IGFBP7

insulin like growth factor binding protein 7, the group of I-set domain containing

Basic information

Region (hg38): 4:57030773-57110385

Links

ENSG00000163453 ∙ NCBI:3490 ∙ OMIM:602867 ∙ HGNC:5476 ∙ Uniprot:Q16270 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial retinal arterial macroaneurysm (Strong), mode of inheritance: AR
• familial retinal arterial macroaneurysm (Moderate), mode of inheritance: AR
• familial retinal arterial macroaneurysm (Supportive), mode of inheritance: AR
• familial retinal arterial macroaneurysm (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinal arterial macroaneurysm with supravalvular pulmonic stenosis	AR	Cardiovascular; Ophthalmologic	Argon laser photocoagulation of the retinal macroaneurysms has been described as resulting in clinical improvement in some individuals; Surgical repair of pulmonic stenosis may be indicated in some individuals	Cardiovascular; Ophthalmologic	12441727; 21835307

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IGFBP7 gene.

• Familial retinal arterial macroaneurysm (1 variants)
• Retinal arterial macroaneurysm with supravascular pulmonic stenosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IGFBP7 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			13	3	1	17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region					1	1
non coding			1		1	2
Total	1	0	14	3	3

Variants in IGFBP7

This is a list of pathogenic ClinVar variants found in the IGFBP7 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-57030912-G-A		not specified	Uncertain significance (Jan 16, 2024)
4-57031325-C-T		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)
4-57031337-C-T		Retinal arterial macroaneurysm with supravascular pulmonic stenosis • Familial retinal arterial macroaneurysm	Pathogenic (Mar 17, 2024)
4-57032426-C-T		Familial retinal arterial macroaneurysm	Pathogenic (Apr 29, 2021)
4-57032525-C-T		Inborn genetic diseases	Uncertain significance (Apr 06, 2022)
4-57032532-T-G		Inborn genetic diseases	Likely benign (Jan 26, 2023)
4-57032562-A-G			Benign (Dec 31, 2019)
4-57033266-C-G		Inborn genetic diseases	Uncertain significance (Mar 15, 2024)
4-57040820-A-T		Familial retinal arterial macroaneurysm	Benign (Aug 10, 2021)
4-57040828-T-C		Inborn genetic diseases	Uncertain significance (May 06, 2024)
4-57040848-C-T			Benign (Dec 31, 2019)
4-57040922-C-G		Inborn genetic diseases	Uncertain significance (May 26, 2022)
4-57109921-C-T		IGFBP7-related disorder • Inborn genetic diseases	Uncertain significance (May 20, 2024)
4-57109949-C-T		IGFBP7-related disorder	Benign (Nov 11, 2019)
4-57109982-C-T		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
4-57110038-G-C		Inborn genetic diseases	Uncertain significance (Jun 30, 2022)
4-57110042-C-T		Inborn genetic diseases	Uncertain significance (Sep 27, 2022)
4-57110078-T-C		Inborn genetic diseases	Uncertain significance (Mar 28, 2024)
4-57110097-C-T		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
4-57110102-C-T		Inborn genetic diseases	Uncertain significance (Jul 13, 2022)
4-57110119-C-T		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)
4-57110123-C-T		Inborn genetic diseases	Uncertain significance (Oct 29, 2021)
4-57110126-C-T		Inborn genetic diseases	Uncertain significance (Oct 05, 2021)
4-57110159-G-A		Inborn genetic diseases	Uncertain significance (Mar 25, 2024)
4-57110185-G-A		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IGFBP7	protein_coding	protein_coding	ENST00000295666	5	79613

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00129	0.868	125715	0	29	125744	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.314	117	127	0.922	0.00000637	1731
Missense in Polyphen		48	60.642	0.79153		721
Synonymous	1.89	34	51.2	0.664	0.00000258	595
Loss of Function	1.31	6	10.6	0.566	4.53e-7	131

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000325	0.000325
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.000163	0.000163
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds IGF-I and IGF-II with a relatively low affinity. Stimulates prostacyclin (PGI2) production. Stimulates cell adhesion. {ECO:0000269|PubMed:8117260, ECO:0000269|PubMed:8939990}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:21835307}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Senescence-Associated Secretory Phenotype (SASP);Simplified Interaction Map Between LOXL4 and Oxidative Stress Pathway;VEGFA-VEGFR2 Signaling Pathway;Senescence and Autophagy in Cancer;Post-translational protein phosphorylation;Senescence-Associated Secretory Phenotype (SASP);Cellular Senescence;Cellular responses to stress;Post-translational protein modification;Metabolism of proteins;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Cellular responses to external stimuli (Consensus)

Recessive Scores

• pRec: 0.113

Haploinsufficiency Scores

• pHI: 0.507
• hipred: Y
• hipred_score: 0.767
• ghis: 0.600

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Igfbp7
• Phenotype: cellular phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype

Zebrafish Information Network

• Gene name: igfbp7
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: regulation of cell growth;cell adhesion;embryo implantation;negative regulation of cell population proliferation;response to heat;response to retinoic acid;cellular response to hormone stimulus;post-translational protein modification;cellular protein metabolic process;regulation of steroid biosynthetic process;response to cortisol
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: extracellular matrix structural constituent;protein binding;insulin-like growth factor binding