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MLH1 mutL homolog 1 [ Homo sapiens (human) ]

Gene ID: 4292, updated on 15-Sep-2014
Official Symbol
MLH1provided by HGNC
Official Full Name
mutL homolog 1provided by HGNC
Primary source
HGNC:HGNC:7127
See related
Ensembl:ENSG00000076242; HPRD:00390; MIM:120436; Vega:OTTHUMG00000130797
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
FCC2; COCA2; HNPCC; hMLH1; HNPCC2
Summary
This gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). It is a human homolog of the E. coli DNA mismatch repair gene mutL, consistent with the characteristic alterations in microsatellite sequences (RER+phenotype) found in HNPCC. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described, but their full-length natures have not been determined.[provided by RefSeq, Nov 2009]
See MLH1 in Epigenomics, MapViewer
Location:
3p21.3
Exon count:
21
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 3 NC_000003.12 (36993350..37050846)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (37034841..37092337)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene protease-associated domain containing 1 pseudogene 1 Neighboring gene EPM2A (laforin) interacting protein 1 Neighboring gene ribosomal protein L29 pseudogene 11 Neighboring gene leucine rich repeat (in FLII) interacting protein 2 Neighboring gene ubiquitin-conjugating enzyme E2D 3 pseudogene 2 Neighboring gene ubiquitin-conjugating enzyme E2F (putative) pseudogene 1

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Professional guidelines

Description
Professional guideline
ACMG 2013

The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in MLH1 that are pathogenic or expected to be pathogenic.

GuidelinePubMed

Associated conditions

Description Tests
Lynch syndrome II
MedGen: C1333991 OMIM: 609310 GeneReviews: Lynch Syndrome
Compare labs
Muir-Torr syndrome
OMIM: 158320GeneReviews: Not available
Muir-Torr syndrome
MedGen: C1321489 GeneReviews: Lynch Syndrome
Compare labs
Turcot syndrome
MedGen: C0265325 OMIM: 276300 GeneReviews: Lynch Syndrome
Compare labs
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Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • MGC5172

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
ATPase activity IBA
Inferred from Biological aspect of Ancestor
more info
 
contributes_to MutSalpha complex binding IDA
Inferred from Direct Assay
more info
PubMed 
guanine/thymine mispair binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
contributes_to protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
contributes_to single-stranded DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
ATP catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
 
double-strand break repair via nonhomologous end joining IEA
Inferred from Electronic Annotation
more info
 
intrinsic apoptotic signaling pathway in response to DNA damage IEA
Inferred from Electronic Annotation
more info
 
isotype switching IEA
Inferred from Electronic Annotation
more info
 
male meiosis chromosome segregation IEA
Inferred from Electronic Annotation
more info
 
meiotic metaphase I plate congression IEA
Inferred from Electronic Annotation
more info
 
mismatch repair IGI
Inferred from Genetic Interaction
more info
 
negative regulation of mitotic recombination IEA
Inferred from Electronic Annotation
more info
 
nuclear-transcribed mRNA poly(A) tail shortening IEA
Inferred from Electronic Annotation
more info
 
oogenesis IEA
Inferred from Electronic Annotation
more info
 
resolution of meiotic recombination intermediates IEA
Inferred from Electronic Annotation
more info
 
somatic hypermutation of immunoglobulin genes IBA
Inferred from Biological aspect of Ancestor
more info
 
spermatogenesis IEA
Inferred from Electronic Annotation
more info
 
spindle midzone assembly involved in meiosis IEA
Inferred from Electronic Annotation
more info
 
synapsis IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
MutLalpha complex IBA
Inferred from Biological aspect of Ancestor
more info
 
chiasma IBA
Inferred from Biological aspect of Ancestor
more info
 
male germ cell nucleus IEA
Inferred from Electronic Annotation
more info
 
membrane IDA
Inferred from Direct Assay
more info
PubMed 
NOT nucleolus IDA
Inferred from Direct Assay
more info
 
nucleus IC
Inferred by Curator
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
 
synaptonemal complex IBA
Inferred from Biological aspect of Ancestor
more info
 
Preferred Names
DNA mismatch repair protein Mlh1
Names
DNA mismatch repair protein Mlh1
mutL homolog 1, colon cancer, nonpolyposis type 2

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_007109.2 

    Range
    5001..62497
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_216

mRNA and Protein(s)

  1. NM_000249.3NP_000240.1  DNA mismatch repair protein Mlh1 isoform 1

    See proteins identical to NP_000240.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    BC006850, CN414955
    Consensus CDS
    CCDS2663.1
    UniProtKB/Swiss-Prot
    P40692
    Related
    ENSP00000231790, OTTHUMP00000161361, ENST00000231790, OTTHUMT00000253337
    Conserved Domains (3) summary
    TIGR00585
    Location:6315
    mutl; DNA mismatch repair protein MutL
    cd00075
    Location:31122
    HATPase_c; Histidine kinase-like ATPases; This family includes several ATP-binding proteins for example: histidine kinase, DNA gyrase B, topoisomerases, heat shock protein HSP90, phytochrome-like ATPases and DNA mismatch repair proteins
    cd03483
    Location:211335
    MutL_Trans_MLH1; MutL_Trans_MLH1: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH1 (MutL homologue 1). This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to ...
  2. NM_001167617.1NP_001161089.1  DNA mismatch repair protein Mlh1 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains a distinct 5'-terminal exon and therefore lacks an in-frame portion of the 5' coding region compared to variant 1. The resulting isoform (2) has a shorter N-terminus compared to isoform 1.
    Source sequence(s)
    AK298583, BC006850, DA517219
    Consensus CDS
    CCDS54562.1
    UniProtKB/Swiss-Prot
    P40692
    Related
    ENSP00000402564, OTTHUMP00000210162, ENST00000435176, OTTHUMT00000341986
    Conserved Domains (2) summary
    TIGR00585
    Location:4217
    mutl; DNA mismatch repair protein MutL
    cd03483
    Location:113237
    MutL_Trans_MLH1; MutL_Trans_MLH1: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH1 (MutL homologue 1). This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to ...
  3. NM_001167618.1NP_001161090.1  DNA mismatch repair protein Mlh1 isoform 3

    See proteins identical to NP_001161090.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains a distinct 5'-terminal exon and uses an alternate splice site in a 5' exon and therefore lacks an in-frame portion of the 5' coding region compared to variant 1. The resulting isoform (3) has a shorter N-terminus compared to isoform 1. Variants 3, 4, 6, and 7 all encode the same isoform (3).
    Source sequence(s)
    AK295359, BC006850, DA517219
    Consensus CDS
    CCDS54563.1
    UniProtKB/TrEMBL
    A0A024R2S9
    UniProtKB/Swiss-Prot
    P40692
    Related
    ENSP00000398272, OTTHUMP00000210161, ENST00000455445, OTTHUMT00000341985
    Conserved Domains (2) summary
    COG0323
    Location:2446
    MutL; DNA mismatch repair enzyme (predicted ATPase) [DNA replication, recombination, and repair]
    cd03483
    Location:194
    MutL_Trans_MLH1; MutL_Trans_MLH1: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH1 (MutL homologue 1). This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to ...
  4. NM_001167619.1NP_001161091.1  DNA mismatch repair protein Mlh1 isoform 3

    See proteins identical to NP_001161091.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) contains a distinct 5'-terminal exon and lacks a 5' exon and therefore lacks an in-frame portion of the 5' coding region compared to variant 1. The resulting isoform (3) has a shorter N-terminus compared to isoform 1. Variants 3, 4, 6, and 7 all encode the same isoform (3).
    Source sequence(s)
    AK316074, BC006850, DA517219
    Consensus CDS
    CCDS54563.1
    UniProtKB/TrEMBL
    A0A024R2S9
    UniProtKB/Swiss-Prot
    P40692
    Related
    ENSP00000443665, ENST00000539477
    Conserved Domains (2) summary
    COG0323
    Location:2446
    MutL; DNA mismatch repair enzyme (predicted ATPase) [DNA replication, recombination, and repair]
    cd03483
    Location:194
    MutL_Trans_MLH1; MutL_Trans_MLH1: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH1 (MutL homologue 1). This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to ...
  5. NM_001258271.1NP_001245200.1  DNA mismatch repair protein Mlh1 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks two alternate in-frame exons compared to variant 1. The resulting isoform (4) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AB209848, BC006850, CN414955
    UniProtKB/Swiss-Prot
    P40692
    UniProtKB/TrEMBL
    Q59EG3
    Related
    ENSP00000416687, OTTHUMP00000208782, ENST00000456676, OTTHUMT00000341983
    Conserved Domains (3) summary
    TIGR00585
    Location:6315
    mutl; DNA mismatch repair protein MutL
    cd00075
    Location:31122
    HATPase_c; Histidine kinase-like ATPases; This family includes several ATP-binding proteins for example: histidine kinase, DNA gyrase B, topoisomerases, heat shock protein HSP90, phytochrome-like ATPases and DNA mismatch repair proteins
    cd03483
    Location:211335
    MutL_Trans_MLH1; MutL_Trans_MLH1: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH1 (MutL homologue 1). This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to ...
  6. NM_001258273.1NP_001245202.1  DNA mismatch repair protein Mlh1 isoform 3

    See proteins identical to NP_001245202.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) lacks an alternate exon compared to variant 1, that causes a frameshift. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1. Variants 3, 4, 6, and 7 all encode the same isoform (3).
    Source sequence(s)
    AK316264, BC006850, CN414955
    Consensus CDS
    CCDS54563.1
    UniProtKB/TrEMBL
    A0A024R2S9
    UniProtKB/Swiss-Prot
    P40692
    Related
    ENSP00000444286, ENST00000536378
    Conserved Domains (2) summary
    COG0323
    Location:2446
    MutL; DNA mismatch repair enzyme (predicted ATPase) [DNA replication, recombination, and repair]
    cd03483
    Location:194
    MutL_Trans_MLH1; MutL_Trans_MLH1: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH1 (MutL homologue 1). This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to ...
  7. NM_001258274.1NP_001245203.1  DNA mismatch repair protein Mlh1 isoform 3

    See proteins identical to NP_001245203.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) differs in the 5' UTR and contains an alternate exon compared to variant 1, that causes a frameshift. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1. Variants 3, 4, 6, and 7 all encode the same isoform (3).
    Source sequence(s)
    AC011816, BC006850, BX648844
    Consensus CDS
    CCDS54563.1
    UniProtKB/TrEMBL
    A0A024R2S9
    UniProtKB/Swiss-Prot
    P40692
    Related
    ENSP00000402667, OTTHUMP00000210160, ENST00000458205, OTTHUMT00000341984
    Conserved Domains (2) summary
    COG0323
    Location:2446
    MutL; DNA mismatch repair enzyme (predicted ATPase) [DNA replication, recombination, and repair]
    cd03483
    Location:194
    MutL_Trans_MLH1; MutL_Trans_MLH1: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH1 (MutL homologue 1). This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000003.12 

    Range
    36993350..37050846
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005265161.1XP_005265218.1  

    Conserved Domains (3) summary
    TIGR00585
    Location:6246
    mutl; DNA mismatch repair protein MutL
    cd00075
    Location:31122
    HATPase_c; Histidine kinase-like ATPases; This family includes several ATP-binding proteins for example: histidine kinase, DNA gyrase B, topoisomerases, heat shock protein HSP90, phytochrome-like ATPases and DNA mismatch repair proteins
    cl02783
    Location:227266
    TopoII_MutL_Trans; MutL_Trans: transducer domain, having a ribosomal S5 domain 2-like fold, conserved in the C-terminal domain of type II DNA topoisomerases (Topo II) and DNA mismatch repair (MutL/MLH1/PMS2) proteins. This transducer domain is homologous to the second ...
  2. XM_005265164.1XP_005265221.1  

    See proteins identical to XP_005265221.1

    UniProtKB/TrEMBL
    A0A024R2S9
    UniProtKB/Swiss-Prot
    P40692
    Conserved Domains (2) summary
    COG0323
    Location:2446
    MutL; DNA mismatch repair enzyme (predicted ATPase) [DNA replication, recombination, and repair]
    cd03483
    Location:194
    MutL_Trans_MLH1; MutL_Trans_MLH1: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH1 (MutL homologue 1). This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to ...
  3. XM_005265166.1XP_005265223.1  

  4. XM_005265163.1XP_005265220.1  

    See proteins identical to XP_005265220.1

    UniProtKB/TrEMBL
    A0A024R2S9
    UniProtKB/Swiss-Prot
    P40692
    Conserved Domains (2) summary
    COG0323
    Location:2446
    MutL; DNA mismatch repair enzyme (predicted ATPase) [DNA replication, recombination, and repair]
    cd03483
    Location:194
    MutL_Trans_MLH1; MutL_Trans_MLH1: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH1 (MutL homologue 1). This transducer domain is homologous to the second domain of the DNA gyrase B subunit, which is known to ...

RNA

  1. XR_427268.1 RNA Sequence

Alternate HuRef

Genomic

  1. AC_000135.1 

    Range
    36975521..37033106
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018914.2 

    Range
    36986471..37043967
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)