MTHFD1

Chr 14q23.3

methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1

MANE:: ENST00000652337.1

OMIM: 172460 ↗NCBI: 4522 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

MTHFD1 · P11586

v62025-08-01

Predicted Aligned Error matrix for MTHFD1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

94.6/ 100

Very high

935 residues

Confidence breakdown

Very high(≥ 90)90%
Confident(70–90)9%
Low(50–70)1%
Very low(< 50)0%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

COVID-19 research
BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease
BIALLELIC, autosomal or pseudoautosomal
Cytopenia - NOT Fanconi anaemia
BIALLELIC, autosomal or pseudoautosomal
Familial Neural Tube Defects
BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism
BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia
0.77
severe combined immunodeficiency
0.47
neural tube defects, folate-sensitive
0.41
isolated spina bifida
0.38
atrial fibrillation
0.36
hereditary disease
0.19
colorectal cancer
0.19
major depressive disorder
0.16
coronary artery disorder
0.10
neoplasm
0.10

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

Protein function (UniProt)

C-1-tetrahydrofolate synthase, cytoplasmic

Trifunctional enzyme that catalyzes the interconversion of three forms of one-carbon-substituted tetrahydrofolate: (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate, 5,10-methenyltetrahydrofolate and (6S)-10-formyltetrahydrofolate (PubMed:10828945, PubMed:18767138, PubMed:1881876). These derivatives of tetrahydrofolate are differentially required in nucleotide and amino acid biosynthesis, (6S)-10-formyltetrahydrofolate being required for purine biosynthesis while (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate is used for serine and methionine biosynthesis for instance (PubMed:18767138, PubMed:25633902)