IGFBP1

Summary

IGFBP1 (insulin like growth factor binding protein 1, HGNC:5469) is a protein-coding gene on chromosome 7p12.3, encoding Insulin-like growth factor-binding protein 1 (P08833). 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 cell migration, proliferation, differentiation or apoptosis in a cell-type specific….

This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP N-terminal domain and a thyroglobulin type-I domain. The encoded protein, mainly expressed in the liver, circulates in the plasma and binds both insulin-like growth factors (IGFs) I and II, prolonging their half-lives and altering their interaction with cell surface receptors. This protein is important in cell migration and metabolism. Low levels of this protein may be associated with impaired glucose tolerance, vascular disease and hypertension in human patients.

Source: NCBI Gene 3484 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 39 total
• Druggable target: yes
• MANE Select transcript: NM_000596

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5469
Approved symbol	IGFBP1
Name	insulin like growth factor binding protein 1
Location	7p12.3
Locus type	gene with protein product
Status	Approved
Aliases	IGF-BP25, AFBP, hIGFBP-1, PP12
Ensembl gene	ENSG00000146678
Ensembl biotype	protein_coding
OMIM	146730
Entrez	3484

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000275525, ENST00000457280, ENST00000468955

RefSeq mRNA: 1 — MANE Select: NM_000596 NM_000596

CCDS: CCDS5504

Canonical transcript exons

ENST00000275525 — 4 exons

Exon	Start	End
ENSE00000976757	45890548	45890717
ENSE00000976758	45891932	45892060
ENSE00001856462	45888488	45889001
ENSE00001907318	45892960	45893660

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 99.66.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 6.5142 / max 2049.8129, expressed in 179 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78498	6.2497	152
78494	0.0943	39
78501	0.0267	10
78496	0.0263	10
78495	0.0224	6
78503	0.0209	6
78499	0.0202	8
78497	0.0167	6
78505	0.0155	6
78502	0.0080	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	99.66	gold quality
right lobe of liver	UBERON:0001114	97.94	gold quality
liver	UBERON:0002107	96.86	gold quality
oocyte	CL:0000023	95.86	gold quality
secondary oocyte	CL:0000655	94.71	gold quality
placenta	UBERON:0001987	88.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.26	gold quality
stromal cell of endometrium	CL:0002255	82.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.39	gold quality
left ovary	UBERON:0002119	77.54	gold quality
ovary	UBERON:0000992	70.41	gold quality
right ovary	UBERON:0002118	68.90	gold quality
pericardium	UBERON:0002407	67.19	gold quality
renal glomerulus	UBERON:0000074	64.23	silver quality
metanephric glomerulus	UBERON:0004736	63.01	silver quality
left uterine tube	UBERON:0001303	61.42	gold quality
adrenal tissue	UBERON:0018303	60.94	gold quality
kidney epithelium	UBERON:0004819	59.56	silver quality
pancreatic ductal cell	CL:0002079	58.76	silver quality
nephron tubule	UBERON:0001231	58.75	silver quality
germinal epithelium of ovary	UBERON:0001304	57.82	silver quality
islet of Langerhans	UBERON:0000006	57.79	gold quality
omental fat pad	UBERON:0010414	56.94	gold quality
peritoneum	UBERON:0002358	56.90	gold quality
fallopian tube	UBERON:0003889	56.35	gold quality
adipose tissue of abdominal region	UBERON:0007808	56.05	gold quality
female reproductive system	UBERON:0000474	55.84	gold quality
adult mammalian kidney	UBERON:0000082	54.79	gold quality
myometrium	UBERON:0001296	54.64	gold quality
metanephros	UBERON:0000081	54.26	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-23	yes	84776.45
E-MTAB-6701	yes	22498.81
E-MTAB-6678	yes	17810.02
E-MTAB-10553	yes	2429.46
E-GEOD-130473	yes	1098.09
E-ANND-3	no	0.97

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, ATF4, CEBPA, CEBPB, CEBPG, CREB1, DBP, DLX4, ESR1, ETS1, EZH2, FOS, FOXA1, FOXA2, FOXM1, FOXO1, FOXO4, HDAC9, HIF1A, HNF1A, HNF1B, HOXA10, HOXA5, HOXB4, HR, IRF8, JUN, KLF12, NFYA, NFYB, NR3C1, PGR, PPARA, PPARG, SP1, SP3, STAT3, STAT5B, TAF1, TEAD4

miRNA regulators (miRDB)

55 targeting IGFBP1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168

Literature-anchored findings (GeneRIF, showing 40)

• IGFBP-1 is elevated in both hypothyroidism and hyperthyroidism (PMID:11762714)
• IGF-binding protein 1 (IGFBP1) gene variant is associated with overfeeding-induced metabolic changes. accumulation of abdominal visceral fat and the early symptoms of the metabolic syndrome. (PMID:11793026)
• Increases in free, unbound insulin-like growth factor I enhance insulin responsiveness in human hepatoma G2 cells in culture. (PMID:11834727)
• reduced fertility in transgenic female mice overexpressing human IGFBP-1 are mainly due to an alteration of terminal follicular growth (PMID:11956162)
• altered IGF-II and IGFBP-1 expression at the fetomaternal interface may be important in the pathophysiology of pre-eclampsia (PMID:11969341)
• after adjustment for age, high serum concentrations carried an increased risk of total mortality due to cardiovascular and coronary heart disease (PMID:11972304)
• determination of blood levels in adult patients with severe liver disease before and after orthotopic liver transplantation (PMID:12006706)
• statistical relationships between IGF-BP1 and blood rheology in athletes (PMID:12082253)
• circulating levels of IGF-1 and IGFBP-1 are significantly related to the extent of myocardial injury in patients with hypertrophic cardiomyopathy. (PMID:12135130)
• IGFBP-1 levels significantly predict distant recurrence and death in breast cancer patients; prognostic effects appear related to known effect of insulin on IGFBP-1 gene expression (PMID:12150454)
• Adolescents with IDDM are characterised by morning hypoinsulinaemia and high circulating IGFBP-1 concentrations (PMID:12153746)
• IGFBP-1 plays a role in placentation and suggests that IGFBP-1 has a pathological role in preeclampsia, a disorder characterized by shallow uterine invasion and altered placental development (PMID:12163461)
• reduction of this protein is associated with thickening of the carotid wall in type 2 diabetes. (PMID:12351482)
• Bone formation in the context of growth retardation induced by hIGFBP-1 overexpression in transgenic mice. Overexpression of hIGFBP-1 causes postnatal growth retardation and a delay in mineralization in transgenic mutant mice. (PMID:12489207)
• FKHR and HOXA10 interact directly and can function cooperatively to stimulate IGFBP-1 promoter activity in endometrial cells (PMID:12493691)
• 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)
• insulin-like growth factor binding protein-1 in the third trimester and cord blood were negatively correlated with birth weight (PMID:12679458)
• When IGFBP-1 was added, prostate cancer LNCaP cell growth was reduced, and apoptosis was induced. (PMID:12746292)
• IGFBP-1 is decreased in human prostate malignancy (PMID:12746836)
• possible stimulatory effect of endogenous GH on IGF and IGF-binding protein 1 levels during fasting. (PMID:12843178)
• insulin-induced stimulation of progesterone or inhibition of IGFBP-1 production in human granulosa cells does not require MAPK activation, whereas similar effects of IGF-I are largely MAPK dependent. (PMID:12843192)
• serum concentrations of insulin-like growth factor binding protein-1 are abnormal in antiphospholipid syndrome pregnancies (PMID:12861174)
• endurance training improves glucose disposal and increases insulin-like growth binding protein-1 and -3 in men and for IGFBP-1 becomes more pronounced with age (PMID:12870155)
• IGFBP-1 plays an important and potentially beneficial role in regulating metabolic and vascular homeostasis. (PMID:12882925)
• elevations in circulating and tissue levels of IGFBP-1 may be an important mediator for the muscle catabolism observed in various stress conditions. (PMID:12933666)
• IGFBP-1 and SHBG are equally sensitive to ambient insulin concentrations in human hepatoma cell cultures, and the production of both proteins is also attenuated by the IGFs. (PMID:14568572)
• Elevation of IGFBP-1 is associated with the metabolic disturbances in liver disease (PMID:14624764)
• low baseline levels of insulin-like growth factor-I and insulin-like growth factor binding protein-1 increase the risk of fatal ischemic heart disease among elderly men and women independent of prevalent risk factors (PMID:14715837)
• Breeding impairment of human insulin-like growth factor-binding protein-1 transgenic males is due at least in part to alteration of spermatogenesis, leading to diminution of sperm production and of its quality. Minor impairment of steroidogenesis. (PMID:14726451)
• During first trimester, serum glycodelin and IGFBP-1 are markedly decreased in polycystic ovary syndrome (PCOS), implicating endometrial epithelial and stromal dysfunction during periimplantation and early pregnancy in early pregnancy loss. (PMID:14764802)
• cleavage of IGFBP-1 is a novel mechanism in the control of placental development by matrix metalloproteases. (PMID:15070833)
• Metabolic, anthropometric, and nutritional factors are important determinants of IGFBP-1 levels in healthy men. (PMID:15070959)
• GH serum levels increased in response to hIGFBP-1 administration, even in the setting of normal IGF-I levels. (PMID:15166120)
• The presence of relative insulin resistance and low fasting IGFBP-1 levels in Asian Indians may contribute to their higher risk of developing diabetes and cardiovascular disease. (PMID:15598684)
• human endometrium is a target for insulin action in the regulation of IGFBP-1. (PMID:15613433)
• in patients with type 2 diabetes there was a blunted increase in IGFBP-1 concentrations with nutritional deprivation (PMID:15736102)
• The IGFBP-1 protein is synthesized as propeptides with a hydrophobic leader sequence, removal of which yields a mature protein composed of 3 recognizable domains of similar size. (PMID:15797461)
• Transcription of IGF-binding protein-1 is stimulated by Foxo1 acetylated by p300. (PMID:15890677)
• Maternal diabetes is associated with suppressed levels of IGFBP-1 in cord serum. (PMID:15959422)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	igfbp1b	ENSDARG00000038666
danio_rerio	igfbp1a	ENSDARG00000099351
mus_musculus	Igfbp1	ENSMUSG00000020429
rattus_norvegicus	Igfbp1	ENSRNOG00000058780

Paralogs (5): IGFBP2 (ENSG00000115457), IGFBP5 (ENSG00000115461), IGFBP4 (ENSG00000141753), IGFBP3 (ENSG00000146674), IGFBP6 (ENSG00000167779)

Protein

Protein identifiers

Insulin-like growth factor-binding protein 1 — P08833 (reviewed: P08833)

Alternative names: Placental protein 12

All UniProt accessions (3): P08833, C9J6H2, C9JXF9

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 cell migration, proliferation, differentiation or apoptosis in a cell-type specific manner. Also plays a positive role in cell migration by interacting with integrin ITGA5:ITGB1 through its RGD motif. Mechanistically, binding to integrins leads to activation of focal adhesion kinase/PTK2 and stimulation of the mitogen-activated protein kinase (MAPK) pathway. Regulates cardiomyocyte apoptosis by suppressing HIF-1alpha/HIF1A ubiquitination and subsequent degradation.

Subunit / interactions. Binds equally well IGF1 and IGF2. Interacts with integrin ITGA5:ITGB1. Interacts with VHL; this interaction inhibits HIF1A degradation.

Subcellular location. Secreted.

Post-translational modifications. Phosphorylated; probably by casein kinase II. Phosphorylation alters the affinity of the protein for IGFs. In amniotic fluid, the unmodified protein is the most abundant form, while mono-, bi-, tri- and tetraphosphorylated forms are present in decreasing amounts. The phosphorylation state may influence the propensity to proteolysis.

RefSeq proteins (1): NP_000587* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000716	Thyroglobulin_1	Domain
IPR000867	IGFBP-like	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR017891	Insulin_GF-bd_Cys-rich_CS	Conserved_site
IPR022321	IGFBP_1-6_chordata	Family
IPR022322	IGFBP1	Family
IPR036857	Thyroglobulin_1_sf	Homologous_superfamily

Pfam: PF00086, PF00219

UniProt features (39 total): modified residue 12, disulfide bond 9, strand 6, sequence variant 3, domain 2, signal peptide 1, chain 1, mutagenesis site 1, sequence conflict 1, helix 1, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1ZT3	X-RAY DIFFRACTION	1.8
1ZT5	X-RAY DIFFRACTION	1.82
2DSQ	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08833-F1	76.74	0.43

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 (12): 156, 157, 158, 193, 194, 199, 242, 45, 120, 123, 126, 144

Disulfide bonds (9): 30–57, 33–59, 41–60, 48–63, 71–84, 78–104, 176–206, 217–228, 230–251

Mutagenesis-validated functional residues (1):

Position	Phenotype
246	loss of binding to itga5.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-380994	ATF4 activates genes in response to endoplasmic reticulum stress
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
R-HSA-9615017	FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes

MSigDB gene sets: 194 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, BENPORATH_ES_WITH_H3K27ME3, HARRIS_HYPOXIA, PID_HNF3B_PATHWAY, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_GROWTH, GOBP_REGENERATION, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, HNF1_Q6, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, SHEPARD_BMYB_MORPHOLINO_DN, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_1_DN, BORLAK_LIVER_CANCER_EGF_UP

GO Biological Process (7): signal transduction (GO:0007165), insulin receptor signaling pathway (GO:0008286), positive regulation of cell growth (GO:0030307), tissue regeneration (GO:0042246), regulation of insulin-like growth factor receptor signaling pathway (GO:0043567), negative regulation of canonical Wnt signaling pathway (GO:0090090), response to insulin (GO:0032868)

GO Molecular Function (6): signaling receptor binding (GO:0005102), insulin-like growth factor binding (GO:0005520), insulin-like growth factor I binding (GO:0031994), insulin-like growth factor II binding (GO:0031995), protein binding (GO:0005515), growth factor binding (GO:0019838)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
PERK regulates gene expression	1
Metabolism of proteins	1
Post-translational protein modification	1
FOXO-mediated transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
insulin-like growth factor binding	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
regeneration	1
developmental growth	1
regulation of signal transduction	1
insulin-like growth factor receptor signaling pathway	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
growth factor binding	1
binding	1
cellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2356 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGFBP1	IGF1	P01343	999
IGFBP1	IGF2	P01344	998
IGFBP1	INS	P01308	994
IGFBP1	IGFBP6	P24592	955
IGFBP1	IGF1R	P08069	885
IGFBP1	IGF2R	P11717	755
IGFBP1	FN1	P02751	740
IGFBP1	PRL	P01236	713
IGFBP1	DLK1	P15803	708
IGFBP1	SHBG	P04278	694
IGFBP1	IGFBP3	P17936	692
IGFBP1	IGFALS	P35858	672
IGFBP1	GHR	P10912	667
IGFBP1	IGFBP7	Q16270	658
IGFBP1	IL6	P05231	656

IntAct

20 interactions, top by confidence:

A	B	Type	Score
IGFBP1	IGF1	psi-mi:“MI:0407”(direct interaction)	0.620
IGF1	IGFBP1	psi-mi:“MI:0407”(direct interaction)	0.620
DMWD	IGFBP1	psi-mi:“MI:0915”(physical association)	0.560
BAG6	IGFBP1	psi-mi:“MI:0915”(physical association)	0.560
KLF11	IGFBP1	psi-mi:“MI:0915”(physical association)	0.560
IGFBP1	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
IGFBP1	SUSD5	psi-mi:“MI:0914”(association)	0.530
IGFBP1	IGF2	psi-mi:“MI:0407”(direct interaction)	0.440
FAM20C	IGFBP1	psi-mi:“MI:0915”(physical association)	0.400
IGFBP1	FAM20C	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (37): PTPN3 (Affinity Capture-MS), TRIP6 (Affinity Capture-MS), SUSD5 (Affinity Capture-MS), ADAMTS1 (Affinity Capture-MS), ZNF696 (Affinity Capture-MS), TIMP1 (Affinity Capture-MS), IGF2 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), ZNF664 (Affinity Capture-MS), SMOC1 (Affinity Capture-MS), GTPBP2 (Affinity Capture-MS), LMF2 (Affinity Capture-MS), TIMP3 (Affinity Capture-MS), CD59 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IKU3, A0A8M9PFP2, A1A5Y0, A2A863, A2VCU8, A5A6L1, B0S5G3, L7VG99, O00622, O08841, O35118, O42493, O93512, P08163, P08833, P16042, P16144, P17668, P18406, Q07663, Q0VCN6, Q13753, Q501P1, Q53RD9, Q5R9Q9, Q61220, Q61592, Q64632, Q6DDW2, Q7T3Q2, Q7ZV46, Q7ZXL5, Q8R4Y4, Q8R553, Q8VDA1, Q91166, Q91167, Q91713, Q99JH7, Q9BQT9

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

4 interactions.

A	Effect	B	Mechanism
FOXO	“up-regulates quantity by expression”	IGFBP1	“transcriptional regulation”
HOXA10	“down-regulates quantity by repression”	IGFBP1	“transcriptional regulation”
HOXB4	“up-regulates quantity by expression”	IGFBP1	“transcriptional regulation”
FOXO1	“up-regulates quantity by expression”	IGFBP1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

363 predictions. Top by Δscore:

Variant	Effect	Δscore
7:45890545:CA:C	acceptor_loss	1.0000
7:45890546:A:AG	acceptor_gain	1.0000
7:45890546:A:C	acceptor_loss	1.0000
7:45890546:AGAG:A	acceptor_gain	1.0000
7:45890547:G:GT	acceptor_gain	1.0000
7:45890547:GA:G	acceptor_gain	1.0000
7:45890547:GAGG:G	acceptor_gain	1.0000
7:45890547:GAGGC:G	acceptor_gain	1.0000
7:45890713:GGAAG:G	donor_gain	1.0000
7:45890714:G:GT	donor_gain	1.0000
7:45890714:GAAG:G	donor_gain	1.0000
7:45890715:A:T	donor_gain	1.0000
7:45890716:AG:A	donor_loss	1.0000
7:45890718:GT:G	donor_loss	1.0000
7:45890719:T:A	donor_loss	1.0000
7:45892056:GACAG:G	donor_gain	1.0000
7:45892958:A:AG	acceptor_gain	1.0000
7:45892959:G:GG	acceptor_gain	1.0000
7:45892959:GT:G	acceptor_gain	1.0000
7:45892959:GTGT:G	acceptor_gain	1.0000
7:45891927:CTTAG:C	acceptor_loss	0.9900
7:45891930:A:AG	acceptor_gain	0.9900
7:45891930:AG:A	acceptor_gain	0.9900
7:45891931:G:GG	acceptor_gain	0.9900
7:45891931:GG:G	acceptor_gain	0.9900
7:45891931:GGA:G	acceptor_gain	0.9900
7:45892057:ACAGG:A	donor_loss	0.9900
7:45892062:T:G	donor_loss	0.9900
7:45892954:TTGCA:T	acceptor_loss	0.9900
7:45892955:TGCAG:T	acceptor_loss	0.9900

AlphaMissense

1671 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:45892028:T:A	C206S	0.999
7:45892029:G:C	C206S	0.999
7:45892998:G:C	W229C	0.999
7:45892998:G:T	W229C	0.999
7:45888902:T:A	C84S	0.997
7:45888903:G:C	C84S	0.997
7:45892960:T:A	C217S	0.997
7:45892961:G:C	C217S	0.997
7:45888884:T:A	C78S	0.996
7:45888885:G:C	C78S	0.996
7:45891938:T:A	C176S	0.996
7:45891939:G:C	C176S	0.996
7:45892046:T:G	Y212D	0.995
7:45892999:T:A	C230S	0.995
7:45893000:G:C	C230S	0.995
7:45893018:G:T	G236V	0.995
7:45888863:T:A	C71S	0.994
7:45888864:G:A	C71Y	0.994
7:45888864:G:C	C71S	0.994
7:45888866:G:T	G72C	0.994
7:45888962:T:A	C104S	0.994
7:45888963:G:C	C104S	0.994
7:45891939:G:A	C176Y	0.994
7:45891940:C:G	C176W	0.994
7:45892029:G:A	C206Y	0.994
7:45892060:G:C	Q216H	0.994
7:45892060:G:T	Q216H	0.994
7:45892999:T:C	C230R	0.994
7:45893062:T:A	C251S	0.994
7:45893063:G:C	C251S	0.994

dbSNP variants (sampled 300 via entrez): RS1000938997 (7:45888508 C>A), RS1001299186 (7:45888978 A>C,G), RS1001841276 (7:45887446 C>A), RS1001934871 (7:45886993 GTC>G), RS1002296260 (7:45888321 G>A), RS1002408544 (7:45893647 A>G), RS1003241894 (7:45893282 A>G,T), RS1003302883 (7:45886920 T>A,C), RS1003308066 (7:45891757 G>A), RS1003948176 (7:45887777 C>A), RS1004015504 (7:45893858 C>A), RS1004313233 (7:45891121 G>A,C), RS1004404936 (7:45887480 G>A), RS1004511412 (7:45892260 A>C,G), RS1004983286 (7:45892850 T>G)

Disease associations

OMIM: gene MIM:146730 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000917_2	Rheumatoid arthritis	5.000000e-07
GCST001850_42	Major depressive disorder	9.000000e-06
GCST003160_3	Subjective response to lithium treatment in bipolar disorder	5.000000e-07
GCST003542_93	Night sleep phenotypes	1.000000e-07
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
GCST006021_24	Systolic blood pressure	4.000000e-08
GCST007705_45	Pulse pressure	5.000000e-09
GCST008363_61	Offspring birth weight	2.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007936	disease prognosis measurement
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4178 (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
8.29	Ki	5.07	nM	CHEMBL292700
7.47	Ki	34.23	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	93211: The compound was tested for binding affinity against insulin-like growth factor binding protein 1	ki	0.0051	uM
1-(3,4-dihydroxybenzoyl)-6,7-dihydroxy-2H-isoquinolin-3-one	93211: The compound was tested for binding affinity against insulin-like growth factor binding protein 1	ki	0.0342	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases secretion, decreases expression, affects cotreatment, decreases reaction, increases expression (+1 more)	11
Medroxyprogesterone Acetate	increases secretion, affects cotreatment, increases expression, increases reaction, decreases reaction (+2 more)	11
Benzo(a)pyrene	affects cotreatment, affects expression, increases expression, increases methylation	10
Progesterone	decreases reaction, increases expression, increases reaction, affects cotreatment, increases secretion (+1 more)	9
Tetrachlorodibenzodioxin	affects expression, increases expression	8
8-Bromo Cyclic Adenosine Monophosphate	increases reaction, affects cotreatment, decreases expression, increases secretion, affects reaction (+2 more)	7
Cyclosporine	affects cotreatment, increases expression	6
Aflatoxin B1	affects expression, decreases methylation, increases expression	6
bisphenol A	affects expression, increases expression, increases secretion, affects cotreatment	4
Cyclic AMP	affects cotreatment, increases expression, increases reaction, decreases reaction	4
Acetaminophen	increases expression, affects cotreatment, decreases expression	3
Bucladesine	affects cotreatment, decreases reaction, increases expression, increases reaction	3
Phenobarbital	increases expression, increases secretion, affects expression	3
benzo(b)fluoranthene	affects cotreatment, affects expression, increases expression	2
perfluorooctanoic acid	decreases expression, increases expression	2
1,2,5,6-dibenzanthracene	increases expression, affects cotreatment, affects expression	2
dibenzo(a,l)pyrene	affects cotreatment, affects expression, increases expression	2
perfluorooctane sulfonic acid	affects expression, increases expression	2
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Troglitazone	increases expression, increases secretion, decreases expression	2
Cadmium	affects cotreatment, decreases reaction, increases expression, decreases expression	2
Deoxycholic Acid	decreases expression, affects cotreatment, increases expression	2
Dexamethasone	increases phosphorylation, increases expression, increases reaction, increases activity	2
Colforsin	increases expression, affects cotreatment	2
Tamoxifen	affects cotreatment, increases expression	2
Triclosan	affects cotreatment, increases expression, increases reaction, increases secretion	2
Tunicamycin	increases expression	2
fluxapyroxad	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
perfluorodecanesulfonic acid	increases expression	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
CHEMBL698356	Binding	The compound was tested for binding affinity against insulin-like growth factor binding protein 1	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.