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MLH3 mutL homolog 3 [ Homo sapiens (human) ]

Gene ID: 27030, updated on 3-Apr-2024

Summary

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Official Symbol
MLH3provided by HGNC
Official Full Name
mutL homolog 3provided by HGNC
Primary source
HGNC:HGNC:7128
See related
Ensembl:ENSG00000119684 MIM:604395; AllianceGenome:HGNC:7128
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
HNPCC7
Summary
This gene is a member of the MutL-homolog (MLH) family of DNA mismatch repair (MMR) genes. MLH genes are implicated in maintaining genomic integrity during DNA replication and after meiotic recombination. The protein encoded by this gene functions as a heterodimer with other family members. Somatic mutations in this gene frequently occur in tumors exhibiting microsatellite instability, and germline mutations have been linked to hereditary nonpolyposis colorectal cancer type 7 (HNPCC7). Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in thyroid (RPKM 5.0), adrenal (RPKM 3.9) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
14q24.3
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (75013775..75051467, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (69222838..69260934, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (75480478..75518170, complement)

Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107984690 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5936 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5937 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5938 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8733 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr14:75431938-75433137 Neighboring gene placental growth factor Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:75446625-75447250 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:75447251-75447876 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:75447877-75448500 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8734 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:75469302-75469982 Neighboring gene eukaryotic translation initiation factor 2B subunit beta Neighboring gene RNA, U6 small nuclear 689, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5939 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8735 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:75535987-75536538 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:75536539-75537090 Neighboring gene acylphosphatase 1 Neighboring gene zinc finger C2HC-type containing 1C Neighboring gene NIMA related kinase 9

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Exonic sequencing and MLH3 gene expression analysis of breast cancer patients. Khailany RA, et al. Cell Mol Biol (Noisy-le-grand), 2021 Nov 25. PMID 34933735
  2. A loss-of-function variant in DNA mismatch repair gene MLH3 underlies severe oligozoospermia. Nawaz S, et al. J Hum Genet, 2021 Jul. PMID 33517345
  3. Biallelic germline nonsense variant of MLH3 underlies polyposis predisposition. Olkinuora A, et al. Genet Med, 2019 Aug. PMID 30573798, Free PMC Article
  4. GAA•TTC repeat expansion in human cells is mediated by mismatch repair complex MutLγ and depends upon the endonuclease domain in MLH3 isoform one. Halabi A, et al. Nucleic Acids Res, 2018 May 4. PMID 29529236, Free PMC Article
  5. Coexistence of MLH3 germline variants in colon cancer patients belonging to families with Lynch syndrome-associated brain tumors. Duraturo F, et al. J Neurooncol, 2016 Sep. PMID 27401157

See all (67) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Exonic sequencing and MLH3 gene expression analysis of breast cancer patients.
    Title: Exonic sequencing and MLH3 gene expression analysis of breast cancer patients.
  2. A loss-of-function variant in DNA mismatch repair gene MLH3 underlies severe oligozoospermia.
    Title: A loss-of-function variant in DNA mismatch repair gene MLH3 underlies severe oligozoospermia.
  3. Genetic evidence for the involvement of mismatch repair proteins, PMS2 and MLH3, in a late step of homologous recombination.
    Title: Genetic evidence for the involvement of mismatch repair proteins, PMS2 and MLH3, in a late step of homologous recombination.
  4. Regulation of the MLH1-MLH3 endonuclease in meiosis.
    Title: Regulation of the MLH1-MLH3 endonuclease in meiosis.
  5. MutLgamma, the MLH1-MLH3 heterodimer, is a unique endonuclease that can initiate triplet repeat DNA expansions.
    Title: Human MutLγ, the MLH1-MLH3 heterodimer, is an endonuclease that promotes DNA expansion.
  6. rs175080 in MLH3 was not significantly different between idiopathic male infertility and control (p > 0.05).
    Title: The association of four SNPs in DNA mismatch repair genes with idiopathic male infertility in northwest China.
  7. Our results show that a biallelic nonsense variant of MLH3 underlies a novel syndrome with susceptibility to classical or attenuated adenomatous polyposis and possibly extracolonic tumors, including breast cancer.
    Title: Biallelic germline nonsense variant of MLH3 underlies polyposis predisposition.
  8. MLH3 isoform 1 is active in GAA*TTC repeat expansion while the nuclease-deficient MLH3 isoform 2 is not.
    Title: GAA•TTC repeat expansion in human cells is mediated by mismatch repair complex MutLγ and depends upon the endonuclease domain in MLH3 isoform one.
  9. The effects of chronic smoking on oral mucosa led to the methylation of genes MRE11A PMS2, XRCC1 and MLH3, but resulted in a reduction of gene expression of MRE11A and PMS2, which showed >/=50% methylation. These results provide evidence that smoking cause methylation and reduced expression of repair genes.
    Title: Screening methylation of DNA repair genes in the oral mucosa of chronic smokers.
  10. MLH3 germline variants are associated with colon cancer patients belonging to families with Lynch syndrome-associated brain tumors.
    Title: Coexistence of MLH3 germline variants in colon cancer patients belonging to families with Lynch syndrome-associated brain tumors.
Submit: New GeneRIF Correction See all GeneRIFs (34)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Colorectal cancer
MedGen: C0346629 OMIM: 114500 GeneReviews: Lynch Syndrome
Compare labs
Colorectal cancer, hereditary nonpolyposis, type 7
MedGen: C1858380 OMIM: 614385 GeneReviews: Not available
Compare labs
Endometrial carcinoma
MedGen: C0476089 OMIM: 608089 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC138372

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables ATP hydrolysis activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ATP-dependent DNA damage sensor activity IEA
Inferred from Electronic Annotation
more info
  
enables centromeric DNA binding IEA
Inferred from Electronic Annotation
more info
  
enables chromatin binding IEA
Inferred from Electronic Annotation
more info
  
enables mismatched DNA binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables satellite DNA binding TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in female meiosis I IEA
Inferred from Electronic Annotation
more info
  
involved_in male meiotic nuclear division IEA
Inferred from Electronic Annotation
more info
  
involved_in mismatch repair IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in mismatch repair NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in protein localization IEA
Inferred from Electronic Annotation
more info
  
involved_in reciprocal meiotic recombination NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in synaptonemal complex assembly IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in chiasma IEA
Inferred from Electronic Annotation
more info
  
located_in male germ cell nucleus IEA
Inferred from Electronic Annotation
more info
  
part_of mismatch repair complex IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleus TAS
Traceable Author Statement
more info
 PubMed 
located_in synaptonemal complex IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
DNA mismatch repair protein Mlh3

NCBI Reference Sequences (RefSeq)

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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_008649.1 RefSeqGene

    Range
    5001..42769
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_217

mRNA and Protein(s)

  1. NM_001040108.2 → NP_001035197.1  DNA mismatch repair protein Mlh3 isoform 1

    See identical proteins and their annotated locations for NP_001035197.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AB039667, AL049780, BX090851, DA805814
    Consensus CDS
    CCDS32123.1
    UniProtKB/Swiss-Prot
    P49751, Q56DK9, Q9P292, Q9UHC0, Q9UHC1
    UniProtKB/TrEMBL
    Q2M1Z1
    Related
    ENSP00000348020.2, ENST00000355774.7
    Conserved Domains (3) summary
    smart00853
    Location:1191 → 1370
    MutL_C; MutL C terminal dimerisation domain
    cd03486
    Location:206 → 349
    MutL_Trans_MLH3; MutL_Trans_MLH3: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to ...
    pfam02518
    Location:22 → 115
    HATPase_c; Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase

  2. NM_014381.3 → NP_055196.2  DNA mismatch repair protein Mlh3 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2), also known as delta7, lacks an alternate in-frame exon, compared to variant 1, resulting in a shorter protein (isoform 2), compared to isoform 1.
    Source sequence(s)
    AL049780, BC112167, BX090851, DA731365, DA805814
    Consensus CDS
    CCDS9837.1
    UniProtKB/TrEMBL
    Q2M1Z1
    Related
    ENSP00000370355.3, ENST00000380968.6
    Conserved Domains (3) summary
    smart00853
    Location:1191 → 1346
    MutL_C; MutL C terminal dimerisation domain
    cd03486
    Location:206 → 349
    MutL_Trans_MLH3; MutL_Trans_MLH3: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to ...
    pfam02518
    Location:22 → 115
    HATPase_c; Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

    Range
    75013775..75051467 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047431265.1 → XP_047287221.1  DNA mismatch repair protein Mlh3 isoform X4

  2. XM_024449538.2 → XP_024305306.1  DNA mismatch repair protein Mlh3 isoform X3

    UniProtKB/TrEMBL
    Q2M1Z1
    Conserved Domains (3) summary
    smart00853
    Location:1156 → 1335
    MutL_C; MutL C terminal dimerisation domain
    cd03486
    Location:206 → 349
    MutL_Trans_MLH3; MutL_Trans_MLH3: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to ...
    cl28386
    Location:1 → 269
    MutL; DNA mismatch repair ATPase MutL [Replication, recombination and repair]

  3. XM_017021219.3 → XP_016876708.1  DNA mismatch repair protein Mlh3 isoform X2

    UniProtKB/TrEMBL
    Q2M1Z1
    Conserved Domains (3) summary
    smart00853
    Location:1191 → 1346
    MutL_C; MutL C terminal dimerisation domain
    cd03486
    Location:206 → 349
    MutL_Trans_MLH3; MutL_Trans_MLH3: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to ...
    pfam02518
    Location:22 → 115
    HATPase_c; Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase

  4. XM_006720116.5 → XP_006720179.1  DNA mismatch repair protein Mlh3 isoform X1

    See identical proteins and their annotated locations for XP_006720179.1

    UniProtKB/Swiss-Prot
    P49751, Q56DK9, Q9P292, Q9UHC0, Q9UHC1
    UniProtKB/TrEMBL
    Q2M1Z1
    Conserved Domains (3) summary
    smart00853
    Location:1191 → 1370
    MutL_C; MutL C terminal dimerisation domain
    cd03486
    Location:206 → 349
    MutL_Trans_MLH3; MutL_Trans_MLH3: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to ...
    pfam02518
    Location:22 → 115
    HATPase_c; Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase

  5. XM_005267533.6 → XP_005267590.1  DNA mismatch repair protein Mlh3 isoform X4

    UniProtKB/TrEMBL
    Q2M1Z1
    Conserved Domains (3) summary
    smart00853
    Location:1156 → 1311
    MutL_C; MutL C terminal dimerisation domain
    cd03486
    Location:206 → 349
    MutL_Trans_MLH3; MutL_Trans_MLH3: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to ...
    pfam02518
    Location:22 → 115
    HATPase_c; Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase

  6. XM_005267532.6 → XP_005267589.1  DNA mismatch repair protein Mlh3 isoform X3

    UniProtKB/TrEMBL
    Q2M1Z1
    Conserved Domains (3) summary
    smart00853
    Location:1156 → 1335
    MutL_C; MutL C terminal dimerisation domain
    cd03486
    Location:206 → 349
    MutL_Trans_MLH3; MutL_Trans_MLH3: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to ...
    cl28386
    Location:1 → 269
    MutL; DNA mismatch repair ATPase MutL [Replication, recombination and repair]

  7. XM_047431266.1 → XP_047287222.1  DNA mismatch repair protein Mlh3 isoform X5

  8. XM_047431268.1 → XP_047287224.1  DNA mismatch repair protein Mlh3 isoform X8

  9. XM_005267534.4 → XP_005267591.1  DNA mismatch repair protein Mlh3 isoform X7

    UniProtKB/TrEMBL
    Q2M1Z1
    Conserved Domains (3) summary
    smart00853
    Location:1191 → 1275
    MutL_C; MutL C terminal dimerisation domain
    cd03486
    Location:206 → 349
    MutL_Trans_MLH3; MutL_Trans_MLH3: transducer domain, having a ribosomal S5 domain 2-like fold, found in proteins similar to yeast and human MLH3 (MutL homologue 3). MLH3 belongs to the DNA mismatch repair (MutL/MLH1/PMS2) family. This transducer domain is homologous to ...
    pfam02518
    Location:22 → 115
    HATPase_c; Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase

  10. XM_047431267.1 → XP_047287223.1  DNA mismatch repair protein Mlh3 isoform X6

  11. XM_047431269.1 → XP_047287225.1  DNA mismatch repair protein Mlh3 isoform X9

RNA

  1. XR_007064005.1 RNA Sequence

  2. XR_007064004.1 RNA Sequence

  3. XR_001750225.3 RNA Sequence

  4. XR_245681.5 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060938.1 Alternate T2T-CHM13v2.0

    Range
    69222838..69260934 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054375855.1 → XP_054231830.1  DNA mismatch repair protein Mlh3 isoform X2

  2. XM_054375857.1 → XP_054231832.1  DNA mismatch repair protein Mlh3 isoform X3

  3. XM_054375859.1 → XP_054231834.1  DNA mismatch repair protein Mlh3 isoform X4

  4. XM_054375854.1 → XP_054231829.1  DNA mismatch repair protein Mlh3 isoform X1

  5. XM_054375858.1 → XP_054231833.1  DNA mismatch repair protein Mlh3 isoform X4

  6. XM_054375856.1 → XP_054231831.1  DNA mismatch repair protein Mlh3 isoform X3

  7. XM_054375860.1 → XP_054231835.1  DNA mismatch repair protein Mlh3 isoform X5

  8. XM_054375863.1 → XP_054231838.1  DNA mismatch repair protein Mlh3 isoform X8

  9. XM_054375862.1 → XP_054231837.1  DNA mismatch repair protein Mlh3 isoform X7

  10. XM_054375861.1 → XP_054231836.1  DNA mismatch repair protein Mlh3 isoform X6

  11. XM_054375864.1 → XP_054231839.1  DNA mismatch repair protein Mlh3 isoform X9

RNA

  1. XR_008488857.1 RNA Sequence

  2. XR_008488856.1 RNA Sequence

  3. XR_008488855.1 RNA Sequence

  4. XR_008488854.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UHC1.3 GenPept UniProtKB/Swiss-Prot:Q9UHC1

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