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mutLBSgeneDB |
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| Gene summary for MLH1 |
 Gene summary |
| Basic gene Info. | Gene symbol | MLH1 |
| Gene name | mutL homolog 1 | |
| Synonyms | COCA2|FCC2|HNPCC|HNPCC2|hMLH1 | |
| Cytomap | UCSC genome browser: 3p21.3 | |
| Type of gene | protein-coding | |
| RefGenes | NM_000249.3, NM_001167617.1,NM_001167618.1,NM_001167619.1,NM_001258271.1, NM_001258273.1,NM_001258274.1, | |
| Description | DNA mismatch repair protein Mlh1mutL homolog 1, colon cancer, nonpolyposis type 2 | |
| Modification date | 20141222 | |
| dbXrefs | MIM : 120436 | |
| HGNC : HGNC | ||
| Ensembl : ENSG00000076242 | ||
| HPRD : 00390 | ||
| Vega : OTTHUMG00000130797 | ||
| Protein | UniProt: P40692 go to UniProt's Cross Reference DB Table | |
| Expression | CleanEX: HS_MLH1 | |
| BioGPS: 4292 | ||
| Pathway | NCI Pathway Interaction Database: MLH1 | |
| KEGG: MLH1 | ||
| REACTOME: MLH1 | ||
| Pathway Commons: MLH1 | ||
| Context | iHOP: MLH1 | |
| ligand binding site mutation search in PubMed: MLH1 | ||
| UCL Cancer Institute: MLH1 | ||
| Assigned class in mutLBSgeneDB | C: This gene just belongs to mutLBSgenes. | |
| Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez |
| GO ID | GO Term | PubMed ID |
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| Ligand binding site mutations for MLH1 |
| Lollipop-style diagram of mutations at LBS in amino-acid sequence. We represented ligand binding site mutations only. (You can see big image via clicking.)  : non-synonymous mutation on LBS, Circle size denotes number of samples. |
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| Cancer type specific mutLBS sorted by frequency |
| LBS | AAchange of nsSNV | Cancer type | # samples | G101 | G101S | GBM | 1 | R100 | G98C | LUAD | 1 | G67 | G67W | UCEC | 1 |
| cf) Cancer type abbreviation. BLCA: Bladder urothelial carcinoma, BRCA: Breast invasive carcinoma, CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma, COAD: Colon adenocarcinoma, GBM: Glioblastoma multiforme, LGG: Brain lower grade glioma, HNSC: Head and neck squamous cell carcinoma, KICH: Kidney chromophobe, KIRC: Kidney renal clear cell carcinoma, KIRP: Kidney renal papillary cell carcinoma, LAML: Acute myeloid leukemia, LUAD: Lung adenocarcinoma, LUSC: Lung squamous cell carcinoma, OV: Ovarian serous cystadenocarcinoma, PAAD: Pancreatic adenocarcinoma, PRAD: Prostate adenocarcinoma, SKCM: Skin cutaneous melanoma, STAD: Stomach adenocarcinoma, THCA: Thyroid carcinoma, UCEC: Uterine corpus endometrial carcinoma. |
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| Protein structure related information for MLH1 |
| Relative protein structure stability change (ΔΔE) using Mupro 1.1 Mupro score denotes assessment of the effect of mutations on thermodynamic stability. (ΔΔE<0: mutation decreases stability, ΔΔE>0: mutation increases stability) |
 : nsSNV at non-LBS : nsSNV at LBS |
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| nsSNVs sorted by the relative stability change of protein structure by each mutation Blue: mutations of positive stability change. and red : the most recurrent mutation for this gene. |
| LBS | AAchange of nsSNV | Relative stability change | G67 | G67W | 0.25566089 | R100 | G98C | -0.42012087 | G101 | G101S | -0.031678505 |
| (MuPro1.1: Jianlin Cheng et al., Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines, PROTEINS: Structure, Function, and Bioinformatics. 2006, 62:1125-1132) |
| Structure image for MLH1 from PDB |
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| Differential gene expression and gene-gene network for MLH1 |
| Differential gene expression between mutated and non-mutated LBS samples in all 16 major cancer types |
| Differential co-expressed gene network based on protein-protein interaction data (CePIN) |
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| Phenotype information for MLH1 |
| Gene level disease information (DisGeNet) |
| Disease ID | Disease name | # PubMed | Association type |
| umls:C0009404 | Colorectal Neoplasms | 71 | AlteredExpression, Biomarker, GeneticVariation, PostTranslationalModification |
| umls:C0009405 | Colorectal Neoplasms, Hereditary Nonpolyposis | 51 | AlteredExpression, Biomarker, GeneticVariation |
| umls:C0265325 | Turcot syndrome | 43 | Biomarker, GeneticVariation |
| umls:C1321489 | Muir-Torre Syndrome | 21 | Biomarker, GeneticVariation |
| umls:C0027627 | Neoplasm Metastasis | 13 | Biomarker, GeneticVariation |
| umls:C0919267 | Ovarian Neoplasms | 11 | AlteredExpression, Biomarker, GeneticVariation, PostTranslationalModification |
| umls:C0024299 | Lymphoma | 8 | AlteredExpression, Biomarker |
| umls:C0033578 | Prostatic Neoplasms | 3 | Biomarker, GeneticVariation |
| umls:C0027672 | Neoplastic Syndromes, Hereditary | 2 | Biomarker, GeneticVariation |
| umls:C1333991 | Lynch Syndrome II | 1 | Biomarker, GeneticVariation |
| Mutation level pathogenic information (ClinVar annotation) |
| Allele ID | AA change | Clinical significance | Origin | Phenotype IDs |
| 32127 | G67W | Pathogenic | Germline | GeneReviews:NBK1211 MedGen:C0265325 OMIM:276300 Orphanet:ORPHA252202 Orphanet:ORPHA99817 SNOMED CT:61665008 GeneReviews:NBK1211 MedGen:C1333990 SNOMED CT:315058005 GeneReviews:NBK1211 MedGen:C1333991 OMIM:609310 Orphanet:ORPHA144 |
| 95611 | G101S | Uncertain significance | Germline | GeneReviews:NBK1211 MedGen:C1333990 SNOMED CT:315058005 |
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| Pharmacological information for MLH1 |
| Gene expression profile of anticancer drug treated cell-lines (CCLE) Heatmap showing the correlation between gene expression and drug response across all the cell-lines. We chose the top 20 among 138 drugs.We used Pearson's correlation coefficient. |
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| Drug information targeting mutLBSgene (Approved drugs only) |
| Drug status | DrugBank ID | Name | Type | Drug structure |
| Gene-centered ligand-gene interaction network |
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| Ligands binding to mutated ligand binding site of MLH1 go to BioLip |
| Ligand ID | Ligand short name | Ligand long name | PDB ID | PDB name | mutLBS | ATP | ATP | 3na3 | A | G67 R100 G101 | ADP | ADP | 4p7a | A | G67 R100 G101 |
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| Conservation information for LBS of MLH1 |
| Multiple alignments for P40692 in multiple species |
| LBS | AA sequence | # species | Species | A103 | GFRGEALASIS | 5 | Homo sapiens, Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Schizosaccharomyces pombe (strain 972 / ATCC 24843), Mus musculus, Rattus norvegicus | A103 | GFRGEALASMT | 1 | Arabidopsis thaliana | A42 | ENCLDAKSTNI | 2 | Mus musculus, Rattus norvegicus | A42 | ENCLDAKSTSI | 1 | Homo sapiens | A42 | ENSIDANATMI | 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | A42 | ENSLDAGSTSI | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | A42 | ENSLDADSSSI | 1 | Arabidopsis thaliana | D41 | IENCLDAKSTS | 1 | Homo sapiens | D41 | MENSIDANATM | 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | D41 | IENSLDAGSTS | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | D41 | VENSLDADSSS | 1 | Arabidopsis thaliana | D41 | IENCLDAKSTN | 1 | Mus musculus | D41 | TENCLDAKSTN | 1 | Rattus norvegicus | D63 | LIQIQDNGTGI | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | D63 | VLQITDNGSGI | 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | D63 | LLQITDNGSGI | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | D63 | LIQVSDDGHGI | 1 | Arabidopsis thaliana | E34 | ANAIKEMIENC | 2 | Homo sapiens, Mus musculus | E34 | VNALKEMMENS | 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | E34 | ENAIKELIENS | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | E34 | VSAVKELVENS | 1 | Arabidopsis thaliana | E34 | ANAIKEMTENC | 1 | Rattus norvegicus | G101 | TYGFRGEALAS | 4 | Homo sapiens, Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Mus musculus, Rattus norvegicus | G101 | TFGFRGEALAS | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | G101 | SMGFRGEALAS | 1 | Arabidopsis thaliana | G67 | QDNGTGIRKED | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | G67 | TDNGSGINKAD | 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | G67 | TDNGSGIQYDD | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | G67 | SDDGHGIRRED | 1 | Arabidopsis thaliana | I68 | DNGTGIRKEDL | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | I68 | DNGSGINKADL | 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | I68 | DNGSGIQYDDL | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | I68 | DDGHGIRREDL | 1 | Arabidopsis thaliana | K84 | RFTTSKLQTFE | 2 | Mus musculus, Rattus norvegicus | K84 | RFTTSKLQSFE | 1 | Homo sapiens | K84 | RFTTSKLQKFE | 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | K84 | RFSTSKIDNFN | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | K84 | RHTTSKLTKFE | 1 | Arabidopsis thaliana | L91 | QSFEDLASIST | 1 | Homo sapiens | L91 | QKFEDLSQIQT | 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | L91 | DNFNDLQHLQT | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | L91 | TKFEDLFSLSS | 1 | Arabidopsis thaliana | L91 | QTFEDLASIST | 1 | Mus musculus | L91 | QTFEDLAMIST | 1 | Rattus norvegicus | N38 | KEMIENCLDAK | 2 | Homo sapiens, Mus musculus | N38 | KEMMENSIDAN | 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | N38 | KELIENSLDAG | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | N38 | KELVENSLDAD | 1 | Arabidopsis thaliana | N38 | KEMTENCLDAK | 1 | Rattus norvegicus | R100 | STYGFRGEALA | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | R100 | QTYGFRGEALA | 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | R100 | QTFGFRGEALA | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | R100 | SSMGFRGEALA | 1 | Arabidopsis thaliana | S83 | ERFTTSKLQTF | 2 | Mus musculus, Rattus norvegicus | S83 | ERFTTSKLQSF | 1 | Homo sapiens | S83 | ERFTTSKLQKF | 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | S83 | QRFSTSKIDNF | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | S83 | ERHTTSKLTKF | 1 | Arabidopsis thaliana | T148 | AGNQGTLITVE | 2 | Mus musculus, Rattus norvegicus | T148 | AGNQGTQITVE | 1 | Homo sapiens | T148 | AGKDGTTILVE | 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | T148 | AGKQGTVITAE | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | T148 | AAVKGTQIMVE | 1 | Arabidopsis thaliana | T81 | VCERFTTSKLQ | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | T81 | LCERFTTSKLQ | 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | T81 | LCQRFSTSKID | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | T81 | LCERHTTSKLT | 1 | Arabidopsis thaliana | T82 | CERFTTSKLQT | 2 | Mus musculus, Rattus norvegicus | T82 | CERFTTSKLQS | 1 | Homo sapiens | T82 | CERFTTSKLQK | 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | T82 | CQRFSTSKIDN | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | T82 | CERHTTSKLTK | 1 | Arabidopsis thaliana | V76 | EDLDIVCERFT | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | V76 | ADLPILCERFT | 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | V76 | DDLPYLCQRFS | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | V76 | EDLPILCERHT | 1 | Arabidopsis thaliana |
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