SHMT2

Chr 12AR

serine hydroxymethyltransferase 2

Also known as: GLYA, HEL-S-51e, NEDCASB, SHMT, mSHMT

This gene encodes the mitochondrial form of a pyridoxal phosphate-dependent enzyme that catalyzes the reversible reaction of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. The encoded product is primarily responsible for glycine synthesis. The activity of the encoded protein has been suggested to be the primary source of intracellular glycine. The gene which encodes the cytosolic form of this enzyme is located on chromosome 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

OMIMResearchGenerating clinical summary…
DNmechanismARLOEUF 0.851 OMIM phenotype
Clinical SummarySHMT2
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Gene-Disease Validity (ClinGen)
neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities · 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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.85LOEUF
pLI 0.000
Z-score 2.16
OE 0.56 (0.380.85)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.52Z-score
OE missense 0.76 (0.680.84)
234 obs / 309.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.56 (0.380.85)
00.351.4
Missense OE?0.76 (0.680.84)
00.61.4
Synonymous OE?1.08
01.21.6
LoF obs/exp: 16 / 28.4Missense obs/exp: 234 / 309.4Syn Z: -0.68
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongSHMT2-related neurodevelopmental syndromeOTHERAR

This gene — mechanism propensity

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

DN
0.7133th %ile
GOF
0.4480th %ile
LOF
0.3744th %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

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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