IGFBP3
protein-codinginsulin like growth factor binding protein 3, 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 forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.6 kbGenCC 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 IGFBP3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000598.5. 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 | 1 | ||||
| missense | 35 | 1 | 36 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 36 | 0 | 2 | 38 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000589.2 | 4 | MANE Select | |
| Ensembl | ENSP00000477772.2 | 4 | MANE Select | |
| RefSeq | NP_001013416.1 | 4 | Standard | |
| Ensembl | ENSP00000370473.4 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| igfbp3 | Danio rerio | Structure: pharyngeal arch Quality: non-functional abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- p53 signaling pathway - Homo sapiens (human)
- Transcriptional misregulation in cancer - Homo sapiens (human)
- Cellular senescence - Homo sapiens (human)
- Celecoxib Pathway, Pharmacodynamics
- Vitamin D Receptor Pathway
Biological Process
- regulation of cell growth
- osteoblast differentiation
- negative regulation of protein phosphorylation
- protein phosphorylation
- apoptotic process
Molecular Function
- fibronectin binding
- protein binding
- insulin-like growth factor binding
- protein tyrosine phosphatase activator activity
- insulin-like growth factor I binding
Cellular Component
- extracellular region
- extracellular space
- nucleus
- endoplasmic reticulum lumen
- insulin-like growth factor binding protein complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000381083
- Coding exons
- 4
- Length
- 9525
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.787 | 96 | 120 | 0.798 | 0.00000720 | 1862 |
| Missense (PolyPhen) | 35 | 52.879 | 0.66189 | 792 | ||
| Synonymous | -0.631 | 54 | 48.4 | 1.12 | 0.00000300 | 611 |
| Loss of Function | 2.58 | 0 | 7.76 | 0.00 | 3.27e-7 | 128 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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. Also exhibits IGF-independent antiproliferative and apoptotic effects mediated by its receptor TMEM219/IGFBP-3R. {ECO:0000269|PubMed:20353938}.;
Recessive Scores
- pRec
- 0.822
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.897
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |