IGFBP7

protein-coding

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

Gene summary

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). [provided by RefSeq, Dec 2011]

MANE transcript

NM_001553.3

Inheritance

ClinVar variants

P:2U:40B:4

Top phenotype

Retinal arterial macroaneurysm with supravalvular pulmonic stenosis

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr4:57,030,773-57,110,385

External References & Databases

Ensembl (ENSG00000163453)

Transcript & Mutation Effects

hg38 • Region Span ~79.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial retinal arterial macroaneurysmLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013640

Submitter: Labcorp Genetics (formerly Invitae)

familial retinal arterial macroaneurysmMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0013640

Submitter: Ambry Genetics

familial retinal arterial macroaneurysmSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013640

Submitter: Orphanet

familial retinal arterial macroaneurysmMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0013640

Submitter: PanelApp Australia

familial retinal arterial macroaneurysmSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013640

Submitter: G2P

Clinical Genomic Database (CGD)

Retinal arterial macroaneurysm with supravalvular pulmonic stenosisAR

Manifestation: Cardiovascular; Ophthalmologic

Intervention: Cardiovascular; Ophthalmologic

Rationale: 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

Refs: 12441727; 21835307

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IGFBP7 variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 35

not providedTotal: 4

IGFBP7-related disorderTotal: 3

Familial retinal arterial macroaneurysmTotal: 2

Retinal arterial macroaneurysm with supravascular pulmonic stenosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001553.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar		1 clinvar	3
missense	1 clinvar		35 clinvar	2 clinvar	1 clinvar	39
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)		1 clinvar	2 clinvar			3
Total	1	1	40	2	2	46

Highest pathogenic variant AF is 0.0000041057306

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001553.3	RefSeq	NP_001544.1	5	MANE Select
ENST00000295666.6	Ensembl	ENSP00000295666.4	5	MANE Select
NM_001253835.2	RefSeq	NP_001240764.1	4	Standard
ENST00000514062.2	Ensembl	ENSP00000486293.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
igfbp7	Danio rerio	Structure: melanocyte Quality: absent abnormal

Gene / Model

Organism

Observed Phenotype

igfbp7

Danio rerio

Structure: melanocyte

Quality: absent

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

regulation of cell growth
cell adhesion
embryo implantation
negative regulation of cell population proliferation
response to heat

Molecular Function

extracellular matrix structural constituent
protein binding
insulin-like growth factor binding

Cellular Component

extracellular region
extracellular space
endoplasmic reticulum lumen
collagen-containing extracellular matrix
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000295666
Coding exons: 5
Length: 79613
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125744
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.314	117	127	0.922	0.00000637	1731
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.113

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

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