TISIDB

Summary
Symbol	MLH1
Name	mutL homolog 1
Aliases	FCC2; HNPCC2; COCA2; mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2); mutL homolog 1, colon can ......
Chromosomal Location	3p22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Nucleus
Domain	PF01119 DNA mismatch repair protein PF16413 DNA mismatch repair protein Mlh1 C-terminus
Function	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.

> Gene Ontology [ TOP ]
Biological Process	GO:0000018 regulation of DNA recombination GO:0000019 regulation of mitotic recombination GO:0000226 microtubule cytoskeleton organization GO:0000288 nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay GO:0000289 nuclear-transcribed mRNA poly(A) tail shortening GO:0000712 resolution of meiotic recombination intermediates GO:0000726 non-recombinational repair GO:0000956 nuclear-transcribed mRNA catabolic process GO:0002200 somatic diversification of immune receptors GO:0002204 somatic recombination of immunoglobulin genes involved in immune response GO:0002208 somatic diversification of immunoglobulins involved in immune response GO:0002250 adaptive immune response GO:0002263 cell activation involved in immune response GO:0002285 lymphocyte activation involved in immune response GO:0002312 B cell activation involved in immune response GO:0002366 leukocyte activation involved in immune response GO:0002377 immunoglobulin production GO:0002381 immunoglobulin production involved in immunoglobulin mediated immune response GO:0002440 production of molecular mediator of immune response GO:0002443 leukocyte mediated immunity GO:0002449 lymphocyte mediated immunity GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002562 somatic diversification of immune receptors via germline recombination within a single locus GO:0002566 somatic diversification of immune receptors via somatic mutation GO:0006298 mismatch repair GO:0006302 double-strand break repair GO:0006303 double-strand break repair via nonhomologous end joining GO:0006310 DNA recombination GO:0006312 mitotic recombination GO:0006401 RNA catabolic process GO:0006402 mRNA catabolic process GO:0007051 spindle organization GO:0007059 chromosome segregation GO:0007060 male meiosis chromosome segregation GO:0007126 meiotic nuclear division GO:0007127 meiosis I GO:0007129 synapsis GO:0007131 reciprocal meiotic recombination GO:0007140 male meiosis GO:0007143 female meiotic division GO:0007281 germ cell development GO:0007283 spermatogenesis GO:0007292 female gamete generation GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage GO:0016064 immunoglobulin mediated immune response GO:0016321 female meiosis chromosome segregation GO:0016444 somatic cell DNA recombination GO:0016445 somatic diversification of immunoglobulins GO:0016446 somatic hypermutation of immunoglobulin genes GO:0016447 somatic recombination of immunoglobulin gene segments GO:0019439 aromatic compound catabolic process GO:0019724 B cell mediated immunity GO:0022412 cellular process involved in reproduction in multicellular organism GO:0034397 telomere localization GO:0034655 nucleobase-containing compound catabolic process GO:0035825 reciprocal DNA recombination GO:0042113 B cell activation GO:0043060 meiotic metaphase I plate congression GO:0044270 cellular nitrogen compound catabolic process GO:0045132 meiotic chromosome segregation GO:0045141 meiotic telomere clustering GO:0045143 homologous chromosome segregation GO:0045190 isotype switching GO:0045910 negative regulation of DNA recombination GO:0045950 negative regulation of mitotic recombination GO:0046700 heterocycle catabolic process GO:0048232 male gamete generation GO:0048477 oogenesis GO:0050000 chromosome localization GO:0051052 regulation of DNA metabolic process GO:0051053 negative regulation of DNA metabolic process GO:0051225 spindle assembly GO:0051255 spindle midzone assembly GO:0051257 meiotic spindle midzone assembly GO:0051303 establishment of chromosome localization GO:0051304 chromosome separation GO:0051307 meiotic chromosome separation GO:0051310 metaphase plate congression GO:0051311 meiotic metaphase plate congression GO:0051321 meiotic cell cycle GO:0051640 organelle localization GO:0051656 establishment of organelle localization GO:0070192 chromosome organization involved in meiotic cell cycle GO:0090220 chromosome localization to nuclear envelope involved in homologous chromosome segregation GO:0097193 intrinsic apoptotic signaling pathway GO:0098813 nuclear chromosome segregation GO:1901361 organic cyclic compound catabolic process GO:1903046 meiotic cell cycle process
Molecular Function	GO:0003682 chromatin binding GO:0003697 single-stranded DNA binding GO:0016887 ATPase activity GO:0030983 mismatched DNA binding GO:0032137 guanine/thymine mispair binding GO:0032404 mismatch repair complex binding GO:0032407 MutSalpha complex binding
Cellular Component	GO:0000793 condensed chromosome GO:0000794 condensed nuclear chromosome GO:0000795 synaptonemal complex GO:0001673 male germ cell nucleus GO:0005712 chiasma GO:0032300 mismatch repair complex GO:0032389 MutLalpha complex GO:0043073 germ cell nucleus GO:0044454 nuclear chromosome part GO:1990391 DNA repair complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa03430 Mismatch repair hsa03460 Fanconi anemia pathway
Reactome	R-HSA-1640170: Cell Cycle R-HSA-73894: DNA Repair R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-1500620: Meiosis R-HSA-912446: Meiotic recombination R-HSA-5358508: Mismatch Repair R-HSA-5358606: Mismatch repair (MMR) directed by MSH2 R-HSA-5358565: Mismatch repair (MMR) directed by MSH2 R-HSA-6796648: TP53 Regulates Transcription of DNA Repair Genes R-HSA-3700989: Transcriptional Regulation by TP53

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa03430 Mismatch repair
hsa03460 Fanconi anemia pathway

Reactome

R-HSA-1640170: Cell Cycle
R-HSA-73894: DNA Repair
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-1500620: Meiosis
R-HSA-912446: Meiotic recombination
R-HSA-5358508: Mismatch Repair
R-HSA-5358606: Mismatch repair (MMR) directed by MSH2
R-HSA-5358565: Mismatch repair (MMR) directed by MSH2
R-HSA-6796648: TP53 Regulates Transcription of DNA Repair Genes
R-HSA-3700989: Transcriptional Regulation by TP53

Summary
Symbol	MLH1
Name	mutL homolog 1
Aliases	FCC2; HNPCC2; COCA2; mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2); mutL homolog 1, colon can ......
Chromosomal Location	3p22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MLH1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between MLH1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29186113	Colorectal Carcinoma	Inhibit immunity	Immune surveillance improved when cancer cells, in which MLH1 had been inactivated, accumulated neoantigens for several generations.

Summary
Symbol	MLH1
Name	mutL homolog 1
Aliases	FCC2; HNPCC2; COCA2; mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2); mutL homolog 1, colon can ......
Chromosomal Location	3p22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of MLH1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	MLH1
Name	mutL homolog 1
Aliases	FCC2; HNPCC2; COCA2; mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2); mutL homolog 1, colon can ......
Chromosomal Location	3p22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of MLH1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.205	0.259
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.429	0.812
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.04	0.976
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.012	0.959
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.23	0.9
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.318	0.892
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.166	0.625
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.103	0.946
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.221	0.895
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.64	0.62
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.06	0.975
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.107	0.0695

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of MLH1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	2.7	1	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	3.4	0.3	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	0	5.3	0.507
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	12.5	0	12.5	0.485
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	MLH1
Name	mutL homolog 1
Aliases	FCC2; HNPCC2; COCA2; mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2); mutL homolog 1, colon can ......
Chromosomal Location	3p22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MLH1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	MLH1
Name	mutL homolog 1
Aliases	FCC2; HNPCC2; COCA2; mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2); mutL homolog 1, colon can ......
Chromosomal Location	3p22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MLH1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MLH1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MLH1
Name	mutL homolog 1
Aliases	FCC2; HNPCC2; COCA2; mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2); mutL homolog 1, colon can ......
Chromosomal Location	3p22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MLH1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	MLH1
Name	mutL homolog 1
Aliases	FCC2; HNPCC2; COCA2; mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2); mutL homolog 1, colon can ......
Chromosomal Location	3p22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MLH1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MLH1
Name	mutL homolog 1
Aliases	FCC2; HNPCC2; COCA2; mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2); mutL homolog 1, colon can ......
Chromosomal Location	3p22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MLH1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MLH1
Name	mutL homolog 1
Aliases	FCC2; HNPCC2; COCA2; mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2); mutL homolog 1, colon can ......
Chromosomal Location	3p22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MLH1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

Browse MLH1