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…

Primary Disease Associations & Inheritance

Cerebral creatine deficiency syndrome 3MIM #612718

Fanconi renotubular syndrome 1MIM #134600

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.53

LOEUF

LOF

Mechanism· G2P

📖

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

Background carrier burden — how many people carry a rare variant somewhere in GATM?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

430 rare PASS variants

Rare truncating (LoF)

1 in 4,600

50 rare PASS variants

Rare synonymous (reference)

1 in 360

182 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GATM. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 190	1 in 5,700
South Asian	~43k	1 in 150	1 in 1,900
Remaining (unassigned)	~30k	1 in 190	≈ 1 in 10,000
European (Finnish)	~27k	1 in 930	none seen
Admixed American	~22k	1 in 260	none seen
African / African American	~21k	1 in 210	1 in 3,000
East Asian	~20k	1 in 360	1 in 930
Ashkenazi Jewish	~13k	1 in 650	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 480	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 9 coding exons well covered in gnomAD exomes; exons 1, 9 marginal. Genomes: all 9.? see exons ↓