GATM

Chr 15ARAD

glycine amidinotransferase

NCBI Gene: 2628ENSG00000171766UniProt: P50440

Transamidinase that catalyzes the transfer of the amidino group of L-arginine onto the amino moiety of acceptor metabolites such as glycine, beta-alanine, gamma-aminobutyric acid (GABA) and taurine yielding the corresponding guanidine derivatives (PubMed:16820567, PubMed:27233232, PubMed:36543883, PubMed:3800397). Catalyzes the rate-limiting step of creatine biosynthesis, namely the transfer of the amidino group from L-arginine to glycine to generate guanidinoacetate, which is then methylated by GAMT to form creatine. Provides creatine as a source for ATP generation in tissues with high energy demands, in particular skeletal muscle, heart and brain (Probable) (PubMed:27233232, PubMed:36543883, PubMed:3800397, PubMed:9266688)

Primary Disease Associations & Inheritance

Cerebral creatine deficiency syndrome 3MIM #612718
AR
Fanconi renotubular syndrome 1MIM #134600
AD
594
ClinVar variants
45
Pathogenic / LP
0.05
pLI score
0
Active trials
Clinical Summary— GATM
🧬
Gene-Disease Validity (ClinGen)
AGAT deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
45 Pathogenic / Likely Pathogenic· 262 VUS of 594 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.53LOEUF
pLI 0.051
Z-score 3.29
OE 0.28 (0.16–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.29Z-score
OE missense 0.59 (0.51–0.68)
144 obs / 244.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.28 (0.16–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.59 (0.51–0.68)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 7 / 24.6Missense obs/exp: 144 / 244.8Syn Z: 0.61

ClinVar Variant Classifications

594 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic19
VUS262
Likely Benign255
Benign27
Conflicting5
26
Pathogenic
19
Likely Pathogenic
262
VUS
255
Likely Benign
27
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
18
0
26
Likely Pathogenic
9
7
3
0
19
VUS
2
220
33
7
262
Likely Benign
0
5
118
132
255
Benign
0
3
20
4
27
Conflicting
—5
Total19235192143594

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GATM · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

GATM-related arginine:glycine amidinotransferase deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cerebral creatine deficiency syndrome 3

MIM #612718

Molecular basis of disorder known

Autosomal recessive

Fanconi renotubular syndrome 1

MIM #134600

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — GATM
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of novel therapeutic targets for chronic kidney disease and kidney function by integrating multi-omics proteome with transcriptome.
Si S et al.·Genome Med
2024
Machine learning-based lactate-related genes signature predicts clinical outcomes and unveils novel therapeutic targets in esophageal squamous cell carcinoma.
Yu C et al.·Cancer Lett
2025
Clinical features of germline BRCA1/2 or ATM pathogenic variant positive pancreatic cancer in Japan.
Kitamura H et al.·Pancreatology
2023
ClinGen variant curation expert panel recommendations for classification of variants in GAMT, GATM and SLC6A8 for cerebral creatine deficiency syndromes.
Goldstein J et al.·Mol Genet Metab
2024
Association of Familial Fanconi Syndrome with a Novel GATM Variant.
Kudo H et al.·Tohoku J Exp Med
2023Case report
Current and potential new treatment strategies for creatine deficiency syndromes.
Fernandes-Pires G et al.·Mol Genet Metab
2022Review
Arginine-Glycine Amidinotransferase Deficiency and Functional Characterization of Missense Variants in GATM.
DesRoches CL et al.·Hum Mutat
2016Functional
Cefadroxil Targeting of SLC15A2/PEPT2 Protects From Colistin Nephrotoxicity.
Fernandez-Prado R et al.·Lab Invest
2025
Somatic and germline ATM variants in non-small-cell lung cancer: Therapeutic implications.
Hernandez-Martinez JM et al.·Crit Rev Oncol Hematol
2023Review
A novel variant in GATM causes idiopathic renal Fanconi syndrome and predicts progression to end-stage kidney disease.
Seaby EG et al.·Clin Genet
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Role of GATM/creatine as energy reserves in the poll gland and rutting activities in male Bactrian camel.
Tang Z et al.·Int J Biol Macromol
2025
Enhancing cardiac repair post-myocardial infarction: a study on GATM/Gel hydrogel therapeutics.
Li T et al.·Cell Biol Toxicol
2025🔓 Open Access
The hidden potential of solasonine: Targeting non-small cell lung cancer (NSCLC) metastasis through GATM and Smad2 pathways.
Hu C et al.·Phytomedicine
2025
Association between GATM gene polymorphism and progression of chronic kidney disease: a mitochondrial related genome-wide Mendelian randomization study.
Liu B et al.·Sci Rep
2024🔓 Open Access
A novel biomarker GATM suppresses proliferation and malignancy of cholangiocarcinoma cells by modulating the JNK/c-Jun signalling pathways.
Yu Y et al.·Heliyon
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools