SHMT2
Chr 12ARserine hydroxymethyltransferase 2
Also known as: GLYA, HEL-S-51e, NEDCASB, SHMT, mSHMT
SHMT2 encodes the mitochondrial serine hydroxymethyltransferase that catalyzes the conversion of serine to glycine while generating 5,10-methylenetetrahydrofolate, which is essential for purine biosynthesis, mitochondrial DNA maintenance, and mitochondrial protein translation. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities. The gene is extremely intolerant to loss-of-function variants (pLI near 1), indicating that complete loss of function is likely incompatible with survival.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SHMT2 · 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