GATM

Chr 15ARAD

glycine amidinotransferase

Also known as: AGAT, AT, CCDS3, FRTS, FRTS1, RFS

The encoded mitochondrial enzyme catalyzes the transfer of a guanido group from L-arginine to glycine to produce guanidinoacetic acid, the immediate precursor of creatine in creatine biosynthesis. Mutations cause cerebral creatine deficiency syndrome 3, characterized by cognitive disability, language impairment, and behavioral disorders, as well as Fanconi renotubular syndrome 1, with both autosomal recessive and autosomal dominant inheritance patterns reported. The pathogenicity results from deficient creatine synthesis leading to cerebral creatine deficiency and associated neurological dysfunction.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 0.532 OMIM phenotypes
VCEP Guidelines: Cerebral Creatine DeficiencyReleased
View SpecificationsClinGen Panel
Clinical SummaryGATM
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Gene-Disease Validity (ClinGen)
AGAT deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.53LOEUF
pLI 0.051
Z-score 3.29
OE 0.28 (0.160.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.29Z-score
OE missense 0.59 (0.510.68)
144 obs / 244.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.28 (0.160.53)
00.351.4
Missense OE0.59 (0.510.68)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 7 / 24.6Missense obs/exp: 144 / 244.8Syn Z: 0.61
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGATM-related arginine:glycine amidinotransferase deficiencyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6356th %ile
GOF
0.4875th %ile
LOF
0.3746th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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