INTRINSIC APOPTOTIC PATHWAY (PW:0000104)
Description Apoptosis, or programmed cell death, removes excess or damaged cells to maintain tissue homeostasis. The two major apoptotic pathways, the extrinsic, triggered by ligands activating the death receptors and the intrinsic (mitochondrial), triggered by intracellular stresses, converge on the activation of executioner caspases. In the intrinsic pathway, the Bcl-2 family of pro- and anti-apoptotic proteins controls the life-to-death switch. Structurally, they share the Bcl homology BH domain. Most pro-survival proteins have four (BH1-4) domains; the pro-apoptotic proteins fall into two subgroups, those with more than one BH domain and the BH3-only group.
Click, to see more on the domain organization of Bcl-2 family . The pro-survival proteins localize to the outer mitochondrial membrane and to a lesser extent, the ER membrane and nuclear envelope. They act to neutralize the action of pro-apoptotic Bax and Bak1 and prevent the release of cytochrome c (Cycs) from the mitochondrion. Their affinity for Bax and Bak1 varies; the interaction may contribute to sequestration of the two pro-apoptotic proteins. The BH3-only proteins are initiator molecules and two activation models have been proposed. In the direct model, they bind to and activate Bax and Bak1; in the indirect model, they bind to and inactivate the pro-survival proteins. BH3-only proteins bind with high affinity to at least some of the pro-survival members. Active Bax and Bak1 form oligomeric complexes at the mitochondrial membrane and facilitate the release of Cycs from the inter-membrane space [eg. PMID:
16474435 ,
17322918 ,
19641503 ]. In the cytosol, Cycs interacts with Apaf1; in the presence of ATP or dATP they form a heptameric complex - the apoptosome that recruits and activates the initiator caspase Casp9, probably by promoting the formation of the active dimer. The N-terminal
CARD domain of Apaf1 recruits Casp9 while the C-terminal
WD40 repeats are involved in Cycs binding. The active Casp9 processes and activates the executioner Casp3 and 7; in the extrinsic pathway different initiators activate them [eg. PMID:
17377525 ,
18931687 ]. The IAP (Inhibitors of Apoptosis Proteins) family members have one or more
BIR domain , many have a
RING zinc-finger domain with E3 ubiquitin ligase activity, two have a CARD domain. Xiap/Birc4 inhibits Casp3, 7 and 9; a direct participation of the other members is still debated and indirect mechanisms have been postulated. Xiap is antagonized by Diablo/Smac or Htra2/Omi which are released from the mitochondrion along with Cycs. Htra2 is serine protease that both disrupts Xiap-caspase interaction and degrades Xiap. IAPs are involved in other pathways and processes [eg. PMID:
17573556 ,
18414036 ]. A complex bi-directional interplay between caspases and kinases/phosphatases modulates their activities and associated outcomes. Alterations of the apoptotic pathways have been associated with several conditions.
To see the ontology report for annotations, GViewer and download, click here [click to see related KEGG map
map04210 and associated entry at Reactome -
REACT_964 .
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Pathway Diagram:
Genes in Pathway:
G
Apaf1
apoptotic peptidase activating factor 1
7
31,699,309
31,784,192
RGD:2313998
G
Bad
BCL2-associated agonist of cell death
1
222,198,516
222,207,459
RGD:1579966 RGD:2314029
G
Bad_v1
BCL2-associated agonist of cell death, variant 1
RGD:1579966
G
Bad_v2
BCL2-associated agonist of cell death, variant 2
RGD:1579966
G
Bak1
BCL2-antagonist/killer 1
20
5,609,620
5,618,899
RGD:2313963 RGD:2313975
G
Bax
BCL2 associated X, apoptosis regulator
1
101,451,801
101,457,207
RGD:1579966 RGD:2314140 RGD:2313998 RGD:2313975 RGD:2313963
G
Bax_v1
BCL2 associated X, apoptosis regulator, variant 1
RGD:1579966
G
Bax_v2
BCL2 associated X, apoptosis regulator, variant 2
RGD:1579966
G
Bbc3
Bcl-2 binding component 3
1
78,261,491
78,267,802
RGD:2313994 RGD:2314029
G
Bcl2
BCL2, apoptosis regulator
13
26,605,426
26,769,374
RGD:1579966 RGD:2314140 RGD:2313998 RGD:2313975
G
Bcl2a1
BCL2-related protein A1
8
96,551,424
96,559,527
RGD:2313975
G
Bcl2l1
Bcl2-like 1
3
148,259,594
148,314,191
RGD:1579966 RGD:2314140 RGD:2313975
G
Bcl2l11
BCL2 like 11
3
120,726,906
120,764,192
RGD:2314029
G
Bcl2l2
Bcl2-like 2
15
33,543,774
33,549,165
RGD:2313963 RGD:2313975
G
Bid
BH3 interacting domain death agonist
4
153,439,812
153,465,247
RGD:2313998 RGD:2314029 RGD:2314002
G
Bik
BCL2-interacting killer
7
124,390,924
124,410,449
RGD:2314029
G
Bmf
Bcl2 modifying factor
3
110,303,515
110,324,125
RGD:2314029
G
Bnip1
BCL2 interacting protein 1
10
16,677,077
16,689,321
RGD:634759 RGD:2314029
G
Bnip3
BCL2 interacting protein 3
1
211,248,098
211,265,282
RGD:2314028 RGD:2314029
G
Bnip3l
BCL2 interacting protein 3 like
15
43,643,897
43,667,123
RGD:2314029
G
Bok
BOK, BCL2 family apoptosis regulator
9
100,829,593
100,840,498
RGD:70678 RGD:2313975
G
Casp3
caspase 3
16
48,845,011
48,863,249
RGD:71121 RGD:2314390 RGD:2314187 RGD:2314002 RGD:2313998 RGD:2313963
G
Casp7
caspase 7
1
277,190,557
277,242,779
RGD:2314187
G
Casp9
caspase 9
5
160,356,211
160,373,774
RGD:2313963 RGD:2314390 RGD:2314187 RGD:2314002 RGD:2313998
G
Cycs
cytochrome c, somatic
4
80,331,226
80,333,326
RGD:2313963 RGD:2313998
G
Fas
Fas cell surface death receptor
1
252,589,785
252,624,790
RGD:1626509
G
Hrk
harakiri, BCL2 interacting protein
12
44,008,879
44,029,211
RGD:70327 RGD:2314029 RGD:2290488
G
Htra2
HtrA serine peptidase 2
4
113,883,671
113,886,833
RGD:2314385
G
Mcl1
MCL1, BCL2 family apoptosis regulator
2
197,786,212
197,788,992
RGD:70678 RGD:2313975
G
Pmaip1
phorbol-12-myristate-13-acetate-induced protein 1
18
62,159,128
62,179,635
RGD:2314029 RGD:2314140
G
Xiap
X-linked inhibitor of apoptosis
X
128,409,425
128,455,786
RGD:2314390
Pathway Gene Annotations
Disease Annotations Associated with Genes in the intrinsic apoptotic pathway
Apaf1 Brain Injuries , Brain Ischemia , Carcinoma, Renal Cell , Carcinoma, Transitional Cell , Craniofacial Abnormalities , Eye Abnormalities , Liver Cirrhosis, Experimental , Mammary Neoplasms, Experimental , Muscular Atrophy , Pancreatic Neoplasms , Parkinson's Disease , Parkinsonian Disorders , Reperfusion Injury , Retinal Detachment , Seizures , Skin Abnormalities Bad Acute Kidney Injury , Alzheimer's Disease , amyotrophic lateral sclerosis , Brain Injuries , Brain Ischemia , Breast Neoplasms , Burns , Carcinoma, Renal Cell , Cardiomegaly , Chemical and Drug Induced Liver Injury , Colonic Neoplasms , diabetes mellitus, experimental , Diabetic Cardiomyopathies , Diabetic Cystopathy , Diabetic Neuropathies , Endometrial Neoplasms , Erectile Dysfunction , gastric ulcer , Glaucoma , glioma , Hypertension , Hypothyroidism , Infarction, Middle Cerebral Artery , Insulin Resistance , Intermittent Claudication , Leukemia , Liver Reperfusion Injury , Macular Degeneration , Mammary Neoplasms, Experimental , Myocardial Reperfusion Injury , non-small cell lung carcinoma , obesity , Osteoarthritis , Pancreatic Neoplasms , Pancreatitis, Chronic , Parkinsonian Disorders , Prostatic Hyperplasia , prostatic neoplasms , Pulmonary Fibrosis , Reperfusion Injury , Retina Reperfusion Injury , Seizures , Sepsis , Shock, Hemorrhagic , Small-For-Size Syndrome , Spinal Cord Reperfusion Injury , transient cerebral ischemia , type 2 diabetes mellitus Bak1 Alzheimer's Disease , amyotrophic lateral sclerosis , Carcinoma, Renal Cell , Colonic Neoplasms , Hypertrophy, Left Ventricular , Intermittent Claudication , Leiomyoma , Liver Cirrhosis, Experimental , Liver Neoplasms, Experimental , Mammary Neoplasms, Experimental , Nerve Degeneration , uterine cervical neoplasms Bax Acute Kidney Injury , Acute Lung Injury , Adrenal Insufficiency , Aging, Premature , Alzheimer's Disease , amyotrophic lateral sclerosis , Anti-Glomerular Basement Membrane Disease , Arthritis, Experimental , Brain Injuries , Breast Neoplasms , Burns , Cerebral Hemorrhage , Chemical and Drug Induced Liver Injury , colon cancer , colon carcinoma , Colonic Neoplasms , colorectal cancer , Colorectal Neoplasms , Dementia , Dementia, Multi-Infarct , diabetes mellitus, experimental , dilated cardiomyopathy , Endometriosis , Endotoxemia , Erectile Dysfunction , Esophageal Neoplasms , Fetal Growth Retardation , Gastrointestinal Hemorrhage , Glaucoma , Heart Diseases , Heart Failure , HIV Infections , Huntington's Disease , Hyperplasia , Hypertension , Hypoxia-Ischemia, Brain , Infarction, Middle Cerebral Artery , Infertility, Male , Intermittent Claudication , Intestinal Diseases , Intestinal Neoplasms , Ischemia , Kashin-Beck Disease , Kidney Reperfusion Injury , Leiomyoma , Liver Reperfusion Injury , Lung Reperfusion Injury , Lymphoma, T-Cell, Cutaneous , Macular Degeneration , Mammary Neoplasms, Experimental , mental depression , Microsatellite Instability , Morphine Dependence , Myocardial Infarction , Myocardial Ischemia , Myocardial Reperfusion Injury , Neoplasm Metastasis , Nerve Degeneration , Optic Nerve Injuries , Osteoarthritis , Osteoarthritis, Knee , Osteoporosis , Polycystic Ovary Syndrome , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , prostatic neoplasms , Reperfusion Injury , Retina Reperfusion Injury , Retinal Degeneration , Sarcopenia , Status Epilepticus , Stress Disorders, Post-Traumatic , Teratoma , Thyroiditis , Toxoplasmosis , transient cerebral ischemia , type 2 diabetes mellitus , urinary bladder cancer , uterine cervical neoplasms Bbc3 Brain Ischemia , Burkitt Lymphoma , Esophageal Neoplasms , Intermittent Claudication , Liver Neoplasms, Experimental , transient cerebral ischemia Bcl2 Acute Kidney Injury , Acute Lung Injury , adenocarcinoma , Adenocarcinoma, Clear Cell , Adenoma , Adrenal Insufficiency , Aging, Premature , AIDS-related Kaposi sarcoma , Alzheimer's Disease , amyotrophic lateral sclerosis , Anti-Glomerular Basement Membrane Disease , Arthritis, Experimental , asthma , Autistic Disorder , Azoospermia , B-Cell CLL/Lymphoma 2 , Brain Injuries , Brain Ischemia , Breast Neoplasms , Burns , Carcinoma , Carcinoma, Intraductal, Noninfiltrating , Carcinoma, Renal Cell , Carcinoma, Squamous Cell , Carcinoma, Transitional Cell , Cardiomyopathy, Hypertrophic , Cell Transformation, Neoplastic , Cerebral Hemorrhage , cervical intraepithelial neoplasia , Chondrosarcoma, Mesenchymal , Colonic Neoplasms , Colorectal Neoplasms , Dementia , Dementia, Multi-Infarct , Dermatitis, Allergic Contact , Dermatitis, Contact , diabetes mellitus, experimental , Diabetic Cardiomyopathies , Disease Progression , Endometrial Neoplasms , Endometriosis , Endotoxemia , Erectile Dysfunction , Esophageal Neoplasms , Fetal Growth Retardation , gallbladder neoplasms , gastric ulcer , Glaucoma , head and neck neoplasms , Heart Failure , Huntington's Disease , Hyperbilirubinemia , Hypertension , Hypothermia , Hypoxia-Ischemia, Brain , Infarction, Middle Cerebral Artery , Infertility, Male , Intestinal Diseases , Intestinal Neoplasms , Intracranial Aneurysm , Kashin-Beck Disease , Kidney Failure, Chronic , Kidney Reperfusion Injury , Learning Disorders , Leiomyoma , Leukemia, Myeloid, Acute , Leukoplakia, Oral , Liver Cirrhosis, Alcoholic , Liver Cirrhosis, Experimental , Liver Neoplasms, Experimental , Liver Reperfusion Injury , Lung Reperfusion Injury , Lymphatic Metastasis , lymphocytic leukemia, chronic, B-cell , Lymphoma, Follicular , Lymphoma, Large B-Cell, Diffuse , Lymphoma, Non-Hodgkin , Mammary Neoplasms, Experimental , Melanoma , Memory Disorders , Mesothelioma, Malignant , Metaplasia , Morphine Dependence , Multiple Myeloma , Myocardial Infarction , Myocardial Ischemia , Myocardial Reperfusion Injury , Nasopharyngeal Carcinoma , Necrosis , Neoplasm Metastasis , Nerve Degeneration , obesity , Optic Nerve Injuries , Osteoarthritis , Osteoarthritis, Knee , Osteochondrodysplasias , Osteoporosis , Ovarian Neoplasms , Plasmacytoma , Polycystic Ovary Syndrome , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Priapism , prostatic neoplasms , pulmonary hypertension , Reperfusion Injury , Retina Reperfusion Injury , Retinal Degeneration , Rhinitis, Allergic , Sarcoma, Synovial , Sarcopenia , Shock, Hemorrhagic , Soft Tissue Neoplasms , Status Epilepticus , Stress Disorders, Post-Traumatic , Tongue Neoplasms , transient cerebral ischemia , type 2 diabetes mellitus , urinary bladder cancer Bcl2a1 allergic hypersensitivity disease , Arthritis, Rheumatoid , Breast Neoplasms , Esophageal Neoplasms Bcl2l1 Acute Kidney Injury , Adenocarcinoma, Colorectal , Adenoma , Alzheimer's Disease , amyotrophic lateral sclerosis , amyotrophic lateral sclerosis type 1 , Brain Ischemia , Breast Neoplasms , Carcinoma , Carcinoma, Hepatocellular , Carcinoma, Renal Cell , Carcinoma, Transitional Cell , Cerebral Hemorrhage , chronic myeloid leukemia , Cryptorchidism , diabetes mellitus, experimental , Endometrial Neoplasms , Endometriosis , Erectile Dysfunction , gastric ulcer , head and neck neoplasms , Hearing Loss , Hematologic Diseases , Hypoxia-Ischemia, Brain , Leiomyoma , Leukemia, Lymphoid , Leukemia, Myeloid, Acute , Liver Diseases , Liver Neoplasms, Experimental , Liver Reperfusion Injury , Lung Neoplasms , Mammary Neoplasms, Experimental , Melanoma , mental depression , Multiple Myeloma , Myocardial Infarction , Myocardial Reperfusion Injury , Neoplasms, Plasma Cell , neurotoxicity syndromes , Ocular Hypertension , Ovarian Neoplasms , Pancreatic Neoplasms , Pancreatitis, Experimental, Acute , polycythemia vera , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , prostatic neoplasms , Pulmonary Disease, Chronic Obstructive , pulmonary hypertension , Retina Reperfusion Injury , Shock, Hemorrhagic , Status Epilepticus , Stomach Neoplasms , Stroke , type 2 diabetes mellitus , urinary bladder cancer , uterine cervical neoplasms , Uterine Neoplasms , Wilms tumor Bcl2l11 Glomerulonephritis , sclerosing cholangitis , type 2 diabetes mellitus Bid amyotrophic lateral sclerosis , Carcinoma, Hepatocellular , Myocardial Reperfusion Injury , Pancreatic Neoplasms , Reperfusion Injury , Stomach Neoplasms Bmf Liver Cirrhosis, Experimental , lymphocytic leukemia, chronic, B-cell Bnip3 Carcinoma, Intraductal, Noninfiltrating , Chronic Intermittent Hypoxia , Heart Failure , Hemorrhage , Hyperoxia , Infarction, Middle Cerebral Artery , Kidney Failure, Chronic , Kidney Reperfusion Injury , Manganese Poisoning , Multiple Myeloma , Myocardial Infarction , Myocardial Reperfusion Injury , necrotizing enterocolitis , obesity , prostatic neoplasms , Pulmonary Disease, Chronic Obstructive , Retinal Detachment , Spinal Cord Injuries , Stomach Neoplasms , Subarachnoid Hemorrhage , transient cerebral ischemia Bnip3l amyotrophic lateral sclerosis , Cerebral Hemorrhage , Chronic Cerebral Hypoperfusion , Diabetes, Gestational , Infarction, Middle Cerebral Artery , pancreatitis , Spinal Cord Injuries Bok Hydrocephalus Casp3 Alzheimer's Disease , amyotrophic lateral sclerosis , Bacterial Infections , Brain Injuries , Brain Ischemia , Breast Neoplasms , Burns , Calcinosis , Carcinoma, Renal Cell , Carcinoma, Transitional Cell , Cardiomyopathy, Hypertrophic , Cerebral Hemorrhage , Colonic Neoplasms , Copper-Overload Cirrhosis , Cryptorchidism , diabetes mellitus, experimental , Diabetic Angiopathies , Diabetic Nephropathies , Diabetic Neuropathies , Diabetic Retinopathy , Edema , Endotoxemia , Erectile Dysfunction , Experimental Encephalomyelitis, Autoimmune , Fetal Growth Retardation , Heart Valve Diseases , Hepatitis, Chronic , Huntington's Disease , Hypertension , Hypoxia , Hypoxia-Ischemia, Brain , Infarction, Middle Cerebral Artery , Intermittent Claudication , Intestinal Diseases , Kidney Reperfusion Injury , Lung Reperfusion Injury , Mammary Neoplasms, Experimental , Mycoplasma Infections , Myocardial Infarction , Myocardial Reperfusion Injury , Neoplasm Metastasis , Nerve Degeneration , Nervous System Diseases , neurotoxicity syndromes , non-small cell lung carcinoma , pancreatitis , Pancreatitis, Acute Necrotizing , Parkinson's Disease , Parkinsonian Disorders , prostatic neoplasms , Reperfusion Injury , Retinal Detachment , Retinal Diseases , Salivary Gland Diseases , Sepsis , Spinal Cord Injuries , Status Epilepticus , Stroke , Subarachnoid Hemorrhage , transient cerebral ischemia , type 1 diabetes mellitus , type 2 diabetes mellitus , ulcerative colitis , urinary bladder cancer , uterine cervical neoplasms Casp7 Arthritis, Rheumatoid , Breast Neoplasms , Colonic Neoplasms , Endotoxemia , Leukemia, Myeloid, Acute , Liver Cirrhosis, Experimental , Lung Neoplasms , Mammary Neoplasms, Experimental , Myocardial Reperfusion Injury , non-small cell lung carcinoma , Reperfusion Injury , Retinitis Pigmentosa , Spinocerebellar Ataxias , type 2 diabetes mellitus , Vitiligo Casp9 amyotrophic lateral sclerosis , Bacterial Infections , Brain Ischemia , Breast Neoplasms , Colorectal Neoplasms , diabetes mellitus, experimental , Diabetic Retinopathy , Edema , Experimental Encephalomyelitis, Autoimmune , Heart Diseases , Huntington's Disease , Lymphatic Metastasis , Mammary Neoplasms, Experimental , Myocardial Reperfusion Injury , Nervous System Diseases , non-small cell lung carcinoma , Pancreatic Neoplasms , Parkinson's Disease , Parkinsonian Disorders , Peripheral Nervous System Diseases , prostatic neoplasms , Reperfusion Injury , Retinal Detachment , transient cerebral ischemia , type 1 diabetes mellitus , type 2 diabetes mellitus , urinary bladder cancer , Varicocele Cycs Brain Ischemia , Chloracne , cholangiocarcinoma , Fatty Liver , Huntington's Disease , Ischemia , Methylmalonic Acidemia , obesity , Pancreatic Neoplasms , Pleomorphic Xanthoastrocytoma , Thrombocytopenia , Thrombocytopenia 4 , transient cerebral ischemia Fas Acute Kidney Injury , Acute Lung Injury , adenocarcinoma of esophagus , Alzheimer's Disease , Anemia, Aplastic , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Aortic Aneurysm, Thoracic , Arthritis, Rheumatoid , asthma , Autoimmune Diseases , autoimmune lymphoproliferative syndrome , Autoimmune Lymphoproliferative Syndrome, Type IA , Barrett esophagus , Behcet Syndrome , Brain Diseases, Metabolic , Brain Injuries , Brain Ischemia , Breast Neoplasms , Carcinoma, Renal Cell , Carcinoma, Squamous Cell , Carcinoma, Transitional Cell , cardiomyopathy , Cataract , Chemical and Drug Induced Liver Injury , Chest Trauma , Chorioamnionitis , chronic conjunctivitis , chronic myeloid leukemia , Chronic Uveitis , Clonorchiasis , Colitis, Experimental , Colonic Neoplasms , Corneal Neovascularization , Cystic Fibrosis , dermatomyositis , diabetes mellitus, experimental , Diabetic Angiopathies , Diabetic Nephropathies , dilated cardiomyopathy , Disease Models, Animal , endophthalmitis , Endotoxemia , Esophageal Neoplasms , Fetal Growth Retardation , Glaucoma , glioma , Glomerulonephritis , Graft vs Host Disease , Graves Disease , Hashimoto Disease , Heart Failure , Hematologic Diseases , Heroin Dependence , HIV Infections , Huntington's Disease , Hyperoxia , hypersplenism , Hypothermia , Hypoxia-Ischemia, Brain , Idiopathic Pulmonary Fibrosis , idiopathic thrombocytopenic purpura , infectious mononucleosis , Infertility, Male , Kashin-Beck Disease , Leukemia, Myeloid, Acute , Leukemia-Lymphoma, Adult T-Cell , Liver Cirrhosis, Experimental , Liver Failure, Acute , Liver Reperfusion Injury , Lung Neoplasms , Lupus Erythematosus, Systemic , Lymphatic Metastasis , lymphocytic leukemia, chronic, B-cell , Lymphoma, Extranodal NK-T-Cell , Lymphoma, Large B-Cell, Diffuse , Lymphoma, T-Cell, Cutaneous , Lymphoproliferative Disorders , Macular Degeneration , Malaria, Falciparum , Mammary Neoplasms, Experimental , Melanoma , Mixed Connective Tissue Disease , Moyamoya Disease , Multiple Sclerosis , Multiple Sclerosis, Relapsing-Remitting , Multiple System Atrophy , Multisystemic Smooth Muscle Dysfunction Syndrome , Myasthenia Gravis , Myelodysplastic Syndromes , Myocardial Reperfusion Injury , Myositis, Inclusion Body , Nasal Polyps , Necrosis , Neoplasm Metastasis , Nephritis , Nephrosis, Puromycin Aminonucleoside , nonalcoholic fatty liver disease , Ocular Hypertension , Osteoarthritis, Temporomandibular Joint , Ovarian Neoplasms , Oxygen-Induced Retinopathy , Parkinson's Disease , Peripheral Vascular Diseases , Pre-Eclampsia , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Pregnancy Complications, Cardiovascular , prostatic neoplasms , Proteinuria , Radiation Injuries, Experimental , Reperfusion Injury , Retinal Detachment , retinoblastoma , Scleroderma, Limited , Seizures , Seminoma , Sepsis , Sjogren's Syndrome , Spinal Cord Compression , Spinal Cord Injuries , Taste Disorders , Testicular Injury , transient cerebral ischemia , type 1 diabetes mellitus , type 2 diabetes mellitus , urinary bladder cancer , Uveitis, Autoimmune, Experimental , Varicocele , Ventricular Dysfunction, Left Hrk amyotrophic lateral sclerosis Htra2 3-methylglutaconic aciduria, type VIII , Aging, Premature , Alzheimer's Disease , asphyxia neonatorum , Carcinoma, Ductal, Breast , cardiomyopathy , Cryptorchidism , Endometrial Neoplasms , Huntington's Disease , Infarction, Middle Cerebral Artery , Infertility, Female , Motor Neuron Disease , Myocardial Reperfusion Injury , Ovarian Neoplasms , Parkinson's Disease , Parkinson's Disease 13 , Parkinsonian Disorders , prostatic neoplasms , Sepsis , Splenomegaly , Status Epilepticus , Stomach Neoplasms , transient cerebral ischemia Mcl1 Barrett esophagus , Leishmaniasis , Lung Neoplasms , Lymphoma, T-Cell, Cutaneous , Multiple Myeloma , sarcoma Pmaip1 lymphocytic leukemia, chronic, B-cell , Substance-Related Disorders Xiap amyotrophic lateral sclerosis type 1 , Breast Neoplasms , Carcinoma, Renal Cell , cervical intraepithelial neoplasia , Esophageal Neoplasms , Lymphoproliferative Disorders , Mammary Neoplasms, Experimental , Myocardial Reperfusion Injury , Ovarian Neoplasms , prostatic neoplasms , uterine cervical neoplasms , X-linked lymphoproliferative syndrome 2
3-methylglutaconic aciduria, type VIII Htra2 Acute Kidney Injury Bad , Bax , Bcl2 , Bcl2l1 , Fas Acute Lung Injury Bax , Bcl2 , Fas adenocarcinoma Bcl2 adenocarcinoma of esophagus Fas Adenocarcinoma, Clear Cell Bcl2 Adenocarcinoma, Colorectal Bcl2l1 Adenoma Bcl2 , Bcl2l1 Adrenal Insufficiency Bax , Bcl2 Aging, Premature Bax , Bcl2 , Htra2 AIDS-related Kaposi sarcoma Bcl2 allergic hypersensitivity disease Bcl2a1 Alzheimer's Disease Bad , Bak1 , Bax , Bcl2 , Bcl2l1 , Casp3 , Fas , Htra2 amyotrophic lateral sclerosis Bad , Bak1 , Bax , Bcl2 , Bcl2l1 , Bid , Bnip3l , Casp3 , Casp9 , Hrk amyotrophic lateral sclerosis type 1 Bcl2l1 , Xiap Anemia, Aplastic Fas Anti-Glomerular Basement Membrane Disease Bax , Bcl2 Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Fas Aortic Aneurysm, Thoracic Fas Arthritis, Experimental Bax , Bcl2 Arthritis, Rheumatoid Bcl2a1 , Casp7 , Fas asphyxia neonatorum Htra2 asthma Bcl2 , Fas Autistic Disorder Bcl2 Autoimmune Diseases Fas autoimmune lymphoproliferative syndrome Fas Autoimmune Lymphoproliferative Syndrome, Type IA Fas Azoospermia Bcl2 B-Cell CLL/Lymphoma 2 Bcl2 Bacterial Infections Casp3 , Casp9 Barrett esophagus Fas , Mcl1 Behcet Syndrome Fas Brain Diseases, Metabolic Fas Brain Injuries Apaf1 , Bad , Bax , Bcl2 , Casp3 , Fas Brain Ischemia Apaf1 , Bad , Bbc3 , Bcl2 , Bcl2l1 , Casp3 , Casp9 , Cycs , Fas Breast Neoplasms Bad , Bax , Bcl2 , Bcl2a1 , Bcl2l1 , Casp3 , Casp7 , Casp9 , Fas , Xiap Burkitt Lymphoma Bbc3 Burns Bad , Bax , Bcl2 , Casp3 Calcinosis Casp3 Carcinoma Bcl2 , Bcl2l1 Carcinoma, Ductal, Breast Htra2 Carcinoma, Hepatocellular Bcl2l1 , Bid Carcinoma, Intraductal, Noninfiltrating Bcl2 , Bnip3 Carcinoma, Renal Cell Apaf1 , Bad , Bak1 , Bcl2 , Bcl2l1 , Casp3 , Fas , Xiap Carcinoma, Squamous Cell Bcl2 , Fas Carcinoma, Transitional Cell Apaf1 , Bcl2 , Bcl2l1 , Casp3 , Fas Cardiomegaly Bad cardiomyopathy Fas , Htra2 Cardiomyopathy, Hypertrophic Bcl2 , Casp3 Cataract Fas Cell Transformation, Neoplastic Bcl2 Cerebral Hemorrhage Bax , Bcl2 , Bcl2l1 , Bnip3l , Casp3 cervical intraepithelial neoplasia Bcl2 , Xiap Chemical and Drug Induced Liver Injury Bad , Bax , Fas Chest Trauma Fas Chloracne Cycs cholangiocarcinoma Cycs Chondrosarcoma, Mesenchymal Bcl2 Chorioamnionitis Fas Chronic Cerebral Hypoperfusion Bnip3l chronic conjunctivitis Fas Chronic Intermittent Hypoxia Bnip3 chronic myeloid leukemia Bcl2l1 , Fas Chronic Uveitis Fas Clonorchiasis Fas Colitis, Experimental Fas colon cancer Bax colon carcinoma Bax Colonic Neoplasms Bad , Bak1 , Bax , Bcl2 , Casp3 , Casp7 , Fas colorectal cancer Bax Colorectal Neoplasms Bax , Bcl2 , Casp9 Copper-Overload Cirrhosis Casp3 Corneal Neovascularization Fas Craniofacial Abnormalities Apaf1 Cryptorchidism Bcl2l1 , Casp3 , Htra2 Cystic Fibrosis Fas Dementia Bax , Bcl2 Dementia, Multi-Infarct Bax , Bcl2 Dermatitis, Allergic Contact Bcl2 Dermatitis, Contact Bcl2 dermatomyositis Fas diabetes mellitus, experimental Bad , Bax , Bcl2 , Bcl2l1 , Casp3 , Casp9 , Fas Diabetes, Gestational Bnip3l Diabetic Angiopathies Casp3 , Fas Diabetic Cardiomyopathies Bad , Bcl2 Diabetic Cystopathy Bad Diabetic Nephropathies Casp3 , Fas Diabetic Neuropathies Bad , Casp3 Diabetic Retinopathy Casp3 , Casp9 dilated cardiomyopathy Bax , Fas Disease Models, Animal Fas Disease Progression Bcl2 Edema Casp3 , Casp9 Endometrial Neoplasms Bad , Bcl2 , Bcl2l1 , Htra2 Endometriosis Bax , Bcl2 , Bcl2l1 endophthalmitis Fas Endotoxemia Bax , Bcl2 , Casp3 , Casp7 , Fas Erectile Dysfunction Bad , Bax , Bcl2 , Bcl2l1 , Casp3 Esophageal Neoplasms Bax , Bbc3 , Bcl2 , Bcl2a1 , Fas , Xiap Experimental Encephalomyelitis, Autoimmune Casp3 , Casp9 Eye Abnormalities Apaf1 Fatty Liver Cycs Fetal Growth Retardation Bax , Bcl2 , Casp3 , Fas gallbladder neoplasms Bcl2 gastric ulcer Bad , Bcl2 , Bcl2l1 Gastrointestinal Hemorrhage Bax Glaucoma Bad , Bax , Bcl2 , Fas glioma Bad , Fas Glomerulonephritis Bcl2l11 , Fas Graft vs Host Disease Fas Graves Disease Fas Hashimoto Disease Fas head and neck neoplasms Bcl2 , Bcl2l1 Hearing Loss Bcl2l1 Heart Diseases Bax , Casp9 Heart Failure Bax , Bcl2 , Bnip3 , Fas Heart Valve Diseases Casp3 Hematologic Diseases Bcl2l1 , Fas Hemorrhage Bnip3 Hepatitis, Chronic Casp3 Heroin Dependence Fas HIV Infections Bax , Fas Huntington's Disease Bax , Bcl2 , Casp3 , Casp9 , Cycs , Fas , Htra2 Hydrocephalus Bok Hyperbilirubinemia Bcl2 Hyperoxia Bnip3 , Fas Hyperplasia Bax hypersplenism Fas Hypertension Bad , Bax , Bcl2 , Casp3 Hypertrophy, Left Ventricular Bak1 Hypothermia Bcl2 , Fas Hypothyroidism Bad Hypoxia Casp3 Hypoxia-Ischemia, Brain Bax , Bcl2 , Bcl2l1 , Casp3 , Fas Idiopathic Pulmonary Fibrosis Fas idiopathic thrombocytopenic purpura Fas Infarction, Middle Cerebral Artery Bad , Bax , Bcl2 , Bnip3 , Bnip3l , Casp3 , Htra2 infectious mononucleosis Fas Infertility, Female Htra2 Infertility, Male Bax , Bcl2 , Fas Insulin Resistance Bad Intermittent Claudication Bad , Bak1 , Bax , Bbc3 , Casp3 Intestinal Diseases Bax , Bcl2 , Casp3 Intestinal Neoplasms Bax , Bcl2 Intracranial Aneurysm Bcl2 Ischemia Bax , Cycs Kashin-Beck Disease Bax , Bcl2 , Fas Kidney Failure, Chronic Bcl2 , Bnip3 Kidney Reperfusion Injury Bax , Bcl2 , Bnip3 , Casp3 Learning Disorders Bcl2 Leiomyoma Bak1 , Bax , Bcl2 , Bcl2l1 Leishmaniasis Mcl1 Leukemia Bad Leukemia, Lymphoid Bcl2l1 Leukemia, Myeloid, Acute Bcl2 , Bcl2l1 , Casp7 , Fas Leukemia-Lymphoma, Adult T-Cell Fas Leukoplakia, Oral Bcl2 Liver Cirrhosis, Alcoholic Bcl2 Liver Cirrhosis, Experimental Apaf1 , Bak1 , Bcl2 , Bmf , Casp7 , Fas Liver Diseases Bcl2l1 Liver Failure, Acute Fas Liver Neoplasms, Experimental Bak1 , Bbc3 , Bcl2 , Bcl2l1 Liver Reperfusion Injury Bad , Bax , Bcl2 , Bcl2l1 , Fas Lung Neoplasms Bcl2l1 , Casp7 , Fas , Mcl1 Lung Reperfusion Injury Bax , Bcl2 , Casp3 Lupus Erythematosus, Systemic Fas Lymphatic Metastasis Bcl2 , Casp9 , Fas lymphocytic leukemia, chronic, B-cell Bcl2 , Bmf , Fas , Pmaip1 Lymphoma, Extranodal NK-T-Cell Fas Lymphoma, Follicular Bcl2 Lymphoma, Large B-Cell, Diffuse Bcl2 , Fas Lymphoma, Non-Hodgkin Bcl2 Lymphoma, T-Cell, Cutaneous Bax , Fas , Mcl1 Lymphoproliferative Disorders Fas , Xiap Macular Degeneration Bad , Bax , Fas Malaria, Falciparum Fas Mammary Neoplasms, Experimental Apaf1 , Bad , Bak1 , Bax , Bcl2 , Bcl2l1 , Casp3 , Casp7 , Casp9 , Fas , Xiap Manganese Poisoning Bnip3 Melanoma Bcl2 , Bcl2l1 , Fas Memory Disorders Bcl2 mental depression Bax , Bcl2l1 Mesothelioma, Malignant Bcl2 Metaplasia Bcl2 Methylmalonic Acidemia Cycs Microsatellite Instability Bax Mixed Connective Tissue Disease Fas Morphine Dependence Bax , Bcl2 Motor Neuron Disease Htra2 Moyamoya Disease Fas Multiple Myeloma Bcl2 , Bcl2l1 , Bnip3 , Mcl1 Multiple Sclerosis Fas Multiple Sclerosis, Relapsing-Remitting Fas Multiple System Atrophy Fas Multisystemic Smooth Muscle Dysfunction Syndrome Fas Muscular Atrophy Apaf1 Myasthenia Gravis Fas Mycoplasma Infections Casp3 Myelodysplastic Syndromes Fas Myocardial Infarction Bax , Bcl2 , Bcl2l1 , Bnip3 , Casp3 Myocardial Ischemia Bax , Bcl2 Myocardial Reperfusion Injury Bad , Bax , Bcl2 , Bcl2l1 , Bid , Bnip3 , Casp3 , Casp7 , Casp9 , Fas , Htra2 , Xiap Myositis, Inclusion Body Fas Nasal Polyps Fas Nasopharyngeal Carcinoma Bcl2 Necrosis Bcl2 , Fas necrotizing enterocolitis Bnip3 Neoplasm Metastasis Bax , Bcl2 , Casp3 , Fas Neoplasms, Plasma Cell Bcl2l1 Nephritis Fas Nephrosis, Puromycin Aminonucleoside Fas Nerve Degeneration Bak1 , Bax , Bcl2 , Casp3 Nervous System Diseases Casp3 , Casp9 neurotoxicity syndromes Bcl2l1 , Casp3 non-small cell lung carcinoma Bad , Casp3 , Casp7 , Casp9 nonalcoholic fatty liver disease Fas obesity Bad , Bcl2 , Bnip3 , Cycs Ocular Hypertension Bcl2l1 , Fas Optic Nerve Injuries Bax , Bcl2 Osteoarthritis Bad , Bax , Bcl2 Osteoarthritis, Knee Bax , Bcl2 Osteoarthritis, Temporomandibular Joint Fas Osteochondrodysplasias Bcl2 Osteoporosis Bax , Bcl2 Ovarian Neoplasms Bcl2 , Bcl2l1 , Fas , Htra2 , Xiap Oxygen-Induced Retinopathy Fas Pancreatic Neoplasms Apaf1 , Bad , Bcl2l1 , Bid , Casp9 , Cycs pancreatitis Bnip3l , Casp3 Pancreatitis, Acute Necrotizing Casp3 Pancreatitis, Chronic Bad Pancreatitis, Experimental, Acute Bcl2l1 Parkinson's Disease Apaf1 , Casp3 , Casp9 , Fas , Htra2 Parkinson's Disease 13 Htra2 Parkinsonian Disorders Apaf1 , Bad , Casp3 , Casp9 , Htra2 Peripheral Nervous System Diseases Casp9 Peripheral Vascular Diseases Fas Plasmacytoma Bcl2 Pleomorphic Xanthoastrocytoma Cycs Polycystic Ovary Syndrome Bax , Bcl2 polycythemia vera Bcl2l1 Pre-Eclampsia Fas Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Bcl2l1 Precursor Cell Lymphoblastic Leukemia-Lymphoma Bcl2 , Bcl2l1 , Fas Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Bax , Bcl2 Pregnancy Complications, Cardiovascular Fas Priapism Bcl2 Prostatic Hyperplasia Bad prostatic neoplasms Bad , Bax , Bcl2 , Bcl2l1 , Bnip3 , Casp3 , Casp9 , Fas , Htra2 , Xiap Proteinuria Fas Pulmonary Disease, Chronic Obstructive Bcl2l1 , Bnip3 Pulmonary Fibrosis Bad pulmonary hypertension Bcl2 , Bcl2l1 Radiation Injuries, Experimental Fas Reperfusion Injury Apaf1 , Bad , Bax , Bcl2 , Bid , Casp3 , Casp7 , Casp9 , Fas Retina Reperfusion Injury Bad , Bax , Bcl2 , Bcl2l1 Retinal Degeneration Bax , Bcl2 Retinal Detachment Apaf1 , Bnip3 , Casp3 , Casp9 , Fas Retinal Diseases Casp3 Retinitis Pigmentosa Casp7 retinoblastoma Fas Rhinitis, Allergic Bcl2 Salivary Gland Diseases Casp3 sarcoma Mcl1 Sarcoma, Synovial Bcl2 Sarcopenia Bax , Bcl2 Scleroderma, Limited Fas sclerosing cholangitis Bcl2l11 Seizures Apaf1 , Bad , Fas Seminoma Fas Sepsis Bad , Casp3 , Fas , Htra2 Shock, Hemorrhagic Bad , Bcl2 , Bcl2l1 Sjogren's Syndrome Fas Skin Abnormalities Apaf1 Small-For-Size Syndrome Bad Soft Tissue Neoplasms Bcl2 Spinal Cord Compression Fas Spinal Cord Injuries Bnip3 , Bnip3l , Casp3 , Fas Spinal Cord Reperfusion Injury Bad Spinocerebellar Ataxias Casp7 Splenomegaly Htra2 Status Epilepticus Bax , Bcl2 , Bcl2l1 , Casp3 , Htra2 Stomach Neoplasms Bcl2l1 , Bid , Bnip3 , Htra2 Stress Disorders, Post-Traumatic Bax , Bcl2 Stroke Bcl2l1 , Casp3 Subarachnoid Hemorrhage Bnip3 , Casp3 Substance-Related Disorders Pmaip1 Taste Disorders Fas Teratoma Bax Testicular Injury Fas Thrombocytopenia Cycs Thrombocytopenia 4 Cycs Thyroiditis Bax Tongue Neoplasms Bcl2 Toxoplasmosis Bax transient cerebral ischemia Bad , Bax , Bbc3 , Bcl2 , Bnip3 , Casp3 , Casp9 , Cycs , Fas , Htra2 type 1 diabetes mellitus Casp3 , Casp9 , Fas type 2 diabetes mellitus Bad , Bax , Bcl2 , Bcl2l1 , Bcl2l11 , Casp3 , Casp7 , Casp9 , Fas ulcerative colitis Casp3 urinary bladder cancer Bax , Bcl2 , Bcl2l1 , Casp3 , Casp9 , Fas uterine cervical neoplasms Bak1 , Bax , Bcl2l1 , Casp3 , Xiap Uterine Neoplasms Bcl2l1 Uveitis, Autoimmune, Experimental Fas Varicocele Casp9 , Fas Ventricular Dysfunction, Left Fas Vitiligo Casp7 Wilms tumor Bcl2l1 X-linked lymphoproliferative syndrome 2 Xiap