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    MTHFS methenyltetrahydrofolate synthetase [ Homo sapiens (human) ]

    Gene ID: 10588, updated on 10-Dec-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (79843547..79897285, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (77706557..77760238, complement)
    RS_2024_09 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. 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
    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. 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
    4. Identification and characterization of human mitochondrial methenyltetrahydrofolate synthetase activity. Bertrand R, et al. Biochim Biophys Acta, 1995 May 12. PMID 7766710
    5. Methenyltetrahydrofolate synthetase regulates folate turnover and accumulation. Anguera MC, et al. J Biol Chem, 2003 Aug 8. PMID 12764149

    See all (35) 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
    		Compare labs

    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)

    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
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    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
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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 
    located_in mitochondrion HTP 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_2024_08

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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