GNMT

Chr 6AR

glycine N-methyltransferase

Also known as: HEL-S-182mP

NCBI Gene: 27232ENSG00000124713UniProt: Q14749

The protein encoded by this gene is an enzyme that catalyzes the conversion of S-adenosyl-L-methionine (along with glycine) to S-adenosyl-L-homocysteine and sarcosine. This protein is found in the cytoplasm and acts as a homotetramer. Defects in this gene are a cause of GNMT deficiency (hypermethioninemia). Alternative splicing results in multiple transcript variants. Naturally occurring readthrough transcription occurs between the upstream CNPY3 (canopy FGF signaling regulator 3) gene and this gene and is represented with GeneID:107080644. [provided by RefSeq, Jan 2016]

Primary Disease Associations & Inheritance

Glycine N-methyltransferase deficiencyMIM #606664
AR
154
ClinVar variants
13
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GNMT
🧬
Gene-Disease Validity (ClinGen)
glycine N-methyltransferase deficiency · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 87 VUS of 154 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.95LOEUF
pLI 0.003
Z-score 1.70
OE 0.48 (0.26–0.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.35Z-score
OE missense 0.92 (0.81–1.05)
159 obs / 172.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.48 (0.26–0.95)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.81–1.05)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.80
0≤1.21.6
LoF obs/exp: 6 / 12.5Missense obs/exp: 159 / 172.1Syn Z: 1.38

ClinVar Variant Classifications

154 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic1
VUS87
Likely Benign33
Benign18
Conflicting3
12
Pathogenic
1
Likely Pathogenic
87
VUS
33
Likely Benign
18
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
9
0
12
Likely Pathogenic
0
0
1
0
1
VUS
3
73
10
1
87
Likely Benign
0
1
12
20
33
Benign
0
1
13
4
18
Conflicting
—3
Total3784525154

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

View in ClinVar →

Protein Context — Lollipop Plot

GNMT · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Glycine N-methyltransferase deficiency

MIM #606664

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Human liver methionine cycle: MAT1A and GNMT gene resequencing, functional genomics, and hepatic genotype-phenotype correlation.
Ji Y et al.·Drug Metab Dispos
2012Functional
Polymorphisms in GNMT and DNMT3b are associated with methotrexate treatment outcome in plaque psoriasis.
Grželj J et al.·Biomed Pharmacother
2021
Carnosine alleviates diabetic nephropathy by targeting GNMT, a key enzyme mediating renal inflammation and fibrosis.
Liu XQ et al.·Clin Sci (Lond)
2020
Identification and validation of molecular subtypes and a 9-gene risk model for breast cancer.
Feng J·Medicine (Baltimore)
2023Functional
Characterization of the neuropsychological phenotype of glycine N-methyltransferase-/- mice and evaluation of its responses to clozapine and sarcosine treatments.
Yang CP et al.·Eur Neuropsychopharmacol
2012
Expression of sarcosine metabolism-related proteins according to metastatic site in breast cancer.
Cha YJ et al.·Int J Clin Exp Pathol
2014
Implications of differences in expression of sarcosine metabolism-related proteins according to the molecular subtype of breast cancer.
Yoon JK et al.·J Transl Med
2014
The glycine N-methyltransferase (GNMT) 1289 C->T variant influences plasma total homocysteine concentrations in young women after restricting folate intake.
Beagle B et al.·J Nutr
2005
Novel significant stage-specific differentially expressed genes in hepatocellular carcinoma.
Sarathi A et al.·BMC Cancer
2019
Total liver phosphatidylcholine content associates with non-alcoholic steatohepatitis and glycine N-methyltransferase expression.
Männistö V et al.·Liver Int
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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