MLH1 [The Human Chemical-Genetic Interaction Map Project]

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======= MLH1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: MLH1
  * **<color #00a2e8>Official Name</color>**: mutL homolog 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=4292|4292]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P40692|P40692]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=MLH1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20MLH1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/120436|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH6) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS- heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with MLH3 to form MutL gamma which plays a role in meiosis. {ECO:0000269|PubMed:16873062, ECO:0000269|PubMed:18206974, ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:9311737}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|HATPase c|
|DNA mis repair|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|late recombination nodule|
|meiotic spindle midzone assembly|
|meiotic metaphase plate congression|
|meiotic metaphase I plate congression|
|chiasma|
|negative regulation of mitotic recombination|
|male meiosis chromosome segregation|
|guanine/thymine mispair binding|
|positive regulation of isotype switching to IgA isotypes|
|female meiosis chromosome segregation|
|regulation of isotype switching to IgA isotypes|
|regulation of mitotic recombination|
|MutSalpha complex binding|
|MutLalpha complex|
|spindle midzone assembly|
|positive regulation of isotype switching to IgG isotypes|
|meiotic telomere clustering|
|regulation of isotype switching to IgG isotypes|
|chromosome localization to nuclear envelope involved in homologous chromosome segregation|
|telomere localization|
|mismatch repair complex|
|male germ cell nucleus|
|somatic hypermutation of immunoglobulin genes|
|resolution of meiotic recombination intermediates|
|somatic diversification of immune receptors via somatic mutation|
|somatic diversification of immunoglobulins involved in immune response|
|somatic recombination of immunoglobulin genes involved in immune response|
|isotype switching|
|meiotic chromosome separation|
|nuclear-transcribed mRNA poly(A) tail shortening|
|somatic recombination of immunoglobulin gene segments|
|synaptonemal complex|
|positive regulation of isotype switching|
|immunoglobulin production involved in immunoglobulin mediated immune response|
|female meiotic nuclear division|
|chromosome separation|
|regulation of isotype switching|
|mismatch repair|
|somatic diversification of immunoglobulins|
|somatic diversification of immune receptors via germline recombination within a single locus|
|somatic cell DNA recombination|
|positive regulation of B cell mediated immunity|
|positive regulation of immunoglobulin mediated immune response|
|positive regulation of DNA recombination|
|positive regulation of immunoglobulin production|
|B cell activation involved in immune response|
|negative regulation of DNA recombination|
|synapsis|
|male meiotic nuclear division|
|somatic diversification of immune receptors|
|regulation of B cell mediated immunity|
|regulation of immunoglobulin mediated immune response|
|reciprocal meiotic recombination|
|homologous recombination|
|metaphase plate congression|
|homologous chromosome segregation|
|double-strand break repair via nonhomologous end joining|
|nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay|
|regulation of immunoglobulin production|
|non-recombinational repair|
|chromosome organization involved in meiotic cell cycle|
|intrinsic apoptotic signaling pathway in response to DNA damage|
|establishment of chromosome localization|
|chromosome localization|
|oogenesis|
|meiotic chromosome segregation|
|positive regulation of production of molecular mediator of immune response|
|spindle assembly|
|positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|regulation of DNA recombination|
|positive regulation of lymphocyte mediated immunity|
|positive regulation of adaptive immune response|
|single-stranded DNA binding|
|meiosis I|
|lymphocyte activation involved in immune response|
|meiosis I cell cycle process|
|negative regulation of DNA metabolic process|
|female gamete generation|
|positive regulation of leukocyte mediated immunity|
|regulation of production of molecular mediator of immune response|
|regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|intrinsic apoptotic signaling pathway|
|regulation of lymphocyte mediated immunity|
|meiotic nuclear division|
|B cell activation|
|spindle organization|
|immunoglobulin production|
|regulation of adaptive immune response|
|meiotic cell cycle process|
|positive regulation of B cell activation|
|production of molecular mediator of immune response|
|double-strand break repair|
|positive regulation of DNA metabolic process|
|nuclear-transcribed mRNA catabolic process|
|regulation of leukocyte mediated immunity|
|immunoglobulin mediated immune response|
|regulation of B cell activation|
|B cell mediated immunity|
|mRNA catabolic process|
|positive regulation of immune effector process|
|nuclear chromosome segregation|
|DNA recombination|
|meiotic cell cycle|
|ATPase activity|
|RNA catabolic process|
|germ cell development|
|lymphocyte mediated immunity|
|chromosome segregation|
|adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|apoptotic signaling pathway|
|nuclear division|
|organelle fission|
|enzyme binding|
|cellular process involved in reproduction in multicellular organism|
|regulation of DNA metabolic process|
|positive regulation of lymphocyte activation|
|establishment of organelle localization|
|nucleobase-containing compound catabolic process|
|lymphocyte activation|
|chromatin binding|
|positive regulation of leukocyte activation|
|positive regulation of cell activation|
|heterocycle catabolic process|
|cellular nitrogen compound catabolic process|
|aromatic compound catabolic process|
|regulation of immune effector process|
|microtubule cytoskeleton organization|
|organic cyclic compound catabolic process|
|DNA repair|
|regulation of lymphocyte activation|
|spermatogenesis|
|male gamete generation|
|organelle localization|
|regulation of leukocyte activation|
|adaptive immune response|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|regulation of cell activation|
|immune system development|
|developmental process involved in reproduction|
|microtubule-based process|
|response to bacterium|
|gamete generation|
|mRNA metabolic process|
|DNA metabolic process|
|organelle assembly|
|leukocyte mediated immunity|
|cellular response to DNA damage stimulus|
|multicellular organismal reproductive process|
|sexual reproduction|
|multicellular organism reproduction|
|positive regulation of immune response|
|cellular macromolecule catabolic process|
|apoptotic process|
|leukocyte activation|
|multi-organism reproductive process|
|cell cycle process|
|macromolecule catabolic process|
|programmed cell death|
|chromosome organization|
|cell activation|
|immune effector process|
|cell death|
|cytoskeleton organization|
|regulation of immune response|
|positive regulation of immune system process|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|cell cycle|
|positive regulation of developmental process|
|reproductive process|
|reproduction|
|negative regulation of nucleobase-containing compound metabolic process|
|ATP binding|
|cell development|
|regulation of immune system process|
|RNA metabolic process|
|intracellular signal transduction|
|cellular response to stress|
|negative regulation of gene expression|
|positive regulation of multicellular organismal process|
|organic substance catabolic process|
|cellular catabolic process|
|establishment of localization in cell|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|membrane|
</modal>
\\

 === CRISPR Data ===
<button type='default' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
No hits were found.
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:h:hgc6.3|HGC6.3]]|0.608|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 7253
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.29 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='MLH1 Expression in NALM6 Cells: 6.29'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>