AHSG (Alpha-2-HS-Glycoprotein) Gene: Structure, Function, and Clinical Significance
Comprehensive biomedical overview of the AHSG gene, encoding fetuin-A, with roles in calcification, insulin resistance, and disease.
Gene Information Card
| Symbol | AHSG |
|---|---|
| Full Name | Alpha-2-HS-Glycoprotein |
| Gene Type | Protein coding |
| Chromosomal Location | 3q27.3 |
| NCBI Gene ID | 197 ncbi.nlm.nih.gov/gene/197 |
| Ensembl ID | ENSG00000145192 |
| UniProt ID | P02765 |
| OMIM ID | 138680 |
| HGNC ID | 349 |
| Aliases | AHS, FETUA, HSGA, alpha-2-HS-glycoprotein, fetuin-A |
Description
The AHSG gene encodes alpha-2-HS-glycoprotein, also known as fetuin-A, a secreted plasma protein predominantly synthesized in the liver. Fetuin-A functions as a systemic inhibitor of ectopic calcification by binding calcium and phosphate ions, and modulates insulin signaling through interaction with the insulin receptor. It is involved in bone metabolism, inflammation, and metabolic disorders. The gene spans approximately 8.5 kb on chromosome 3q27.3 and contains 7 exons.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Calciphylaxis (calcific uremic arteriolopathy) | Loss of AHSG function reduces inhibition of vascular calcification, promoting calcium deposition in small arteries. | ClinVar; OMIM #138680 |
| Insulin resistance / Type 2 diabetes | Elevated fetuin-A levels inhibit insulin receptor tyrosine kinase activity, impairing insulin signaling. | NCBI Gene; PMID: 12086903 |
| Metabolic syndrome | AHSG polymorphisms (e.g., rs4917) are associated with altered fetuin-A levels and increased risk of metabolic syndrome. | ClinVar; PMID: 20089926 |
| Osteoporosis | Fetuin-A deficiency leads to increased bone resorption and reduced bone mineral density. | OMIM; PMID: 12588800 |
| Coronary artery calcification | Reduced AHSG expression or function correlates with increased coronary artery calcification in chronic kidney disease. | ClinVar; PMID: 17456899 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 127.5 | High |
| Adipose tissue | 8.2 | Low |
| Kidney | 3.1 | Low |
| Heart | 1.5 | Not detected |
| Brain | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (hepatocellular carcinoma) | 142.3 | High expression; liver-derived cell line |
| Huh-7 (hepatoma) | 118.7 | High expression |
| 3T3-L1 (adipocyte) | 6.4 | Low expression; differentiation-dependent |
| HEK293 (embryonic kidney) | 2.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.742C>T (p.Arg248Cys) | Missense | 0.01% (gnomAD) | Reduced secretion and impaired calcification inhibition; associated with calciphylaxis |
| c.763G>A (p.Val255Met) | Missense | 0.02% (gnomAD) | Altered insulin receptor binding; linked to insulin resistance |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of translation initiation; likely loss-of-function |
| c.1066_1067del (p.Leu356Valfs*12) | Frameshift | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Mutations leading to reduced secretion or complete loss of fetuin-A (e.g., start loss, frameshift) impair inhibition of ectopic calcification, increasing risk of vascular calcification and calciphylaxis.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported; elevated wild-type expression is associated with insulin resistance.
Dominant Negative (DN)
No dominant-negative mutations described; AHSG functions as a monomeric secreted protein.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Regulation of insulin-like growth factor (IGF) transport and uptake by insulin-like growth factor binding proteins (IGFBPs)
• Mineral absorption (KEGG hsa04978)
• Complement and coagulation cascades (KEGG hsa04610) – fetuin-A as a minor component
• Endochondral ossification – inhibition of BMP signaling
Protein Summary
Fetuin-A (AHSG) is a 60-65 kDa glycoprotein composed of two chains (A and B) linked by disulfide bonds. It is synthesized as a single polypeptide and proteolytically processed. The protein contains two cystatin-like domains and a calcium-binding region. Fetuin-A is a major carrier of free calcium in serum and a potent inhibitor of hydroxyapatite formation. It also binds to the insulin receptor, reducing tyrosine kinase activity and contributing to insulin resistance. Its expression is primarily hepatic, with lower levels in adipose and bone tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AHSG Knockout HEK293 Cell Line | EDJ-KQ3769 | Human | 197 | Details Get a Quote |
| AHSG Knockout HeLa Cell Line | EDJ-KQ52585 | Human | 197 | Details Get a Quote |
| AHSG Knockout A-549 Cell Line | EDJ-KQ61063 | Human | 197 | Details Get a Quote |
| AHSG Knockout HCT 116 Cell Line | EDJ-KQ69546 | Human | 197 | Details Get a Quote |
