LOCUS       NM_005956               3154 bp    mRNA    linear   PRI 01-AUG-2024
DEFINITION  Homo sapiens methylenetetrahydrofolate dehydrogenase,
            cyclohydrolase and formyltetrahydrofolate synthetase 1 (MTHFD1),
            transcript variant 1, mRNA.
ACCESSION   NM_005956
VERSION     NM_005956.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 3154)
  AUTHORS   Guan,J., Li,M., Wang,Y., Zhang,Y., Que,Y., Lu,S., Wang,J., Zhu,J.,
            Huang,J., Zhen,Z., Sun,F., Song,M. and Zhang,Y.
  TITLE     MTHFD1 regulates the NADPH redox homeostasis in MYCN-amplified
            neuroblastoma
  JOURNAL   Cell Death Dis 15 (2), 124 (2024)
   PUBMED   38336749
  REMARK    GeneRIF: MTHFD1 regulates the NADPH redox homeostasis in
            MYCN-amplified neuroblastoma.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 3154)
  AUTHORS   Rao,K., Zheng,K., Zhao,Q., He,J., Zhou,B., Hou,G., Sha,N., Wang,W.,
            Yan,M., Zhou,Y., Jin,Y., Jiang,Y. and Xia,Q.
  TITLE     The negative effect of G1958A polymorphism on MTHFD1 protein
            stability and HCC growth
  JOURNAL   Cell Oncol (Dordr) 46 (3), 735-744 (2023)
   PUBMED   36913067
  REMARK    GeneRIF: The negative effect of G1958A polymorphism on MTHFD1
            protein stability and HCC growth.
REFERENCE   3  (bases 1 to 3154)
  AUTHORS   Purohit,M.R., Saikrishna,L., Verma,H., Bhaskar,L.V.K.S. and
            Hussain,S.A.
  TITLE     Association Between MTHFD1 1958G > A Variant and non-Syndromic
            Cleft lip and Palate: An Updated Meta-Analysis
  JOURNAL   Cleft Palate Craniofac J 59 (11), 1422-1427 (2022)
   PUBMED   34904448
  REMARK    GeneRIF: Association Between MTHFD1 1958G > A Variant and
            non-Syndromic Cleft lip and Palate: An Updated Meta-Analysis.
REFERENCE   4  (bases 1 to 3154)
  AUTHORS   Chen,Q., Huang,P., Song,X.L., Liu,Y.P., Sun,M.T., Wang,T.T.,
            Zhang,S.M. and Qin,J.B.
  TITLE     [Association of maternal MTHFD1 and MTHFD2 gene polymorphisms with
            congenital heart disease in offspring]
  JOURNAL   Zhongguo Dang Dai Er Ke Za Zhi 24 (7), 797-805 (2022)
   PUBMED   35894196
  REMARK    GeneRIF: [Association of maternal MTHFD1 and MTHFD2 gene
            polymorphisms with congenital heart disease in offspring].', trans
            'MTHFD1MTHFD2.
REFERENCE   5  (bases 1 to 3154)
  AUTHORS   Song,X., Li,Q., Diao,J., Li,J., Li,Y., Zhang,S., Zhao,L., Chen,L.,
            Wei,J., Shu,J., Liu,Y., Sun,M., Huang,P., Wang,T. and Qin,J.
  TITLE     Association of MTHFD1 gene polymorphisms and maternal smoking with
            risk of congenital heart disease: a hospital-based case-control
            study
  JOURNAL   BMC Pregnancy Childbirth 22 (1), 88 (2022)
   PUBMED   35100977
  REMARK    GeneRIF: Association of MTHFD1 gene polymorphisms and maternal
            smoking with risk of congenital heart disease: a hospital-based
            case-control study.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 3154)
  AUTHORS   Hum,D.W. and MacKenzie,R.E.
  TITLE     Expression of active domains of a human folate-dependent
            trifunctional enzyme in Escherichia coli
  JOURNAL   Protein Eng 4 (4), 493-500 (1991)
   PUBMED   1881876
REFERENCE   7  (bases 1 to 3154)
  AUTHORS   Schild,D., Brake,A.J., Kiefer,M.C., Young,D. and Barr,P.J.
  TITLE     Cloning of three human multifunctional de novo purine biosynthetic
            genes by functional complementation of yeast mutations
  JOURNAL   Proc Natl Acad Sci U S A 87 (8), 2916-2920 (1990)
   PUBMED   2183217
REFERENCE   8  (bases 1 to 3154)
  AUTHORS   Peri,K.G., Belanger,C. and Mackenzie,R.E.
  TITLE     Nucleotide sequence of the human NAD-dependent methylene
            tetrahydrofolate dehydrogenase-cyclohydrolase
  JOURNAL   Nucleic Acids Res 17 (21), 8853 (1989)
   PUBMED   2587219
REFERENCE   9  (bases 1 to 3154)
  AUTHORS   Rozen,R., Barton,D., Du,J., Hum,D.W., MacKenzie,R.E. and Francke,U.
  TITLE     Chromosomal localization of the gene for the human trifunctional
            enzyme, methylenetetrahydrofolate
            dehydrogenase-methenyltetrahydrofolate
            cyclohydrolase-formyltetrahydrofolate synthetase
  JOURNAL   Am J Hum Genet 44 (6), 781-786 (1989)
   PUBMED   2786332
REFERENCE   10 (bases 1 to 3154)
  AUTHORS   Hum,D.W., Bell,A.W., Rozen,R. and MacKenzie,R.E.
  TITLE     Primary structure of a human trifunctional enzyme. Isolation of a
            cDNA encoding methylenetetrahydrofolate
            dehydrogenase-methenyltetrahydrofolate
            cyclohydrolase-formyltetrahydrofolate synthetase
  JOURNAL   J Biol Chem 263 (31), 15946-15950 (1988)
   PUBMED   3053686
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BQ959308.1, J04031.1 and
            AL122035.6.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jul 5, 2018 this sequence version replaced NM_005956.3.
            
            Summary: This gene encodes a protein that possesses three distinct
            enzymatic activities, 5,10-methylenetetrahydrofolate dehydrogenase,
            5,10-methenyltetrahydrofolate cyclohydrolase and
            10-formyltetrahydrofolate synthetase. 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. [provided
            by RefSeq, Jul 2008].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1803613.225324.1,
                                           SRR1803615.99280.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000652337.1/ ENSP00000498336.1
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-22                BQ959308.1         125-146
            23-475              J04031.1           1-453
            476-476             AL122035.6         70973-70973         c
            477-3134            J04031.1           455-3112
            3135-3154           AL122035.6         26610-26629         c
FEATURES             Location/Qualifiers
     source          1..3154
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="14"
                     /map="14q23.3"
     gene            1..3154
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /note="methylenetetrahydrofolate dehydrogenase,
                     cyclohydrolase and formyltetrahydrofolate synthetase 1"
                     /db_xref="GeneID:4522"
                     /db_xref="HGNC:HGNC:7432"
                     /db_xref="MIM:172460"
     exon            1..116
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     CDS             76..2883
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /EC_number="1.5.1.5"
                     /EC_number="6.3.4.3"
                     /EC_number="3.5.4.9"
                     /note="isoform 1 is encoded by transcript variant 1;
                     5,10-methylenetetrahydrofolate dehydrogenase,
                     5,10-methylenetetrahydrofolate cyclohydrolase,
                     10-formyltetrahydrofolate synthetase; cytoplasmic
                     C-1-tetrahydrofolate synthase; C1-THF synthase;
                     C-1-tetrahydrofolate synthase, cytoplasmic; epididymis
                     secretory sperm binding protein; methylenetetrahydrofolate
                     dehydrogenase (NADP+ dependent) 1,
                     methenyltetrahydrofolate cyclohydrolase,
                     formyltetrahydrofolate synthetase"
                     /codon_start=1
                     /product="C-1-tetrahydrofolate synthase, cytoplasmic
                     isoform 1"
                     /protein_id="NP_005947.3"
                     /db_xref="CCDS:CCDS9763.1"
                     /db_xref="GeneID:4522"
                     /db_xref="HGNC:HGNC:7432"
                     /db_xref="MIM:172460"
                     /translation="MAPAEILNGKEISAQIRARLKNQVTQLKEQVPGFTPRLAILQVG
                     NRDDSNLYINVKLKAAEEIGIKATHIKLPRTTTESEVMKYITSLNEDSTVHGFLVQLP
                     LDSENSINTEEVINAIAPEKDVDGLTSINAGKLARGDLNDCFIPCTPKGCLELIKETG
                     VPIAGRHAVVVGRSKIVGAPMHDLLLWNNATVTTCHSKTAHLDEEVNKGDILVVATGQ
                     PEMVKGEWIKPGAIVIDCGINYVPDDKKPNGRKVVGDVAYDEAKERASFITPVPGGVG
                     PMTVAMLMQSTVESAKRFLEKFKPGKWMIQYNNLNLKTPVPSDIDISRSCKPKPIGKL
                     AREIGLLSEEVELYGETKAKVLLSALERLKHRPDGKYVVVTGITPTPLGEGKSTTTIG
                     LVQALGAHLYQNVFACVRQPSQGPTFGIKGGAAGGGYSQVIPMEEFNLHLTGDIHAIT
                     AANNLVAAAIDARIFHELTQTDKALFNRLVPSVNGVRRFSDIQIRRLKRLGIEKTDPT
                     TLTDEEINRFARLDIDPETITWQRVLDTNDRFLRKITIGQAPTEKGHTRTAQFDISVA
                     SEIMAVLALTTSLEDMRERLGKMVVASSKKGEPVSAEDLGVSGALTVLMKDAIKPNLM
                     QTLEGTPVFVHAGPFANIAHGNSSIIADRIALKLVGPEGFVVTEAGFGADIGMEKFFN
                     IKCRYSGLCPHVVVLVATVRALKMHGGGPTVTAGLPLPKAYIQENLELVEKGFSNLKK
                     QIENARMFGIPVVVAVNAFKTDTESELDLISRLSREHGAFDAVKCTHWAEGGKGALAL
                     AQAVQRAAQAPSSFQLLYDLKLPVEDKIRIIAQKIYGADDIELLPEAQHKAEVYTKQG
                     FGNLPICMAKTHLSLSHNPEQKGVPTGFILPIRDIRASVGAGFLYPLVGTMSTMPGLP
                     TRPCFYDIDLDPETEQVNGLF"
     exon            117..201
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            202..261
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            262..315
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            316..452
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            453..553
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            554..690
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            691..802
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            803..930
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            931..1028
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            1029..1202
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            1203..1339
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            1340..1386
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            1387..1494
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            1495..1569
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            1570..1672
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            1673..1749
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            1750..1890
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            1891..1959
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            1960..2071
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            2072..2211
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            2212..2253
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            2254..2354
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            2355..2532
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            2533..2640
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            2641..2793
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            2794..2887
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     exon            2888..3154
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3112..3117
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /note="hexamer: AATAAA"
     regulatory      3122..3127
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /note="hexamer: AACAAG"
     polyA_site      3134
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
                     /note="major polyA site"
     polyA_site      3154
                     /gene="MTHFD1"
                     /gene_synonym="CIMAH; MTHFC; MTHFD"
ORIGIN      
        1 gtcctgcttg gctgcggagg gagtggaacc tcgatattgg tggtgtccat cgtgggcagc
       61 ggactaataa aggccatggc gccagcagaa atcctgaacg ggaaggagat ctccgcgcaa
      121 ataagggcga gactgaaaaa tcaagtcact cagttgaagg agcaagtacc tggtttcaca
      181 ccacgcctgg caatattaca ggttggcaac agagatgatt ccaatcttta tataaatgtg
      241 aagctgaagg ctgctgaaga gattgggatc aaagccactc acattaagtt accaagaaca
      301 accacagaat ctgaggtgat gaagtacatt acatctttga atgaagactc tactgtacat
      361 gggttcttag tgcagctacc tttagattca gagaattcca ttaacactga agaagtgatc
      421 aatgctattg cacccgagaa ggatgtggat ggattgacta gcatcaatgc tgggaaactt
      481 gctagaggtg acctcaatga ctgtttcatt ccttgtacgc ctaagggatg cttggaactc
      541 atcaaagaga caggggtgcc gattgccgga aggcatgctg tggtggttgg gcgcagtaaa
      601 atagttgggg ccccgatgca tgacttgctt ctgtggaaca atgccacagt gaccacctgc
      661 cactccaaga ctgcccatct ggatgaggag gtaaataaag gtgacatcct ggtggttgca
      721 actggtcagc ctgaaatggt taaaggggag tggatcaaac ctggggcaat agtcatcgac
      781 tgtggaatca attatgtccc agatgataaa aaaccaaatg ggagaaaagt tgtgggtgat
      841 gtggcatacg acgaggccaa agagagggcg agcttcatca ctcctgttcc tggcggcgta
      901 gggcccatga cagttgcaat gctcatgcag agcacagtag agagtgccaa gcgtttcctg
      961 gagaaattta agccaggaaa gtggatgatt cagtataaca accttaacct caagacacct
     1021 gttccaagtg acattgatat atcacgatct tgtaaaccga agcccattgg taagctggct
     1081 cgagaaattg gtctgctgtc tgaagaggta gaattatatg gtgaaacaaa ggccaaagtt
     1141 ctgctgtcag cactagaacg cctgaagcac cggcctgatg ggaaatacgt ggtggtgact
     1201 ggaataactc caacacccct gggagaaggg aaaagcacaa ctacaatcgg gctagtgcaa
     1261 gcccttggtg cccatctcta ccagaatgtc tttgcgtgtg tgcgacagcc ttctcagggc
     1321 cccacctttg gaataaaagg tggcgctgca ggaggcggct actcccaggt cattcctatg
     1381 gaagagttta atctccacct cacaggtgac atccatgcca tcactgcagc taataacctc
     1441 gttgctgcgg ccattgatgc tcggatattt catgaactga cccagacaga caaggctctc
     1501 tttaatcgtt tggtgccatc agtaaatgga gtgagaaggt tctctgacat ccaaatccga
     1561 aggttaaaga gactaggcat tgaaaagact gaccctacca cactgacaga tgaagagata
     1621 aacagatttg caagattgga cattgatcca gaaaccataa cttggcaaag agtgttggat
     1681 accaatgata gattcctgag gaagatcacg attggacagg ctccaacgga gaagggtcac
     1741 acacggacgg cccagtttga tatctctgtg gccagtgaaa ttatggctgt cctggctctc
     1801 accacttctc tagaagacat gagagagaga ctgggcaaaa tggtggtggc atccagtaag
     1861 aaaggagagc ccgtcagtgc cgaagatctg ggggtgagtg gtgcactgac agtgcttatg
     1921 aaggacgcaa tcaagcccaa tctcatgcag acactggagg gcactccagt gtttgtccat
     1981 gctggcccgt ttgccaacat cgcacatggc aattcctcca tcattgcaga ccggatcgca
     2041 ctcaagcttg ttggcccaga agggtttgta gtgacggaag caggatttgg agcagacatt
     2101 ggaatggaaa agttttttaa catcaaatgc cggtattccg gcctctgccc ccacgtggtg
     2161 gtgcttgttg ccactgtcag ggctctcaag atgcacgggg gcggccccac ggtcactgct
     2221 ggactgcctc ttcccaaggc ttacatacag gagaacctgg agctggttga aaaaggcttc
     2281 agtaacttga agaaacaaat tgaaaatgcc agaatgtttg gaattccagt agtagtggcc
     2341 gtgaatgcat tcaagacgga tacagagtct gagctggacc tcatcagccg cctttccaga
     2401 gaacatgggg cttttgatgc cgtgaagtgc actcactggg cagaaggggg caagggtgcc
     2461 ttagccctgg ctcaggccgt ccagagagca gcacaagcac ccagcagctt ccagctcctt
     2521 tatgacctca agctcccagt tgaggataaa atcaggatca ttgcacagaa gatctatgga
     2581 gcagatgaca ttgaattact tcccgaagct caacacaaag ctgaagtcta cacgaagcag
     2641 ggctttggga atctccccat ctgcatggct aaaacacact tgtctttgtc tcacaaccca
     2701 gagcaaaaag gtgtccctac aggcttcatt ctgcccattc gcgacatccg cgccagcgtt
     2761 ggggctggtt ttctgtaccc cttagtagga acgatgagca caatgcctgg actccccacc
     2821 cggccctgtt tttatgatat tgatttggac cctgaaacag aacaggtgaa tggattattc
     2881 taaacagatc accatccatc ttcaagaagc tactttgaaa gtctggccag tgtctattca
     2941 ggcccactgg gagttaggaa gtataagtaa gccaagagaa gtcagcccct gcccagaaga
     3001 tctgaaacta atagtaggag tttccccaga agtcattttc agccttaatt ctcatcatgt
     3061 ataaattaac ataaatcatg catgtctgtt tactttagtg acgttccaca gaataaaagg
     3121 aaacaagttt gccatcttgg tgttgcaata tgaa
//
