SHMT2

Chr 12q13.3

serine hydroxymethyltransferase 2

Aliases:: mSHMT
MANE:: ENST00000328923.8

OMIM: 138450 ↗NCBI: 6472 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

SHMT2 · P34897

v62025-08-01

Predicted Aligned Error matrix for SHMT2 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

93.3/ 100

Very high

504 residues

Confidence breakdown

Very high(≥ 90)90%
Confident(70–90)2%
Low(50–70)1%
Very low(< 50)7%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism
BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities
0.77
microcephaly
0.37
polymicrogyria
0.37
neurodevelopmental disorder
0.34
hereditary disease
0.19
schizophrenia
0.13
neoplasm
0.11
breast carcinoma
0.11
breast cancer
0.11
autism spectrum disorder
0.11

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Serine hydroxymethyltransferase, mitochondrial

Catalyzes the cleavage of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis (PubMed:24075985, PubMed:25619277, PubMed:29364879, PubMed:33015733). Serine provides the major source of folate one-carbon in cells by catalyzing the transfer of one carbon from serine to tetrahydrofolate (PubMed:25619277). Contributes to the de novo mitochondrial thymidylate biosynthesis pathway via its role in glycine and tetrahydrofolate metabolism: thymidylate biosynthesis is required to prevent uracil accumulation in mtDNA (PubMed:21876188). Also required for mitochondrial translation by producing 5,10-methylenetetrahydrofolate; 5,10-methylenetetrahydrofolate providing methyl donors to produce the taurinomethyluridine base at the wobble position of some mitochondrial tRNAs (PubMed:29364879, PubMed:29452640). Associates with mitochondrial DNA (PubMed:18063578). In addition to its role in mitochondria, also plays a role in the deubiquitination of target proteins as component of the BRISC complex: required for IFNAR1 deubiquitination by the BRISC complex (PubMed:24075985)