GATM (Glycine AmidinoTransferase)
A key enzyme in creatine biosynthesis, implicated in cerebral creatine deficiency syndromes and potential cancer relevance.
Gene Information Card
| Symbol | GATM |
|---|---|
| Full Name | Glycine amidinotransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 15q21.1 (GRCh38) |
| NCBI Gene ID | 2628 ncbi.nlm.nih.gov/gene/2628 |
| Ensembl ID | ENSG00000171766 |
| UniProt ID | P50440 |
| OMIM ID | 602360 |
| HGNC ID | 4176 |
| Aliases | AGAT, AT, CCDS3, MGC116894 |
Description
The GATM gene encodes glycine amidinotransferase (AGAT), a mitochondrial enzyme that catalyzes the first and rate-limiting step in creatine biosynthesis, converting glycine and arginine into guanidinoacetate and ornithine. This enzyme is expressed primarily in kidney, pancreas, and liver, and its deficiency leads to cerebral creatine deficiency syndrome, characterized by intellectual disability, speech delay, and seizures. GATM mutations are also studied in the context of cancer and other metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cerebral creatine deficiency syndrome (CCDS) due to AGAT deficiency | Loss-of-function mutations in GATM impair creatine synthesis, leading to low brain creatine levels and neurological symptoms. | OMIM #612718; ClinVar entries with pathogenic variants. |
| Arginine:glycine amidinotransferase deficiency (AGAT deficiency) | Autosomal recessive disorder caused by biallelic mutations in GATM, resulting in guanidinoacetate deficiency and creatine depletion. | OMIM #612718; multiple case reports in literature. |
| Potential cancer relevance | Altered GATM expression and mutations have been observed in various cancers, though the mechanistic role is not fully established. | COSMIC database lists somatic mutations in GATM across cancer types. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | High (e.g., ~50 nTPM) | High |
| Pancreas | Moderate (e.g., ~20 nTPM) | Medium |
| Liver | Moderate (e.g., ~15 nTPM) | Medium |
| Brain | Low (e.g., ~5 nTPM) | Low |
| Muscle | Low (e.g., ~3 nTPM) | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | Moderate (e.g., ~10 nTPM) | Embryonic kidney cells; used in functional studies. |
| HepG2 | Moderate (e.g., ~12 nTPM) | Liver carcinoma cell line; expresses GATM. |
| A549 | Low (e.g., ~2 nTPM) | Lung carcinoma; low expression. |
| MCF7 | Low (e.g., ~1 nTPM) | Breast cancer; low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.484C>T (p.Arg162Ter) | Nonsense | Rare (found in AGAT deficiency patients) | Loss of function; premature truncation. |
| c.638G>A (p.Arg213His) | Missense | Rare (pathogenic in CCDS) | Impairs enzyme activity. |
| c.122G>A (p.Arg41Gln) | Missense | Rare (likely pathogenic) | Reduced catalytic activity. |
| c.748C>T (p.Arg250Ter) | Nonsense | Rare (reported in AGAT deficiency) | Loss of function. |
Mutation functional classification
Loss of Function (LOF)
Most GATM mutations associated with AGAT deficiency are loss-of-function, leading to reduced or absent enzyme activity, causing creatine deficiency.
Gain of Function (GOF)
No evidence of gain-of-function mutations in GATM; such mutations are not reported in literature or databases.
Dominant Negative (DN)
No evidence of dominant-negative effects; AGAT deficiency is autosomal recessive, requiring biallelic mutations.
View complete mutation data：
Gene Ontology (GO)
| • amidinotransferase activity (GO:0004013) | • glycine amidinotransferase activity (GO:0004013) |
| • creatine biosynthetic process (GO:0006601) | • mitochondrion (GO:0005739) |
| • response to starvation (GO:0042594) |
Pathways
• Creatine metabolism (Reactome: R-HSA-71291)
• Arginine and proline metabolism (KEGG: map00330)
Protein Summary
Glycine amidinotransferase (AGAT) is a 423-amino acid mitochondrial enzyme that catalyzes the transfer of an amidino group from arginine to glycine, producing guanidinoacetate, the direct precursor of creatine. The enzyme functions as a homodimer and is regulated by creatine levels via feedback inhibition. Defects in AGAT lead to cerebral creatine deficiency, which can be treated with creatine supplementation. The protein is also implicated in cellular energy homeostasis and has been studied in cancer metabolism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GATM Knockout HEK293 Cell Line | EDJ-KQ4684 | Human | 2628 | Details Get a Quote |
| GATM Knockout A-549 Cell Line | EDJ-KQ26145 | Human | 2628 | Details Get a Quote |
| GATM Knockout HCT 116 Cell Line | EDJ-KQ27388 | Human | 2628 | Details Get a Quote |
| GATM Knockout HeLa Cell Line | EDJ-KQ27389 | Human | 2628 | Details Get a Quote |
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