IGFBP7

Summary

IGFBP7 (insulin like growth factor binding protein 7, HGNC:5476) is a protein-coding gene on chromosome 4q12, encoding Insulin-like growth factor-binding protein 7 (Q16270). Binds IGF1 and IGF2 with a relatively low affinity.

This gene encodes a member of the insulin-like growth factor (IGF)-binding protein (IGFBP) family. IGFBPs bind IGFs with high affinity, and regulate IGF availability in body fluids and tissues and modulate IGF binding to its receptors. This protein binds IGF-I and IGF-II with relatively low affinity, and belongs to a subfamily of low-affinity IGFBPs. It also stimulates prostacyclin production and cell adhesion. Alternatively spliced transcript variants encoding different isoforms have been described for this gene, and one variant has been associated with retinal arterial macroaneurysm (PMID:21835307).

Source: NCBI Gene 3490 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial retinal arterial macroaneurysm (Strong, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 57 total — 1 pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_001553

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5476
Approved symbol	IGFBP7
Name	insulin like growth factor binding protein 7
Location	4q12
Locus type	gene with protein product
Status	Approved
Aliases	MAC25, IGFBP-7, PSF, FSTL2
Ensembl gene	ENSG00000163453
Ensembl biotype	protein_coding
OMIM	602867
Entrez	3490

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000295666, ENST00000512512, ENST00000514062, ENST00000896419, ENST00000896420, ENST00000896421, ENST00000896422, ENST00000896423, ENST00000896424, ENST00000896425, ENST00000896426, ENST00000947223

RefSeq mRNA: 2 — MANE Select: NM_001553 NM_001253835, NM_001553

CCDS: CCDS3512, CCDS58900

Canonical transcript exons

ENST00000295666 — 5 exons

Exon	Start	End
ENSE00001171265	57109877	57110385
ENSE00003464629	57033195	57033311
ENSE00003545573	57032426	57032552
ENSE00003641018	57030773	57031336
ENSE00003647922	57040824	57040933

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 763.9947 / max 9669.4478, expressed in 1534 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52248	763.4398	1533
52245	0.3326	94
52242	0.0908	46
52244	0.0857	49
52243	0.0459	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	99.97	gold quality
vena cava	UBERON:0004087	99.97	gold quality
blood vessel layer	UBERON:0004797	99.97	gold quality
choroid plexus epithelium	UBERON:0003911	99.96	gold quality
saphenous vein	UBERON:0007318	99.96	gold quality
superficial temporal artery	UBERON:0001614	99.95	gold quality
descending thoracic aorta	UBERON:0002345	99.95	gold quality
pericardium	UBERON:0002407	99.95	gold quality
urethra	UBERON:0000057	99.94	gold quality
ascending aorta	UBERON:0001496	99.94	gold quality
thoracic aorta	UBERON:0001515	99.94	gold quality
right coronary artery	UBERON:0001625	99.94	gold quality
aorta	UBERON:0000947	99.93	gold quality
popliteal artery	UBERON:0002250	99.92	gold quality
tibial artery	UBERON:0007610	99.92	gold quality
coronary artery	UBERON:0001621	99.91	gold quality
left coronary artery	UBERON:0001626	99.91	gold quality
visceral pleura	UBERON:0002401	99.89	gold quality
metanephros cortex	UBERON:0010533	99.89	gold quality
renal glomerulus	UBERON:0000074	99.87	gold quality
seminal vesicle	UBERON:0000998	99.87	gold quality
metanephric glomerulus	UBERON:0004736	99.87	gold quality
pleura	UBERON:0000977	99.86	gold quality
kidney epithelium	UBERON:0004819	99.86	gold quality
parietal pleura	UBERON:0002400	99.85	gold quality
cauda epididymis	UBERON:0004360	99.83	gold quality
adult organism	UBERON:0007023	99.83	gold quality
lower lobe of lung	UBERON:0008949	99.83	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.82	gold quality
metanephros	UBERON:0000081	99.80	gold quality

Single-cell (SCXA)

Detected in 68 experiment(s), a significant marker in 62.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	18730.77
E-CURD-126	yes	14766.06
E-HCAD-36	yes	13062.19
E-MTAB-8322	yes	12362.65
E-MTAB-6701	yes	12358.70
E-GEOD-134144	yes	12271.71
E-HCAD-24	yes	11516.53
E-MTAB-8410	yes	11035.69
E-HCAD-11	yes	10990.16
E-MTAB-9841	yes	10821.97
E-MTAB-10553	yes	9978.28
E-MTAB-6308	yes	9797.78
E-MTAB-10596	yes	9785.60
E-MTAB-10885	yes	9472.02
E-MTAB-10287	yes	9256.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOS, JDP2, JUN, KAT7, SKIL, SP1, TAF1, TBP, TP53, TP63

miRNA regulators (miRDB)

16 targeting IGFBP7, 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-153-5P	99.89	73.86	6317
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-1-5P	98.70	68.66	1017
HSA-MIR-4718	98.55	68.61	814
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-3198	97.84	65.64	579
HSA-MIR-4309	97.84	65.45	588
HSA-MIR-938	97.41	68.28	656
HSA-MIR-148B-5P	97.29	66.30	992
HSA-MIR-6874-3P	97.29	66.34	975
HSA-MIR-6879-3P	93.93	64.00	759

Literature-anchored findings (GeneRIF, showing 40)

• that IGFBP-rP1 is an inhibitor of MCF-7 breast cancer cell proliferation and may act via a cellular senescence-like mechanism. (PMID:12065244)
• In prostate cancer cells, one of the downstream mediators of the senescence-associated tumor suppression effect of mac25/IGFBP-rP1 is superoxide dismutase 2 (PMID:12592389)
• discovered the implication of insulin-like growth factor-binding protein-related protein 1 in endometrial physiology, which seems related to endometrial receptivity (PMID:12679483)
• tumor-suppressive activity is through induction of apoptosis in an IGF-I independent manner in prostate cancer (PMID:14633696)
• SOX9 contributes to growth regulation by mac25 via inhibition of cell growth and promotion of differentiation (PMID:15077158)
• data suggest that mac25/IGFBP-rP1 and 25.1 may play a functional role in the NE differentiation of NSCLC cell lines and may provide a novel therapeutic target for treating lung cancers, in particular NSCLC with NE differentiation (PMID:16302002)
• findings show for the first time that circulating IGF-binding protein (IGFBP)-related protein 1 (IGFBP-rP1) is increased with insulin resistance (PMID:16873698)
• IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1. (PMID:17048309)
• mRNA expression was lost in six out of eight CRC cell lines as compared to normal colon cells. DNA methylation was found in the region of exon 1 and intron 1 of IGFBP-7. (PMID:17136345)
• IGFBP7 plays a potential tumor suppressor role in colorectal carcinogenesis. (PMID:17312390)
• Expression in tumor cells may reduce the anchorage-independent growth ability, leading to the marked loss of tumorigenicity. (PMID:17465992)
• This study supports the role of IGFBP-1, -3 and -7 as potential tumour suppressor genes in human breast cancer. (PMID:17972510)
• A genome-wide RNA-interference screening to identify genes required for an activated BRAF oncogene to block proliferation of fibroblasts and melanocytes revealed that a IGFBP7, has a central role in BRAF-mediated senescence and apoptosis. (PMID:18267069)
• Cultured human brain endothelial cells. exposed to either hypoxia or media conditioned by the human glioblastoma cell line are induced to express IGFBP-7 mRNA. (PMID:18711401)
• 5-aza-2’-deoxycytidine(5-aza-dC) may have anticancer function for colon cancer and restoration of IGFBP7 may involve the biological effects induced by 5-aza-dC in colon cancer cell lines. (PMID:18981723)
• Patients with endometriosis and those with type II diabetes mellitus undergoing hemodialysis had significantly higher serum concentrations of IGFBP7 than the relevant control subjects. (PMID:19019211)
• IGFBP7 blocks VEGF-induced angiogenesis in human vascular endothelial cells. (PMID:19374835)
• Results demonstrate that the vascular-specific marker angiomodulin (AGM) modulates vascular remodeling in part by temporizing the proangiogenic effects of VEGF-A. (PMID:19542015)
• Epigenetic inactivation of IGFBP7 appears to play a key role in tumorigenesis of colorectal cancers with the CpG island methylator phenotype by enabling escape from p53-induced senescence. (PMID:19638426)
• IGFBP7 is a regulator of KC proliferation and differentiation (PMID:19710688)
• data argues against obligatory downregulation in IGFBP7 expression in BRAF mutated melanoma cells (PMID:19829302)
• Similar to oncogenic BRAF-positive common naevi without atypia, enhanced expression of the tumour suppressor IGFBP7 in oncogenic BRAF-positive atypical genital nevi supports that they are biologically inert. (PMID:19919630)
• Results suggest that IGFBP7 regulates morphological changes of glandular cells by interfering with the normal PKA and MAPK signaling pathways that are associated with the transformation and/or differentiation of endometrial glands. (PMID:20029996)
• IGFBP7 could be a useful predictor of the response to interferon-based therapy in advanced hepatocellular carcinoma (PMID:20407444)
• HSP60 is an important downstream molecule of IGFBP7 in colorectal carcinoma (PMID:20433702)
• data suggest that loss of IGFBP7 expression has a functional role in thyroid carcinogenesis, and it may represent a possible basis for therapeutic strategies (PMID:20440262)
• Expression of Insulin like growth factor binding protein-7 reduces growth of human breast cancer cells (PMID:20464481)
• Study concludes that the secreted protein IGFBP7 is dispensable for B-RAF(V600E)-induced senescence in human melanocytes. (PMID:20478260)
• In contrast to BAALC, which likely represents only a surrogate marker of treatment failure in acute leukemia, IGFBP7 regulates the proliferation of leukemic cells and might be involved in chemotherapy resistance (PMID:20535151)
• IGFBP-rP1 was a potential key molecule associated with colon cancer differentiation. (PMID:20977730)
• aberrant IGFBP7 expression is regulated by DNA methylation in acute leukemia. (PMID:21040219)
• IGFBP7 is inactivated in lung cancer by DNA hypermethylation in both lung cancer cell lines and primary lung tumors (PMID:21095038)
• Results indicated that IGFBP7 expression correlated significantly with the malignant potential in hepatocellular carcinoma cells. (PMID:21328580)
• IGFBP7 plays a positive contributing role in the interaction between leukemia cells and microenvironment, which may promote the leukemic cells’ adhesion, invasion, and migration (PMID:21413833)
• IGFBP7 is involved in early metastatic dissemination in colorectal cancer (PMID:21525788)
• IGFBP7 is involved in the pathogenesis of psoriasis (PMID:21562573)
• The BRAF/MEK/ERK pathway is upregulated in progressive retinal arterial macroaneurysm patients, caused by mutation in IGFBP7. (PMID:21835307)
• Findings provide evidence that IGFBP7 functions as a novel putative tumor suppressor for HCC and establish the corollary that IGFBP7 downregulation can effectively modify AEG-1 function. (PMID:21908579)
• higher IGFBP7 mRNA levels were associated with lower leukemia-free survival (Cox regression model, P=0.003) in precursor B-cell Ph(-) ALL patients (n=147) treated with a contemporary polychemotherapy protocol (PMID:22005787)
• The externalization of saw-tooth architecture in serrated polyps was endoscopically observed more frequently in those with high levels of IGFBP7 methylation (P = 0.03). (PMID:22173745)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	igfbp7	ENSDARG00000104138
mus_musculus	Igfbp7	ENSMUSG00000036256
rattus_norvegicus	Igfbp7	ENSRNOG00000002050

Paralogs (2): KAZALD1 (ENSG00000107821), IGFBPL1 (ENSG00000137142)

Protein

Protein identifiers

Insulin-like growth factor-binding protein 7 — Q16270 (reviewed: Q16270)

Alternative names: IGFBP-rP1, MAC25 protein, PGI2-stimulating factor, Prostacyclin-stimulating factor, Tumor-derived adhesion factor

All UniProt accessions (1): Q16270

UniProt curated annotations — full annotation on UniProt →

Function. Binds IGF1 and IGF2 with a relatively low affinity. Stimulates prostacyclin (PGI2) production. Stimulates cell adhesion. Acts as a ligand for CD93 to play a role in angiogenesis.

Subunit / interactions. May interact with VPS24/CHMP3; the relevance of such interaction however remains unclear. Interacts with CD93; this interaction plays a role in endothelial cells angiogenesis.

Subcellular location. Secreted.

Post-translational modifications. N-glycosylated.

Disease relevance. Retinal arterial macroaneurysm with supravalvular pulmonic stenosis (RAMSVPS) [MIM:614224] An autosomal recessive condition characterized by the bilateral appearance of ‘beading’ along the major retinal arterial trunks, with the subsequent formation of macroaneurysms. Affected individuals also have supravalvular pulmonic stenosis, often requiring surgical correction. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16270-1	1	yes
Q16270-2	2

RefSeq proteins (2): NP_001240764, NP_001544* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000867	IGFBP-like	Domain
IPR002350	Kazal_dom	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR011390	IGFBP_rP_mac25	Family
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036058	Kazal_dom_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF00219, PF07648, PF07679

UniProt features (34 total): strand 10, disulfide bond 8, sequence conflict 4, sequence variant 3, domain 3, signal peptide 1, chain 1, splice variant 1, helix 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8IVD	X-RAY DIFFRACTION	3.24

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16270-F1	85.11	0.67

Functional residue map

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

Post-translational modifications (1): 239

Disulfide bonds (8): 48–63, 71–87, 81–111, 120–156, 181–248, 32–57, 35–59, 40–60

Glycosylation sites (1): 171

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation

MSigDB gene sets: 375 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_RESPONSE_TO_PROSTAGLANDIN_E, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_CORTICOSTEROID, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_CELLULAR_RESPONSE_TO_PROSTAGLANDIN_STIMULUS, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_GROWTH, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, XU_HGF_SIGNALING_NOT_VIA_AKT1_48HR_DN, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, WEINMANN_ADAPTATION_TO_HYPOXIA_UP, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (12): angiogenesis (GO:0001525), regulation of cell growth (GO:0001558), cell adhesion (GO:0007155), embryo implantation (GO:0007566), negative regulation of cell population proliferation (GO:0008285), regulation of signal transduction (GO:0009966), response to retinoic acid (GO:0032526), regulation of steroid biosynthetic process (GO:0050810), response to cortisol (GO:0051414), cellular response to prostaglandin E stimulus (GO:0071380), signal transduction (GO:0007165), cellular response to hormone stimulus (GO:0032870)

GO Molecular Function (5): insulin-like growth factor binding (GO:0005520), receptor ligand activity (GO:0048018), extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515), growth factor binding (GO:0019838)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cellular Senescence	1
Metabolism of proteins	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
signal transduction	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
response to lipid	1
response to oxygen-containing compound	1
steroid biosynthetic process	1
regulation of steroid metabolic process	1
regulation of lipid biosynthetic process	1
response to glucocorticoid	1
response to alcohol	1
response to ketone	1
response to prostaglandin E	1
cellular response to prostaglandin stimulus	1
cellular response to alcohol	1
cellular response to ketone	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
response to hormone	1
cellular response to chemical stimulus	1
cellular response to endogenous stimulus	1
growth factor binding	1
signaling receptor binding	1
signaling receptor activator activity	1
structural molecule activity	1
extracellular matrix	1

Protein interactions and networks

STRING

1780 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGFBP7	IGF1	P01343	992
IGFBP7	INS	P01308	990
IGFBP7	IGF2	P01344	986
IGFBP7	CCN1	O00622	919
IGFBP7	CCN2	P29279	904
IGFBP7	TIMP2	P16035	862
IGFBP7	IGF1R	P08069	840
IGFBP7	IGFBP3	P17936	741
IGFBP7	VWF	P04275	731
IGFBP7	CHMP3	Q9Y3E7	720
IGFBP7	A0A140T963	A0A140T963	720
IGFBP7	HAVCR1	Q96D42	720
IGFBP7	P4HB	P07237	719
IGFBP7	LCN2	P30150	716
IGFBP7	CCN3	P48745	702

IntAct

21 interactions, top by confidence:

A	B	Type	Score
DCC	IGFBP7	psi-mi:“MI:0407”(direct interaction)	0.440
IGDCC3	IGFBP7	psi-mi:“MI:0407”(direct interaction)	0.440
IGDCC4	IGFBP7	psi-mi:“MI:0407”(direct interaction)	0.440
IL6R	IGFBP7	psi-mi:“MI:0407”(direct interaction)	0.440
IGFBP7	ISLR2	psi-mi:“MI:0407”(direct interaction)	0.440
IGFBP7	NEO1	psi-mi:“MI:0407”(direct interaction)	0.440
PRTG	IGFBP7	psi-mi:“MI:0407”(direct interaction)	0.440
ST14	IGFBP7	psi-mi:“MI:0194”(cleavage reaction)	0.440
IGFBP7	MPIG6B	psi-mi:“MI:0915”(physical association)	0.400
IGFBP7	RBBP8	psi-mi:“MI:0915”(physical association)	0.370
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
ENG	IGKV2-28	psi-mi:“MI:0914”(association)	0.350
GGH	CLGN	psi-mi:“MI:0914”(association)	0.350
	IGFBP7	psi-mi:“MI:0915”(physical association)	0.000
IGFBP7		psi-mi:“MI:0915”(physical association)	0.000
IGFBP7	ORF99	psi-mi:“MI:0915”(physical association)	0.000
asnB	IGFBP7	psi-mi:“MI:0915”(physical association)	0.000
IGFBP7	hldE	psi-mi:“MI:0915”(physical association)	0.000
clcA	IGFBP7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): IGFBP7 (Affinity Capture-MS), IGFBP7 (Reconstituted Complex), IGFBP7 (Affinity Capture-MS), IGF1 (Reconstituted Complex), IGF2 (Reconstituted Complex), CHMP3 (Two-hybrid), IGFBP7 (Affinity Capture-Western), CHMP3 (Affinity Capture-Western), VEGFA (Reconstituted Complex), IGFBP7 (Negative Genetic), COL4A1 (Reconstituted Complex), IGFBP7 (Proximity Label-MS), INS (Reconstituted Complex), IGFBP7 (Affinity Capture-MS), IGFBP7 (Affinity Capture-MS)

ESM2 similar proteins: A2A9Q0, A5A8Y8, A5PKD8, F1SAM7, O00468, O60500, O75325, P0C7J6, P12843, P13384, P18065, P24853, P49705, P50895, P60827, P60882, Q16270, Q24JP5, Q29400, Q2WF71, Q50LG9, Q5W7P8, Q61581, Q641Q3, Q6IQX7, Q6UKI2, Q6UWL6, Q75ZP3, Q7TSU7, Q7Z7M0, Q80W15, Q8BHA1, Q8BJ66, Q8IZ52, Q8N2S1, Q8NDA2, Q8WX77, Q91ZV8, Q96I82, Q96MS0

Diamond homologs: A0JNK3, A2RNT9, A2RT60, A4IHA1, A4XSC0, A5PKD8, A5W8F5, A6VUA4, A6YFB5, A9JRB3, B0KV30, B1J4D7, B3LVG7, B3P3J9, B4G316, B4HEM8, B4JTT7, B4K835, B4LY58, B4N937, B4PST0, B4QZU6, D0ZY51, D3ZA76, D3ZKF5, E1BJW1, E1V4H2, F1N152, F6AA62, O05942, O06291, O22609, O31754, O34358, O43464, O53896, O85291, P05676, P0A3Z5, P0AEE3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 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.

GO biological processes:

GO term	Partners	Fold	FDR
cell-cell adhesion	5	33.8×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	35
Likely benign	2
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1252043	NM_001553.3(IGFBP7):c.829G>A (p.Gly277Ser)	Pathogenic

SpliceAI

764 predictions. Top by Δscore:

Variant	Effect	Δscore
4:57032550:TACC:T	acceptor_loss	1.0000
4:57032551:ACC:A	acceptor_loss	1.0000
4:57032553:C:A	acceptor_loss	1.0000
4:57032554:T:G	acceptor_loss	1.0000
4:57033187:GTACT:G	donor_loss	1.0000
4:57033190:CTCA:C	donor_loss	1.0000
4:57033191:TCA:T	donor_loss	1.0000
4:57033193:A:AC	donor_gain	1.0000
4:57033193:A:AT	donor_loss	1.0000
4:57033194:C:CC	donor_gain	1.0000
4:57033194:C:G	donor_loss	1.0000
4:57033214:T:TA	donor_gain	1.0000
4:57033307:TTTAC:T	acceptor_gain	1.0000
4:57033308:TTAC:T	acceptor_gain	1.0000
4:57033309:TAC:T	acceptor_gain	1.0000
4:57033310:ACCT:A	acceptor_loss	1.0000
4:57033311:CCT:C	acceptor_loss	1.0000
4:57033312:C:CC	acceptor_gain	1.0000
4:57033312:C:CG	acceptor_loss	1.0000
4:57033315:C:CT	acceptor_gain	1.0000
4:57033321:C:CT	acceptor_gain	1.0000
4:57033322:A:T	acceptor_gain	1.0000
4:57030893:TTTCA:T	acceptor_loss	0.9900
4:57030894:TTCAG:T	acceptor_loss	0.9900
4:57030895:TCA:T	acceptor_loss	0.9900
4:57030896:CAG:C	acceptor_loss	0.9900
4:57030897:A:AG	acceptor_gain	0.9900
4:57030897:AGA:A	acceptor_loss	0.9900
4:57030898:G:GG	acceptor_gain	0.9900
4:57033186:GGTAC:G	donor_loss	0.9900

AlphaMissense

1791 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:57033201:C:A	W232C	1.000
4:57033201:C:G	W232C	1.000
4:57040830:C:A	W193C	1.000
4:57040830:C:G	W193C	1.000
4:57040832:A:G	W193R	1.000
4:57040832:A:T	W193R	1.000
4:57040867:C:T	C181Y	1.000
4:57032511:G:C	C248W	0.999
4:57032512:C:G	C248S	0.999
4:57032512:C:T	C248Y	0.999
4:57032513:A:G	C248R	0.999
4:57032513:A:T	C248S	0.999
4:57032518:T:C	Y246C	0.999
4:57033196:A:G	L234P	0.999
4:57033203:A:G	W232R	0.999
4:57033203:A:T	W232R	0.999
4:57040831:C:G	W193S	0.999
4:57040843:G:T	P189H	0.999
4:57040855:C:T	G185E	0.999
4:57040866:A:C	C181W	0.999
4:57040867:C:A	C181F	0.999
4:57040867:C:G	C181S	0.999
4:57040868:A:G	C181R	0.999
4:57040868:A:T	C181S	0.999
4:57109885:C:G	C156S	0.999
4:57109885:C:T	C156Y	0.999
4:57109886:A:T	C156S	0.999
4:57109993:C:G	C120S	0.999
4:57109994:A:T	C120S	0.999
4:57032506:G:T	A250E	0.998

dbSNP variants (sampled 300 via entrez): RS1000095677 (4:57105530 T>C), RS1000107071 (4:57061872 A>C,T), RS1000107310 (4:57064831 T>C), RS1000134709 (4:57106149 G>A), RS1000164998 (4:57103862 T>C), RS1000177762 (4:57076064 G>C), RS1000178237 (4:57066415 C>G,T), RS1000218160 (4:57071006 T>C), RS1000238591 (4:57068363 A>C,G), RS1000277573 (4:57032058 G>A), RS1000369948 (4:57050559 A>G), RS1000432331 (4:57038237 G>A,T), RS1000450197 (4:57099307 G>A), RS1000488346 (4:57090993 T>C), RS10004910 (4:57102278 G>A)

Disease associations

OMIM: gene MIM:602867 | disease phenotypes: MIM:614224

GenCC curated gene-disease

Disease	Classification	Inheritance
familial retinal arterial macroaneurysm	Strong	Autosomal recessive

Mondo (1): familial retinal arterial macroaneurysm (MONDO:0013640)

Orphanet (1): Familial retinal arterial macroaneurysm (Orphanet:284247)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001642	Pulmonic stenosis
HP:0012231	Serous retinal detachment
HP:0025355	Retinal arteriolar macroaneurysms

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001232_2	Age-related macular degeneration	2.000000e-08
GCST004721_18	Congenital heart disease (maternal effect)	8.000000e-06
GCST004797_1	Brain volume in infants (grey matter)	4.000000e-10
GCST005441_3	Alcohol consumption (max-drinks)	9.000000e-06
GCST005929_2	Severity of nausea and vomiting of pregnancy	9.000000e-24
GCST005930_2	Hyperemesis gravidarum	9.000000e-12
GCST006288_521	Heel bone mineral density	7.000000e-10
GCST006585_504	Blood protein levels	6.000000e-28
GCST006630_61	Diastolic blood pressure	5.000000e-09
GCST010241_280	Apolipoprotein A1 levels	5.000000e-09
GCST012311_35	Schizophrenia x sex interaction	7.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0008368	infant grey matter volume measurement
EFO:0009265	nausea and vomiting of pregnancy severity measurement
EFO:0009270	heel bone mineral density
EFO:0006336	diastolic blood pressure
EFO:0004614	apolipoprotein A 1 measurement
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11934877	IGFBP7		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, affects cotreatment	7
Benzo(a)pyrene	affects methylation, increases expression	5
Decitabine	increases expression, affects methylation, decreases expression, decreases reaction	4
Cyclosporine	decreases expression, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Tetrachlorodibenzodioxin	decreases expression	3
Aflatoxin B1	affects expression, increases expression	3
graphene oxide	increases expression	2
methylmercuric chloride	decreases expression, increases expression	2
sodium arsenite	affects cotreatment, decreases expression, increases expression	2
cobaltous chloride	decreases expression, decreases secretion	2
mercuric bromide	increases expression, affects cotreatment	2
chloropicrin	decreases expression	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Dasatinib	decreases reaction, increases expression	2
Arsenic Trioxide	decreases reaction, increases expression, decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	increases expression	2
Copper	affects cotreatment, increases expression, affects binding	2
Doxorubicin	increases expression, affects response to substance	2
Paraquat	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, decreases reaction, increases abundance	2
Tretinoin	increases expression, decreases expression	2
TAK-243	increases sumoylation	1
lead acetate	affects cotreatment, decreases expression	1
sodium arsenate	increases abundance, increases expression	1
salinomycin	decreases expression	1
decabromobiphenyl ether	affects expression	1

Clinical trials (associated diseases)

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