GAMT

Chr 19

guanidinoacetate N-methyltransferase

Also known as: CCDS2, HEL-S-20, PIG2, TP53I2

NCBI Gene: 2593ENSG00000130005UniProt: Q14353

The protein encoded by this gene is a methyltransferase that converts guanidoacetate to creatine, using S-adenosylmethionine as the methyl donor. Defects in this gene have been implicated in neurologic syndromes and muscular hypotonia, probably due to creatine deficiency and accumulation of guanidinoacetate in the brain of affected individuals. Two transcript variants encoding different isoforms have been described for this gene. Pseudogenes of this gene are found on chromosomes 2 and 13. [provided by RefSeq, Feb 2012]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCerebral creatine deficiency syndrome 2

Clinical highlights

Gene-disease validity (ClinGen)
guanidinoacetate methyltransferase deficiency · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
47
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
1.26
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — GAMT
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.26LOEUF
pLI 0.009
Z-score 1.11
OE 0.55 (0.27–1.26)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.09Z-score
OE missense 1.02 (0.89–1.17)
153 obs / 150.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.55 (0.27–1.26)
0≤0.351.4
Missense OE?1.02 (0.89–1.17)
0≤0.61.4
Synonymous OE?1.00
0≤1.21.6
LoF obs/exp: 4 / 7.2Missense obs/exp: 153 / 150.0Syn Z: 0.02

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GAMT · protein map & ClinVar variants

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

VCEP specificationsCerebral Creatine DeficiencyReleased
Specifications ↗Panel ↗

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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients