IGFBP4

protein-coding

insulin like growth factor binding protein 4, the group of Insulin like growth factor binding proteins

Gene summary

This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein binds both insulin-like growth factors (IGFs) I and II and circulates in the plasma in both glycosylated and non-glycosylated forms. Binding of this protein prolongs the half-life of the IGFs and alters their interaction with cell surface receptors. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001552.3

Inheritance

—

ClinVar variants

P:1U:31B:3

Top phenotype

Abnormal brain morphology

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr17:40,443,450-40,457,725

External References & Databases

Ensembl (ENSG00000141753)

Transcript & Mutation Effects

hg38 • Region Span ~14.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IGFBP4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 30

not providedTotal: 3

Abnormal brain morphologyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001552.3. 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			1 clinvar	1 clinvar	1 clinvar	3
missense		1 clinvar	30 clinvar	1 clinvar		32
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	1	31	2	1	35

Highest pathogenic variant AF is 0.0000061968544

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001552.3	RefSeq	NP_001543.2	4	MANE Select
ENST00000269593.5	Ensembl	ENSP00000269593.4	4	MANE Select
ENST00000906679.1	Ensembl	ENSP00000576738.1	4	Standard
ENST00000906679.2	Ensembl	ENSP00000576738.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Myometrial Relaxation and Contraction Pathways
Senescence-Associated Secretory Phenotype (SASP)
Post-translational protein phosphorylation
Post-translational protein modification
Metabolism of proteins

Biological Process

skeletal system development
regulation of cell growth
DNA metabolic process
inflammatory response
signal transduction

Molecular Function

signaling receptor binding
protein binding
insulin-like growth factor I binding
insulin-like growth factor II binding

Cellular Component

extracellular region
extracellular space
endoplasmic reticulum lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000269593
Coding exons: 4
Length: 14282
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125737
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.854	117	146	0.801	0.00000903	1621
Missense (PolyPhen)		44	66.201	0.66465		661
Synonymous	1.38	47	60.7	0.775	0.00000355	519
Loss of Function	1.62	4	9.34	0.428	4.67e-7	102

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000032	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.;

Recessive Scores

pRec: 0.350

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.829

Gene Damage Prediction

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