IGFBP3 (Insulin Like Growth Factor Binding Protein 3)
Key regulator of IGF bioavailability and growth signaling
Gene Information Card
| Symbol | IGFBP3 |
|---|---|
| Full Name | Insulin Like Growth Factor Binding Protein 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 7p12.3 |
| NCBI Gene ID | 3486 ncbi.nlm.nih.gov/gene/3486 |
| Ensembl ID | ENSG00000146674 |
| UniProt ID | P17936 |
| OMIM ID | 146731 |
| HGNC ID | 5472 |
| Aliases | IGFBP-3, BP-53, IBP3 |
Description
IGFBP3 encodes insulin-like growth factor binding protein 3, the major carrier protein for IGFs in circulation. It modulates IGF bioavailability, inhibits IGF-mediated growth, and has IGF-independent pro-apoptotic and anti-proliferative effects. The protein is secreted and binds to cell surface receptors, influencing cell growth, differentiation, and apoptosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Laron syndrome (primary IGF deficiency) | Reduced IGFBP3 levels due to GH receptor defects impair IGF transport and growth | OMIM #262500 |
| Short stature (idiopathic) | Polymorphisms in IGFBP3 associated with reduced height | ClinVar, NCBI |
| Colorectal cancer | Low IGFBP3 levels linked to increased risk; IGFBP3 inhibits IGF1R signaling | COSMIC, NCBI |
| Prostate cancer | IGFBP3 suppresses tumor growth via IGF-independent apoptosis | COSMIC, NCBI |
| Breast cancer | Altered IGFBP3 expression correlates with prognosis; promotes apoptosis | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 120.5 | High |
| Kidney | 45.2 | Medium |
| Lung | 32.1 | Medium |
| Heart | 18.7 | Low |
| Brain | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 150.0 | Highest expression |
| MCF7 (breast) | 60.0 | Moderate expression |
| A549 (lung) | 40.0 | Moderate expression |
| HEK293 (embryonic kidney) | 25.0 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.01% | Loss of start codon; reduced protein |
| c.203G>A (p.Gly68Asp) | missense | <0.01% | Impaired IGF binding |
| c.500C>T (p.Pro167Leu) | missense | <0.01% | Altered stability |
| c.700G>A (p.Gly234Ser) | missense | <0.01% | Reduced secretion |
Mutation functional classification
Loss of Function (LOF)
Mutations reducing IGF binding or secretion (e.g., p.Gly68Asp, p.Gly234Ser) lead to decreased IGF transport and growth impairment.
Gain of Function (GOF)
Not well documented; overexpression in some cancers may promote apoptosis.
Dominant Negative (DN)
No confirmed dominant-negative variants; heterozygous loss may contribute to short stature.
View complete mutation data：
Gene Ontology (GO)
Pathways
• IGF1R signaling pathway (Reactome: R-HSA-2404192)
• PI3K/AKT signaling (Reactome: R-HSA-1257604)
• Apoptosis (Reactome: R-HSA-109581)
• p53-independent DNA damage response (Reactome: R-HSA-5693565)
Protein Summary
IGFBP3 is a 264-amino acid secreted glycoprotein (UniProt P17936) with three domains: N-terminal IGF-binding domain, central linker region, and C-terminal heparin-binding domain. It binds IGF-I and IGF-II with high affinity, prolonging their half-life and modulating receptor activation. IGFBP3 also translocates to the nucleus and interacts with nuclear receptors to regulate transcription. Proteolytic cleavage by proteases (e.g., MMPs) reduces IGF binding affinity, releasing free IGFs.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IGFBP3 Knockout HEK293 Cell Line | EDJ-KQ3460 | Human | 3486 | Details Get a Quote |
| IGFBP3 Knockout A-549 Cell Line | EDJ-KQ25206 | Human | 3486 | Details Get a Quote |
| IGFBP3 Knockout HCT 116 Cell Line | EDJ-KQ25207 | Human | 3486 | Details Get a Quote |
| IGFBP3 Knockout HeLa Cell Line | EDJ-KQ23828 | Human | 3486 | Details Get a Quote |
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