LOCUS       NM_001354628            2401 bp    mRNA    linear   PRI 20-FEB-2025
DEFINITION  Homo sapiens mutL homolog 1 (MLH1), transcript variant 21, mRNA.
ACCESSION   NM_001354628
VERSION     NM_001354628.2
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 2401)
  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 2401)
  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 2401)
  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 2401)
  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 2401)
  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 2401)
  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 2401)
  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 2401)
  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 2401)
  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 2401)
  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_001354628.1.
            
            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].
            
            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 :: SRR14038192.1429058.1,
                                           SRR14038195.20928.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [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
            147-237             AC011816.17        146277-146367
            238-336             AC011816.17        150613-150711
            337-410             AC011816.17        154059-154132
            411-483             AC011816.17        156649-156721
            484-575             AC011816.17        158472-158563
            576-618             AC011816.17        161478-161520
            619-707             AC011816.17        161669-161757
            708-820             AC011816.17        164090-164202
            821-914             AC011816.17        167164-167257
            915-1068            AC006583.31        99563-99716         c
            1069-1439           AC006583.31        94019-94389         c
            1440-1588           AC006583.31        91094-91242         c
            1589-1697           AC006583.31        79732-79840         c
            1698-1761           AC006583.31        77695-77758         c
            1762-1926           AC006583.31        72343-72507         c
            1927-2040           AC006583.31        71009-71122         c
            2041-2401           AC006583.31        69180-69540         c
FEATURES             Location/Qualifiers
     source          1..2401
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3p22.2"
     gene            1..2401
                     /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"
     CDS             31..2208
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /note="isoform 7 is encoded by transcript variant 21; DNA
                     mismatch repair protein Mlh1; mutL homolog 1, colon
                     cancer, nonpolyposis type 2"
                     /codon_start=1
                     /product="DNA mismatch repair protein Mlh1 isoform 7"
                     /protein_id="NP_001341557.1"
                     /db_xref="GeneID:4292"
                     /db_xref="HGNC:HGNC:7127"
                     /db_xref="MIM:120436"
                     /translation="MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKS
                     TSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRGE
                     ALASISHVAHVTITTKTADGKCAYRASYSDGKLKAPPKPCAGNQGTQITVEDLFYNIA
                     TRRKALKNPSEEYGKILEVVGRYSVHNAGISFSVKKQGETVADVRTLPNASTVDNIRS
                     IFGNAVSRELIEIGCEDKTLAFKMNGYISNANYSVKKCIFLLFINHRLVESTSLRKAI
                     ETVYAAYLPKNTHPFLYLSLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKL
                     LGSNSSRMYFTQTLLPGLAGPSGEMVKSTTSLTSSSTSGSSDKVYAHQMVRTDSREQK
                     LDAFLQPLSKPLSSQPQAIVTEDKTDISSGRARQQDEEMLELPAPAEVAAKNQSLEGD
                     TTKGTSEMSEKRGPTSSNPRKRHREDSDVEMVEDDSRKEMTAACTPRRRIINLTSVLS
                     LQEEINEQGHEVLREMLHNHSFVGCVNPQWALAQHQTKLYLLNTTKLSEELFYQILIY
                     DFANFGVLRLSEPAPLFDLAMLALDSPESGWTEEDGPKEGLAEYIVEFLKKKAEMLAD
                     YFSLEIDEVNWDEEKECFESLSKECAMFYSIRKQYISEESTLSGQQSEVPGSIPNSWK
                     WTVEHIVYKALRSHILPPKHFTEDGNILQLANLPDLYKVFERC"
     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..2040
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     exon            2041..2401
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2377..2382
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /note="hexamer: AATAAA"
     regulatory      2381..2386
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /note="hexamer: AATAGA"
     polyA_site      2396
                     /gene="MLH1"
                     /gene_synonym="COCA2; FCC2; hMLH1; HNPCC; HNPCC2; LYNCH2;
                     MLH-1; MMRCS1"
                     /note="major polyA site"
     polyA_site      2401
                     /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 gatgaggtga attgggacga agaaaaggaa tgttttgaaa gcctcagtaa agaatgcgct
     1981 atgttctatt ccatccggaa gcagtacata tctgaggagt cgaccctctc aggccagcag
     2041 agtgaagtgc ctggctccat tccaaactcc tggaagtgga ctgtggaaca cattgtctat
     2101 aaagccttgc gctcacacat tctgcctcct aaacatttca cagaagatgg aaatatcctg
     2161 cagcttgcta acctgcctga tctatacaaa gtctttgaga ggtgttaaat atggttattt
     2221 atgcactgtg ggatgtgttc ttctttctct gtattccgat acaaagtgtt gtatcaaagt
     2281 gtgatataca aagtgtacca acataagtgt tggtagcact taagacttat acttgccttc
     2341 tgatagtatt cctttataca cagtggattg attataaata aatagatgtg tcttaacata
     2401 a
//
