LOCUS       NM_015506               5049 bp    mRNA    linear   PRI 08-OCT-2024
DEFINITION  Homo sapiens metabolism of cobalamin associated C (MMACHC),
            transcript variant 1, mRNA.
ACCESSION   NM_015506 XM_032397
VERSION     NM_015506.3
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 5049)
  AUTHORS   Demaret,T., Bedard,K., Soucy,J.F., Watkins,D., Allard,P.,
            Levtova,A., O'Brien,A., Brunel-Guitton,C., Rosenblatt,D.S. and
            Mitchell,G.A.
  TITLE     The MMACHC variant c.158T>C: Mild clinical and biochemical
            phenotypes and marked hydroxocobalamin response in cblC patients
  JOURNAL   Mol Genet Metab 142 (1), 108345 (2024)
   PUBMED   38387306
  REMARK    GeneRIF: The MMACHC variant c.158T>C: Mild clinical and biochemical
            phenotypes and marked hydroxocobalamin response in cblC patients.
REFERENCE   2  (bases 1 to 5049)
  AUTHORS   Yuan,Y., Ma,Y., Wu,Q., Huo,L., Liu,C.F. and Liu,X.
  TITLE     Clinical and electroencephalogram characteristics of methylmalonic
            acidemia with MMACHC and MUT gene mutations
  JOURNAL   BMC Pediatr 24 (1), 119 (2024)
   PUBMED   38355526
  REMARK    GeneRIF: Clinical and electroencephalogram characteristics of
            methylmalonic acidemia with MMACHC and MUT gene mutations.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 5049)
  AUTHORS   Chen,C., Zhang,Y., Ge,L., Liu,L., Zhang,X., Mei,S. and Luo,S.
  TITLE     [Analysis of clinical phenotypes and MMACHC gene variants in 65
            children with Methylmalonic acidemia and homocysteinemia]
  JOURNAL   Zhonghua Yi Xue Yi Chuan Xue Za Zhi 40 (9), 1086-1092 (2023)
   PUBMED   37643953
  REMARK    GeneRIF: [Analysis of clinical phenotypes and MMACHC gene variants
            in 65 children with Methylmalonic acidemia and homocysteinemia].
REFERENCE   4  (bases 1 to 5049)
  AUTHORS   He,R., Mo,R., Zhang,Y., Shen,M., Kang,L., Chen,Z., Liu,Y., Song,J.,
            Zhang,H., Yao,H., Liu,Y., Dong,H., Jin,Y., Li,M., Qin,J., Zheng,H.,
            Chen,Y., Wei,H., Li,D., Li,X., Zheng,R., Zhang,H., Huang,M.,
            Zhang,C., Jiang,Y., Liang,D., Tian,Y. and Yang,Y.
  TITLE     [Factors affecting phenotypes in the patients with MMACHC gene
            c.609G>A homozygous variant cblC type methylmalonic acidemia
            combined with homocysteinuria]
  JOURNAL   Zhonghua Yi Xue Yi Chuan Xue Za Zhi 39 (6), 565-570 (2022)
   PUBMED   35773756
  REMARK    GeneRIF: [Factors affecting phenotypes in the patients with MMACHC
            gene c.609G>A homozygous variant cblC type methylmalonic acidemia
            combined with homocysteinuria].
REFERENCE   5  (bases 1 to 5049)
  AUTHORS   Passantino,R., Mangione,M.R., Ortore,M.G., Costa,M.A.,
            Provenzano,A., Amenitsch,H., Sabbatella,R., Alfano,C., Martorana,V.
            and Vilasi,S.
  TITLE     Investigation on a MMACHC mutant from cblC disease: The c.394C>T
            variant
  JOURNAL   Biochim Biophys Acta Proteins Proteom 1870 (6), 140793 (2022)
   PUBMED   35618206
  REMARK    GeneRIF: Investigation on a MMACHC mutant from cblC disease: The
            c.394C>T variant.
REFERENCE   6  (bases 1 to 5049)
  AUTHORS   Thauvin-Robinet,C., Roze,E., Couvreur,G., Horellou,M.H., Sedel,F.,
            Grabli,D., Bruneteau,G., Tonneti,C., Masurel-Paulet,A.,
            Perennou,D., Moreau,T., Giroud,M., de Baulny,H.O., Giraudier,S. and
            Faivre,L.
  TITLE     The adolescent and adult form of cobalamin C disease: clinical and
            molecular spectrum
  JOURNAL   J Neurol Neurosurg Psychiatry 79 (6), 725-728 (2008)
   PUBMED   18245139
  REMARK    GeneRIF: Most patients (eight of nine patients investigated) were
            compound heterozygotes for the 271dupA mutation and a missense
            mutation.
REFERENCE   7  (bases 1 to 5049)
  AUTHORS   Nogueira,C., Aiello,C., Cerone,R., Martins,E., Caruso,U.,
            Moroni,I., Rizzo,C., Diogo,L., Leao,E., Kok,F., Deodato,F.,
            Schiaffino,M.C., Boenzi,S., Danhaive,O., Barbot,C., Sequeira,S.,
            Locatelli,M., Santorelli,F.M., Uziel,G., Vilarinho,L. and
            Dionisi-Vici,C.
  TITLE     Spectrum of MMACHC mutations in Italian and Portuguese patients
            with combined methylmalonic aciduria and homocystinuria, cblC type
  JOURNAL   Mol Genet Metab 93 (4), 475-480 (2008)
   PUBMED   18164228
  REMARK    GeneRIF: c.271dupA (accounting for 55% of the MMACH alleles in our
            cohort) followed by c.394C>T (16%) and c.331C>T (9%) were the most
            frequent mutations.
REFERENCE   8  (bases 1 to 5049)
  AUTHORS   Ben-Omran,T.I., Wong,H., Blaser,S. and Feigenbaum,A.
  TITLE     Late-onset cobalamin-C disorder: a challenging diagnosis
  JOURNAL   Am J Med Genet A 143A (9), 979-984 (2007)
   PUBMED   17431913
  REMARK    GeneRIF: Mutation analysis of the MMACHC gene showed that both
            patients were homozygous for 394C --> T which suggests a founder
            effect in Late onset cobalamin C disorder.
REFERENCE   9  (bases 1 to 5049)
  AUTHORS   Lerner-Ellis,J.P., Tirone,J.C., Pawelek,P.D., Dore,C.,
            Atkinson,J.L., Watkins,D., Morel,C.F., Fujiwara,T.M., Moras,E.,
            Hosack,A.R., Dunbar,G.V., Antonicka,H., Forgetta,V., Dobson,C.M.,
            Leclerc,D., Gravel,R.A., Shoubridge,E.A., Coulton,J.W., Lepage,P.,
            Rommens,J.M., Morgan,K. and Rosenblatt,D.S.
  TITLE     Identification of the gene responsible for methylmalonic aciduria
            and homocystinuria, cblC type
  JOURNAL   Nat Genet 38 (1), 93-100 (2006)
   PUBMED   16311595
  REMARK    GeneRIF: One mutation, 271dupA, in MMACHC accounted for 40% of all
            disease alleles.
            Erratum:[Nat Genet. 2006 Aug;38(8):957]
REFERENCE   10 (bases 1 to 5049)
  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
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK098537.1, BU839693.1,
            BM980565.1, AL451136.11 and BU632364.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 24, 2018 this sequence version replaced NM_015506.2.
            
            Summary: The exact function of the protein encoded by this gene is
            not known, however, its C-terminal region shows similarity to TonB,
            a bacterial protein involved in energy transduction for cobalamin
            (vitamin B12) uptake. Hence, it is postulated that this protein may
            have a role in the binding and intracellular trafficking of
            cobalamin. Mutations in this gene are associated with methylmalonic
            aciduria and homocystinuria type cblC. [provided by RefSeq, Oct
            2009].
            
            Transcript Variant: This variant (1) encodes the longer isoform
            (1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The extent of this transcript is
            supported by transcript alignments.
            
            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 :: SRR1163657.361188.1,
                                           SRR1163658.420767.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000401061.9/ ENSP00000383840.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-63                AK098537.1         117-179
            64-715              BU839693.1         35-686
            716-962             BM980565.1         18-264              c
            963-2266            AL451136.11        125611-126914
            2267-2734           BU632364.1         17-484              c
            2735-5049           AL451136.11        127383-129697
FEATURES             Location/Qualifiers
     source          1..5049
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p34.1"
     gene            1..5049
                     /gene="MMACHC"
                     /gene_synonym="cblC"
                     /note="metabolism of cobalamin associated C"
                     /db_xref="GeneID:25974"
                     /db_xref="HGNC:HGNC:24525"
                     /db_xref="MIM:609831"
     exon            1..114
                     /gene="MMACHC"
                     /gene_synonym="cblC"
                     /inference="alignment:Splign:2.1.0"
     CDS             34..882
                     /gene="MMACHC"
                     /gene_synonym="cblC"
                     /EC_number="1.16.1.6"
                     /EC_number="2.5.1.151"
                     /note="isoform 1 is encoded by transcript variant 1;
                     methylmalonic aciduria and homocystinuria type C protein;
                     cyanocobalamin reductase (cyanide-eliminating);
                     methylmalonic aciduria (cobalamin deficiency) cblC type,
                     with homocystinuria; alkylcobalamin:glutathione
                     S-alkyltransferase; cyanocobalamin reductase /
                     alkylcobalamin dealkylase"
                     /codon_start=1
                     /product="cyanocobalamin reductase / alkylcobalamin
                     dealkylase isoform 1"
                     /protein_id="NP_056321.2"
                     /db_xref="CCDS:CCDS41324.1"
                     /db_xref="GeneID:25974"
                     /db_xref="HGNC:HGNC:24525"
                     /db_xref="MIM:609831"
                     /translation="MEPKVAELKQKIEDTLCPFGFEVYPFQVAWYNELLPPAFHLPLP
                     GPTLAFLVLSTPAMFDRALKPFLQSCHLRMLTDPVDQCVAYHLGRVRESLPELQIEII
                     ADYEVHPNRRPKILAQTAAHVAGAAYYYQRQDVEADPWGNQRISGVCIHPRFGGWFAI
                     RGVVLLPGIEVPDLPPRKPHDCVPTRADRIALLEGFNFHWRDWTYRDAVTPQERYSEE
                     QKAYFSTPPAQRLALLGLAQPSEKPSSPSPDLPFTTPAPKKPGNPSRARSWLSPRVSP
                     PASPGP"
     exon            115..309
                     /gene="MMACHC"
                     /gene_synonym="cblC"
                     /inference="alignment:Splign:2.1.0"
     exon            310..462
                     /gene="MMACHC"
                     /gene_synonym="cblC"
                     /inference="alignment:Splign:2.1.0"
     exon            463..5049
                     /gene="MMACHC"
                     /gene_synonym="cblC"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1783..1788
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MMACHC"
                     /gene_synonym="cblC"
                     /note="hexamer: AATAAA"
     polyA_site      1814
                     /gene="MMACHC"
                     /gene_synonym="cblC"
                     /note="major polyA site"
     regulatory      2700..2705
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MMACHC"
                     /gene_synonym="cblC"
                     /note="hexamer: AATAAA"
     polyA_site      2734
                     /gene="MMACHC"
                     /gene_synonym="cblC"
                     /note="major polyA site"
     regulatory      4862..4867
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MMACHC"
                     /gene_synonym="cblC"
                     /note="hexamer: AATAAA"
     polyA_site      4880
                     /gene="MMACHC"
                     /gene_synonym="cblC"
                     /note="major polyA site"
     regulatory      5028..5033
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MMACHC"
                     /gene_synonym="cblC"
                     /note="hexamer: AATAAA"
     polyA_site      5049
                     /gene="MMACHC"
                     /gene_synonym="cblC"
ORIGIN      
        1 attccccagc aagctcagcg tgtaacgtgc gctatggagc cgaaagtcgc agagctgaag
       61 cagaagatcg aggacacgct atgtcctttt ggcttcgagg tttacccctt ccaggtggca
      121 tggtacaatg aactcttgcc tccagccttc cacctaccgc tgccaggacc taccctggcc
      181 ttcctggtac tcagcacgcc tgccatgttt gaccgggccc tcaagccctt cttgcagagc
      241 tgccacctcc gaatgctgac tgacccagtg gaccagtgtg tggcctacca tctgggccgt
      301 gttagagaga gcctcccaga gctgcagata gaaatcattg ctgactacga ggtgcacccc
      361 aaccgacgcc ccaagatcct ggcccagaca gcagcccatg tagctggggc tgcttactac
      421 taccaacgac aagatgtgga ggctgaccca tgggggaacc agcgcatatc aggtgtgtgc
      481 atacaccccc gatttggggg ctggtttgcc atccgagggg tagtgctgct gccagggata
      541 gaggtgccag atctgccacc cagaaaacct catgactgtg tacctacaag agctgaccgt
      601 atcgccctac tcgaaggctt caatttccac tggcgtgatt ggacttaccg ggatgctgtg
      661 acaccccagg agcgctactc agaagagcag aaggcctact tctccactcc acctgcccaa
      721 cgattggccc tattgggctt ggctcagccc tcagagaagc ctagttctcc ctccccggac
      781 cttcccttta ccacacccgc ccccaagaag cctgggaatc ccagcagagc ccggagctgg
      841 ctcagcccca gggtctcacc acctgcatcc cctggccctt gattttctcc catgtggacc
      901 ctgatttatg gtggtacttg ctaggactta attggctttg gcaaagcaaa aggttttgag
      961 tacaagatta ctatttttga taatatagta gagatcttcc atgaagataa caaggctcaa
     1021 ggaagttagg tttggccaag ataaaggcca gggaaccaga attcccatct gccttcaaat
     1081 gagttttttt ttttttttta gacagagtct tactctgtca cctaggctgg agtgcagtgg
     1141 cacagtctct actcactgca acctctgcct cctgggttca agcaattatc tgcctcagcc
     1201 tcctgagtag ctgggatgac aggtgcctgc cactacacct ggctaatttt ttgtattttt
     1261 agtagagatg gggtttcatc atattggcca ggctggtctt taactcctga cctcgtgatc
     1321 cacccatctt ggcctcccaa agtcctggga ttacaggaat gagccaccgc acccagccaa
     1381 gactctatct gttcccattt ctaagcagtt ccccaagatg ttgttacagg gcctaagggg
     1441 caaatatcct ctaaagagta cctaccagca gggtgtggtg gctcccgcct gtaatcccag
     1501 cactctggga ggccgaggca ggtggatcat gaggtcgagt ttgagaccag cctggccaat
     1561 acagtgaaac cccgtctcta ctaaaaatgc aaagttagcc gggcatggta gcgcaggcct
     1621 gtagtcccag ctactcagga ggctgaggca gtagaatcat ttgaaccagg gaggcagaga
     1681 ttgcagtgag ccgagattgc atggctgcac tctagcctgg gtgacagtgt gagactctgt
     1741 ctcaaaaaaa aaaaaaaaag tacctacctc aggtagggac tgaataaaca cgtgtaaggc
     1801 actttggaaa aatacctggc atatatagta agcagtatgt tggccattac caaaggccct
     1861 gggaattctg tactgctgct catgggtgta gtcggttcta gaggggtggg caggtgggag
     1921 tagctgagga agacaagtgg ctggaatggt atcacatgat acacagaagt atcctcagtt
     1981 ctgaatctac cttggcctca agggcccagg agaataactt ttcccagctg acagcctctc
     2041 tgaggacaat gacatatgaa tgaggatcaa aacgagcttt ggccaggcac tgtggcgctc
     2101 acctgtaatc ccaccatttt gggaggctga ggcggaggac cgcctgaggc aaggaattca
     2161 gaaccactct gggcaacata atgacactaa aaaagactat ctctaatcaa ggctagaacc
     2221 aagggaaggc taagaattgc ccagtactgt gcaactacga aagccctacc caaggccacc
     2281 agccttgtct tcctctttcc tctgtcagtt caaaaagaac agaaacctcc agctctttta
     2341 catagcaggt accaggcatt tatcagaaga ggccaagctt ctggttccca tgcagccctt
     2401 tgaatagtgt gtctaaacaa aaataggtgt ccaagtagtc acactgagac tttaactggt
     2461 aacccagcct gtggcgtcag tcgcagtgct ctggccaaca ctatagcagg gcttattctt
     2521 ctccctcatg tgtagtgaaa caaaatgtaa caccttgggt tcattcagtt ccattcccta
     2581 tatctacctg tgtcaatata attccctgat ttggaggcag ctctcctcat tttccccaaa
     2641 acagggaaag caaggagtaa attcctctta aaatcaaaag ctaataatat gcttcctaaa
     2701 ataaagactc atcaaggtct cagttcaagt ttaatacaaa ctacaaaaga ttaatgggtt
     2761 gctctactaa tacatcatac aaaccagtag cctgcccaca acgccaactc aggccattcc
     2821 taccaaagga agaaaggctg gtctctccac cccctgtagg aaaggcctgc cttgtaagac
     2881 accacaattc ggctgaatct gaagtcttgt gttttactaa tggaaaaaaa aaatacagaa
     2941 gaggttttgt tctcatggct gcccaccgca gcctggcact aaaacagccc agcgctcact
     3001 tctgcttgga gaaatattct ttgctctttt ggacatcagg cttgatggta tcactgccag
     3061 gtttccagcc agctgggcac actgcaagag aaaggcacca ctaattaata accttctcaa
     3121 tggtatgcac caccattctc ctatggacaa aaccagttct gcacctgaac actcagatac
     3181 caggaaacct acccctgcaa tcagtcttag atcattcacc cttttagtat gagctaacca
     3241 ttttacaaac atataatcat caccacagcc ttaagatact atcatgccta atttattcat
     3301 gtagcacttg aaatttaaat tttccacaaa aaaaggcaaa gtttaaataa tttgccaaca
     3361 ctctctaatc cttaagggga aaaaaaagct aaataaacga cacacatagg actatgtaaa
     3421 cccttaacac taaactgttt ctgacagccc ttcagagctc tgaagacagc aaactcagtc
     3481 tgccttctca gcattcttct aactctacca aactggatag cctgaacctt ataaaggatc
     3541 aagaacttaa cagaagcccc cgcttgtttc attaagtaac tgccatctac cccttggtaa
     3601 gcaaaaggca gagtttgaaa tttttcatag atttatacag aaagcacagc cttcaacctt
     3661 ttcctgacaa tgcctaagaa tgtgcctcag gctagcctga agaaaatgag gcaaggggac
     3721 taatctctta tttttctttt tttttttttt tttttttttt tttgagatgg agtctccctc
     3781 tgttgcccag gctggagtac ggtggcgcaa tctccacctc cgtctcactg caacctcggt
     3841 ctcccgggtt caagcgattc tcctgcatca gcctcccaaa tagctaggat tacaggcgcc
     3901 caccaccaca cctggctaat ttttgagaca gtctcacatt gtcgcccagg ctggagtgca
     3961 gtggcgcgat ctcagctcac tgcaagctcc acctccgggg ttcatgccat tctcctgcct
     4021 cagcctcccg agtagctggg actatacaaa aatagtgggg cgtggtggtg gacccctgta
     4081 gtcctagcta ctcaggaggc tgaggcaaga gaatcacttg aacccaggag gtggaggctg
     4141 cagtgagctg agatcacacc actgcactcc agtctgggcg acaaaacaag actctgtctc
     4201 aaaaaaaaaa agtgtttggc attcattggc tcttaaatgg tacctattta agaggctgta
     4261 catgttccag tgggatggga agcagcagag accaacagag tctgaagaag caagcttctg
     4321 agttatgaaa gcctgggttc aggagactaa cctatatgta ggttcctagg aaagtccagt
     4381 taaagggcct actttgccac tgctgcctcc ttcttaatgc tgaacctcat ctcccacaag
     4441 ggggcagtct cagcaggtgt cagctgagcc atgtgtcatc tgtccaggct aactgcccac
     4501 acatccttct gcaaagggta cctcttggtt atcagtgctc actgatccct atataatcag
     4561 actctaatcc ctgtaaaaag attacttggt gctagccaag ctagcacctt tgggtcttcc
     4621 caaacataca ccactaatcc agactctaat aacttcattt cctttaaatt acaagatcag
     4681 agctgaaata ggccttagaa agctagtctg ggctgggcgc aatggctcag gggaggcgga
     4741 ggttgcagtg agccaagact gcgccactgc actccagcct gggcaacaga gcaagactcc
     4801 atcttgcaaa aaataaataa ataaataaaa atatgaacta tatggattaa cctcttctct
     4861 caataaagtt atttaaaaaa tggcatgctt tatctctaga ggtgattccc aaccattttg
     4921 ttttgcccta atacatctgt gagatcatcc tacattcagt aagttagatc tttgggagtg
     4981 actgattcta aatgagcagg acagaagaga ggagtatgta tactttgaat aaaaagcctt
     5041 tatattctc
//
