MTHFD1

Methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 (MTHFD1) is a gene located in humans on chromosome 14^[4] that encodes a protein, C-1-tetrahydrofolate synthase, cytoplasmic also known as C1-THF synthase, with three distinct enzymatic activities.^[5][6][7]

MTHFD1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1A4I, 1DIA, 1DIB, 1DIG
Identifiers
Aliases	MTHFD1, MTHFC, MTHFD, C1-THF-Synthase, methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1, CIMAH
External IDs	OMIM: 172460; MGI: 1342005; HomoloGene: 55940; GeneCards: MTHFD1; OMA:MTHFD1 - orthologs
Gene location (Mouse) Chr. Chromosome 12 (mouse)[1] Band 12|12 C3 Start 76,302,072 bp[1] End 76,366,577 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver gastrocnemius muscle Achilles tendon adipose tissue ganglionic eminence subcutaneous adipose tissue caudate nucleus nucleus accumbens right coronary artery kidney Top expressed in Paneth cell primitive streak right lobe of liver left lobe of liver right kidney epiblast Epithelium of choroid plexus human kidney left lung right lung lobe More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding methylenetetrahydrofolate dehydrogenase (NADP+) activity methylenetetrahydrofolate dehydrogenase (NAD+) activity ligase activity methylenetetrahydrofolate dehydrogenase [NAD(P)+ activity] catalytic activity oxidoreductase activity ATP binding hydrolase activity protein binding formate-tetrahydrofolate ligase activity methenyltetrahydrofolate cyclohydrolase activity Cellular component membrane mitochondrion extracellular exosome cytoplasm cytosol Biological process purine nucleotide biosynthetic process transsulfuration neutrophil homeostasis one-carbon metabolic process serine family amino acid metabolic process embryonic neurocranium morphogenesis tetrahydrofolate interconversion histidine biosynthetic process cellular amino acid biosynthetic process somite development serine family amino acid biosynthetic process methionine biosynthetic process heart development methionine metabolic process neural tube closure folic acid metabolic process embryonic viscerocranium morphogenesis metabolism purine nucleobase biosynthetic process 10-formyltetrahydrofolate biosynthetic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4522 108156 Ensembl n/a ENSMUSG00000021048 UniProt P11586 Q922D8 RefSeq (mRNA) NM_005956 NM_001364837 NM_138745 RefSeq (protein) NP_005947 NP_001351766 NP_620084 Location (UCSC) n/a Chr 12: 76.3 – 76.37 Mb PubMed search [2] [3]
Wikidata
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Function

This gene encodes a protein that possesses three distinct enzymatic activities, methylenetetrahydrofolate dehydrogenase (1.5.1.5), methenyltetrahydrofolate cyclohydrolase (3.5.4.9) and formate–tetrahydrofolate ligase (6.3.4.3). Each of these activities catalyzes one of three sequential reactions in the interconversion of 1-carbon derivatives of tetrahydrofolate, which are substrates for methionine, thymidylate, and de novo purine syntheses. The trifunctional enzymatic activities are conferred by two major domains, an aminoterminal portion containing the dehydrogenase and cyclohydrolase activities and a larger synthetase domain.^[7][8]

Clinical significance

Mutations of the MTHFD1 gene may cause methylenetetrahydrofolate dehydrogenase 1 deficiency, also known as combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia (CIMAH).^[8]