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MTHFS methenyltetrahydrofolate synthetase [ Homo sapiens (human) ]

Gene ID: 10588, updated on 5-Mar-2024

Summary

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Official Symbol
MTHFSprovided by HGNC
Official Full Name
methenyltetrahydrofolate synthetaseprovided by HGNC
Primary source
HGNC:HGNC:7437
See related
Ensembl:ENSG00000136371 MIM:604197; AllianceGenome:HGNC:7437
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
NEDMEHM; HsT19268
Summary
The protein encoded by this gene is an enzyme that catalyzes the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate, a precursor of reduced folates involved in 1-carbon metabolism. An increased activity of the encoded protein can result in an increased folate turnover rate and folate depletion. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]
Expression
Broad expression in liver (RPKM 20.2), kidney (RPKM 14.0) and 23 other tissues See more
Orthologs
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Genomic context

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See MTHFS in Genome Data Viewer
Location:
15q25.1
Exon count:
4
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (79843547..79897285, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (77706557..77760238, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (80135889..80189627, complement)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene RNA, U6 small nuclear 667, pseudogene Neighboring gene uncharacterized LOC124903536 Neighboring gene ST20-MTHFS readthrough Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:80146049-80146550 Neighboring gene Sharpr-MPRA regulatory region 2833 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6724 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9934 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6725 Neighboring gene suppressor of tumorigenicity 20 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6726 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6727 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6728 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9935 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6729 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9936 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:80216673-80217333 Neighboring gene ST20 antisense RNA 1 Neighboring gene farnesyl diphosphate synthase pseudogene 9

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The impact of 5,10-methenyltetrahydrofolate synthetase polymorphism on diabetic nephropathy in the Taiwanese population. Lin CJ, et al. Genet Test Mol Biomarkers, 2012 Feb. PMID 21895484
  2. Genome-wide association study for renal traits in the Framingham Heart and Atherosclerosis Risk in Communities Studies. Kottgen A, et al. BMC Med Genet, 2008 Jun 3. PMID 18522750, Free PMC Article
  3. Human liver methenyltetrahydrofolate synthetase: improved purification and increased affinity for folate polyglutamate substrates. Bertrand R, et al. Biochim Biophys Acta, 1987 Jan 30. PMID 3801490
  4. Methenyltetrahydrofolate synthetase regulates folate turnover and accumulation. Anguera MC, et al. J Biol Chem, 2003 Aug 8. PMID 12764149
  5. Identification and characterization of human mitochondrial methenyltetrahydrofolate synthetase activity. Bertrand R, et al. Biochim Biophys Acta, 1995 May 12. PMID 7766710

See all (32) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The intronic Single nucleotide polymorphism in MTHFS had no significant effect on the risk of diabetic nephropathy in Taiwanese patients with T2D.
    Title: The impact of 5,10-methenyltetrahydrofolate synthetase polymorphism on diabetic nephropathy in the Taiwanese population.
  2. Observational study of gene-disease association. (HuGE Navigator)
    Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
  3. Observational study and meta-analysis of gene-disease association. (HuGE Navigator)
    Title: One-carbon metabolism gene polymorphisms and risk of non-Hodgkin lymphoma in Australia.
  4. Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
    Title: Oral facial clefts and gene polymorphisms in metabolism of folate/one-carbon and vitamin A: a pathway-wide association study.
  5. Methenyltetrahydrofolate synthetase regulates folate turnover and accumulation
    Title: Methenyltetrahydrofolate synthetase regulates folate turnover and accumulation.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination
MedGen: C5193057 OMIM: 618367 GeneReviews: Not available
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EBI GWAS Catalog

Description
Genome-wide association study of chronic periodontitis in a general German population.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Readthrough ST20-MTHFS

Readthrough gene: ST20-MTHFS, Included gene: ST20

Homology

Clone Names

  • FLJ30410

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 5-formyltetrahydrofolate cyclo-ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables 5-formyltetrahydrofolate cyclo-ligase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables 5-formyltetrahydrofolate cyclo-ligase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables 5-formyltetrahydrofolate cyclo-ligase activity NAS
Non-traceable Author Statement
more info
 PubMed 
enables 5-formyltetrahydrofolate cyclo-ligase activity TAS
Traceable Author Statement
more info
  
enables ATP binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables folic acid binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in folic acid catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in folic acid metabolic process TAS
Traceable Author Statement
more info
  
involved_in folic acid-containing compound biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in formate metabolic process NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in glutamate metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in tetrahydrofolate interconversion IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in tetrahydrofolate interconversion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in tetrahydrofolate metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in mitochondrial matrix IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
5-formyltetrahydrofolate cyclo-ligase
Names
5,10-methenyltetrahydrofolate synthetase (5-formyltetrahydrofolate cyclo-ligase)
methenyl-THF synthetase
NP_001186687.1
NP_006432.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_029243.1 RefSeqGene

    Range
    5272..58739
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001199758.1 → NP_001186687.1  5-formyltetrahydrofolate cyclo-ligase isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (b) is shorter than isoform a.
    Source sequence(s)
    AC021483, AL109717, BM313547, CB995322, L38928
    UniProtKB/Swiss-Prot
    P49914
    Conserved Domains (1) summary
    pfam01812
    Location:1 → 141
    5-FTHF_cyc-lig; 5-formyltetrahydrofolate cyclo-ligase family

  2. NM_006441.4 → NP_006432.1  5-formyltetrahydrofolate cyclo-ligase isoform a

    See identical proteins and their annotated locations for NP_006432.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (a).
    Source sequence(s)
    AC021483, AL109717, BC019921, L38928
    Consensus CDS
    CCDS10311.1
    UniProtKB/Swiss-Prot
    H3BQ75, P49914
    UniProtKB/TrEMBL
    Q96EE9
    Related
    ENSP00000258874.4, ENST00000258874.4
    Conserved Domains (1) summary
    pfam01812
    Location:10 → 198
    5-FTHF_cyc-lig; 5-formyltetrahydrofolate cyclo-ligase family

RNA

  1. NR_037654.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) has an alternate 5' exon and is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC015871, AC021483, AL109717, BM450865, DB464304, L38928

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

    Range
    79843547..79897285 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060939.1 Alternate T2T-CHM13v2.0

    Range
    77706557..77760238 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P49914.2 GenPept UniProtKB/Swiss-Prot:P49914

Gene LinkOut

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