AMT Gene (Aminomethyltransferase): Function, Disease Associations, and Clinical Significance
Comprehensive guide to the AMT gene, encoding aminomethyltransferase, its role in glycine cleavage, associated disorders, and genetic variants.
Gene Information Card
| Symbol | AMT |
|---|---|
| Full Name | Aminomethyltransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 275 ncbi.nlm.nih.gov/gene/275 |
| Ensembl ID | ENSG00000145020 |
| UniProt ID | P48728 |
| OMIM ID | 238310 |
| HGNC ID | 473 |
| Aliases | GCVT, NKH |
Description
The AMT gene encodes aminomethyltransferase, also known as glycine cleavage system T-protein. This mitochondrial enzyme is a component of the glycine cleavage system, which catalyzes the degradation of glycine. The protein transfers the methylene group from glycine to tetrahydrofolate, producing 5,10-methylenetetrahydrofolate, ammonia, and carbon dioxide. Mutations in AMT cause nonketotic hyperglycinemia (NKH), a severe neurometabolic disorder characterized by accumulation of glycine in body fluids.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Nonketotic hyperglycinemia (NKH) | Loss-of-function mutations in AMT impair glycine cleavage, leading to elevated glycine levels in plasma, cerebrospinal fluid, and brain, causing neurological symptoms. | ClinVar, OMIM |
| Glycine encephalopathy | Same as NKH; AMT mutations result in defective T-protein, disrupting the glycine cleavage system and causing glycine accumulation. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.4 | Medium |
| Kidney | 8.1 | Low |
| Brain | 6.3 | Low |
| Heart | 5.2 | Low |
| Skeletal Muscle | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 15.2 | Highest expression |
| A549 (lung) | 4.5 | Moderate |
| MCF7 (breast) | 2.3 | Low |
| K562 (leukemia) | 1.1 | Very low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare | Loss of start codon, likely no protein |
| c.IVS3+1G>A | Splice site | Rare | Splicing defect, exon skipping |
| c.742C>T (p.Arg248Ter) | Nonsense | Rare | Premature stop, truncated protein |
| c.1082delC (p.Pro361LeufsTer5) | Frameshift | Rare | Frameshift, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most AMT mutations are loss-of-function, leading to reduced or absent aminomethyltransferase activity, causing glycine accumulation.
Gain of Function (GOF)
No gain-of-function mutations reported for AMT.
Dominant Negative (DN)
No dominant-negative effects described; AMT mutations are typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • aminomethyltransferase activity | • glycine cleavage system |
| • mitochondrion | • glycine metabolic process |
| • one-carbon metabolic process |
Pathways
• Glycine cleavage system
• Glycine
• serine and threonine metabolism
• Metabolic pathways
Protein Summary
Aminomethyltransferase (AMT) is a mitochondrial enzyme composed of 403 amino acids. It forms the T-protein component of the glycine cleavage system, a multi-enzyme complex that also includes P-protein (GLDC), H-protein (GCSH), and L-protein (DLD). AMT catalyzes the transfer of the methylene group from glycine-loaded H-protein to tetrahydrofolate, producing 5,10-methylenetetrahydrofolate, ammonia, and CO2. The protein is essential for glycine catabolism; defects lead to glycine accumulation and severe neurological impairment.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AMTN Knockout HEK293 Cell Line | EDJ-KQ11622 | Human | 401138 | Details Get a Quote |
| AMTN Knockout HeLa Cell Line | EDJ-KQ39970 | Human | 401138 | Details Get a Quote |
| AMT Knockout HEK293 Cell Line | EDJ-KQ50116 | Human | 275 | Details Get a Quote |
| AMT Knockout HeLa Cell Line | EDJ-KQ52611 | Human | 275 | Details Get a Quote |
| AMT Knockout A-549 Cell Line | EDJ-KQ61090 | Human | 275 | Details Get a Quote |
| AMTN Knockout A-549 Cell Line | EDJ-KQ68753 | Human | 401138 | Details Get a Quote |
| AMT Knockout HCT 116 Cell Line | EDJ-KQ69573 | Human | 275 | Details Get a Quote |
| AMTN Knockout HCT 116 Cell Line | EDJ-KQ77120 | Human | 401138 | Details Get a Quote |
