GATM

Chr 15ARAD

glycine amidinotransferase

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

NCBI Gene: 2628 ENSG00000171766 UniProt: P50440 OMIM: 602360

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a mitochondrial enzyme that belongs to the amidinotransferase family. This enzyme is involved in creatine biosynthesis, whereby it catalyzes the transfer of a guanido group from L-arginine to glycine, resulting in guanidinoacetic acid, the immediate precursor of creatine. Mutations in this gene cause arginine:glycine amidinotransferase deficiency, an inborn error of creatine synthesis characterized by cognitive disability, language impairment, and behavioral disorders. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismAR/ADLOEUF 0.532 OMIM phenotypes

VCEP Guidelines: Cerebral Creatine DeficiencyReleased

View Specifications ClinGen Panel

Clinical Summary— GATM

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Gene-Disease Validity (ClinGen)

AGAT deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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Population Constraint (gnomAD)

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

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ClinVar Variants

39 unique Pathogenic / Likely Pathogenic· 302 VUS of 669 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — GATM

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

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?

LoF OE?0.28 (0.16–0.53)

0≤0.351.4

Missense OE?0.59 (0.51–0.68)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

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

This gene — mechanism propensity

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

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

669 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18

Likely Pathogenic21

VUS302

Likely Benign283

Benign37

Conflicting6

Pathogenic

Likely Pathogenic

302

VUS

283

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	16	1	1	0	18
Likely Pathogenic	13	8	0	0	21
VUS	4	262	28	8	302
Likely Benign	0	4	132	147	283
Benign	0	3	30	4	37
Conflicting	—				6
Total	33	278	191	159	667

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap GATM — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →