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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
GATM
glycine amidinotransferase
Chromosome 15 Β· 15q21.1
NCBI Gene: 2628Ensembl: ENSG00000171766.18HGNC: HGNC:4175UniProt: A0A140VK19
63PubMed Papers
22Diseases
0Drugs
38Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
mitochondrionprotein bindingamidinotransferase activityglycine amidinotransferase activityAGAT deficiencyArginine:glycine amidinotransferase deficiencyFanconi renotubular syndrome 1chronic kidney disease
✦AI Summary

GATM (glycine amidinotransferase) is a mitochondrial transamidinase that catalyzes the rate-limiting step of creatine biosynthesis by transferring the amidino group from L-arginine to glycine, generating guanidinoacetate 12. Beyond glycine, GATM can aminidinoylate other acceptor metabolites including beta-alanine, GABA, and taurine 3. The resulting creatine serves as an ATP energy source in tissues with high metabolic demands, particularly skeletal muscle, heart, and brain 4. GATM exhibits tissue-specific expression, showing higher levels in type 2 muscle fibers 5. Pathologically, GATM upregulation promotes cancer metastasis across multiple tumor typesβ€”colorectal, breast, and pancreatic cancersβ€”through creatine-mediated activation of EMT pathways and Smad2/3 signaling 678. In glioblastoma, myeloid cells expressing GATM provide creatine to tumor cells in hypoxic niches, promoting growth 9. Conversely, reduced GATM expression associates with chr15 kidney disease progression, suggesting a protective role in renal function 1011. GATM mutations cause cerebral creatine deficiency syndrome 3. Given its dual role in both metabolic homeostasis and pathological processes, GATM represents a potential therapeutic target for cancer prevention and kidney disease management.

Sources cited
1
GATM catalyzes creatine biosynthesis and transfers amidino groups to glycine and other acceptors
PMID: 27233232
2
GATM is the rate-limiting enzyme in creatine biosynthesis
PMID: 36543883
3
GATM catalyzes amidino transfer to multiple acceptor metabolites including beta-alanine, GABA, and taurine
PMID: 16820567
4
Creatine from GATM-catalyzed biosynthesis provides ATP generation in high-demand tissues
PMID: 9266688
5
GATM shows higher expression in type 2 muscle fibers in spatial transcriptomic analysis
PMID: 39786556
6
GATM upregulation in cancer metastases promotes colorectal and breast cancer progression through Smad2/3 activation
PMID: 33811821
7
GATM in adipocytes mediates creatine-dependent obesity-driven breast cancer progression
PMID: 33596409
8
GATM-mediated guanidinoacetic acid synthesis promotes pancreatic cancer liver metastasis and EMT
PMID: 37370109
9
Myeloid cell-derived creatine via GATM promotes glioblastoma growth in hypoxic niches
PMID: 38134929
10
Increased GATM expression associates with reduced chronic kidney disease risk and better eGFR
PMID: 39284843
11
GATM identified as candidate therapeutic target for chronic kidney disease
PMID: 38898508
12
GATM (GATM-CCDC155 gene-disease pair) recommended by rare disease experts for newborn genome screening
PMID: 37155167
Disease Associationsβ“˜22
AGAT deficiencyOpen Targets
0.81Strong
Arginine:glycine amidinotransferase deficiencyOpen Targets
0.78Strong
Fanconi renotubular syndrome 1Open Targets
0.75Strong
chronic kidney diseaseOpen Targets
0.39Weak
primary Fanconi syndromeOpen Targets
0.37Weak
kidney failureOpen Targets
0.36Weak
Abnormality of the skeletal systemOpen Targets
0.36Weak
neurodegenerative diseaseOpen Targets
0.33Weak
neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalitiesOpen Targets
0.26Weak
hypertensive heart diseaseOpen Targets
0.21Weak
genetic disorderOpen Targets
0.19Weak
kidney diseaseOpen Targets
0.18Weak
neuroinflammatory disorderOpen Targets
0.17Weak
Alzheimer diseaseOpen Targets
0.13Weak
albuminuriaOpen Targets
0.12Weak
Parkinson diseaseOpen Targets
0.12Weak
lysosomal storage diseaseOpen Targets
0.12Weak
multiple sclerosisOpen Targets
0.12Weak
COVID-19Open Targets
0.11Weak
SeizureOpen Targets
0.11Weak
Cerebral creatine deficiency syndrome 3UniProt
Fanconi renotubular syndrome 1UniProt
Pathogenic Variants38
NM_001482.3(GATM):c.778C>T (p.Arg260Ter)Likely pathogenic
not provided|Arginine:glycine amidinotransferase deficiency
β˜…β˜…β˜…β˜†2025β†’ Residue 260
NM_001482.3(GATM):c.216G>A (p.Trp72Ter)Likely pathogenic
Arginine:glycine amidinotransferase deficiency
β˜…β˜…β˜…β˜†2025β†’ Residue 72
NM_001482.3(GATM):c.553G>C (p.Ala185Pro)Likely pathogenic
Arginine:glycine amidinotransferase deficiency
β˜…β˜…β˜…β˜†2025β†’ Residue 185
NM_001482.3(GATM):c.608A>C (p.Tyr203Ser)Likely pathogenic
Arginine:glycine amidinotransferase deficiency
β˜…β˜…β˜…β˜†2025β†’ Residue 203
NM_001482.3(GATM):c.1238G>A (p.Arg413Gln)Likely pathogenic
Arginine:glycine amidinotransferase deficiency
β˜…β˜…β˜…β˜†2025β†’ Residue 413
NM_001482.3(GATM):c.959del (p.Pro320fs)Likely pathogenic
Arginine:glycine amidinotransferase deficiency
β˜…β˜…β˜…β˜†2025β†’ Residue 320
NM_001482.3(GATM):c.1237C>T (p.Arg413Trp)Likely pathogenic
not provided|Arginine:glycine amidinotransferase deficiency
β˜…β˜…β˜…β˜†2024β†’ Residue 413
NM_001482.3(GATM):c.629G>A (p.Trp210Ter)Pathogenic
Arginine:glycine amidinotransferase deficiency
β˜…β˜…β˜…β˜†2023β†’ Residue 210
NM_001482.3(GATM):c.484+1G>TPathogenic
Arginine:glycine amidinotransferase deficiency|Fanconi renotubular syndrome 1;Arginine:glycine amidinotransferase deficiency
β˜…β˜…β˜…β˜†2022
NM_001482.3(GATM):c.446G>A (p.Trp149Ter)Pathogenic
Arginine:glycine amidinotransferase deficiency
β˜…β˜…β˜…β˜†2022β†’ Residue 149
NM_001482.3(GATM):c.505C>T (p.Arg169Ter)Pathogenic
Arginine:glycine amidinotransferase deficiency|Arginine:glycine amidinotransferase deficiency;Fanconi renotubular syndrome 1
β˜…β˜…β˜…β˜†2022β†’ Residue 169
NM_001482.3(GATM):c.1111dup (p.Met371fs)Pathogenic
Arginine:glycine amidinotransferase deficiency
β˜…β˜…β˜…β˜†2022β†’ Residue 371
NM_001482.3(GATM):c.580C>T (p.Arg194Ter)Pathogenic
Arginine:glycine amidinotransferase deficiency|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 194
NM_001482.3(GATM):c.141dup (p.Asn48fs)Pathogenic
Arginine:glycine amidinotransferase deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 48
NM_001482.3(GATM):c.964C>T (p.Arg322Ter)Pathogenic
Arginine:glycine amidinotransferase deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 322
NM_001482.3(GATM):c.608A>G (p.Tyr203Cys)Likely pathogenic
Arginine:glycine amidinotransferase deficiency
β˜…β˜†β˜†β˜†2024β†’ Residue 203
NM_001482.3(GATM):c.5_33del (p.Leu2fs)Pathogenic
Arginine:glycine amidinotransferase deficiency
β˜…β˜†β˜†β˜†2024β†’ Residue 2
NM_001482.3(GATM):c.217_250dup (p.Glu84fs)Likely pathogenic
Arginine:glycine amidinotransferase deficiency;Fanconi renotubular syndrome 1
β˜…β˜†β˜†β˜†2024β†’ Residue 84
NM_001482.3(GATM):c.92G>A (p.Trp31Ter)Pathogenic
Arginine:glycine amidinotransferase deficiency
β˜…β˜†β˜†β˜†2024β†’ Residue 31
NM_001482.3(GATM):c.979-1_979insTLikely pathogenic
Arginine:glycine amidinotransferase deficiency
β˜…β˜†β˜†β˜†2024
View on ClinVar β†—
Related Genes
AZIN2Protein interaction98%NOS2Protein interaction97%GLDCProtein interaction97%NOS3Protein interaction97%SHMT1Protein interaction96%SHMT2Protein interaction96%
Tissue Expression6 tissues
Liver
100%
Ovary
9%
Brain
8%
Heart
5%
Bone Marrow
1%
Lung
0%
Gene Interaction Network
Click a node to explore
GATMAZIN2NOS2GLDCNOS3SHMT1SHMT2
PROTEIN STRUCTURE
Preparing viewer…
PDB1JDW Β· 1.90 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.60Moderately Constrained
pLIβ“˜
0.33Tolerant
Observed/Expected LoF0.41 [0.28–0.60]
RankingsWhere GATM stands among ~20K protein-coding genes
  • #7,363of 20,598
    Most Researched63
  • #1,597of 5,498
    Most Pathogenic Variants38
  • #4,082of 17,882
    Most Constrained (LOEUF)0.60 Β· top quartile
Genes detectedGATM
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Creatine promotes cancer metastasis through activation of Smad2/3.
PMID: 33811821
Cell Metab Β· 2021
1.00
2
Identification of novel therapeutic targets for chronic kidney disease and kidney function by integrating multi-omics proteome with transcriptome.
PMID: 38898508
Genome Med Β· 2024
0.90
3
Creatine-mediated crosstalk between adipocytes and cancer cells regulates obesity-driven breast cancer.
PMID: 33596409
Cell Metab Β· 2021
0.80
4
Epigenetic reprogramming-induced guanidinoacetic acid synthesis promotes pancreatic cancer metastasis and transcription-activating histone modifications.
PMID: 37370109
J Exp Clin Cancer Res Β· 2023
0.70
5
Myeloid cell-derived creatine in the hypoxic niche promotes glioblastoma growth.
PMID: 38134929
Cell Metab Β· 2024
0.60