IGFBP2

Summary

IGFBP2 (insulin like growth factor binding protein 2, HGNC:5471) is a protein-coding gene on chromosome 2q35, encoding Insulin-like growth factor-binding protein 2 (P18065). 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.

The protein encoded by this gene is one of six similar proteins that bind insulin-like growth factors I and II (IGF-I and IGF-II). The encoded protein can be secreted into the bloodstream, where it binds IGF-I and IGF-II with high affinity, or it can remain intracellular, interacting with many different ligands. High expression levels of this protein promote the growth of several types of tumors and may be predictive of the chances of recovery of the patient. Several transcript variants, one encoding a secreted isoform and the others encoding nonsecreted isoforms, have been found for this gene.

Source: NCBI Gene 3485 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 6 total
• Druggable target: yes
• MANE Select transcript: NM_000597

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5471
Approved symbol	IGFBP2
Name	insulin like growth factor binding protein 2
Location	2q35
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000115457
Ensembl biotype	protein_coding
OMIM	146731
Entrez	3485

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 retained_intron

ENST00000233809, ENST00000434997, ENST00000436812, ENST00000456764, ENST00000490362, ENST00000902079, ENST00000902080, ENST00000902081, ENST00000902082, ENST00000912966, ENST00000912967

RefSeq mRNA: 4 — MANE Select: NM_000597 NM_000597, NM_001313990, NM_001313992, NM_001313993

CCDS: CCDS42815, CCDS82570

Canonical transcript exons

ENST00000233809 — 4 exons

Exon	Start	End
ENSE00000785610	216661858	216661998
ENSE00000966026	216633420	216633965
ENSE00001175330	216663940	216664436
ENSE00003547231	216660557	216660786

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 76.0697 / max 1951.7583, expressed in 1271 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25223	43.8082	1207
25222	23.0345	992
25221	8.5151	893
25224	0.6184	274
25226	0.0745	36
25227	0.0190	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
descending thoracic aorta	UBERON:0002345	99.71	gold quality
ascending aorta	UBERON:0001496	99.65	gold quality
thoracic aorta	UBERON:0001515	99.65	gold quality
decidua	UBERON:0002450	99.51	gold quality
right coronary artery	UBERON:0001625	99.50	gold quality
body of stomach	UBERON:0001161	99.24	gold quality
ventricular zone	UBERON:0003053	99.03	gold quality
stomach	UBERON:0000945	99.00	gold quality
ganglionic eminence	UBERON:0004023	98.84	gold quality
cortical plate	UBERON:0005343	98.82	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.80	gold quality
epithelium of bronchus	UBERON:0002031	98.73	gold quality
bronchial epithelial cell	CL:0002328	98.72	gold quality
embryo	UBERON:0000922	98.72	gold quality
left uterine tube	UBERON:0001303	98.71	gold quality
aorta	UBERON:0000947	98.70	gold quality
left coronary artery	UBERON:0001626	98.70	gold quality
spleen	UBERON:0002106	98.70	gold quality
left ovary	UBERON:0002119	98.70	gold quality
right lobe of liver	UBERON:0001114	98.68	gold quality
bronchus	UBERON:0002185	98.64	gold quality
coronary artery	UBERON:0001621	98.62	gold quality
fundus of stomach	UBERON:0001160	98.54	gold quality
metanephros cortex	UBERON:0010533	98.54	gold quality
right ovary	UBERON:0002118	98.45	gold quality
body of pancreas	UBERON:0001150	98.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.25	gold quality
pharyngeal mucosa	UBERON:0000355	98.18	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.17	gold quality
lower esophagus	UBERON:0013473	98.15	gold quality

Single-cell (SCXA)

Detected in 29 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-MTAB-9435	yes	10137.06
E-MTAB-10662	yes	3665.45
E-MTAB-10485	yes	2443.34
E-MTAB-10018	yes	2439.05
E-MTAB-10287	yes	2241.29
E-CURD-126	yes	1710.54
E-GEOD-84465	yes	1660.86
E-MTAB-8221	yes	1514.27
E-MTAB-8205	yes	1505.98
E-MTAB-9154	yes	1097.60
E-HCAD-23	yes	871.55
E-CURD-79	yes	632.98
E-MTAB-6701	yes	129.05
E-GEOD-81608	yes	51.24
E-GEOD-134144	yes	39.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, KLF9, NEUROD1, NFKB, PBX1, SATB1, SMARCA1, SP1, STAT3, TP63, TXK

miRNA regulators (miRDB)

13 targeting IGFBP2, 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-3667-3P	99.99	67.17	1636
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-4475	97.36	66.95	761
HSA-MIR-6131	97.22	66.72	960

Literature-anchored findings (GeneRIF, showing 40)

• determination of blood levels in adult patients with severe liver disease before and after orthotopic liver transplantation (PMID:12006706)
• Elevated level of IGFBP-2 is associated with pleural effusions of solid tumors (PMID:12102164)
• 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)
• IGFBP-2 may play a role in the progression, but not in the initiation of the prostate cancer disease process, suggesting the existence of a molecular switch transitioning IGFBP-2 from a growth inhibitor to a pro-carcinogenic molecule (PMID:12672024)
• Data suggest that insulin-like growth factor-II (IGF-II) is complexed in vivo with intact insulin-like growth factor binding proteins (IGFBP-2) and with processed IGFBP-2 fragments, which do not impair the activity of IGF-II on cell survival. (PMID:12727212)
• Castration-induced increases in this protein promotes proliferation of androgen-independent human prostate LNCaP tumors. (PMID:12839944)
• Data provide evidence that IGFBP2 contributes to glioma progression in part by enhancing MMP-2 gene transcription and in turn tumor cell invasion. (PMID:12907597)
• IGF-II-stimulated IGFBP-2 production appears to inhibit the mitogenic effect of IGF-II, and may have an autocrine effect on the maturation, differentiation, and survival of fetal podocytes. (PMID:12955485)
• IGF-1, IGFBP-2 levels were related to IL levels, disease activity and anatomical distribution, consistent with active inflammation modifying the IGF-IGFBP system, possibly relevant to disturbance of growth. (PMID:14691340)
• effect of IGFBP-2 overexpression on the activity of various antioxidative enzymes in two malignant cell lines (PMID:14710363)
• IGFBP2 expression increases from benign and dysplastic nevi to primary and metastatic melanomas and suggests that it may play a role in melanoma progression. (PMID:14744083)
• Of all the IGFBPs, only IGFBP-2 is expressed in activated microglia/macrophages; therefore IGFBP-2 may have an important role in IGF-I actions in human brain. (PMID:15147770)
• Data demonstrate that insulin-like growth factor binding protein-2 can act in an IGF-independent manner, at least in part by an interaction with alpha5beta1-integrin. (PMID:15171717)
• These findings suggest that overexpression of IGFBP-2 induces an increase in MMP-2 production, resulting in the enhanced metastatic potential of bladder cancer. (PMID:15643522)
• 1,25-Dihydroxyvitamin D3 decreased mRNA levels of the growth stimulatory IGFBP-2 and induced IGFBP-3 mRNA in prostate cancer cells (PMID:15651061)
• The expression of certain IGFBP is significantly altered in renal cell carcinoma (PMID:15661050)
• IGFBP2 enhances the invasion capacity of ovarian cancer cells (PMID:15686601)
• leptin and the IGF system of IGF-I, IGFBP-2, and IGF-I receptor do not interact directly in a cell culture model of neuroepithelioma cells (PMID:15932773)
• C-domain of IGFBP-2 plays a key role in binding regions of IGF-I and -II that are also involved in binding to the type-1 IGF receptor and thereby blocking ligand binding to this receptor (PMID:15956340)
• The heparin binding domain of IGFBP-2 is involved in the control and regulation of neuroblastoma growth and invasion. (PMID:15994346)
• These results suggest that the mechanism of action whereby IGFBP2 excess impairs long bone development is to inhibit IGF-mediated proliferation and matrix synthesis. (PMID:16183342)
• Regions upstream and downstream of the CWCV motif in IGFBP2 participate in IGF-1 binding. (PMID:16306230)
• Acute myelocytic leukemia patienets with elevated IGFBP2 concentrations had a poorer outcome after sten cell transplantation. (PMID:16444283)
• there are several conserved residues in the IGFBP-5 N-terminal region that are critical for transactivation and IGFBP-2 and -3 also have strong transactivation activity in their N-domains (PMID:16543235)
• one mechanism by which IGFBP2 activates IGFBP2-induced cell mobility is through its interaction with integrin alpha5 and this interaction is specifically mediated through the RGD domain on IGFBP2 (PMID:16569642)
• High expression of insulin-like growth factor binding protein-2 messenger RNA is associated with epithelial ovarian cancers (PMID:16884361)
• IGFBP-2 as a marker for antiestrogen resistant breast cancer cell lines. (PMID:16893667)
• Results suggest that IGFBP-2-induced gene expressions are of functional significance for proliferation, cell adhesion, cell migration and apoptosis, and showed that IGFBP-2 can promote apoptosis in tumor cells independent of IGF. (PMID:16901920)
• the solution structure of the C-terminal domain of IGFBP-2 was determined and its backbone dynamics based on 15N relaxation parameters analyzed with NMR. (PMID:17020769)
• These findings suggest that continuous K-Ras activation accelerates cell growth and evokes a feedback system through IGFBP-4/2 to prevent excessive growth. (PMID:17071580)
• IGFBP-2 may be involved in carcinogenesis and progression of gastric carcinoma by promoting cell proliferation. (PMID:17072950)
• p53 protein binds IGFBP-2 intronic sequences in an electrophoretic mobility shift assay, and activates transcription in a luciferase assay. (PMID:17102589)
• circulating levels significantly higher in cancer patients than in controls (PMID:17113753)
• This is the first evidence for PKA-dependent regulation of IGFBP-2 expression in adrenocortical cells. (PMID:17280861)
• Overexpression of the IGFBP-2 is associated with astrocytomas (PMID:17285230)
• IGFBP-2 is regulated predominantly through the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathway (PMID:17289850)
• The results provide further evidence that IGFBP-2 and IGF-II in breast milk are relevant factors for the early development of preterm infants. (PMID:17341887)
• Higher serum IGFBP-2, which is predictive of lower BMD, is associated with increased markers of bone resorption, independent of age, body mass, and sex hormones. (PMID:17352648)
• IGF-II and IGFBP-2 differentially regulate PTEN in human breast cancer cells (PMID:17369847)
• PTEN and IGFBP-2 expression are inversely correlated in human brain and prostate cancers (PMID:17372210)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	igfbp2b	ENSDARG00000031422
danio_rerio	igfbp2a	ENSDARG00000052470
mus_musculus	Igfbp2	ENSMUSG00000039323
rattus_norvegicus	Igfbp2	ENSRNOG00000016957

Paralogs (5): IGFBP5 (ENSG00000115461), IGFBP4 (ENSG00000141753), IGFBP3 (ENSG00000146674), IGFBP1 (ENSG00000146678), IGFBP6 (ENSG00000167779)

Protein

Protein identifiers

Insulin-like growth factor-binding protein 2 — P18065 (reviewed: P18065)

All UniProt accessions (4): C9JMY1, C9JW52, P18065, H7C1H0

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. Functions coordinately with receptor protein tyrosine phosphatase beta/PTPRB and the IGF1 receptor to regulate IGF1-mediated signaling by stimulating the phosphorylation of PTEN leading to its inactivation and AKT1 activation. Plays a positive role in cell migration via interaction with integrin alpha5/ITGA5 through an RGD motif. Additionally, interaction with ITGA5/ITGB1 enhances the adhesion of endothelial progenitor cells to endothelial cells. Upon mitochondrial damage, facilitates apoptosis with ITGA5 of podocytes, and then activates the phosphorylation of focal adhesion kinase (FAK)-mediated mitochondrial injury.

Subunit / interactions. Interacts with IGF1. Interacts with IGF2. Interacts (via RGD motif) with integrin alpha5/ITGA5; this interaction induces cell migration, adhesion or apoptosis according to the context. Interacts with PTPRB; this interaction leads to PTPRB dimerization and inactivation.

Subcellular location. Secreted.

Post-translational modifications. Cleaved by MMP9 leading to release of free IGF2 from IGFBP2-IGF2 complex, which contributes to enhance the motility and the growth of astrocytes. O-glycosylated.

Domain organisation. The C-terminus is required for IGF-binding and growth inhibition.

RefSeq proteins (4): NP_000588, NP_001300919, NP_001300921, NP_001300922 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000716	Thyroglobulin_1	Domain
IPR000867	IGFBP-like	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR012210	IGFBP-2	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 (27 total): disulfide bond 9, sequence conflict 4, strand 3, mutagenesis site 2, domain 2, signal peptide 1, chain 1, sequence variant 1, helix 1, turn 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2H7T	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18065-F1	66.96	0.17

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (9): 98–111, 105–131, 227–261, 272–283, 285–306, 42–84, 45–86, 53–87, 75–90

Mutagenesis-validated functional residues (2):

Position	Phenotype
216–219	does not disrupt growth-inhibiting activity.
303	does not disrupt growth-inhibiting activity. loss of endothelial progenitor cells-endothelial adhesion activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)

MSigDB gene sets: 315 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_52, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, WANG_CLIM2_TARGETS_UP, CHIBA_RESPONSE_TO_TSA_UP, HARRIS_HYPOXIA, GOBP_RESPONSE_TO_ESTRADIOL, KANG_FLUOROURACIL_RESISTANCE_UP, BROWNE_HCMV_INFECTION_8HR_UP, GOBP_RESPONSE_TO_CORTICOSTEROID, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_OSTEOBLAST_DIFFERENTIATION, MCBRYAN_TERMINAL_END_BUD_UP, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, BROWNE_HCMV_INFECTION_12HR_UP

GO Biological Process (16): osteoblast differentiation (GO:0001649), female pregnancy (GO:0007565), response to nutrient (GO:0007584), response to xenobiotic stimulus (GO:0009410), response to mechanical stimulus (GO:0009612), response to estradiol (GO:0032355), response to retinoic acid (GO:0032526), cellular response to hormone stimulus (GO:0032870), positive regulation of activated T cell proliferation (GO:0042104), regulation of insulin-like growth factor receptor signaling pathway (GO:0043567), response to estrogen (GO:0043627), response to glucocorticoid (GO:0051384), negative regulation of canonical Wnt signaling pathway (GO:0090090), response to insulin (GO:0032868), negative regulation of osteoblast differentiation (GO:0045668), response to steroid hormone (GO:0048545)

GO Molecular Function (9): signaling receptor binding (GO:0005102), insulin-like growth factor I binding (GO:0031994), insulin-like growth factor II binding (GO:0031995), receptor ligand inhibitor activity (GO:0141069), protein phosphatase inhibitor activity (GO:0004864), protein binding (GO:0005515), insulin-like growth factor binding (GO:0005520), growth factor binding (GO:0019838), signaling receptor inhibitor activity (GO:0030547)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), apical plasma membrane (GO:0016324), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to lipid	3
response to hormone	3
response to chemical	2
response to oxygen-containing compound	2
protein binding	2
insulin-like growth factor binding	2
molecular function inhibitor activity	2
ossification	1
cell differentiation	1
multi-organism reproductive process	1
multi-multicellular organism process	1
response to nutrient levels	1
response to external stimulus	1
response to abiotic stimulus	1
cellular response to chemical stimulus	1
cellular response to endogenous stimulus	1
positive regulation of T cell proliferation	1
regulation of activated T cell proliferation	1
activated T cell proliferation	1
regulation of signal transduction	1
insulin-like growth factor receptor signaling pathway	1
response to corticosteroid	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
response to peptide hormone	1
osteoblast differentiation	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
receptor ligand activity	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
binding	1
growth factor binding	1
signaling receptor regulator activity	1
signaling receptor activity	1
cellular anatomical structure	1
apical part of cell	1
plasma membrane region	1

Protein interactions and networks

STRING

1931 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGFBP2	IGF1	P01343	999
IGFBP2	IGF2	P01344	999
IGFBP2	INS	P01308	982
IGFBP2	NIPA2	Q8N8Q9	915
IGFBP2	TUBGCP5	Q96RT8	915
IGFBP2	NIPA1	Q7RTP0	905
IGFBP2	MIIP	Q5JXC2	862
IGFBP2	CYFIP1	Q7L576	841
IGFBP2	IGFBP3	P17936	831
IGFBP2	IGF1R	P08069	808
IGFBP2	PTPRB	P23467	806
IGFBP2	IGFALS	P35858	776
IGFBP2	IGF2R	P11717	703
IGFBP2	SHBG	P04278	693
IGFBP2	LEP	P41159	678

IntAct

14 interactions, top by confidence:

A	B	Type	Score
INO80B	IGFBP2	psi-mi:“MI:0915”(physical association)	0.600
IGFBP2	INO80B	psi-mi:“MI:0403”(colocalization)	0.600
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
IGFBP2	HDAC6	psi-mi:“MI:0915”(physical association)	0.400
GSDMB	IGFBP2	psi-mi:“MI:0915”(physical association)	0.370
IGF2	POTEF	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
NUP35	IGFBP2	psi-mi:“MI:0914”(association)	0.350
IGF2	CALU	psi-mi:“MI:0914”(association)	0.350
IGFBP2	aroP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): EGFR (Affinity Capture-Western), IGFBP2 (Affinity Capture-Western), EGFR (Co-localization), IGFBP2 (Affinity Capture-MS), IGFBP2 (Proximity Label-MS), IGFBP2 (Co-purification), ITGA5 (Affinity Capture-Western), IGFBP2 (Affinity Capture-MS), IGFBP2 (Affinity Capture-MS), IGFBP2 (Affinity Capture-MS), IGFBP2 (Affinity Capture-MS), HDAC6 (Affinity Capture-MS), IGFBP2 (Affinity Capture-MS), CDKN1A (Affinity Capture-Western), IGFBP2 (Affinity Capture-Western)

ESM2 similar proteins: A1A4M2, A4IFG4, A5D8P8, A6NKD9, A7E2M3, B4F7F3, E9Q6B2, F1MX48, F1SAM7, O97676, P18065, P36956, P47877, P49705, P56720, P56873, Q00709, Q00973, Q09200, Q0IHY5, Q15465, Q24JP5, Q2YD98, Q3TAS6, Q58CS8, Q5QQ49, Q5UCC4, Q60416, Q60698, Q641Q3, Q68FE7, Q6AYH6, Q6DVA0, Q6P7K5, Q6UKI2, Q6WVG3, Q80WF4, Q8IW70, Q8JGM4, Q8K064

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

1 interactions.

A	Effect	B	Mechanism
SATB1	“up-regulates quantity by expression”	IGFBP2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

866 predictions. Top by Δscore:

Variant	Effect	Δscore
2:216660785:GG:G	donor_gain	1.0000
2:216660786:GG:G	donor_gain	1.0000
2:216661998:GGTG:G	donor_loss	1.0000
2:216661999:G:GA	donor_loss	1.0000
2:216633960:TTGC:T	donor_gain	0.9900
2:216633961:TGCA:T	donor_gain	0.9900
2:216633962:GCAG:G	donor_gain	0.9900
2:216633962:GCAGG:G	donor_loss	0.9900
2:216633963:CAGG:C	donor_loss	0.9900
2:216633964:AG:A	donor_loss	0.9900
2:216633965:GG:G	donor_loss	0.9900
2:216633966:G:GA	donor_loss	0.9900
2:216633967:T:A	donor_loss	0.9900
2:216660551:T:A	acceptor_gain	0.9900
2:216660552:GGCA:G	acceptor_loss	0.9900
2:216660553:GCA:G	acceptor_loss	0.9900
2:216660554:CA:C	acceptor_loss	0.9900
2:216660555:A:AG	acceptor_gain	0.9900
2:216660555:A:C	acceptor_loss	0.9900
2:216660556:G:GA	acceptor_gain	0.9900
2:216660556:GAC:G	acceptor_gain	0.9900
2:216660556:GACA:G	acceptor_gain	0.9900
2:216660762:G:GT	donor_gain	0.9900
2:216660766:C:G	donor_gain	0.9900
2:216660787:G:GG	donor_gain	0.9900
2:216660788:T:G	donor_loss	0.9900
2:216660790:A:AG	donor_gain	0.9900
2:216660791:G:GG	donor_gain	0.9900
2:216661851:C:CA	acceptor_gain	0.9900
2:216661856:A:AG	acceptor_gain	0.9900

AlphaMissense

2073 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:216661966:T:A	C261S	1.000
2:216661967:G:A	C261Y	1.000
2:216661967:G:C	C261S	1.000
2:216661967:G:T	C261F	1.000
2:216661995:A:C	K270N	1.000
2:216661995:A:T	K270N	1.000
2:216663940:T:A	C272S	1.000
2:216663941:G:C	C272S	1.000
2:216663973:T:A	C283S	1.000
2:216663973:T:C	C283R	1.000
2:216663974:G:C	C283S	1.000
2:216663978:G:C	W284C	1.000
2:216663978:G:T	W284C	1.000
2:216663979:T:A	C285S	1.000
2:216663979:T:C	C285R	1.000
2:216663980:G:C	C285S	1.000
2:216664042:T:A	C306S	1.000
2:216664042:T:C	C306R	1.000
2:216664043:G:C	C306S	1.000
2:216633836:T:A	C105S	0.999
2:216633837:G:C	C105S	0.999
2:216633854:T:A	C111S	0.999
2:216633854:T:C	C111R	0.999
2:216633855:G:C	C111S	0.999
2:216633856:C:G	C111W	0.999
2:216633914:T:A	C131S	0.999
2:216633915:G:C	C131S	0.999
2:216661864:T:A	C227S	0.999
2:216661864:T:C	C227R	0.999
2:216661865:G:A	C227Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000009766 (2:216646520 G>A), RS1000011307 (2:216650288 C>T), RS1000028824 (2:216634242 A>G), RS1000032078 (2:216639657 T>C), RS1000076699 (2:216647687 T>A), RS1000247062 (2:216662613 C>G), RS1000322404 (2:216646062 T>G), RS1000335167 (2:216646241 G>A), RS1000420470 (2:216651232 C>G), RS1000533716 (2:216661356 G>A), RS1000548185 (2:216651097 G>A), RS1000584687 (2:216661536 G>C), RS1000692102 (2:216656084 G>A), RS1000750190 (2:216649861 G>A), RS1000757843 (2:216657337 T>TA)

Disease associations

OMIM: gene MIM:146731 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003094_2	Mitral valve prolapse	3.000000e-11
GCST003400_34	Type 2 diabetes	2.000000e-24
GCST004292_51	Glomerular filtration rate (creatinine)	2.000000e-06
GCST008165_2	Thyroid stimulating hormone levels	2.000000e-19
GCST010818_9	Gut microbiota alpha diversity (PD_whole_tree index)	4.000000e-06
GCST010819_1	Gut microbiota alpha diversity (Chao1 index)	2.000000e-07
GCST90007000_15	Gut microbiota relative abundance (unclassified genus belonging to family Ruminococcaceae)	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3088 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.68	Ki	2.07	nM	CHEMBL292700
7.77	Ki	17.13	nM	CHEMBL130994

PubChem BioAssay actives

2 with measured affinity, of 2 total; 2 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	93212: The compound was tested for binding affinity against insulin-like growth factor binding protein 2	ki	0.0021	uM
1-(3,4-dihydroxybenzoyl)-6,7-dihydroxy-2H-isoquinolin-3-one	93212: The compound was tested for binding affinity against insulin-like growth factor binding protein 2	ki	0.0171	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Benzo(a)pyrene	increases methylation, affects expression, decreases expression, increases expression	5
Estradiol	decreases expression, affects cotreatment, increases secretion, increases expression	5
Arsenic Trioxide	affects cotreatment, decreases expression, affects binding, decreases reaction	4
Aflatoxin B1	increases expression, increases methylation, affects expression	4
sodium arsenite	affects expression, decreases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression	3
Tretinoin	decreases expression	3
Cyclosporine	decreases expression	3
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects expression, affects cotreatment	2
chloropicrin	decreases expression	2
(+)-JQ1 compound	affects cotreatment, increases expression, decreases expression	2
Resveratrol	increases expression	2
Cisplatin	decreases expression, increases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Progesterone	affects cotreatment, increases secretion, decreases expression	2
Rotenone	decreases expression	2
Testosterone	increases expression	2
Cadmium Chloride	increases abundance, decreases expression, decreases reaction	2
Particulate Matter	decreases expression, increases abundance	2
GSK-J4	increases expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
arsenite	increases methylation	1
trimellitic anhydride	affects expression	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
sodium tungstate(VI)	affects expression	1
benzo(e)pyrene	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL698357	Binding	The compound was tested for binding affinity against insulin-like growth factor binding protein 2	Discovery of a series of nonpeptide small molecules that inhibit the binding of insulin-like growth factor (IGF) to IGF-binding proteins. — J Med Chem

Clinical trials (associated diseases)

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