases expression	4
Cadmium Chloride	increases abundance, increases expression	4
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects expression, decreases expression, affects cotreatment	3
(+)-JQ1 compound	affects cotreatment, decreases expression	3
Arsenic	decreases expression, increases abundance, affects methylation, affects cotreatment	3
Dust	increases expression, increases abundance	3
Quercetin	increases expression, increases secretion	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
Valproic Acid	increases expression, decreases expression	3
Genistein	decreases expression, affects cotreatment, increases expression	3
bisphenol A	affects expression, decreases expression	2
trichostatin A	affects acetylation, affects expression, decreases expression	2
mono-(2-ethylhexyl)phthalate	decreases expression, increases methylation	2
perfluorooctanoic acid	affects cotreatment, affects expression, increases expression	2
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, decreases expression	2
mercuric bromide	decreases expression, affects cotreatment	2

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL698358	Binding	Ability of compound to displace Insulin-Like Growth Factor (IGF-I) from its binding to Insulin-like growth factor binding protein 3 (IGFBP-3)	Quinoline-carboxylic acids are potent inhibitors that inhibit the binding of insulin-like growth factor (IGF) to IGF-binding proteins. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C6VU	OVTW59-P4-pBIG2i-hIGFBP3	Cancer cell line	Female

Clinical trials (associated diseases)

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