LOCUS       NM_001354625            2144 bp    mRNA    linear   PRI 20-FEB-2025
DEFINITION  Homo sapiens mutL homolog 1 (MLH1), transcript variant 18, mRNA.
ACCESSION   NM_001354625
VERSION     NM_001354625.2
KEYWORDS    RefSeq.
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 2144)
  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 2144)
  AUTHORS   Liu,W.J., Lu,J., Zhou,W.X., Liu,J.Z. and Zhou,L.
  TITLE     MLH1 Inhibits Metastatic Potential of Pancreatic Ductal
            Adenocarcinoma via Downregulation of GPRC5C
  JOURNAL   Lab Invest 104 (9), 102107 (2024)
   PUBMED   38964504
  REMARK    GeneRIF: MLH1 Inhibits Metastatic Potential of Pancreatic Ductal
            Adenocarcinoma via Downregulation of GPRC5C.
REFERENCE   3  (bases 1 to 2144)
  AUTHORS   Zou,Z.J., Hong,S.F., Zhang,Z.H., Lin,S.Q., Zeng,L.Y., Jiang,X.Y.,
            Chen,B.L. and Ren,J.
  TITLE     [Analysis of gene mutation in a family with Muir-Torre syndrome
            accompanied with extraorbital cystic sebaceous carcinoma]
  JOURNAL   Zhonghua Yi Xue Za Zhi 104 (33), 3154-3157 (2024)
   PUBMED   39168847
  REMARK    GeneRIF: [Analysis of gene mutation in a family with Muir-Torre
            syndrome accompanied with extraorbital cystic sebaceous carcinoma].
REFERENCE   4  (bases 1 to 2144)
  AUTHORS   Mirbahari,S.N., Fatemi,N., Savabkar,S., Chaleshi,V., Zali,N.,
            Taleghani,M.Y., Mirzaei,E., Rejali,L., Moghadam,P.K. and
            Mojarad,E.N.
  TITLE     Unmasking early colorectal cancer clues: in silico and in vitro
            investigation of downregulated IGF2, SOCS1, MLH1, and CACNA1G in
            SSA polyps
  JOURNAL   Mol Biol Rep 51 (1), 764 (2024)
   PUBMED   38874740
  REMARK    GeneRIF: Unmasking early colorectal cancer clues: in silico and in
            vitro investigation of downregulated IGF2, SOCS1, MLH1, and CACNA1G
            in SSA polyps.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 2144)
  AUTHORS   Provasek,V.E., Kodavati,M., Kim,B., Mitra,J. and Hegde,M.L.
  TITLE     TDP43 interacts with MLH1 and MSH6 proteins in a DNA
            damage-inducible manner
  JOURNAL   Mol Brain 17 (1), 32 (2024)
   PUBMED   38840222
  REMARK    GeneRIF: TDP43 interacts with MLH1 and MSH6 proteins in a DNA
            damage-inducible manner.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 2144)
  AUTHORS   Nystrom-Lahti,M., Kristo,P., Nicolaides,N.C., Chang,S.Y.,
            Aaltonen,L.A., Moisio,A.L., Jarvinen,H.J., Mecklin,J.P.,
            Kinzler,K.W., Vogelstein,B. et al.
  TITLE     Founding mutations and Alu-mediated recombination in hereditary
            colon cancer
  JOURNAL   Nat Med 1 (11), 1203-1206 (1995)
   PUBMED   7584997
REFERENCE   7  (bases 1 to 2144)
  AUTHORS   Charbonnier,F., Martin,C., Scotte,M., Sibert,L., Moreau,V. and
            Frebourg,T.
  TITLE     Alternative splicing of MLH1 messenger RNA in human normal cells
  JOURNAL   Cancer Res 55 (9), 1839-1841 (1995)
   PUBMED   7728749
REFERENCE   8  (bases 1 to 2144)
  AUTHORS   Paraf,F., Sasseville,D., Watters,A.K., Narod,S., Ginsburg,O.,
            Shibata,H. and Jothy,S.
  TITLE     Clinicopathological relevance of the association between
            gastrointestinal and sebaceous neoplasms: the Muir-Torre syndrome
  JOURNAL   Hum Pathol 26 (4), 422-427 (1995)
   PUBMED   7705822
  REMARK    Review article
REFERENCE   9  (bases 1 to 2144)
  AUTHORS   Hamilton,S.R., Liu,B., Parsons,R.E., Papadopoulos,N., Jen,J.,
            Powell,S.M., Krush,A.J., Berk,T., Cohen,Z., Tetu,B. et al.
  TITLE     The molecular basis of Turcot's syndrome
  JOURNAL   N Engl J Med 332 (13), 839-847 (1995)
   PUBMED   7661930
REFERENCE   10 (bases 1 to 2144)
  AUTHORS   Idos,G. and Valle,L.
  TITLE     Lynch Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301390
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC011816.17 and AC006583.31.
            
            On Aug 13, 2020 this sequence version replaced NM_001354625.1.
            
            Summary: The protein encoded by this gene can heterodimerize with
            mismatch repair endonuclease PMS2 to form MutL alpha, part of the
            DNA mismatch repair system. When MutL alpha is bound by MutS beta
            and some accessory proteins, the PMS2 subunit of MutL alpha
            introduces a single-strand break near DNA mismatches, providing an
            entry point for exonuclease degradation. The encoded protein is
            also involved in DNA damage signaling and can heterodimerize with
            DNA mismatch repair protein MLH3 to form MutL gamma, which is
            involved in meiosis. This gene was identified as a locus frequently
            mutated in hereditary nonpolyposis colon cancer (HNPCC). [provided
            by RefSeq, Aug 2017].
            
            Transcript Variant: This variant (18), as well as variants 17, 19,
            and 20, encodes isoform 6.
            
            Sequence Note: The RefSeq transcript and protein were derived from
            genomic sequence to make the sequence consistent with the reference
            genome assembly. The genomic coordinates used for the transcript
            record were based on 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 :: SRR1803616.175657.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA1968968
                                           [ECO:0000348]
            ##Evidence-Data-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-146               AC011816.17        143176-143321
            147-232             AC011816.17        146282-146367
            233-326             AC011816.17        150613-150706
            327-400             AC011816.17        154059-154132
            401-473             AC011816.17        156649-156721
            474-516             AC011816.17        161478-161520
            517-605             AC011816.17        161669-161757
            606-718             AC011816.17        164090-164202
            719-1089            AC006583.31        94019-94389         c
            1090-1238           AC006583.31        91094-91242         c
            1239-1347           AC006583.31        79732-79840         c
            1348-1411           AC006583.31        77695-77758         c
            1412-1576           AC006583.31        72343-72507         c
            1577-1669           AC006583.31        71417-71509         c
            1670-1783           AC006583.31        71009-71122         c
            1784-2144           AC006583.31        69180-69540         c
FEATURES             Location/Qualifiers
     source          1..2144
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3p22.2"
     gene            1..2144
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /note="mutL homolog 1"
                     /db_xref="GeneID:4292"
                     /db_xref="HGNC:HGNC:7127"
                     /db_xref="MIM:120436"
     exon            1..146
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            147..232
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            233..326
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            327..400
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            401..473
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            474..516
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            517..605
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            606..718
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            719..1089
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     CDS             755..1951
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /note="isoform 6 is encoded by transcript variant 18; DNA
                     mismatch repair protein Mlh1; mutL homolog 1, colon
                     cancer, nonpolyposis type 2"
                     /codon_start=1
                     /product="DNA mismatch repair protein Mlh1 isoform 6"
                     /protein_id="NP_001341554.1"
                     /db_xref="GeneID:4292"
                     /db_xref="HGNC:HGNC:7127"
                     /db_xref="MIM:120436"
                     /translation="MVKSTTSLTSSSTSGSSDKVYAHQMVRTDSREQKLDAFLQPLSK
                     PLSSQPQAIVTEDKTDISSGRARQQDEEMLELPAPAEVAAKNQSLEGDTTKGTSEMSE
                     KRGPTSSNPRKRHREDSDVEMVEDDSRKEMTAACTPRRRIINLTSVLSLQEEINEQGH
                     EVLREMLHNHSFVGCVNPQWALAQHQTKLYLLNTTKLSEELFYQILIYDFANFGVLRL
                     SEPAPLFDLAMLALDSPESGWTEEDGPKEGLAEYIVEFLKKKAEMLADYFSLEIDEEG
                     NLIGLPLLIDNYVPPLEGLPIFILRLATEVNWDEEKECFESLSKECAMFYSIRKQYIS
                     EESTLSGQQSEVPGSIPNSWKWTVEHIVYKALRSHILPPKHFTEDGNILQLANLPDLY
                     KVFERC"
     exon            1090..1238
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1239..1347
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1348..1411
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1412..1576
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1577..1669
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1670..1783
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1784..2144
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2120..2125
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /note="hexamer: AATAAA"
     regulatory      2124..2129
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /note="hexamer: AATAGA"
     polyA_site      2139
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /note="major polyA site"
     polyA_site      2144
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /note="major polyA site"
ORIGIN      
        1 agacgtttcc ttggctcttc tggcgccaaa atgtcgttcg tggcaggggt tattcggcgg
       61 ctggacgaga cagtggtgaa ccgcatcgcg gcgggggaag ttatccagcg gccagctaat
      121 gctatcaaag agatgattga gaactgatgc aaaatccaca agtattcaag tgattgttaa
      181 agagggaggc ctgaagttga ttcagatcca agacaatggc accgggatca ggaaagaaga
      241 tctggatatt gtatgtgaaa ggttcactac tagtaaactg cagtcctttg aggatttagc
      301 cagtatttct acctatggct ttcgaggctt tggccagcat aagccatgtg gctcatgtta
      361 ctattacaac gaaaacagct gatggaaagt gtgcatacag agcaagttac tcagatggaa
      421 aactgaaagc ccctcctaaa ccatgtgctg gcaatcaagg gacccagatc acggtattca
      481 gtacacaatg caggcattag tttctcagtt aaaaaacaag gagagacagt agctgatgtt
      541 aggacactac ccaatgcctc aaccgtggac aatattcgct ccatctttgg aaatgctgtt
      601 agtcgagaac tgatagaaat tggatgtgag gataaaaccc tagccttcaa aatgaatggt
      661 tacatatcca atgcaaacta ctcagtgaag aagtgcatct tcttactctt catcaaccac
      721 tttgctacca ggacttgctg gcccctctgg ggagatggtt aaatccacaa caagtctgac
      781 ctcgtcttct acttctggaa gtagtgataa ggtctatgcc caccagatgg ttcgtacaga
      841 ttcccgggaa cagaagcttg atgcatttct gcagcctctg agcaaacccc tgtccagtca
      901 gccccaggcc attgtcacag aggataagac agatatttct agtggcaggg ctaggcagca
      961 agatgaggag atgcttgaac tcccagcccc tgctgaagtg gctgccaaaa atcagagctt
     1021 ggagggggat acaacaaagg ggacttcaga aatgtcagag aagagaggac ctacttccag
     1081 caaccccaga aagagacatc gggaagattc tgatgtggaa atggtggaag atgattcccg
     1141 aaaggaaatg actgcagctt gtaccccccg gagaaggatc attaacctca ctagtgtttt
     1201 gagtctccag gaagaaatta atgagcaggg acatgaggtt ctccgggaga tgttgcataa
     1261 ccactccttc gtgggctgtg tgaatcctca gtgggccttg gcacagcatc aaaccaagtt
     1321 ataccttctc aacaccacca agcttagtga agaactgttc taccagatac tcatttatga
     1381 ttttgccaat tttggtgttc tcaggttatc ggagccagca ccgctctttg accttgccat
     1441 gcttgcctta gatagtccag agagtggctg gacagaggaa gatggtccca aagaaggact
     1501 tgctgaatac attgttgagt ttctgaagaa gaaggctgag atgcttgcag actatttctc
     1561 tttggaaatt gatgaggaag ggaacctgat tggattaccc cttctgattg acaactatgt
     1621 gccccctttg gagggactgc ctatcttcat tcttcgacta gccactgagg tgaattggga
     1681 cgaagaaaag gaatgttttg aaagcctcag taaagaatgc gctatgttct attccatccg
     1741 gaagcagtac atatctgagg agtcgaccct ctcaggccag cagagtgaag tgcctggctc
     1801 cattccaaac tcctggaagt ggactgtgga acacattgtc tataaagcct tgcgctcaca
     1861 cattctgcct cctaaacatt tcacagaaga tggaaatatc ctgcagcttg ctaacctgcc
     1921 tgatctatac aaagtctttg agaggtgtta aatatggtta tttatgcact gtgggatgtg
     1981 ttcttctttc tctgtattcc gatacaaagt gttgtatcaa agtgtgatat acaaagtgta
     2041 ccaacataag tgttggtagc acttaagact tatacttgcc ttctgatagt attcctttat
     2101 acacagtgga ttgattataa ataaatagat gtgtcttaac ataa
//
