IGFALS: Insulin Like Growth Factor Binding Protein Acid Labile Subunit
Key regulator of IGF bioavailability and growth hormone signaling
Gene Information Card
| Symbol | IGFALS |
|---|---|
| Full Name | Insulin Like Growth Factor Binding Protein Acid Labile Subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 3483 ncbi.nlm.nih.gov/gene/3483 |
| Ensembl ID | ENSG00000103197 |
| UniProt ID | P35858 |
| OMIM ID | 601489 |
| HGNC ID | 5468 |
| Aliases | ALS, IGFBP-3 ALS, acid labile subunit |
Description
IGFALS encodes the acid-labile subunit (ALS) of the insulin-like growth factor (IGF) binding protein complex. ALS forms a ternary complex with IGF-I or IGF-II and IGFBP-3 or IGFBP-5, stabilizing IGFs in the circulation and regulating their bioavailability. Mutations in IGFALS cause acid-labile subunit deficiency, leading to growth hormone insensitivity and short stature.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acid-labile subunit deficiency | Loss-of-function mutations in IGFALS impair ternary complex formation, reducing circulating IGF-I half-life and causing growth hormone insensitivity. | OMIM #601489; ClinVar |
| Short stature (idiopathic) | Homozygous or compound heterozygous IGFALS mutations lead to moderate short stature with delayed puberty. | OMIM; PubMed |
| IGF-I deficiency (secondary) | Reduced ALS levels decrease IGF-I stability, mimicking primary IGF deficiency. | OMIM; NCBI GeneReviews |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 3.2 | Medium |
| Lung | 1.8 | Low |
| Heart | 0.9 | Low |
| Brain | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 8.7 | Hepatocellular carcinoma cell line |
| HEK293 | 2.1 | Embryonic kidney cells |
| A549 | 0.5 | Lung carcinoma cells |
| MCF7 | 0.2 | Breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.133C>T (p.Arg45*) | Nonsense | Rare | Premature stop; loss of ALS protein |
| c.656G>A (p.Cys219Tyr) | Missense | Rare | Disrupts disulfide bond; impaired secretion |
| c.1045C>T (p.Arg349Trp) | Missense | Rare | Reduced binding to IGFBP-3 |
| c.1468C>T (p.Arg490*) | Nonsense | Rare | Truncated protein; no ternary complex formation |
Mutation functional classification
Loss of Function (LOF)
Most IGFALS mutations are loss-of-function, leading to reduced or absent ALS protein, impaired ternary complex formation, and decreased circulating IGF-I half-life.
Gain of Function (GOF)
No gain-of-function mutations reported in IGFALS.
Dominant Negative (DN)
Heterozygous carriers may have mildly reduced ALS levels but are typically asymptomatic; dominant-negative effects are not established.
View complete mutation data：
Gene Ontology (GO)
| • Insulin-like growth factor binding | • Protein binding |
| • Extracellular space | • Blood microparticle |
| • Growth factor binding |
Pathways
• IGF transport and uptake by IGFBPs (Reactome: R-HSA-381426)
• Growth hormone signaling (Reactome: R-HSA-982772)
Protein Summary
The acid-labile subunit (ALS) is a 85 kDa glycoprotein secreted primarily by the liver. It binds to IGFBP-3 or IGFBP-5 in complex with IGF-I or IGF-II, forming a 150 kDa ternary complex that prolongs the half-life of IGFs in the circulation. ALS deficiency results in rapid clearance of IGFs, leading to growth retardation and metabolic abnormalities.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IGFALS Knockout HEK293 Cell Line | EDJ-KQ50386 | Human | 3483 | Details Get a Quote |
| IGFALS Knockout HeLa Cell Line | EDJ-KQ53624 | Human | 3483 | Details Get a Quote |
| IGFALS Knockout A-549 Cell Line | EDJ-KQ62095 | Human | 3483 | Details Get a Quote |
| IGFALS Knockout HCT 116 Cell Line | EDJ-KQ70579 | Human | 3483 | Details Get a Quote |
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