GAMT
Chr 19ARguanidinoacetate N-methyltransferase
Also known as: CCDS2, HEL-S-20, PIG2, TP53I2
This gene encodes guanidinoacetate N-methyltransferase, which converts guanidinoacetate to creatine using S-adenosylmethionine as the methyl donor. Mutations cause cerebral creatine deficiency syndrome 2, an autosomal recessive disorder characterized by neurologic abnormalities and muscular hypotonia due to creatine deficiency and guanidinoacetate accumulation in the brain. The gene shows tolerance to loss-of-function variants (low constraint), and affected individuals typically present in infancy or early childhood with developmental delays and seizures.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
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
100 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 8 | 1 | 3 | 0 | 12 |
Likely Pathogenic | 3 | 0 | 0 | 0 | 3 |
VUS | 0 | 44 | 4 | 1 | 49 |
Likely Benign | 0 | 0 | 16 | 20 | 36 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 11 | 45 | 23 | 21 | 100 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools