LOCUS       NM_015702               1392 bp    mRNA    linear   PRI 09-OCT-2024
DEFINITION  Homo sapiens metabolism of cobalamin associated D (MMADHC), mRNA.
ACCESSION   NM_015702
VERSION     NM_015702.3
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 1392)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   2  (bases 1 to 1392)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   3  (bases 1 to 1392)
  AUTHORS   Cancho Garcia,E., Gean,E., Oliver Tormo,B., Torrents,A. and Esteban
            Duran,E.
  TITLE     Mutation of the MMADHC gene in adult-onset cobalamin D deficiency:
            A report of 2 potentially treatable cases
  JOURNAL   Neurologia (Engl Ed) 34 (6), 419-421 (2019)
   PUBMED   28939051
  REMARK    GeneRIF: The study of genes involved in methylmalonic acidaemia
            with homocystinuria detected a homozygous mutation (c.748C>T) in
            the MMADHC gene (found in the DNA of both sisters), which generates
            a stop codon that results in a truncated protein, provoking the
            disease.
REFERENCE   4  (bases 1 to 1392)
  AUTHORS   Bassila,C., Ghemrawi,R., Flayac,J., Froese,D.S., Baumgartner,M.R.,
            Gueant,J.L. and Coelho,D.
  TITLE     Methionine synthase and methionine synthase reductase interact with
            MMACHC and with MMADHC
  JOURNAL   Biochim Biophys Acta Mol Basis Dis 1863 (1), 103-112 (2017)
   PUBMED   27771510
  REMARK    GeneRIF: These data show that the processing of cobalamin in
            cytoplasm occurs in a multiprotein complex composed of at least
            methionine synthase, methionine synthase reductase, MMACHC and
            MMADHC.
REFERENCE   5  (bases 1 to 1392)
  AUTHORS   Bailey,S.D., Xie,C., Do,R., Montpetit,A., Diaz,R., Mohan,V.,
            Keavney,B., Yusuf,S., Gerstein,H.C., Engert,J.C. and Anand,S.
  CONSRTM   DREAM investigators
  TITLE     Variation at the NFATC2 locus increases the risk of
            thiazolidinedione-induced edema in the Diabetes REduction
            Assessment with ramipril and rosiglitazone Medication (DREAM) study
  JOURNAL   Diabetes Care 33 (10), 2250-2253 (2010)
   PUBMED   20628086
  REMARK    GeneRIF: Observational study of gene-disease association,
            gene-environment interaction, and pharmacogenomic / toxicogenomic.
            (HuGE Navigator)
REFERENCE   6  (bases 1 to 1392)
  AUTHORS   Talmud,P.J., Drenos,F., Shah,S., Shah,T., Palmen,J., Verzilli,C.,
            Gaunt,T.R., Pallas,J., Lovering,R., Li,K., Casas,J.P., Sofat,R.,
            Kumari,M., Rodriguez,S., Johnson,T., Newhouse,S.J., Dominiczak,A.,
            Samani,N.J., Caulfield,M., Sever,P., Stanton,A., Shields,D.C.,
            Padmanabhan,S., Melander,O., Hastie,C., Delles,C., Ebrahim,S.,
            Marmot,M.G., Smith,G.D., Lawlor,D.A., Munroe,P.B., Day,I.N.,
            Kivimaki,M., Whittaker,J., Humphries,S.E. and Hingorani,A.D.
  CONSRTM   ASCOT investigators; NORDIL investigators; BRIGHT Consortium
  TITLE     Gene-centric association signals for lipids and apolipoproteins
            identified via the HumanCVD BeadChip
  JOURNAL   Am J Hum Genet 85 (5), 628-642 (2009)
   PUBMED   19913121
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   7  (bases 1 to 1392)
  AUTHORS   Coelho,D., Suormala,T., Stucki,M., Lerner-Ellis,J.P.,
            Rosenblatt,D.S., Newbold,R.F., Baumgartner,M.R. and Fowler,B.
  TITLE     Gene identification for the cblD defect of vitamin B12 metabolism
  JOURNAL   N Engl J Med 358 (14), 1454-1464 (2008)
   PUBMED   18385497
  REMARK    GeneRIF: mutations in a gene designated MMADHC (currently named
            C2orf25) are responsible for the cblD defect in vitamin B12
            metabolism; various mutations are associated with each of the three
            biochemical phenotypes of the disorder
REFERENCE   8  (bases 1 to 1392)
  AUTHORS   Sloan,J.L., Carrillo,N., Adams,D. and Venditti,C.P.
  TITLE     Disorders of Intracellular Cobalamin Metabolism
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301503
REFERENCE   9  (bases 1 to 1392)
  AUTHORS   Manoli,I., Sloan,J.L. and Venditti,C.P.
  TITLE     Isolated Methylmalonic Acidemia
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301409
REFERENCE   10 (bases 1 to 1392)
  AUTHORS   Klein,C., Lohmann,K., Marras,C. and Munchau,A.
  TITLE     Hereditary Dystonia Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301334
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BU570084.1, BC000932.2,
            BG610637.1 and BM456421.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_015702.2.
            
            Summary: This gene encodes a mitochondrial protein that is involved
            in an early step of vitamin B12 metabolism. Vitamin B12 (cobalamin)
            is essential for normal development and survival in humans.
            Mutations in this gene cause methylmalonic aciduria and
            homocystinuria type cblD (MMADHC), a disorder of cobalamin
            metabolism that is characterized by decreased levels of the
            coenzymes adenosylcobalamin and methylcobalamin. Pseudogenes have
            been identified on chromosomes 11 and X.[provided by RefSeq, Nov
            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 :: SRR3476690.1084604.1,
                                           SRR3476690.442192.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: inferred from homology
            MANE Ensembl match                 :: ENST00000303319.10/
                                                  ENSP00000301920.5
            RefSeq Select criteria             :: based on single
                                                  protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-10                BU570084.1         45-54
            11-616              BC000932.2         1-606
            617-632             BG610637.1         608-623
            633-1143            BC000932.2         623-1133
            1144-1392           BM456421.1         109-357
FEATURES             Location/Qualifiers
     source          1..1392
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q23.2"
     gene            1..1392
                     /gene="MMADHC"
                     /gene_synonym="C2orf25; cblD; CL25022; HMAD; MACD; MAHCD"
                     /note="metabolism of cobalamin associated D"
                     /db_xref="GeneID:27249"
                     /db_xref="HGNC:HGNC:25221"
                     /db_xref="MIM:611935"
     exon            1..112
                     /gene="MMADHC"
                     /gene_synonym="C2orf25; cblD; CL25022; HMAD; MACD; MAHCD"
                     /inference="alignment:Splign:2.1.0"
     exon            113..173
                     /gene="MMADHC"
                     /gene_synonym="C2orf25; cblD; CL25022; HMAD; MACD; MAHCD"
                     /inference="alignment:Splign:2.1.0"
     CDS             165..1055
                     /gene="MMADHC"
                     /gene_synonym="C2orf25; cblD; CL25022; HMAD; MACD; MAHCD"
                     /note="protein C2orf25, mitochondrial; methylmalonic
                     aciduria and homocystinuria type D protein, mitochondrial;
                     methylmalonic aciduria (cobalamin deficiency) cblD type,
                     with homocystinuria"
                     /codon_start=1
                     /product="cobalamin trafficking protein CblD"
                     /protein_id="NP_056517.1"
                     /db_xref="CCDS:CCDS2189.1"
                     /db_xref="GeneID:27249"
                     /db_xref="HGNC:HGNC:25221"
                     /db_xref="MIM:611935"
                     /translation="MANVLCNRARLVSYLPGFCSLVKRVVNPKAFSTAGSSGSDESHV
                     AAAPPDICSRTVWPDETMGPFGPQDQRFQLPGNIGFDCHLNGTASQKKSLVHKTLPDV
                     LAEPLSSERHEFVMAQYVNEFQGNDAPVEQEINSAETYFESARVECAIQTCPELLRKD
                     FESLFPEVANGKLMILTVTQKTKNDMTVWSEEVEIEREVLLEKFINGAKEICYALRAE
                     GYWADFIDPSSGLAFFGPYTNNTLFETDERYRHLGFSVDDLGCCKVIRHSLWGTHVVV
                     GSIFTNATPDSHIMKKLSGN"
     exon            174..318
                     /gene="MMADHC"
                     /gene_synonym="C2orf25; cblD; CL25022; HMAD; MACD; MAHCD"
                     /inference="alignment:Splign:2.1.0"
     exon            319..536
                     /gene="MMADHC"
                     /gene_synonym="C2orf25; cblD; CL25022; HMAD; MACD; MAHCD"
                     /inference="alignment:Splign:2.1.0"
     exon            537..642
                     /gene="MMADHC"
                     /gene_synonym="C2orf25; cblD; CL25022; HMAD; MACD; MAHCD"
                     /inference="alignment:Splign:2.1.0"
     exon            643..773
                     /gene="MMADHC"
                     /gene_synonym="C2orf25; cblD; CL25022; HMAD; MACD; MAHCD"
                     /inference="alignment:Splign:2.1.0"
     exon            774..860
                     /gene="MMADHC"
                     /gene_synonym="C2orf25; cblD; CL25022; HMAD; MACD; MAHCD"
                     /inference="alignment:Splign:2.1.0"
     exon            861..1392
                     /gene="MMADHC"
                     /gene_synonym="C2orf25; cblD; CL25022; HMAD; MACD; MAHCD"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1369..1374
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MMADHC"
                     /gene_synonym="C2orf25; cblD; CL25022; HMAD; MACD; MAHCD"
                     /note="hexamer: AATAAA"
     polyA_site      1392
                     /gene="MMADHC"
                     /gene_synonym="C2orf25; cblD; CL25022; HMAD; MACD; MAHCD"
                     /note="major polyA site"
ORIGIN      
        1 cctttgcctg ctcaccgcca gcgtaggtgc taccaccgct gccgtcgccg ccgccatttt
       61 gatggcagga agagtccggt tctgggacag ctggagacag tggtggtgac tgaaataact
      121 ttaccaaagg aaagctattt tgcgaactat cttctccagc ggagatggcc aatgtgcttt
      181 gtaacagagc cagactggtt tcctatctcc caggattttg ctctttagtt aaaagggttg
      241 tcaatcccaa agccttttcg actgcaggat catcaggttc ggatgagtct catgtggctg
      301 ctgcacctcc agatatatgc tctcgaacag tgtggcctga tgaaactatg ggaccctttg
      361 gacctcaaga tcagaggttc cagcttcctg ggaacatagg ttttgattgt cacctcaatg
      421 ggactgcttc acagaagaaa agcctggttc ataaaacttt gcctgatgtt ctagcagaac
      481 ctttatcaag tgaaagacat gagtttgtga tggcacaata tgtgaatgaa tttcagggta
      541 atgatgcacc tgttgaacaa gaaattaaca gtgcagaaac ttactttgaa agtgccagag
      601 tagagtgtgc aatacagaca tgtccagaat tgctgcgaaa agattttgaa tcactgtttc
      661 cagaagtagc taatggcaaa ctaatgattc tgactgtaac acaaaaaact aagaatgata
      721 tgactgtttg gagtgaagaa gtagaaattg aaagagaagt gctcttagaa aagttcatca
      781 atggtgctaa ggaaatttgc tatgctcttc gagctgaggg ttattgggct gactttattg
      841 acccatcatc tggtttggca ttttttggac catatacaaa caacactctt tttgaaactg
      901 atgaacgcta ccgacattta ggattctctg ttgatgacct tggatgctgt aaagtgattc
      961 gtcatagtct ctggggtacc catgtagttg tagggagtat cttcactaat gcaacaccag
     1021 acagccatat tatgaagaaa ttaagtggaa attagcagaa atatccattc atttgctgta
     1081 ctatttgtat gtaatatttg ggttgatcta taaacactgt cagactaaag tttttaaaat
     1141 atatttattt ctaagtattt atttcagcat ttatgaattt acaacattgg caagtgattt
     1201 gggattttaa aattgcaaat gttcatttat tcatatcatt gaatacacgt tgaacacatc
     1261 cacattgtat aggatgtggt aattagcttg taaccagggt atgatctgct attgttattt
     1321 ctcctcttta ttggaaaaag gcctcagttt taattatttt cttcccaaaa taaatcacac
     1381 atttggttac aa
//
