AMT

Chr 3

aminomethyltransferase

Also known as: GCE, GCE2, GCST, GCVT, NKH

The protein is one of four essential components of the glycine cleavage system that catalyzes the degradation of glycine. Mutations cause glycine encephalopathy, a severe neurometabolic disorder that typically presents in the neonatal period with hypotonia, seizures, and developmental delay. Inheritance is autosomal recessive.

GeneReviewsResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismLOEUF 0.79
Clinical SummaryAMT
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Gene-Disease Validity (ClinGen)
glycine encephalopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
38 unique Pathogenic / Likely Pathogenic· 41 VUS of 200 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — AMT
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

Tolerant — LoF & missense variants common in population
LoF Constraint
0.79LOEUF
pLI 0.003
Z-score 2.19
OE 0.42 (0.240.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.10Z-score
OE missense 1.02 (0.921.13)
244 obs / 239.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.42 (0.240.79)
00.351.4
Missense OE1.02 (0.921.13)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 7 / 16.7Missense obs/exp: 244 / 239.6Syn Z: -0.47
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveAMT-related glycine encephalopathyLOFAR

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

DN
0.74top 25%
GOF
0.73top 25%
LOF
0.3453th %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

200 submitted variants in ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic22
VUS41
Likely Benign110
Benign1
Conflicting3
16
Pathogenic
22
Likely Pathogenic
41
VUS
110
Likely Benign
1
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
1
4
0
16
Likely Pathogenic
17
3
2
0
22
VUS
0
35
5
1
41
Likely Benign
0
1
69
40
110
Benign
0
0
1
0
1
Conflicting
3
Total28408141193

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

View in ClinVar →

Protein Context — Lollipop Plot

AMT · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Gene therapy for hemophilia.
Nathwani AC·Hematology Am Soc Hematol Educ Program
2022Review
Huntington's disease clinical trials update: March 2025.
Farag M et al.·J Huntingtons Dis
2025Review
Huntington's Disease Clinical Trials Corner: March 2024.
Estevez-Fraga C et al.·J Huntingtons Dis
2024
Top 5 results · since 2015Search PubMed ↗