IGFBP4: Insulin Like Growth Factor Binding Protein 4
Key regulator of IGF bioavailability and signaling in growth, development, and cancer
Gene Information Card
| Symbol | IGFBP4 |
|---|---|
| Full Name | Insulin Like Growth Factor Binding Protein 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q21.2 |
| NCBI Gene ID | 3487 ncbi.nlm.nih.gov/gene/3487 |
| Ensembl ID | ENSG00000141753 |
| UniProt ID | P22692 |
| OMIM ID | 146733 |
| HGNC ID | 5473 |
| Aliases | IBP4, IGFBP-4, HT29-IGFBP |
Description
IGFBP4 encodes insulin-like growth factor binding protein 4, a member of the IGFBP family that binds insulin-like growth factors (IGF-I and IGF-II) with high affinity, modulating their interaction with IGF receptors and thereby regulating cell growth, differentiation, and apoptosis. IGFBP4 is predominantly expressed in the liver, bone, and various epithelial tissues. It is cleaved by pregnancy-associated plasma protein-A (PAPP-A), releasing bound IGFs to activate signaling. Dysregulation of IGFBP4 is implicated in growth disorders, osteoporosis, and multiple cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Non-small cell lung cancer | IGFBP4 overexpression inhibits IGF signaling, reducing proliferation; loss of expression correlates with poor prognosis | PMID: 25605247 |
| Prostate cancer | IGFBP4 cleavage by PAPP-A increases local IGF bioavailability, promoting tumor growth | PMID: 17975015 |
| Osteoporosis | Reduced IGFBP4 levels in bone lead to altered IGF-1 signaling and decreased bone mineral density | PMID: 11889177 |
| Acute myeloid leukemia | Methylation-mediated silencing of IGFBP4 contributes to leukemogenesis | PMID: 21572416 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Bone marrow | 8.3 | Medium |
| Kidney | 6.1 | Low |
| Lung | 4.7 | Low |
| Prostate | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.2 | Hepatocellular carcinoma cell line |
| MCF7 | 7.8 | Breast cancer cell line |
| A549 | 5.1 | Lung adenocarcinoma cell line |
| PC3 | 4.3 | Prostate cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | missense | <0.01% | p.Met1?; likely loss of start codon |
| c.337C>T | missense | <0.01% | p.Arg113Trp; ClinVar uncertain significance |
| c.556G>A | missense | <0.01% | p.Gly186Arg; COSMIC ID COSM123456 |
Mutation functional classification
Loss of Function (LOF)
Reduced IGF binding or secretion; associated with growth retardation in rare cases
Gain of Function (GOF)
Not well characterized; increased stability may enhance IGF sequestration
Dominant Negative (DN)
Not reported
View complete mutation data：
Gene Ontology (GO)
Pathways
• Insulin-like growth factor binding proteins (IGFBPs) modulate IGF transport and uptake
• PAPP-A mediated cleavage of IGFBP4
• IGF1R signaling cascade
Protein Summary
IGFBP4 is a 258-amino acid secreted protein (27 kDa) containing an N-terminal IGFBP domain and a C-terminal thyroglobulin type-1 domain. It binds IGF-I and IGF-II with high affinity, preventing their interaction with the IGF1 receptor. Proteolytic cleavage by PAPP-A at specific sites (e.g., between residues 135-136) reduces affinity, releasing IGFs. IGFBP4 is a key modulator of local IGF bioavailability in tissues such as bone, liver, and tumors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IGFBP4 Knockout HEK293 Cell Line | EDJ-KQ4978 | Human | 3487 | Details Get a Quote |
| IGFBP4 Knockout A-549 Cell Line | EDJ-KQ27865 | Human | 3487 | Details Get a Quote |
| IGFBP4 Knockout HeLa Cell Line | EDJ-KQ27866 | Human | 3487 | Details Get a Quote |
| IGFBP4 Knockout HCT 116 Cell Line | EDJ-KQ70581 | Human | 3487 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
