MISMATCH REPAIR PATHWAY (PW:0000662)
Description
DNA
mismatch repair (MMR) represents a highly conserved pathway that assures the correct
base matching of the duplex. Despite the high replication fidelity of
polymerases, mismatched bases may be introduced into the daughter strand during
DNA replication; small deletion/insertion loops may be introduced during replication
of repetitive DNA tracts. If uncorrected, mismatches will give rise to potentially
deleterious mutations. MMR pathway has been well studied and characterized in E. coli. In eukaryotes, the best characterized
system is
S. cerevisiae ; human
components have been identified and assayed in cell extracts and reconstituted
systems.
E. coli MMR is initiated by
recognition of mismatched bases by MutS; MutL relays MutS activity to downstream
events. Msh proteins are the mammalian counterparts of MutS; Mlh and Pms
proteins are the counterparts of MutL. Base excision is mediated by Exo1; protection
of ssDNA and prevention of hairpin formation is provided by Rpa - a trimeric
single-stranded DNA-binding protein complex. Repair of the single-stranded gap
involves re-synthesis and ligation carried out by DNA polymerase delta and DNA
ligase 1. Several polymerases maintain the integrity of the genome by carrying
out DNA replication, recombination and repair. Delta and epsilon polymerases are
involved in DNA replication and in DNA base and strand repair pathways; only delta
appears to be specifically involved in MMR. Base excision and nucleotide
excision are base repair pathways that fix DNA damaged by exogenous or
endogenous agents. Polymerase delta requires a moving platform; this is
provided by the processivity factor Pcna (known as the clamp) and a pentameric
protein complex Rfc (Replication factor C) that loads it (known as the
clamp-loader). Rfc binds the ring shaped Pcna in the presence of ATP; ATP-bound
Rfc binds DNA and this event prompts ATP hydrolysis and ejection of the Rfc
complex. The now closed Pcna clamp on DNA is in the proper orientation for use
by the polymerase. Delta polymerase and Rcf appear to bind/compete for the same
site on the Pcna clamp. Interactions between components of MMR and between some
of these components and other proteins have been established; the significance
of many remains elusive. And so are many of the molecular details of the
pathway such as strand specificity and recognition or Rpa clearance amongst
them. Alterations in MMR pathway have been implicated in colorectal and other
forms of cancer.
To see the ontology report for annotations, GViewer and
download, click here [click to see the ontology
report for associated GO term - GO:0006298 and KEGG map - map03430 ]...(less)
Pathway Diagram:
Genes in Pathway:
G
Exo1 exonuclease 1
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr13:87,809,725...87,834,654
G
Hmgb1 high mobility group box 1
ISO RGD
PMID:18157157 RGD:2306716
NCBI chr12:5,972,950...5,979,658
G
Lig1 DNA ligase 1
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr 1:74,165,688...74,204,400
G
Mlh1 mutL homolog 1
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr 8:111,196,468...111,233,721
G
Mlh3 mutL homolog 3
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr 6:104,881,483...104,917,686
G
Msh2 mutS homolog 2
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr 6:6,813,793...6,872,960
G
Msh3 mutS homolog 3
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr 2:23,444,326...23,585,777
G
Msh6 mutS homolog 6
ISO RGD
PMID:18157157 RGD:2306716
NCBI chr 6:6,562,631...6,579,995
G
Pcna proliferating cell nuclear antigen
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr 3:119,499,039...119,502,911
G
Pms1 PMS1 homolog 1, mismatch repair system component
ISO RGD
PMID:18157157 RGD:2306716
NCBI chr 9:48,229,403...48,340,237
G
Pms2 PMS1 homolog 2, mismatch repair system component
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr12:10,676,818...10,701,161
G
Pold1 DNA polymerase delta 1, catalytic subunit
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr 1:95,025,462...95,041,559
G
Pold2 DNA polymerase delta 2, accessory subunit
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr14:80,748,971...80,755,188
G
Pold3 DNA polymerase delta 3, accessory subunit
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr 1:154,417,893...154,456,687
G
Pold4 DNA polymerase delta 4, accessory subunit
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr 1:201,526,591...201,528,406
G
Rfc1 replication factor C subunit 1
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr14:42,966,279...43,041,372
G
Rfc2 replication factor C subunit 2
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr12:22,120,449...22,133,576
G
Rfc3 replication factor C subunit 3
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr12:1,000,987...1,011,778
G
Rfc4 replication factor C subunit 4
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr11:77,749,642...77,764,123
G
Rfc5 replication factor C subunit 5
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr12:39,207,484...39,217,041
G
Rpa1 replication protein A1
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr10:60,148,869...60,199,970
G
Rpa2 replication protein A2
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr 5:144,976,789...144,989,445
G
Rpa3 replication protein A3
ISO IEA KEGG PMID:18157157 rno:03430, RGD:2306716
NCBI chr 4:36,304,649...36,307,755
G
Ssbp1 single stranded DNA binding protein 1
IEA KEGG rno:03430
NCBI chr 4:69,266,024...69,276,135
G
Mlh1 mutL homolog 1
ISO RGD
PMID:11900875 PMID:19078924 RGD:2306714 , RGD:4143515
NCBI chr 8:111,196,468...111,233,721
G
Msh2 mutS homolog 2
ISO RGD
PMID:11900875 RGD:2306714
NCBI chr 6:6,813,793...6,872,960
G
Msh6 mutS homolog 6
ISO RGD
PMID:11900875 RGD:2306714
NCBI chr 6:6,562,631...6,579,995
G
Pms1 PMS1 homolog 1, mismatch repair system component
ISO RGD
PMID:11900875 RGD:2306714
NCBI chr 9:48,229,403...48,340,237
G
Pms2 PMS1 homolog 2, mismatch repair system component
ISO RGD
PMID:11900875 RGD:2306714
NCBI chr12:10,676,818...10,701,161
Pathway Gene Annotations
Disease Annotations Associated with Genes in the mismatch repair pathway
Exo1 Breast Neoplasms , Colorectal Neoplasms , COVID-19 , developmental and epileptic encephalopathy 54 , fumarase deficiency , gastrointestinal stromal tumor , hepatocellular carcinoma , hereditary breast ovarian cancer syndrome , Hereditary Leiomyomatosis and Renal Cell Cancer , Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 2 , Neurodevelopmental Disorders , parathyroid carcinoma Hmgb1 Acute Experimental Pancreatitis , Acute Lung Injury , Acute-On-Chronic Liver Failure , Alzheimer's disease , amyotrophic lateral sclerosis , atherosclerosis , Brachyphalangy, Polydactyly, and Tibial Aplasia/Hypoplasia , brain infarction , Brain Injuries , Burns , Cardiomegaly , cerebral infarction , Chemical and Drug Induced Liver Injury , Chronic Allograft Dysfunction , colon adenocarcinoma , congestive heart failure , Drug-Related Side Effects and Adverse Reactions , Endotoxemia , esophagus squamous cell carcinoma , essential hypertension , Experimental Arthritis , Experimental Autoimmune Myocarditis , Experimental Colitis , Experimental Diabetes Mellitus , extrahepatic cholestasis , Fever , genetic disease , Heat Stroke , high grade glioma , hydrocephalus , Hyperalgesia , hypertension , Inflammation , Intestinal Reperfusion Injury , Kawasaki disease , Knee Osteoarthritis , leukostasis , Liver Reperfusion Injury , Lung Reperfusion Injury , Lymphatic Metastasis , middle cerebral artery infarction , Multiple Organ Failure , myocardial infarction , Myocardial Ischemia , Myocardial Reperfusion Injury , Necrosis , Neuralgia , obstructive jaundice , osteoarthritis , Oxygen-Induced Retinopathy , Painful Neuropathy , periodontitis , Premature Aging , pulmonary fibrosis , pulmonary hypertension , Reperfusion Injury , Retina Reperfusion Injury , sciatic neuropathy , Sepsis , Spinal Cord Injuries , systemic scleroderma , Systemic Vasculitis , transient cerebral ischemia , Ventilator-Induced Lung Injury Lig1 epilepsy with generalized tonic-clonic seizures , Immunodeficiency 96 , inherited metabolic disorder , primary immunodeficiency disease , urinary bladder cancer Mlh1 adrenocortical carcinoma , bile duct cancer , breast cancer , Breast Cancer, Familial , breast carcinoma , cataract , cervix uteri carcinoma in situ , colon cancer , colon carcinoma , Colonic Neoplasms , colorectal cancer , Colorectal Neoplasms , Developmental Disabilities , endometrial carcinoma , Endometrial Neoplasms , esophagus squamous cell carcinoma , gastric adenocarcinoma , Germ Cell and Embryonal Neoplasms , hereditary breast ovarian cancer syndrome , Hereditary Neoplastic Syndromes , hereditary nonpolyposis colorectal cancer type 2 , Hydatidiform Mole , hydrocephalus , Intestinal Polyps , laryngeal squamous cell carcinoma , lung adenocarcinoma , lung cancer , lung carcinoma , lung non-small cell carcinoma , lymphoma , Lynch syndrome , Lynch syndrome 1 , malignant pleural mesothelioma , mismatch repair cancer syndrome , Mismatch Repair Cancer Syndrome 1 , Muir-Torre syndrome , Multiple Primary Neoplasms , Neoplasm Metastasis , ovarian cancer , Ovarian Neoplasms , peritoneal carcinoma , Prostatic Neoplasms , renal cell carcinoma , sporadic breast cancer , squamous cell carcinoma , stomach cancer , urinary bladder cancer , Uterine Cervical Neoplasms , Visceral Heterotaxy 4, Autosomal , Vulvar Neoplasms Mlh3 breast cancer , Breast Cancer, Familial , breast carcinoma , colon carcinoma , colorectal cancer , Colorectal Neoplasms , endometrial cancer , endometrial carcinoma , Endometrial Neoplasms , Esophageal Neoplasms , Hereditary Neoplastic Syndromes , hereditary nonpolyposis colorectal cancer type 7 , IDH-mutant anaplastic astrocytoma , intellectual disability , Leukoencephalopathies , leukoencephalopathy with vanishing white matter , Lynch syndrome , Lynch syndrome 1 , ovarian cancer , primary ovarian insufficiency Msh2 ascending colon cancer , bile duct cancer , breast cancer , breast carcinoma , cervix uteri carcinoma in situ , colitis , colon cancer , colon carcinoma , Colon Diverticulum , Colonic Polyps , colorectal adenocarcinoma , colorectal cancer , Colorectal Neoplasms , endometrial carcinoma , Endometrial Neoplasms , esophagus squamous cell carcinoma , Germ Cell and Embryonal Neoplasms , glioblastoma , hepatoblastoma , hereditary breast ovarian cancer syndrome , Hereditary Neoplastic Syndromes , hereditary nonpolyposis colorectal cancer type 2 , hereditary nonpolyposis colorectal cancer type 4 , high grade glioma , Huntington's disease , Hydatidiform Mole , Hydatidiform Mole, Invasive , laryngeal squamous cell carcinoma , lung adenocarcinoma , lung cancer , lung non-small cell carcinoma , Lymphatic Metastasis , Lynch syndrome , Lynch syndrome 1 , mismatch repair cancer syndrome , Mismatch Repair Cancer Syndrome 1 , Mismatch Repair Cancer Syndrome 2 , Muir-Torre syndrome , Neoplasm Metastasis , oculocutaneous albinism type IV , osteosarcoma , ovarian cancer , ovarian cyst , Ovarian Neoplasms , Pitt-Hopkins-like syndrome 2 , prostate cancer , renal cell carcinoma , Renal Cell Carcinoma 1 , rhabdomyosarcoma , sarcoma , sigmoid colon cancer , sigmoid neoplasm , stomach cancer , transitional cell carcinoma , urinary bladder cancer , Urogenital Neoplasms , Uterine Cervical Neoplasms , uterine corpus cancer , visual epilepsy , Vulvar Neoplasms Msh3 cavernous sinus meningioma , colorectal carcinoma , Digestive System Neoplasms , endometrial cancer , endometrial carcinoma , Endometrial Neoplasms , familial adenomatous polyposis , familial adenomatous polyposis 4 , gastrointestinal stromal tumor , hepatocellular carcinoma , Hereditary Neoplastic Syndromes , lung adenocarcinoma , lung cancer , lung non-small cell carcinoma , Megaloblastic Anemia due to Dihydrofolate Reductase Deficiency , Microsatellite Instability , Neurodevelopmental Disorders , Prostatic Neoplasms Msh6 adrenocortical carcinoma , ataxia telangiectasia , autosomal recessive limb-girdle muscular dystrophy type 2B , autosomal recessive nonsyndromic deafness 3 , autosomal recessive progressive external ophthalmoplegia 1 , B-lymphoblastic leukemia/lymphoma with BCR-ABL1 , bilateral breast cancer , breast cancer , Breast Cancer, Familial , breast carcinoma , CEREBELLAR ATAXIA INFANTILE WITH PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA , cerebellar medulloblastoma , colon adenocarcinoma , colon carcinoma , colorectal cancer , colorectal carcinoma , Colorectal Neoplasms , Digestive System Neoplasms , endometrial cancer , endometrial carcinoma , Endometrial Neoplasms , endometrial serous adenocarcinoma , Familial Prostate Cancer , Gaucher's disease , Gaucher's disease type I , genetic disease , Genetic Predisposition to Disease , hepatoblastoma , hereditary breast ovarian cancer syndrome , Hereditary Neoplastic Syndromes , hereditary nonpolyposis colorectal cancer type 4 , hereditary nonpolyposis colorectal cancer type 5 , INTELLECTUAL DEVELOPMENTAL DISORDER WITH DYSMORPHIC FACIES AND BEHAVIORAL ABNORMALITIES , lung adenocarcinoma , lung sarcomatoid carcinoma , Lynch syndrome , Lynch syndrome 1 , Microsatellite Instability , mismatch repair cancer syndrome , Mismatch Repair Cancer Syndrome 1 , Mismatch Repair Cancer Syndrome 3 , Neurodevelopmental Disorders , osteosarcoma , ovarian cancer , ovarian carcinoma , Ovarian Neoplasms , Pitt-Hopkins-like syndrome 2 , progressive myoclonus epilepsy 5 , prostate cancer , rhabdomyosarcoma , sensory ataxic neuropathy, dysarthria, and ophthalmoparesis , sigmoid colon cancer , sigmoid neoplasm , stomach cancer , Thyroid Neoplasms , urinary bladder cancer , Urogenital Neoplasms , uterine corpus cancer , xeroderma pigmentosum group D Pcna adenocarcinoma , Ataxia Telangiectasia Like Disorder , ataxia-telangiectasia-like disorder-2 , brain ischemia , Brain Neoplasms , Breast Neoplasms , Carotid Artery Injuries , Chagas Cardiomyopathy , Colonic Neoplasms , Experimental Mammary Neoplasms , Experimental Neoplasms , Experimental Radiation Injuries , focal segmental glomerulosclerosis , Germ Cell and Embryonal Neoplasms , hepatoblastoma , hepatocellular carcinoma , Huntington's disease-like 1 , hypothyroidism , Inosine Triphosphatase Deficiency , Intimal Hyperplasia , invasive ductal carcinoma , ischemia , leiomyoma , Lewy body dementia , liver cancer , Liver Injury , Lung Neoplasms , mucositis , Neoplasm Metastasis , nephroblastoma , obstructive jaundice , osteoporosis , pantothenate kinase-associated neurodegeneration , Phyllodes Tumor , psoriasis , Pulmonary Hypertension, Hypoxia-Induced , renal cell carcinoma , sciatic neuropathy , seminoma , stomach cancer , Testicular Neoplasms , transient cerebral ischemia Pms1 breast cancer , Colonic Polyps , colorectal cancer , Colorectal Neoplasms , dermatomyositis , hereditary breast ovarian cancer syndrome , immunodeficiency 31B , Lynch syndrome , Lynch syndrome 1 , Neurodevelopmental Disorders , ovarian cancer , pancreatic ductal carcinoma , polymyositis , Prostatic Neoplasms Pms2 autosomal recessive progressive external ophthalmoplegia 1 , Brain Neoplasms , breast cancer , Breast Cancer, Familial , breast carcinoma , Breast Neoplasms , Cafe-au-Lait Spots , colon cancer , colon carcinoma , Colonic Neoplasms , Colonic Polyps , Colorectal Neoplasms , diffuse large B-cell lymphoma , diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype , dilated cardiomyopathy 1G , endometrial carcinoma , hepatocellular carcinoma , hereditary breast ovarian cancer syndrome , Hereditary Neoplastic Syndromes , hereditary nonpolyposis colorectal cancer type 4 , hereditary nonpolyposis colorectal cancer type 5 , hypertrophic cardiomyopathy 9 , Lynch syndrome , Lynch syndrome 1 , mismatch repair cancer syndrome , Mismatch Repair Cancer Syndrome 1 , Mismatch Repair Cancer Syndrome 4 , Neoplasm Metastasis , ovarian cancer , Ovarian Neoplasms , pituitary carcinoma , Primitive Neuroectodermal Tumors , prostate cancer , Pulmonary Arterial Hypertension , rhabdomyosarcoma , stomach cancer , Supratentorial Neoplasms , urinary bladder cancer Pold1 bile duct cancer , breast cancer , colon cancer , colon carcinoma , colorectal cancer , Colorectal Cancer 10 , colorectal carcinoma , Colorectal Neoplasms , congenital myopathy 1A , Deafness , Drug-induced Neutropenia , endometrial carcinoma , Endometrial Neoplasms , extrahepatic bile duct carcinoma , familial adenomatous polyposis , Hereditary Neoplastic Syndromes , hypogonadism , intellectual disability , Jaw Abnormalities , lipodystrophy , lung adenocarcinoma , Mandibular Hypoplasia, Deafness, Progeroid Features, and Lipodystrophy Syndrome , Multiple Abnormalities , ovarian cancer , pancreatic carcinoma Pold2 pleomorphic xanthoastrocytoma Pold3 3-methylglutaconic aciduria type 7b , Colorectal Neoplasms , Immunodeficiency 122 , intellectual disability Pold4 Aicardi-Goutieres Syndrome 3 , intellectual disability , Recurrent Infections, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations Rfc1 Bilateral Vestibulopathy , cerebellar ataxia , Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome , Colonic Neoplasms , congenital heart disease , genetic disease , hereditary breast ovarian cancer syndrome , Hyperglycinemia, Lactic Acidosis, and Seizures , motor peripheral neuropathy , osteosarcoma , primary pulmonary hypertension , Right Ventricular Hypertrophy , West Nile fever Rfc2 autism spectrum disorder , autistic disorder , intestinal volvulus , Neurodevelopmental Disorders , pleomorphic xanthoastrocytoma , schizophrenia , Volvulus Of Midgut , Williams-Beuren syndrome Rfc4 3MC syndrome 1 , Animal Disease Models , lung adenocarcinoma Rpa1 Chloracne , Pulmonary Fibrosis and/or Bone Marrow Failure Syndrome, Telomere-Related, 6 Ssbp1 Arsenic Poisoning , cone-rod dystrophy , genetic disease , Hereditary Pancreatitis , Optic Atrophy 13 , RASopathy , Sengers syndrome , skin disease
3-methylglutaconic aciduria type 7b Pold3 3MC syndrome 1 Rfc4 Acute Experimental Pancreatitis Hmgb1 Acute Lung Injury Hmgb1 Acute-On-Chronic Liver Failure Hmgb1 adenocarcinoma Pcna adrenocortical carcinoma Mlh1 , Msh6 Aicardi-Goutieres Syndrome 3 Pold4 Alzheimer's disease Hmgb1 amyotrophic lateral sclerosis Hmgb1 Animal Disease Models Rfc4 Arsenic Poisoning Ssbp1 ascending colon cancer Msh2 ataxia telangiectasia Msh6 Ataxia Telangiectasia Like Disorder Pcna ataxia-telangiectasia-like disorder-2 Pcna atherosclerosis Hmgb1 autism spectrum disorder Rfc2 autistic disorder Rfc2 autosomal recessive limb-girdle muscular dystrophy type 2B Msh6 autosomal recessive nonsyndromic deafness 3 Msh6 autosomal recessive progressive external ophthalmoplegia 1 Msh6 , Pms2 B-lymphoblastic leukemia/lymphoma with BCR-ABL1 Msh6 bilateral breast cancer Msh6 Bilateral Vestibulopathy Rfc1 bile duct cancer Mlh1 , Msh2 , Pold1 Brachyphalangy, Polydactyly, and Tibial Aplasia/Hypoplasia Hmgb1 brain infarction Hmgb1 Brain Injuries Hmgb1 brain ischemia Pcna Brain Neoplasms Pcna , Pms2 breast cancer Mlh1 , Mlh3 , Msh2 , Msh6 , Pms1 , Pms2 , Pold1 Breast Cancer, Familial Mlh1 , Mlh3 , Msh6 , Pms2 breast carcinoma Mlh1 , Mlh3 , Msh2 , Msh6 , Pms2 Breast Neoplasms Exo1 , Pcna , Pms2 Burns Hmgb1 Cafe-au-Lait Spots Pms2 Cardiomegaly Hmgb1 Carotid Artery Injuries Pcna cataract Mlh1 cavernous sinus meningioma Msh3 cerebellar ataxia Rfc1 CEREBELLAR ATAXIA INFANTILE WITH PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA Msh6 Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome Rfc1 cerebellar medulloblastoma Msh6 cerebral infarction Hmgb1 cervix uteri carcinoma in situ Mlh1 , Msh2 Chagas Cardiomyopathy Pcna Chemical and Drug Induced Liver Injury Hmgb1 Chloracne Rpa1 Chronic Allograft Dysfunction Hmgb1 colitis Msh2 colon adenocarcinoma Hmgb1 , Msh6 colon cancer Mlh1 , Msh2 , Pms2 , Pold1 colon carcinoma Mlh1 , Mlh3 , Msh2 , Msh6 , Pms2 , Pold1 Colon Diverticulum Msh2 Colonic Neoplasms Mlh1 , Pcna , Pms2 , Rfc1 Colonic Polyps Msh2 , Pms1 , Pms2 colorectal adenocarcinoma Msh2 colorectal cancer Mlh1 , Mlh3 , Msh2 , Msh6 , Pms1 , Pold1 Colorectal Cancer 10 Pold1 colorectal carcinoma Msh3 , Msh6 , Pold1 Colorectal Neoplasms Exo1 , Mlh1 , Mlh3 , Msh2 , Msh6 , Pms1 , Pms2 , Pold1 , Pold3 cone-rod dystrophy Ssbp1 congenital heart disease Rfc1 congenital myopathy 1A Pold1 congestive heart failure Hmgb1 COVID-19 Exo1 Deafness Pold1 dermatomyositis Pms1 developmental and epileptic encephalopathy 54 Exo1 Developmental Disabilities Mlh1 diffuse large B-cell lymphoma Pms2 diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype Pms2 Digestive System Neoplasms Msh3 , Msh6 dilated cardiomyopathy 1G Pms2 Drug-induced Neutropenia Pold1 Drug-Related Side Effects and Adverse Reactions Hmgb1 endometrial cancer Mlh3 , Msh3 , Msh6 endometrial carcinoma Mlh1 , Mlh3 , Msh2 , Msh3 , Msh6 , Pms2 , Pold1 Endometrial Neoplasms Mlh1 , Mlh3 , Msh2 , Msh3 , Msh6 , Pold1 endometrial serous adenocarcinoma Msh6 Endotoxemia Hmgb1 epilepsy with generalized tonic-clonic seizures Lig1 Esophageal Neoplasms Mlh3 esophagus squamous cell carcinoma Hmgb1 , Mlh1 , Msh2 essential hypertension Hmgb1 Experimental Arthritis Hmgb1 Experimental Autoimmune Myocarditis Hmgb1 Experimental Colitis Hmgb1 Experimental Diabetes Mellitus Hmgb1 Experimental Mammary Neoplasms Pcna Experimental Neoplasms Pcna Experimental Radiation Injuries Pcna extrahepatic bile duct carcinoma Pold1 extrahepatic cholestasis Hmgb1 familial adenomatous polyposis Msh3 , Pold1 familial adenomatous polyposis 4 Msh3 Familial Prostate Cancer Msh6 Fever Hmgb1 focal segmental glomerulosclerosis Pcna fumarase deficiency Exo1 gastric adenocarcinoma Mlh1 gastrointestinal stromal tumor Exo1 , Msh3 Gaucher's disease Msh6 Gaucher's disease type I Msh6 genetic disease Hmgb1 , Msh6 , Rfc1 , Ssbp1 Genetic Predisposition to Disease Msh6 Germ Cell and Embryonal Neoplasms Mlh1 , Msh2 , Pcna glioblastoma Msh2 Heat Stroke Hmgb1 hepatoblastoma Msh2 , Msh6 , Pcna hepatocellular carcinoma Exo1 , Msh3 , Pcna , Pms2 hereditary breast ovarian cancer syndrome Exo1 , Mlh1 , Msh2 , Msh6 , Pms1 , Pms2 , Rfc1 Hereditary Leiomyomatosis and Renal Cell Cancer Exo1 Hereditary Neoplastic Syndromes Mlh1 , Mlh3 , Msh2 , Msh3 , Msh6 , Pms2 , Pold1 hereditary nonpolyposis colorectal cancer type 2 Mlh1 , Msh2 hereditary nonpolyposis colorectal cancer type 4 Msh2 , Msh6 , Pms2 hereditary nonpolyposis colorectal cancer type 5 Msh6 , Pms2 hereditary nonpolyposis colorectal cancer type 7 Mlh3 Hereditary Pancreatitis Ssbp1 high grade glioma Hmgb1 , Msh2 Huntington's disease Msh2 Huntington's disease-like 1 Pcna Hydatidiform Mole Mlh1 , Msh2 Hydatidiform Mole, Invasive Msh2 hydrocephalus Hmgb1 , Mlh1 Hyperalgesia Hmgb1 Hyperglycinemia, Lactic Acidosis, and Seizures Rfc1 hypertension Hmgb1 hypertrophic cardiomyopathy 9 Pms2 hypogonadism Pold1 hypothyroidism Pcna IDH-mutant anaplastic astrocytoma Mlh3 Immunodeficiency 122 Pold3 immunodeficiency 31B Pms1 Immunodeficiency 96 Lig1 Inflammation Hmgb1 inherited metabolic disorder Lig1 Inosine Triphosphatase Deficiency Pcna INTELLECTUAL DEVELOPMENTAL DISORDER WITH DYSMORPHIC FACIES AND BEHAVIORAL ABNORMALITIES Msh6 intellectual disability Mlh3 , Pold1 , Pold3 , Pold4 Intestinal Polyps Mlh1 Intestinal Reperfusion Injury Hmgb1 intestinal volvulus Rfc2 Intimal Hyperplasia Pcna invasive ductal carcinoma Pcna ischemia Pcna Jaw Abnormalities Pold1 Kawasaki disease Hmgb1 Knee Osteoarthritis Hmgb1 laryngeal squamous cell carcinoma Mlh1 , Msh2 leiomyoma Pcna Leukoencephalopathies Mlh3 leukoencephalopathy with vanishing white matter Mlh3 leukostasis Hmgb1 Lewy body dementia Pcna lipodystrophy Pold1 liver cancer Pcna Liver Injury Pcna Liver Reperfusion Injury Hmgb1 lung adenocarcinoma Mlh1 , Msh2 , Msh3 , Msh6 , Pold1 , Rfc4 lung cancer Mlh1 , Msh2 , Msh3 lung carcinoma Mlh1 Lung Neoplasms Pcna lung non-small cell carcinoma Mlh1 , Msh2 , Msh3 Lung Reperfusion Injury Hmgb1 lung sarcomatoid carcinoma Msh6 Lymphatic Metastasis Hmgb1 , Msh2 lymphoma Mlh1 Lynch syndrome Mlh1 , Mlh3 , Msh2 , Msh6 , Pms1 , Pms2 Lynch syndrome 1 Mlh1 , Mlh3 , Msh2 , Msh6 , Pms1 , Pms2 malignant pleural mesothelioma Mlh1 Mandibular Hypoplasia, Deafness, Progeroid Features, and Lipodystrophy Syndrome Pold1 Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 2 Exo1 Megaloblastic Anemia due to Dihydrofolate Reductase Deficiency Msh3 Microsatellite Instability Msh3 , Msh6 middle cerebral artery infarction Hmgb1 mismatch repair cancer syndrome Mlh1 , Msh2 , Msh6 , Pms2 Mismatch Repair Cancer Syndrome 1 Mlh1 , Msh2 , Msh6 , Pms2 Mismatch Repair Cancer Syndrome 2 Msh2 Mismatch Repair Cancer Syndrome 3 Msh6 Mismatch Repair Cancer Syndrome 4 Pms2 motor peripheral neuropathy Rfc1 mucositis Pcna Muir-Torre syndrome Mlh1 , Msh2 Multiple Abnormalities Pold1 Multiple Organ Failure Hmgb1 Multiple Primary Neoplasms Mlh1 myocardial infarction Hmgb1 Myocardial Ischemia Hmgb1 Myocardial Reperfusion Injury Hmgb1 Necrosis Hmgb1 Neoplasm Metastasis Mlh1 , Msh2 , Pcna , Pms2 nephroblastoma Pcna Neuralgia Hmgb1 Neurodevelopmental Disorders Exo1 , Msh3 , Msh6 , Pms1 , Rfc2 obstructive jaundice Hmgb1 , Pcna oculocutaneous albinism type IV Msh2 Optic Atrophy 13 Ssbp1 osteoarthritis Hmgb1 osteoporosis Pcna osteosarcoma Msh2 , Msh6 , Rfc1 ovarian cancer Mlh1 , Mlh3 , Msh2 , Msh6 , Pms1 , Pms2 , Pold1 ovarian carcinoma Msh6 ovarian cyst Msh2 Ovarian Neoplasms Mlh1 , Msh2 , Msh6 , Pms2 Oxygen-Induced Retinopathy Hmgb1 Painful Neuropathy Hmgb1 pancreatic carcinoma Pold1 pancreatic ductal carcinoma Pms1 pantothenate kinase-associated neurodegeneration Pcna parathyroid carcinoma Exo1 periodontitis Hmgb1 peritoneal carcinoma Mlh1 Phyllodes Tumor Pcna Pitt-Hopkins-like syndrome 2 Msh2 , Msh6 pituitary carcinoma Pms2 pleomorphic xanthoastrocytoma Pold2 , Rfc2 polymyositis Pms1 Premature Aging Hmgb1 primary immunodeficiency disease Lig1 primary ovarian insufficiency Mlh3 primary pulmonary hypertension Rfc1 Primitive Neuroectodermal Tumors Pms2 progressive myoclonus epilepsy 5 Msh6 prostate cancer Msh2 , Msh6 , Pms2 Prostatic Neoplasms Mlh1 , Msh3 , Pms1 psoriasis Pcna Pulmonary Arterial Hypertension Pms2 pulmonary fibrosis Hmgb1 Pulmonary Fibrosis and/or Bone Marrow Failure Syndrome, Telomere-Related, 6 Rpa1 pulmonary hypertension Hmgb1 Pulmonary Hypertension, Hypoxia-Induced Pcna RASopathy Ssbp1 Recurrent Infections, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations Pold4 renal cell carcinoma Mlh1 , Msh2 , Pcna Renal Cell Carcinoma 1 Msh2 Reperfusion Injury Hmgb1 Retina Reperfusion Injury Hmgb1 rhabdomyosarcoma Msh2 , Msh6 , Pms2 Right Ventricular Hypertrophy Rfc1 sarcoma Msh2 schizophrenia Rfc2 sciatic neuropathy Hmgb1 , Pcna seminoma Pcna Sengers syndrome Ssbp1 sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Msh6 Sepsis Hmgb1 sigmoid colon cancer Msh2 , Msh6 sigmoid neoplasm Msh2 , Msh6 skin disease Ssbp1 Spinal Cord Injuries Hmgb1 sporadic breast cancer Mlh1 squamous cell carcinoma Mlh1 stomach cancer Mlh1 , Msh2 , Msh6 , Pcna , Pms2 Supratentorial Neoplasms Pms2 systemic scleroderma Hmgb1 Systemic Vasculitis Hmgb1 Testicular Neoplasms Pcna Thyroid Neoplasms Msh6 transient cerebral ischemia Hmgb1 , Pcna transitional cell carcinoma Msh2 urinary bladder cancer Lig1 , Mlh1 , Msh2 , Msh6 , Pms2 Urogenital Neoplasms Msh2 , Msh6 Uterine Cervical Neoplasms Mlh1 , Msh2 uterine corpus cancer Msh2 , Msh6 Ventilator-Induced Lung Injury Hmgb1 Visceral Heterotaxy 4, Autosomal Mlh1 visual epilepsy Msh2 Volvulus Of Midgut Rfc2 Vulvar Neoplasms Mlh1 , Msh2 West Nile fever Rfc1 Williams-Beuren syndrome Rfc2 xeroderma pigmentosum group D Msh6
