ALTERED TRANSFORMING GROWTH FACTOR-BETA SMAD DEPENDENT SIGNALING PATHWAY (PW:0000614)
Description
Transforming growth
factor-beta superfamily mediated pathways are central regulators of
proliferation and survival, migration and differentiation, angiogenesis,
embryonic development and wound healing. The transforming growth factor-beta
(Tgf-b) Smad-dependent pathway is one of the best characterized modules of the
Tgf-b superfamily signaling. Deregulation of Tgf-b Smad-dependent signaling
renders the otherwise tumor-suppressive and growth-inhibitory pathway, a
pro-growth and pro-tumorigenic one by mechanisms that are poorly understood. In
the normal pathway, binding of Tgf to receptor type II leads to activation of
receptor type I, recruitment and phosphorylation of Smad proteins that subsequently
translocate to the nucleus. Selective interactions with co-factors regulate the
expression of distinct sets of target genes. Scaffolds, co-receptor, inhibitory
Smad(s), ligand binding proteins provide various layers of regulation
. [To access the diagram page for the
normal Tgf-beta signaling pathway click here.] . Genes whose mutations have
been associated with colorectal cancer (CRC) include both type I and II Tgf-b receptors.
Insertions/deletions mutations within a polyadenine tract in the coding
sequence of receptor type II have been found in more than 50% of CRC cases
associated with defects in DNA mismatch repair pathway, a well known cause of
the hereditary form and a fraction of the sporadic form of the disease. Defective
Smads have also been identified. Smad4 - originally cloned as deleted in
pancreatic cancer 4 - is mutated or deleted in ~20% of cases; Smad2 mutations
have been detected in a smaller fraction of cases; Smad3 was not thought to be
involved in the disease but a missense mutation in a CRC cell line has been found.
Elevated levels of Tgf1 or Smad7 have been found in patients with the disease
and Smad7 polymorphism has been reported. Altered Tgf-beta signaling has also
been implicated in other types of cancer such as pancreatic, prostate and
gastric among others. Alterations in the core components of the pathway lead to
defective or non-functional genes affecting or even abrogating the outcomes of
Tgf-beta Smad-dependent signaling. Altered genes are color coded.
To see the ontology report for annotations,
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Pathway Diagram:
Genes in Pathway:
G
Smad2
SMAD family member 2
ISO
RGD
PMID:17613544 PMID:18662538
RGD:2306282 , RGD:2308865
NCBI chr18:69,849,884...69,918,926
Ensembl chr18:69,850,377...69,912,323
G
Smad3
SMAD family member 3
ISO
RGD
PMID:17613544 PMID:18772397
RGD:2306282 , RGD:5490966
NCBI chr 8:64,126,829...64,236,960
Ensembl chr 8:64,110,039...64,236,960
G
Smad4
SMAD family member 4
ISO
RGD
PMID:17613544 PMID:18662538 PMID:18772397 PMID:19506583
RGD:2306282 , RGD:2308865 , RGD:5490966 , RGD:5490965
NCBI chr18:67,243,742...67,274,438
Ensembl chr18:67,243,742...67,274,438
G
Smad7
SMAD family member 7
ISO
RGD
PMID:18662538
RGD:2308865
NCBI chr18:68,988,429...69,016,774
Ensembl chr18:68,988,429...69,016,765
G
Tgfb1
transforming growth factor, beta 1
ISO
RGD
PMID:18313409 PMID:17613544
RGD:2299005 , RGD:2306282
NCBI chr 1:81,196,532...81,212,848
Ensembl chr 1:81,196,532...81,212,847
G
Tgfbr1
transforming growth factor, beta receptor 1
ISO
RGD
PMID:18313409 PMID:17613544
RGD:2299005 , RGD:2306282
NCBI chr 5:61,653,773...61,710,777
Ensembl chr 5:61,653,233...61,710,777
G
Tgfbr2
transforming growth factor, beta receptor 2
ISO
RGD
PMID:18313409 PMID:17613544 PMID:18662538 PMID:18772397 PMID:19506583
RGD:2299005 , RGD:2306282 , RGD:2308865 , RGD:5490966 , RGD:5490965
NCBI chr 8:115,794,537...115,883,615
Ensembl chr 8:115,794,537...115,883,228
Pathway Gene Annotations
Disease Annotations Associated with Genes in the altered transforming growth factor-beta Smad dependent signaling pathway
Smad2 acromicric dysplasia , breast carcinoma , cervical cancer , Chronic Hepatitis , colon cancer , CONGENITAL HEART DEFECTS, MULTIPLE TYPES, 8, WITH OR WITHOUT HETEROTAXY , Copper-Overload Cirrhosis , Craniofacial Abnormalities , endometrial cancer , Experimental Liver Cirrhosis , female reproductive system disease , genetic disease , hepatocellular carcinoma , Hypoglossal Nerve Injuries , idiopathic pulmonary fibrosis , intellectual disability , LOEYS-DIETZ SYNDROME 6 , Lynch syndrome , Microcephaly, Epilepsy, and Diabetes Syndrome , myocardial infarction , ovarian cancer , ovarian carcinoma , pancreatic cancer , pancreatic ductal adenocarcinoma , renal cell carcinoma , scimitar syndrome , urinary bladder cancer , Ventricular Remodeling , Vici syndrome Smad3 alcoholic liver cirrhosis , Aneurysm , aortic aneurysm , aortic disease , aortic dissection , aortic valve disease 2 , ARTERIAL DISSECTION , Bloom syndrome , cervical squamous cell carcinoma , Cocaine-Related Disorders , colorectal cancer , Colorectal Neoplasms , connective tissue disease , coronary artery disease , Craniofacial Abnormalities , Crohn's disease , Dissecting Aneurysm , Ehlers-Danlos syndrome , endometrial cancer , Experimental Liver Cirrhosis , Familial Thoracic Aortic Aneurysm 1 , Familial Thoracic Aortic Aneurysm 6 , genetic disease , Hypoglossal Nerve Injuries , juvenile rheumatoid arthritis , leiomyoma , liver cirrhosis , Loeys-Dietz syndrome , Loeys-Dietz syndrome 3 , lung cancer , lung non-small cell carcinoma , Lynch syndrome , myocardial infarction , Myocardial Reperfusion Injury , neuronal ceroid lipofuscinosis , osteoarthritis , Osteoarthritis, Hip , pancreatic cancer , pre-malignant neoplasm , prostate cancer , thoracic aortic aneurysm , Tubulointerstitial Fibrosis , ureteral obstruction , Uterine Neoplasms , Ventricular Remodeling Smad4 Acro-Osteolysis , aortic disease , brachydactyly , breast cancer , Breast Neoplasms , cervical cancer , cholangiocarcinoma , Chronic Hepatitis C , chronic myeloid leukemia , chronic obstructive pulmonary disease , Cicatrix , cognitive disorder , colon cancer , colon carcinoma , colorectal adenoma , colorectal cancer , colorectal carcinoma , Colorectal Neoplasms , Craniofacial Abnormalities , Cronkhite-Canada syndrome , Deafness , endometrial carcinoma , esophageal carcinoma , esophagus adenocarcinoma , Experimental Colitis , Experimental Liver Cirrhosis , gallbladder cancer , Gallstones , gastric adenocarcinoma , gastrointestinal system cancer , genetic disease , Growth Mental Deficiency Syndrome of Myhre , head and neck squamous cell carcinoma , hemorrhagic disease , hepatocellular carcinoma , hereditary breast ovarian cancer syndrome , hereditary hemorrhagic telangiectasia , Hereditary Hemorrhagic Telangiectasia, Type 1 , Hereditary Neoplastic Syndromes , Heterotopic Ossification , Human Viral Hepatitis , Hypoglossal Nerve Injuries , intellectual disability , intrahepatic cholangiocarcinoma , invasive ductal carcinoma , juvenile polyposis syndrome , juvenile polyposis-hereditary hemorrhagic telangiectasia syndrome , Liver Metastasis , lung adenocarcinoma , lung cancer , Lymphatic Metastasis , Lynch syndrome , metabolic dysfunction-associated steatohepatitis , Microphthalmia, Cataracts, and Iris Abnormalities , muscular disease , myocardial infarction , Myocardial Reperfusion Injury , Neoplasm Metastasis , nephroblastoma , Odontogenic Cysts , osteogenesis imperfecta , ovarian cancer , pancreatic adenocarcinoma , pancreatic cancer , pancreatic carcinoma , pancreatic ductal carcinoma , Parasitic Liver Diseases , pre-malignant neoplasm , Primary Pulmonary Hypertension, 1 , prostate adenocarcinoma , prostate carcinoma in situ , Prostatic Neoplasms , prostatitis , Pulmonary Arterial Hypertension , pulmonary fibrosis , pulmonary hypertension , renal cell carcinoma , seminoma , stomach cancer , Stomach Neoplasms , thoracic aortic aneurysm , transitional cell carcinoma , type 2 diabetes mellitus , urinary bladder cancer , Uterine Cervical Neoplasms , vascular dementia Smad7 atrial fibrillation , colorectal cancer , Colorectal Neoplasms , endometrial cancer , genetic disease , hepatocellular carcinoma , hereditary breast ovarian cancer syndrome , Hypoglossal Nerve Injuries , intellectual disability , liver cirrhosis , nephritis , Ovarian Neoplasms , pancreatic adenocarcinoma , pancreatic cancer , Paraquat Lung , pulmonary fibrosis , pulmonary hypertension Tgfb1 acromicric dysplasia , actinic keratosis , acute kidney failure , Acute Lung Injury , adenocarcinoma , alcoholic liver cirrhosis , allergic conjunctivitis , allergic disease , allergic rhinitis , Anetoderma , anogenital venereal wart , aortic valve insufficiency , aphthous stomatitis , aplastic anemia , arteriosclerosis , asthma , atopic dermatitis , atrial fibrillation , autoimmune hepatitis , autoimmune thrombocytopenic purpura , bacterial pneumonia , Behcet's disease , berylliosis , biliary atresia , brain disease , brain ischemia , breast cancer , Cachexia , calcinosis , Camurati-Engelmann disease , carcinoma , carcinosarcoma , Cardiac Fibrosis , Cardiomegaly , carotid artery disease , Carotid Artery Injuries , Carpenter Syndrome 2 , Chemical and Drug Induced Liver Injury , chlamydia , cholangiocarcinoma , chorioamnionitis , Chronic Experimental Pancreatitis , Chronic Hepatitis , Chronic Hepatitis B , chronic myeloid leukemia , chronic obstructive pulmonary disease , cleft palate , colon adenocarcinoma , colon cancer , colon carcinoma , colorectal cancer , Colorectal Neoplasms , congenital hypoplastic anemia , Copper-Overload Cirrhosis , coronary artery disease , craniosynostosis , cystic fibrosis , degenerative disc disease , diabetes mellitus , Diabetic Nephropathies , diabetic neuropathy , Diamond-Blackfan anemia , Diaphragmatic Hernia , Dilatation, Pathologic , dry eye syndrome , Duchenne muscular dystrophy , duodenal ulcer , Ehlers-Danlos syndrome , end stage renal disease , endomyocardial fibrosis , eosinophilic esophagitis , epilepsy , essential thrombocythemia , Experimental Arthritis , Experimental Autoimmune Encephalomyelitis , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , Experimental Liver Neoplasms , Experimental Mammary Neoplasms , extrahepatic cholestasis , factor VIII deficiency , familial hyperlipidemia , Fibrosis , focal segmental glomerulosclerosis , Gallbladder Neoplasms , genetic disease , gout , Graves' disease , heart disease , Heart Injuries , Hemorrhagic Shock , hepatic encephalopathy , Hepatic Insufficiency , hepatocellular carcinoma , Hepatomegaly , Hereditary Hemorrhagic Telangiectasia, Type 1 , Hyperoxia , Hyperplasia , hypertension , hypertrophic cardiomyopathy , hyperuricemia , IgA glomerulonephritis , impotence , Infant, Newborn, Diseases , Inflammation , inflammatory bowel disease , INFLAMMATORY BOWEL DISEASE, IMMUNODEFICIENCY, AND ENCEPHALOPATHY , insulinoma , interstitial lung disease , Joubert syndrome 1 , kidney disease , Kidney Reperfusion Injury , liver cirrhosis , localized scleroderma , lung disease , Lung Neoplasms , Lymphomatoid Papulosis , maple syrup urine disease , Meckel Syndrome 10 , metabolic dysfunction-associated steatotic liver disease , Metabolic Syndrome , middle cerebral artery infarction , multiple myeloma , muscular disease , myelofibrosis , myocardial infarction , Myocardial Reperfusion Injury , Nasal Polyps , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplastic Cell Transformation , nephrolithiasis , nephrosclerosis , nephrotic syndrome , nephrotoxicity , Neuralgia , obesity , occupational asthma , Occupational Diseases , oral submucous fibrosis , osteoarthritis , osteochondrodysplasia , osteoporosis , pancreatic cancer , pancreatic ductal adenocarcinoma , pancreatic ductal carcinoma , papilloma , Paraquat Lung , Peritoneal Fibrosis , Peyronie's disease , pleural disease , pneumonia , Posterior Leukoencephalopathy Syndrome , Postmenopausal Osteoporosis , primary biliary cholangitis , Progressive Diaphyseal Dysplasia 1 , prostate cancer , Prostatic Neoplasms , proteinuria , psoriasis , pulmonary emphysema , pulmonary fibrosis , pulmonary hypertension , pulmonary sarcoidosis , Radiation Pneumonitis , renal cell carcinoma , rhinitis , Right Ventricular Hypertrophy , sarcoidosis , Sepsis , severe acute respiratory syndrome , sickle cell anemia , Sjogren's syndrome , Skin Neoplasms , Spinal Cord Injuries , Spontaneous Abortions , Spontaneous Neoplasm Regression , squamous cell carcinoma , Stroke , thrombocytopenia , tracheal stenosis , traumatic brain injury , Tubulointerstitial Fibrosis , type 1 diabetes mellitus , type 2 diabetes mellitus , uremia , ureteral obstruction , urethral obstruction , urticaria , uveitis , Ventricular Remodeling , vitiligo , Wallerian Degeneration , Wounds and Injuries Tgfbr1 acute kidney failure , Animal Disease Models , aortic aneurysm , aortic disease , Carotid Artery Injuries , Charlevoix-Saguenay spastic ataxia , Chemical and Drug Induced Liver Injury , colorectal cancer , Colorectal Neoplasms , congenital disorder of glycosylation Ii , congenital disorder of glycosylation type II , congenital myasthenic syndrome 14 , connective tissue disease , craniosynostosis , Craniosynostosis Syndrome, Autosomal Recessive , diffuse scleroderma , Disproportionate Tall Stature , Dissecting Aneurysm , Ehlers-Danlos syndrome , Ehlers-Danlos syndrome classic type 1 , Experimental Liver Cirrhosis , Experimental Mammary Neoplasms , Familial Thoracic Aortic Aneurysm 6 , Ferguson-Smith tumor , genetic disease , Hyperalgesia , intellectual disability , kidney disease , leiomyoma , liver cirrhosis , Loeys-Dietz syndrome , Loeys-Dietz syndrome 1 , Lynch syndrome , Marfan syndrome , Marfanoid Hypermobility Syndrome , myocardial infarction , myoepithelioma , Neoplasm Metastasis , nephronophthisis , osteoarthritis , osteochondrodysplasia , pancreatic ductal adenocarcinoma , Pulmonary Arterial Hypertension , pulmonary hypertension , Skin Neoplasms , Spontaneous Abortions , thoracic aortic aneurysm , uremia , urinary bladder cancer Tgfbr2 aortic aneurysm , arteriosclerosis , bone disease , Bone Fractures , Bone Neoplasms , Brain Neoplasms , carcinoma , Carotid Artery Injuries , cholangiocarcinoma , cleft soft palate , colon cancer , Colonic Neoplasms , colorectal cancer , connective tissue disease , Craniofacial Abnormalities , Diabetic Nephropathies , DiGeorge syndrome , Dissecting Aneurysm , Ehlers-Danlos syndrome , esophageal cancer , Esophageal Neoplasms , esophagus squamous cell carcinoma , Experimental Arthritis , Experimental Liver Cirrhosis , Experimental Mammary Neoplasms , Eye Abnormalities , Familial Thoracic Aortic Aneurysm 1 , Fatigue , gastrointestinal stromal tumor , genetic disease , hepatoblastoma , hepatocellular carcinoma , hereditary nonpolyposis colorectal cancer type 6 , Hyperplasia , inguinal hernia , kidney disease , Loeys-Dietz syndrome , Loeys-Dietz syndrome 1 , Loeys-Dietz syndrome 2 , Loeys-Dietz Syndrome, Type 1b , Lung Neoplasms , Lynch syndrome , Marfan syndrome , Marfan Syndrome Type 2 , Marfanoid Hypermobility Syndrome , membranoproliferative glomerulonephritis , Microsatellite Instability , migraine , mismatch repair cancer syndrome , multiple acyl-CoA dehydrogenase deficiency , myocardial infarction , Neoplasm Metastasis , pancreatic cancer , pancreatic ductal carcinoma , prostate cancer , Prostatic Neoplasms , pulmonary fibrosis , pulmonary hypertension , Radiation Injuries , Reperfusion Injury , thoracic aortic aneurysm , type 2 diabetes mellitus , vasculogenic impotence , Wolff-Parkinson-White syndrome
Acro-Osteolysis Smad4 acromicric dysplasia Smad2 , Tgfb1 actinic keratosis Tgfb1 acute kidney failure Tgfb1 , Tgfbr1 Acute Lung Injury Tgfb1 adenocarcinoma Tgfb1 alcoholic liver cirrhosis Smad3 , Tgfb1 allergic conjunctivitis Tgfb1 allergic disease Tgfb1 allergic rhinitis Tgfb1 Anetoderma Tgfb1 Aneurysm Smad3 Animal Disease Models Tgfbr1 anogenital venereal wart Tgfb1 aortic aneurysm Smad3 , Tgfbr1 , Tgfbr2 aortic disease Smad3 , Smad4 , Tgfbr1 aortic dissection Smad3 aortic valve disease 2 Smad3 aortic valve insufficiency Tgfb1 aphthous stomatitis Tgfb1 aplastic anemia Tgfb1 ARTERIAL DISSECTION Smad3 arteriosclerosis Tgfb1 , Tgfbr2 asthma Tgfb1 atopic dermatitis Tgfb1 atrial fibrillation Smad7 , Tgfb1 autoimmune hepatitis Tgfb1 autoimmune thrombocytopenic purpura Tgfb1 bacterial pneumonia Tgfb1 Behcet's disease Tgfb1 berylliosis Tgfb1 biliary atresia Tgfb1 Bloom syndrome Smad3 bone disease Tgfbr2 Bone Fractures Tgfbr2 Bone Neoplasms Tgfbr2 brachydactyly Smad4 brain disease Tgfb1 brain ischemia Tgfb1 Brain Neoplasms Tgfbr2 breast cancer Smad4 , Tgfb1 breast carcinoma Smad2 Breast Neoplasms Smad4 Cachexia Tgfb1 calcinosis Tgfb1 Camurati-Engelmann disease Tgfb1 carcinoma Tgfb1 , Tgfbr2 carcinosarcoma Tgfb1 Cardiac Fibrosis Tgfb1 Cardiomegaly Tgfb1 carotid artery disease Tgfb1 Carotid Artery Injuries Tgfb1 , Tgfbr1 , Tgfbr2 Carpenter Syndrome 2 Tgfb1 cervical cancer Smad2 , Smad4 cervical squamous cell carcinoma Smad3 Charlevoix-Saguenay spastic ataxia Tgfbr1 Chemical and Drug Induced Liver Injury Tgfb1 , Tgfbr1 chlamydia Tgfb1 cholangiocarcinoma Smad4 , Tgfb1 , Tgfbr2 chorioamnionitis Tgfb1 Chronic Experimental Pancreatitis Tgfb1 Chronic Hepatitis Smad2 , Tgfb1 Chronic Hepatitis B Tgfb1 Chronic Hepatitis C Smad4 chronic myeloid leukemia Smad4 , Tgfb1 chronic obstructive pulmonary disease Smad4 , Tgfb1 Cicatrix Smad4 cleft palate Tgfb1 cleft soft palate Tgfbr2 Cocaine-Related Disorders Smad3 cognitive disorder Smad4 colon adenocarcinoma Tgfb1 colon cancer Smad2 , Smad4 , Tgfb1 , Tgfbr2 colon carcinoma Smad4 , Tgfb1 Colonic Neoplasms Tgfbr2 colorectal adenoma Smad4 colorectal cancer Smad3 , Smad4 , Smad7 , Tgfb1 , Tgfbr1 , Tgfbr2 colorectal carcinoma Smad4 Colorectal Neoplasms Smad3 , Smad4 , Smad7 , Tgfb1 , Tgfbr1 congenital disorder of glycosylation Ii Tgfbr1 congenital disorder of glycosylation type II Tgfbr1 CONGENITAL HEART DEFECTS, MULTIPLE TYPES, 8, WITH OR WITHOUT HETEROTAXY Smad2 congenital hypoplastic anemia Tgfb1 congenital myasthenic syndrome 14 Tgfbr1 connective tissue disease Smad3 , Tgfbr1 , Tgfbr2 Copper-Overload Cirrhosis Smad2 , Tgfb1 coronary artery disease Smad3 , Tgfb1 Craniofacial Abnormalities Smad2 , Smad3 , Smad4 , Tgfbr2 craniosynostosis Tgfb1 , Tgfbr1 Craniosynostosis Syndrome, Autosomal Recessive Tgfbr1 Crohn's disease Smad3 Cronkhite-Canada syndrome Smad4 cystic fibrosis Tgfb1 Deafness Smad4 degenerative disc disease Tgfb1 diabetes mellitus Tgfb1 Diabetic Nephropathies Tgfb1 , Tgfbr2 diabetic neuropathy Tgfb1 Diamond-Blackfan anemia Tgfb1 Diaphragmatic Hernia Tgfb1 diffuse scleroderma Tgfbr1 DiGeorge syndrome Tgfbr2 Dilatation, Pathologic Tgfb1 Disproportionate Tall Stature Tgfbr1 Dissecting Aneurysm Smad3 , Tgfbr1 , Tgfbr2 dry eye syndrome Tgfb1 Duchenne muscular dystrophy Tgfb1 duodenal ulcer Tgfb1 Ehlers-Danlos syndrome Smad3 , Tgfb1 , Tgfbr1 , Tgfbr2 Ehlers-Danlos syndrome classic type 1 Tgfbr1 end stage renal disease Tgfb1 endometrial cancer Smad2 , Smad3 , Smad7 endometrial carcinoma Smad4 endomyocardial fibrosis Tgfb1 eosinophilic esophagitis Tgfb1 epilepsy Tgfb1 esophageal cancer Tgfbr2 esophageal carcinoma Smad4 Esophageal Neoplasms Tgfbr2 esophagus adenocarcinoma Smad4 esophagus squamous cell carcinoma Tgfbr2 essential thrombocythemia Tgfb1 Experimental Arthritis Tgfb1 , Tgfbr2 Experimental Autoimmune Encephalomyelitis Tgfb1 Experimental Colitis Smad4 Experimental Diabetes Mellitus Tgfb1 Experimental Liver Cirrhosis Smad2 , Smad3 , Smad4 , Tgfb1 , Tgfbr1 , Tgfbr2 Experimental Liver Neoplasms Tgfb1 Experimental Mammary Neoplasms Tgfb1 , Tgfbr1 , Tgfbr2 extrahepatic cholestasis Tgfb1 Eye Abnormalities Tgfbr2 factor VIII deficiency Tgfb1 familial hyperlipidemia Tgfb1 Familial Thoracic Aortic Aneurysm 1 Smad3 , Tgfbr2 Familial Thoracic Aortic Aneurysm 6 Smad3 , Tgfbr1 Fatigue Tgfbr2 female reproductive system disease Smad2 Ferguson-Smith tumor Tgfbr1 Fibrosis Tgfb1 focal segmental glomerulosclerosis Tgfb1 gallbladder cancer Smad4 Gallbladder Neoplasms Tgfb1 Gallstones Smad4 gastric adenocarcinoma Smad4 gastrointestinal stromal tumor Tgfbr2 gastrointestinal system cancer Smad4 genetic disease Smad2 , Smad3 , Smad4 , Smad7 , Tgfb1 , Tgfbr1 , Tgfbr2 gout Tgfb1 Graves' disease Tgfb1 Growth Mental Deficiency Syndrome of Myhre Smad4 head and neck squamous cell carcinoma Smad4 heart disease Tgfb1 Heart Injuries Tgfb1 hemorrhagic disease Smad4 Hemorrhagic Shock Tgfb1 hepatic encephalopathy Tgfb1 Hepatic Insufficiency Tgfb1 hepatoblastoma Tgfbr2 hepatocellular carcinoma Smad2 , Smad4 , Smad7 , Tgfb1 , Tgfbr2 Hepatomegaly Tgfb1 hereditary breast ovarian cancer syndrome Smad4 , Smad7 hereditary hemorrhagic telangiectasia Smad4 Hereditary Hemorrhagic Telangiectasia, Type 1 Smad4 , Tgfb1 Hereditary Neoplastic Syndromes Smad4 hereditary nonpolyposis colorectal cancer type 6 Tgfbr2 Heterotopic Ossification Smad4 Human Viral Hepatitis Smad4 Hyperalgesia Tgfbr1 Hyperoxia Tgfb1 Hyperplasia Tgfb1 , Tgfbr2 hypertension Tgfb1 hypertrophic cardiomyopathy Tgfb1 hyperuricemia Tgfb1 Hypoglossal Nerve Injuries Smad2 , Smad3 , Smad4 , Smad7 idiopathic pulmonary fibrosis Smad2 IgA glomerulonephritis Tgfb1 impotence Tgfb1 Infant, Newborn, Diseases Tgfb1 Inflammation Tgfb1 inflammatory bowel disease Tgfb1 INFLAMMATORY BOWEL DISEASE, IMMUNODEFICIENCY, AND ENCEPHALOPATHY Tgfb1 inguinal hernia Tgfbr2 insulinoma Tgfb1 intellectual disability Smad2 , Smad4 , Smad7 , Tgfbr1 interstitial lung disease Tgfb1 intrahepatic cholangiocarcinoma Smad4 invasive ductal carcinoma Smad4 Joubert syndrome 1 Tgfb1 juvenile polyposis syndrome Smad4 juvenile polyposis-hereditary hemorrhagic telangiectasia syndrome Smad4 juvenile rheumatoid arthritis Smad3 kidney disease Tgfb1 , Tgfbr1 , Tgfbr2 Kidney Reperfusion Injury Tgfb1 leiomyoma Smad3 , Tgfbr1 liver cirrhosis Smad3 , Smad7 , Tgfb1 , Tgfbr1 Liver Metastasis Smad4 localized scleroderma Tgfb1 Loeys-Dietz syndrome Smad3 , Tgfbr1 , Tgfbr2 Loeys-Dietz syndrome 1 Tgfbr1 , Tgfbr2 Loeys-Dietz syndrome 2 Tgfbr2 Loeys-Dietz syndrome 3 Smad3 LOEYS-DIETZ SYNDROME 6 Smad2 Loeys-Dietz Syndrome, Type 1b Tgfbr2 lung adenocarcinoma Smad4 lung cancer Smad3 , Smad4 lung disease Tgfb1 Lung Neoplasms Tgfb1 , Tgfbr2 lung non-small cell carcinoma Smad3 Lymphatic Metastasis Smad4 Lymphomatoid Papulosis Tgfb1 Lynch syndrome Smad2 , Smad3 , Smad4 , Tgfbr1 , Tgfbr2 maple syrup urine disease Tgfb1 Marfan syndrome Tgfbr1 , Tgfbr2 Marfan Syndrome Type 2 Tgfbr2 Marfanoid Hypermobility Syndrome Tgfbr1 , Tgfbr2 Meckel Syndrome 10 Tgfb1 membranoproliferative glomerulonephritis Tgfbr2 metabolic dysfunction-associated steatohepatitis Smad4 metabolic dysfunction-associated steatotic liver disease Tgfb1 Metabolic Syndrome Tgfb1 Microcephaly, Epilepsy, and Diabetes Syndrome Smad2 Microphthalmia, Cataracts, and Iris Abnormalities Smad4 Microsatellite Instability Tgfbr2 middle cerebral artery infarction Tgfb1 migraine Tgfbr2 mismatch repair cancer syndrome Tgfbr2 multiple acyl-CoA dehydrogenase deficiency Tgfbr2 multiple myeloma Tgfb1 muscular disease Smad4 , Tgfb1 myelofibrosis Tgfb1 myocardial infarction Smad2 , Smad3 , Smad4 , Tgfb1 , Tgfbr1 , Tgfbr2 Myocardial Reperfusion Injury Smad3 , Smad4 , Tgfb1 myoepithelioma Tgfbr1 Nasal Polyps Tgfb1 Neoplasm Invasiveness Tgfb1 Neoplasm Metastasis Smad4 , Tgfb1 , Tgfbr1 , Tgfbr2 Neoplastic Cell Transformation Tgfb1 nephritis Smad7 nephroblastoma Smad4 nephrolithiasis Tgfb1 nephronophthisis Tgfbr1 nephrosclerosis Tgfb1 nephrotic syndrome Tgfb1 nephrotoxicity Tgfb1 Neuralgia Tgfb1 neuronal ceroid lipofuscinosis Smad3 obesity Tgfb1 occupational asthma Tgfb1 Occupational Diseases Tgfb1 Odontogenic Cysts Smad4 oral submucous fibrosis Tgfb1 osteoarthritis Smad3 , Tgfb1 , Tgfbr1 Osteoarthritis, Hip Smad3 osteochondrodysplasia Tgfb1 , Tgfbr1 osteogenesis imperfecta Smad4 osteoporosis Tgfb1 ovarian cancer Smad2 , Smad4 ovarian carcinoma Smad2 Ovarian Neoplasms Smad7 pancreatic adenocarcinoma Smad4 , Smad7 pancreatic cancer Smad2 , Smad3 , Smad4 , Smad7 , Tgfb1 , Tgfbr2 pancreatic carcinoma Smad4 pancreatic ductal adenocarcinoma Smad2 , Tgfb1 , Tgfbr1 pancreatic ductal carcinoma Smad4 , Tgfb1 , Tgfbr2 papilloma Tgfb1 Paraquat Lung Smad7 , Tgfb1 Parasitic Liver Diseases Smad4 Peritoneal Fibrosis Tgfb1 Peyronie's disease Tgfb1 pleural disease Tgfb1 pneumonia Tgfb1 Posterior Leukoencephalopathy Syndrome Tgfb1 Postmenopausal Osteoporosis Tgfb1 pre-malignant neoplasm Smad3 , Smad4 primary biliary cholangitis Tgfb1 Primary Pulmonary Hypertension, 1 Smad4 Progressive Diaphyseal Dysplasia 1 Tgfb1 prostate adenocarcinoma Smad4 prostate cancer Smad3 , Tgfb1 , Tgfbr2 prostate carcinoma in situ Smad4 Prostatic Neoplasms Smad4 , Tgfb1 , Tgfbr2 prostatitis Smad4 proteinuria Tgfb1 psoriasis Tgfb1 Pulmonary Arterial Hypertension Smad4 , Tgfbr1 pulmonary emphysema Tgfb1 pulmonary fibrosis Smad4 , Smad7 , Tgfb1 , Tgfbr2 pulmonary hypertension Smad4 , Smad7 , Tgfb1 , Tgfbr1 , Tgfbr2 pulmonary sarcoidosis Tgfb1 Radiation Injuries Tgfbr2 Radiation Pneumonitis Tgfb1 renal cell carcinoma Smad2 , Smad4 , Tgfb1 Reperfusion Injury Tgfbr2 rhinitis Tgfb1 Right Ventricular Hypertrophy Tgfb1 sarcoidosis Tgfb1 scimitar syndrome Smad2 seminoma Smad4 Sepsis Tgfb1 severe acute respiratory syndrome Tgfb1 sickle cell anemia Tgfb1 Sjogren's syndrome Tgfb1 Skin Neoplasms Tgfb1 , Tgfbr1 Spinal Cord Injuries Tgfb1 Spontaneous Abortions Tgfb1 , Tgfbr1 Spontaneous Neoplasm Regression Tgfb1 squamous cell carcinoma Tgfb1 stomach cancer Smad4 Stomach Neoplasms Smad4 Stroke Tgfb1 thoracic aortic aneurysm Smad3 , Smad4 , Tgfbr1 , Tgfbr2 thrombocytopenia Tgfb1 tracheal stenosis Tgfb1 transitional cell carcinoma Smad4 traumatic brain injury Tgfb1 Tubulointerstitial Fibrosis Smad3 , Tgfb1 type 1 diabetes mellitus Tgfb1 type 2 diabetes mellitus Smad4 , Tgfb1 , Tgfbr2 uremia Tgfb1 , Tgfbr1 ureteral obstruction Smad3 , Tgfb1 urethral obstruction Tgfb1 urinary bladder cancer Smad2 , Smad4 , Tgfbr1 urticaria Tgfb1 Uterine Cervical Neoplasms Smad4 Uterine Neoplasms Smad3 uveitis Tgfb1 vascular dementia Smad4 vasculogenic impotence Tgfbr2 Ventricular Remodeling Smad2 , Smad3 , Tgfb1 Vici syndrome Smad2 vitiligo Tgfb1 Wallerian Degeneration Tgfb1 Wolff-Parkinson-White syndrome Tgfbr2 Wounds and Injuries Tgfb1