Jump to content

MTHFD1

From Wikipedia, the free encyclopedia
(Redirected from MTHFD1 deficiency)
MTHFD1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMTHFD1, MTHFC, MTHFD, C1-THF-Synthase, methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1, CIMAH
External IDsOMIM: 172460; MGI: 1342005; HomoloGene: 55940; GeneCards: MTHFD1; OMA:MTHFD1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005956
NM_001364837

NM_138745

RefSeq (protein)

NP_005947
NP_001351766

NP_620084

Location (UCSC)n/aChr 12: 76.3 – 76.37 Mb
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Function

[edit]

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

[edit]

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]

References

[edit]
  1. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021048Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Symbol report for MTHFD1". HUGO. HUGO Gene Nomenclature Committee. Retrieved 13 March 2024.
  5. ^ Hum DW, Bell AW, Rozen R, MacKenzie RE (November 1988). "Primary structure of a human trifunctional enzyme. Isolation of a cDNA encoding methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase". The Journal of Biological Chemistry. 263 (31): 15946–15950. doi:10.1016/S0021-9258(18)37540-9. PMID 3053686.
  6. ^ Rozen R, Barton D, Du J, Hum DW, MacKenzie RE, Francke U (June 1989). "Chromosomal localization of the gene for the human trifunctional enzyme, methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase". American Journal of Human Genetics. 44 (6): 781–786. PMC 1715669. PMID 2786332.
  7. ^ a b "Entrez Gene: MTHFD1 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase".
  8. ^ a b Watkins D, Schwartzentruber JA, Ganesh J, Orange JS, Kaplan BS, Nunez LD, et al. (September 2011). "Novel inborn error of folate metabolism: identification by exome capture and sequencing of mutations in the MTHFD1 gene in a single proband". Journal of Medical Genetics. 48 (9): 590–592. doi:10.1136/jmedgenet-2011-100286. PMID 21813566. S2CID 9623450.

Further reading

[edit]
[edit]
  • Overview of all the structural information available in the PDB for UniProt: P11586 (C-1-tetrahydrofolate synthase, cytoplasmic) at the PDBe-KB.