LOCUS       NM_000249               2494 bp    mRNA    linear   PRI 12-OCT-2024
DEFINITION  Homo sapiens mutL homolog 1 (MLH1), transcript variant 1, mRNA.
ACCESSION   NM_000249
VERSION     NM_000249.4
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 2494)
  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   2  (bases 1 to 2494)
  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   3  (bases 1 to 2494)
  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   4  (bases 1 to 2494)
  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   5  (bases 1 to 2494)
  AUTHORS   Yue,Q., Wang,Z., Shen,Y., Lan,Y., Zhong,X., Luo,X., Yang,T.,
            Zhang,M., Zuo,B., Zeng,T., Lu,J., Wang,Y., Liu,B. and Guo,H.
  TITLE     Histone H3K9 Lactylation Confers Temozolomide Resistance in
            Glioblastoma via LUC7L2-Mediated MLH1 Intron Retention
  JOURNAL   Adv Sci (Weinh) 11 (19), e2309290 (2024)
   PUBMED   38477507
  REMARK    GeneRIF: Histone H3K9 Lactylation Confers Temozolomide Resistance
            in Glioblastoma via LUC7L2-Mediated MLH1 Intron Retention.
REFERENCE   6  (bases 1 to 2494)
  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 2494)
  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 2494)
  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 2494)
  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 2494)
  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 BC006850.1.
            
            On Nov 13, 2019 this sequence version replaced NM_000249.3.
            
            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 (1) encodes the longest isoform
            (1).
            
            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 :: BC006850.1, U07343.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000231790.8/ ENSP00000231790.3
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-2494              BC006850.1         21-2514
FEATURES             Location/Qualifiers
     source          1..2494
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3p22.2"
     gene            1..2494
                     /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..237
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            238..336
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            337..410
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            411..483
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            484..575
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            576..618
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            619..707
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            708..820
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            821..914
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            915..1068
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1069..1439
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1440..1588
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1589..1697
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1698..1761
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1762..1926
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            1927..2019
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            2020..2133
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            2134..2494
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2470..2475
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /note="hexamer: AATAAA"
     regulatory      2474..2479
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /note="hexamer: AATAGA"
     polyA_site      2489
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /note="major polyA site"
     polyA_site      2494
                     /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 gaactgttta gatgcaaaat ccacaagtat tcaagtgatt
      181 gttaaagagg gaggcctgaa gttgattcag atccaagaca atggcaccgg gatcaggaaa
      241 gaagatctgg atattgtatg tgaaaggttc actactagta aactgcagtc ctttgaggat
      301 ttagccagta tttctaccta tggctttcga ggtgaggctt tggccagcat aagccatgtg
      361 gctcatgtta ctattacaac gaaaacagct gatggaaagt gtgcatacag agcaagttac
      421 tcagatggaa aactgaaagc ccctcctaaa ccatgtgctg gcaatcaagg gacccagatc
      481 acggtggagg acctttttta caacatagcc acgaggagaa aagctttaaa aaatccaagt
      541 gaagaatatg ggaaaatttt ggaagttgtt ggcaggtatt cagtacacaa tgcaggcatt
      601 agtttctcag ttaaaaaaca aggagagaca gtagctgatg ttaggacact acccaatgcc
      661 tcaaccgtgg acaatattcg ctccatcttt ggaaatgctg ttagtcgaga actgatagaa
      721 attggatgtg aggataaaac cctagccttc aaaatgaatg gttacatatc caatgcaaac
      781 tactcagtga agaagtgcat cttcttactc ttcatcaacc atcgtctggt agaatcaact
      841 tccttgagaa aagccataga aacagtgtat gcagcctatt tgcccaaaaa cacacaccca
      901 ttcctgtacc tcagtttaga aatcagtccc cagaatgtgg atgttaatgt gcaccccaca
      961 aagcatgaag ttcacttcct gcacgaggag agcatcctgg agcgggtgca gcagcacatc
     1021 gagagcaagc tcctgggctc caattcctcc aggatgtact tcacccagac tttgctacca
     1081 ggacttgctg gcccctctgg ggagatggtt aaatccacaa caagtctgac ctcgtcttct
     1141 acttctggaa gtagtgataa ggtctatgcc caccagatgg ttcgtacaga ttcccgggaa
     1201 cagaagcttg atgcatttct gcagcctctg agcaaacccc tgtccagtca gccccaggcc
     1261 attgtcacag aggataagac agatatttct agtggcaggg ctaggcagca agatgaggag
     1321 atgcttgaac tcccagcccc tgctgaagtg gctgccaaaa atcagagctt ggagggggat
     1381 acaacaaagg ggacttcaga aatgtcagag aagagaggac ctacttccag caaccccaga
     1441 aagagacatc gggaagattc tgatgtggaa atggtggaag atgattcccg aaaggaaatg
     1501 actgcagctt gtaccccccg gagaaggatc attaacctca ctagtgtttt gagtctccag
     1561 gaagaaatta atgagcaggg acatgaggtt ctccgggaga tgttgcataa ccactccttc
     1621 gtgggctgtg tgaatcctca gtgggccttg gcacagcatc aaaccaagtt ataccttctc
     1681 aacaccacca agcttagtga agaactgttc taccagatac tcatttatga ttttgccaat
     1741 tttggtgttc tcaggttatc ggagccagca ccgctctttg accttgccat gcttgcctta
     1801 gatagtccag agagtggctg gacagaggaa gatggtccca aagaaggact tgctgaatac
     1861 attgttgagt ttctgaagaa gaaggctgag atgcttgcag actatttctc tttggaaatt
     1921 gatgaggaag ggaacctgat tggattaccc cttctgattg acaactatgt gccccctttg
     1981 gagggactgc ctatcttcat tcttcgacta gccactgagg tgaattggga cgaagaaaag
     2041 gaatgttttg aaagcctcag taaagaatgc gctatgttct attccatccg gaagcagtac
     2101 atatctgagg agtcgaccct ctcaggccag cagagtgaag tgcctggctc cattccaaac
     2161 tcctggaagt ggactgtgga acacattgtc tataaagcct tgcgctcaca cattctgcct
     2221 cctaaacatt tcacagaaga tggaaatatc ctgcagcttg ctaacctgcc tgatctatac
     2281 aaagtctttg agaggtgtta aatatggtta tttatgcact gtgggatgtg ttcttctttc
     2341 tctgtattcc gatacaaagt gttgtatcaa agtgtgatat acaaagtgta ccaacataag
     2401 tgttggtagc acttaagact tatacttgcc ttctgatagt attcctttat acacagtgga
     2461 ttgattataa ataaatagat gtgtcttaac ataa
//
