IGFBP6
protein-codinginsulin like growth factor binding protein 6, the group of Insulin like growth factor binding proteins
Gene summary
Enables identical protein binding activity and insulin-like growth factor II binding activity. Involved in cell migration and positive regulation of stress-activated MAPK cascade. Part of insulin-like growth factor binary complex. Implicated in obesity. Biomarker of breast cancer; in situ carcinoma; leiomyoma; and neovascular inflammatory vitreoretinopathy. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.9 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 IGFBP6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002178.3. 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 | 2 | ||||
| missense | 32 | 4 | 1 | 37 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 34 | 4 | 3 | 41 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002169.1 | 4 | MANE Select | |
| Ensembl | ENSP00000301464.3 | 4 | MANE Select | |
| Ensembl | ENSP00000449344.1 | 3 | Standard | |
| Ensembl | ENSP00000448953.1 | 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)
- Metabolism of proteins
- IGF signaling
- Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
Biological Process
- regulation of cell growth
- signal transduction
- negative regulation of cell population proliferation
- regulation of insulin-like growth factor receptor signaling pathway
- cellular protein metabolic process
Molecular Function
- fibronectin binding
- signaling receptor binding
- insulin-like growth factor I binding
- insulin-like growth factor II binding
Cellular Component
- extracellular region
- extracellular space
- Golgi apparatus
- insulin-like growth factor binary complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000301464
- Coding exons
- 4
- Length
- 4910
- Individuals with no LoFs
- 125716
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 125748
- p
- 0.000127
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.231 | 121 | 128 | 0.943 | 0.00000736 | 1481 |
| Missense (PolyPhen) | 44 | 51.687 | 0.85128 | 548 | ||
| Synonymous | -1.40 | 63 | 50.3 | 1.25 | 0.00000251 | 519 |
| Loss of Function | 1.74 | 4 | 9.93 | 0.403 | 5.83e-7 | 95 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00018 | 0.00018 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00033 | 0.00033 | rare |
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.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.797
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |