HMGCS2
3-hydroxy-3-methylglutaryl-CoA synthase 2
Gene Information Card
| Symbol | HMGCS2 |
|---|---|
| Full Name | 3-hydroxy-3-methylglutaryl-CoA synthase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p12 |
| NCBI Gene ID | 3158 ncbi.nlm.nih.gov/gene/3158 |
| Ensembl ID | ENSG00000134240 |
| UniProt ID | P54868 |
| OMIM ID | 600234 |
| HGNC ID | 5008 |
| Aliases | HMGCS2, HMG-CoA synthase 2, mitochondrial HMG-CoA synthase |
Description
HMGCS2 encodes the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, a key enzyme in ketogenesis. It catalyzes the condensation of acetoacetyl-CoA with acetyl-CoA to form HMG-CoA, the rate-limiting step in ketone body production. The enzyme is primarily expressed in liver and colon, and its deficiency leads to HMG-CoA synthase deficiency, a disorder of ketone body metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| HMG-CoA synthase deficiency | Loss-of-function mutations in HMGCS2 impair ketogenesis, leading to hypoketotic hypoglycemia and metabolic acidosis during fasting or illness. | ClinVar, OMIM |
| Hyperinsulinemic hypoglycemia | Altered HMGCS2 expression may contribute to dysregulated insulin secretion and hypoglycemia. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 14.5 | High |
| Colon | 8.2 | Medium |
| Kidney | 4.1 | Low |
| Small intestine | 3.8 | Low |
| Adipose tissue | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 12.3 | Hepatocellular carcinoma cell line |
| Caco-2 | 6.7 | Colorectal adenocarcinoma cell line |
| HEK 293 | 0.5 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.100G>A (p.Gly34Arg) | Missense | Rare | Loss of enzymatic activity; associated with HMG-CoA synthase deficiency |
| c.464T>C (p.Leu155Pro) | Missense | Rare | Impaired protein stability and reduced ketogenesis |
| c.1172delC | Frameshift | Very rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported HMGCS2 mutations are loss-of-function, reducing or abolishing HMG-CoA synthase activity, leading to ketone body deficiency.
Gain of Function (GOF)
No gain-of-function mutations have been reported for HMGCS2.
Dominant Negative (DN)
No dominant-negative mutations have been described for HMGCS2.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004421 (GO:0004421) | • GO:0005739 (GO:0005739) |
| • GO:0006631 (GO:0006631) | • GO:0046951 (GO:0046951) |
Pathways
• Ketogenesis (Reactome: R-HSA-77111)
• Metabolism of lipids (Reactome: R-HSA-556833)
Protein Summary
HMGCS2 is a mitochondrial enzyme (UniProt P54868) that catalyzes the first committed step of ketogenesis. It is a homodimer with a molecular weight of approximately 57 kDa. The protein is highly expressed in liver and colon, and its activity is regulated by succinylation and acetylation. Deficiency leads to metabolic crisis with hypoketotic hypoglycemia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HMGCS2 Knockout HEK293 Cell Line | EDJ-KQ2610 | Human | 3158 | Details Get a Quote |
| HMGCS2 Knockout HeLa Cell Line | EDJ-KQ53533 | Human | 3158 | Details Get a Quote |
| HMGCS2 Knockout A-549 Cell Line | EDJ-KQ62006 | Human | 3158 | Details Get a Quote |
| HMGCS2 Knockout HCT 116 Cell Line | EDJ-KQ70483 | Human | 3158 | Details Get a Quote |
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