LOCUS       NM_000143               1791 bp    mRNA    linear   PRI 20-FEB-2025
DEFINITION  Homo sapiens fumarate hydratase (FH), mRNA; nuclear gene for
            mitochondrial product.
ACCESSION   NM_000143
VERSION     NM_000143.4
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 1791)
  AUTHORS   Khoroshkin,M., Buyan,A., Dodel,M., Navickas,A., Yu,J., Trejo,F.,
            Doty,A., Baratam,R., Zhou,S., Lee,S.B., Joshi,T., Garcia,K.,
            Choi,B., Miglani,S., Subramanyam,V., Modi,H., Carpenter,C.,
            Markett,D., Corces,M.R., Mardakheh,F.K., Kulakovskiy,I.V. and
            Goodarzi,H.
  TITLE     Systematic identification of post-transcriptional regulatory
            modules
  JOURNAL   Nat Commun 15 (1), 7872 (2024)
   PUBMED   39251607
  REMARK    Erratum:[Nat Commun. 2024 Oct 28;15(1):9277. doi:
            10.1038/s41467-024-52903-4.. PMID: 39468017]
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 1791)
  AUTHORS   Jovanovic,L., Milenkovic,S., Andric,L., Stefanovic,R.,
            Milosevic,B., Micic,J., Pilic,I., Beleslin,A., Mihaljevic,O. and
            Dokic,M.
  TITLE     Uterine Leiomyomas with Specific Histology Features of Two Fumarate
            Hydratase/Succinate Dehydrogenase-Deficient Tumors: A Double Case
            Report
  JOURNAL   Medicina (Kaunas) 60 (5), 825 (2024)
   PUBMED   38793008
  REMARK    GeneRIF: Uterine Leiomyomas with Specific Histology Features of Two
            Fumarate Hydratase/Succinate Dehydrogenase-Deficient Tumors: A
            Double Case Report.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 1791)
  AUTHORS   Fontanges,Q., Dubos,P., Lesluyes,T., Laizet,Y., Velasco,V.,
            Melendez,B., D'Haene,N., Oliva,E., Young,R.H., Mayeur,L.,
            Rebier,F., Alame,M., Larmonier,C., Devouassoux-Shisheboran,M.,
            Arnould,L., Soubeyran,I., Chakiba,C., Floquet,A., Babin,G.,
            Guyon,F., Mery,E., Le Guellec,S., Noel,J.C., Croce,S. and Chibon,F.
  TITLE     Genomic profile analysis of leiomyomas with bizarre nuclei and
            fumarate hydratase deficient leiomyomas: Strengths, weaknesses, and
            limitations of array-CGH interpretation
  JOURNAL   Genes Chromosomes Cancer 63 (3), e23229 (2024)
   PUBMED   38481055
  REMARK    GeneRIF: Genomic profile analysis of leiomyomas with bizarre nuclei
            and fumarate hydratase deficient leiomyomas: Strengths, weaknesses,
            and limitations of array-CGH interpretation.
REFERENCE   4  (bases 1 to 1791)
  AUTHORS   Tomlinson,I.P., Alam,N.A., Rowan,A.J., Barclay,E., Jaeger,E.E.,
            Kelsell,D., Leigh,I., Gorman,P., Lamlum,H., Rahman,S.,
            Roylance,R.R., Olpin,S., Bevan,S., Barker,K., Hearle,N.,
            Houlston,R.S., Kiuru,M., Lehtonen,R., Karhu,A., Vilkki,S.,
            Laiho,P., Eklund,C., Vierimaa,O., Aittomaki,K., Hietala,M.,
            Sistonen,P., Paetau,A., Salovaara,R., Herva,R., Launonen,V. and
            Aaltonen,L.A.
  CONSRTM   Multiple Leiomyoma Consortium
  TITLE     Germline mutations in FH predispose to dominantly inherited uterine
            fibroids, skin leiomyomata and papillary renal cell cancer
  JOURNAL   Nat Genet 30 (4), 406-410 (2002)
   PUBMED   11865300
  REMARK    GeneRIF: Germline mutations in FH predispose to dominantly
            inherited uterine fibroids, skin leiomyomata and papillary renal
            cell cancer
REFERENCE   5  (bases 1 to 1791)
  AUTHORS   Bourgeron,T., Chretien,D., Poggi-Bach,J., Doonan,S., Rabier,D.,
            Letouze,P., Munnich,A., Rotig,A., Landrieu,P. and Rustin,P.
  TITLE     Mutation of the fumarase gene in two siblings with progressive
            encephalopathy and fumarase deficiency
  JOURNAL   J Clin Invest 93 (6), 2514-2518 (1994)
   PUBMED   8200987
REFERENCE   6  (bases 1 to 1791)
  AUTHORS   Coman,D., Kranc,K.R. and Christodoulou,J.
  TITLE     Fumarate Hydratase Deficiency
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301679
REFERENCE   7  (bases 1 to 1791)
  AUTHORS   Kamihara,J., Schultz,K.A. and Rana,H.Q.
  TITLE     FH Tumor Predisposition Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301430
REFERENCE   8  (bases 1 to 1791)
  AUTHORS   Beeckmans,S., Van Driessche,E. and Kanarek,L.
  TITLE     The visualization by affinity electrophoresis of a specific
            association between the consecutive citric acid cycle enzymes
            fumarase and malate dehydrogenase
  JOURNAL   Eur J Biochem 183 (2), 449-454 (1989)
   PUBMED   2759092
REFERENCE   9  (bases 1 to 1791)
  AUTHORS   Edwards,Y.H. and Hopkinson,D.A.
  TITLE     The genetic determination of fumarase isozymes in human tissues
  JOURNAL   Ann Hum Genet 42 (3), 303-313 (1979)
   PUBMED   434773
REFERENCE   10 (bases 1 to 1791)
  AUTHORS   Craig,I., Tolley,E. and Bobrow,M.
  TITLE     Mitochondrial and cytoplasmic forms of fumarate hydratase assigned
            to chromosome 1
  JOURNAL   Cytogenet Cell Genet 16 (1-5), 118-121 (1976)
   PUBMED   975868
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA129148.1, BC003108.1 and
            AA669797.1.
            
            On Nov 30, 2019 this sequence version replaced NM_000143.3.
            
            Summary: The protein encoded by this gene is an enzymatic component
            of the tricarboxylic acid (TCA) cycle, or Krebs cycle, and
            catalyzes the formation of L-malate from fumarate. It exists in
            both a cytosolic form and an N-terminal extended form, differing
            only in the translation start site used. The N-terminal extended
            form is targeted to the mitochondrion, where the removal of the
            extension generates the same form as in the cytoplasm. It is
            similar to some thermostable class II fumarases and functions as a
            homotetramer. Mutations in this gene can cause fumarase deficiency
            and lead to progressive encephalopathy. [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 :: U59309.1, BC003108.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000366560.4/
                                                  ENSP00000355518.4
            RefSeq Select criteria             :: based on single
                                                  protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-8                 DA129148.1         31-38
            9-1614              BC003108.1         1-1606
            1615-1791           AA669797.1         4-180               c
FEATURES             Location/Qualifiers
     source          1..1791
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q43"
     gene            1..1791
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /note="fumarate hydratase"
                     /db_xref="GeneID:2271"
                     /db_xref="HGNC:HGNC:3700"
                     /db_xref="MIM:136850"
     exon            1..165
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /inference="alignment:Splign:2.1.0"
     CDS             34..1566
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /EC_number="4.2.1.2"
                     /note="fumarase; epididymis secretory sperm binding
                     protein"
                     /codon_start=1
                     /product="fumarate hydratase, mitochondrial"
                     /protein_id="NP_000134.2"
                     /db_xref="CCDS:CCDS1617.1"
                     /db_xref="GeneID:2271"
                     /db_xref="HGNC:HGNC:3700"
                     /db_xref="MIM:136850"
                     /translation="MYRALRLLARSRPLVRAPAAALASAPGLGGAAVPSFWPPNAARM
                     ASQNSFRIEYDTFGELKVPNDKYYGAQTVRSTMNFKIGGVTERMPTPVIKAFGILKRA
                     AAEVNQDYGLDPKIANAIMKAADEVAEGKLNDHFPLVVWQTGSGTQTNMNVNEVISNR
                     AIEMLGGELGSKIPVHPNDHVNKSQSSNDTFPTAMHIAAAIEVHEVLLPGLQKLHDAL
                     DAKSKEFAQIIKIGRTHTQDAVPLTLGQEFSGYVQQVKYAMTRIKAAMPRIYELAAGG
                     TAVGTGLNTRIGFAEKVAAKVAALTGLPFVTAPNKFEALAAHDALVELSGAMNTTACS
                     LMKIANDIRFLGSGPRSGLGELILPENEPGSSIMPGKVNPTQCEAMTMVAAQVMGNHV
                     AVTVGGSNGHFELNVFKPMMIKNVLHSARLLGDASVSFTENCVVGIQANTERINKLMN
                     ESLMLVTALNPHIGYDKAAKIAKTAHKNGSTLKETAIELGYLTAEQFDEWVKPKDMLG
                     PK"
     exon            166..300
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /inference="alignment:Splign:2.1.0"
     exon            301..411
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /inference="alignment:Splign:2.1.0"
     exon            412..588
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /inference="alignment:Splign:2.1.0"
     exon            589..771
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /inference="alignment:Splign:2.1.0"
     exon            772..937
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /inference="alignment:Splign:2.1.0"
     exon            938..1141
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /inference="alignment:Splign:2.1.0"
     exon            1142..1269
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /inference="alignment:Splign:2.1.0"
     exon            1270..1423
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /inference="alignment:Splign:2.1.0"
     exon            1424..1791
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1598..1603
                     /regulatory_class="polyA_signal_sequence"
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /note="hexamer: TATAAA"
     polyA_site      1614
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /note="major polyA site"
     regulatory      1755..1760
                     /regulatory_class="polyA_signal_sequence"
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /note="hexamer: AATACA"
     regulatory      1768..1773
                     /regulatory_class="polyA_signal_sequence"
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
                     /note="hexamer: AATAAA"
     polyA_site      1775
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
     polyA_site      1791
                     /gene="FH"
                     /gene_synonym="FMRD; HLRCC; HsFH; LRCC; MCL; MCUL1"
ORIGIN      
        1 gcccagaaat tctacccaag ctccctcagc accatgtacc gagcacttcg gctcctcgcg
       61 cgctcgcgtc ccctcgtgcg ggctccagcc gcagccttag cttcggctcc cggcttgggt
      121 ggcgcggccg tgccctcgtt ttggcctccg aacgcggctc gaatggcaag ccaaaattcc
      181 ttccggatag aatatgatac ctttggtgaa ctaaaggtgc caaatgataa gtattatggc
      241 gcccagaccg tgagatctac gatgaacttt aagattggag gtgtgacaga acgcatgcca
      301 accccagtta ttaaagcttt tggcatcttg aagcgagcgg ccgctgaagt aaaccaggat
      361 tatggtcttg atccaaagat tgctaatgca ataatgaagg cagcagatga ggtagctgaa
      421 ggtaaattaa atgatcattt tcctctcgtg gtatggcaga ctggatcagg aactcagaca
      481 aatatgaatg taaatgaagt cattagcaat agagcaattg aaatgttagg aggtgaactt
      541 ggcagcaaga tacctgtgca tcccaacgat catgttaata aaagccagag ctcaaatgat
      601 acttttccca cagcaatgca cattgctgct gcaatagaag ttcatgaagt actgttacca
      661 ggactacaga agttacatga tgctcttgat gcaaaatcca aagagtttgc acagatcatc
      721 aagattggac gtactcatac tcaggatgct gttccactta ctcttgggca ggaatttagt
      781 ggttatgttc aacaagtaaa atatgcaatg acaagaataa aagctgccat gccaagaatc
      841 tatgagctcg cagctggagg cactgctgtt ggtacaggtt taaatactag aattggcttt
      901 gcagaaaagg ttgctgcaaa agtggctgca cttacaggct tgccttttgt cactgctccg
      961 aataaatttg aagctctggc tgctcatgac gctctggttg agctcagtgg agccatgaac
     1021 actactgcct gcagtctgat gaagatagca aatgatattc gatttttggg ttctggtcct
     1081 cggtcaggtc tgggagaatt gatcttgcct gaaaatgaac caggaagcag tatcatgcca
     1141 ggcaaggtga accctactca gtgtgaagca atgaccatgg ttgcagccca agtcatgggg
     1201 aaccatgttg ctgtcactgt cggaggcagc aatggacatt ttgagttgaa tgttttcaag
     1261 ccaatgatga ttaaaaatgt gttacactca gccaggctgc tgggggatgc ttcagtttcc
     1321 tttacagaaa actgcgtggt gggaatccag gccaatacag aaaggatcaa caagctgatg
     1381 aatgagtctc taatgttggt gacagctctc aatcctcata tagggtatga caaggcagca
     1441 aagattgcta agacagcaca caaaaatgga tcaaccttaa aggaaactgc tatcgaactt
     1501 ggctatctca cagcagagca gtttgacgaa tgggtaaaac ctaaggacat gctgggtcca
     1561 aagtgattta cataaattta taatgaaaat aaacatgtat aaaatttaaa aaaacagact
     1621 cccatttctt aaaaacggat aagtttgaaa ggaaactgct attgaactta agcatctcta
     1681 gcagagcaat ttgatcagta tataaaaccc taggatgtgc taggtctaag atggattaaa
     1741 caagtataaa ataaaataca tttataaaat aaaaaggaaa acagacttaa a
//
