FASL MEDIATED SIGNALING PATHWAY (PW:0000681)

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Description

FasL mediated signaling is one of the major extrinsic apoptotic pathways engaging the death receptors. FasL (official symbol Faslg) and its receptor Fas, also known as CD95/APO-1, belong to the tumor necrosis superfamily (TNF) of ligands and receptors. The receptor contains an extracellular CRD (cysteine-rich domain) while the cytoplasmic part contains a DD (death domain) responsible for the interaction with adapter/effector proteins. Fas, which is ubiquitously expressed, is found at the plasma

Pathway Diagram:

Ariadne Genomics Inc. caspase targets Fadd Faslg Fas Bid Casp7 ---> caspase targets Casp7 ---> caspase targets intrinsic apoptotic pathway Cflar ---| Casp8 Casp8 Cflar clustering Fas ---- Faslg Cflar ---- Fadd Casp8 ---> Bid Casp8 --+> Bid Casp8 --+> Casp7 Casp8 ---> Casp7 Casp8 ---> Casp3 Casp8 --+> Casp3 Casp7 Casp3 Casp3 ---> caspase targets Casp3 ---> caspase targets Fadd ---- Fas Casp8 ---- Fadd
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Genes in Pathway:

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FasL mediated signaling pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Akt1 AKT serine/threonine kinase 1 JBrowse link 6 137,218,398 137,239,970 RGD:6484113
G Bid BH3 interacting domain death agonist JBrowse link 4 153,439,812 153,465,247 RGD:2314002
RGD:6484113
RGD:4143196
G Birc2 baculoviral IAP repeat-containing 2 JBrowse link 8 6,014,014 6,036,668 RGD:6484113
G Birc3 baculoviral IAP repeat-containing 3 JBrowse link 8 6,048,590 6,076,828 RGD:6484113
G Btk Bruton tyrosine kinase JBrowse link X 105,360,922 105,390,580 RGD:6484113
G Casp3 caspase 3 JBrowse link 16 48,845,011 48,863,249 RGD:4143196
RGD:6484113
G Casp7 caspase 7 JBrowse link 1 277,190,557 277,242,779 RGD:4143196
G Casp8 caspase 8 JBrowse link 9 65,614,142 65,662,624 RGD:2314002
RGD:6484113
RGD:4143196
G Cflar CASP8 and FADD-like apoptosis regulator JBrowse link 9 65,534,608 65,586,395 RGD:4143196
RGD:8662854
RGD:6484113
G Chuk conserved helix-loop-helix ubiquitous kinase JBrowse link 1 263,848,829 263,884,354 RGD:6484113
G Cltc clathrin heavy chain JBrowse link 10 74,014,560 74,070,578 RGD:6484113
G Ezr ezrin JBrowse link 1 47,287,872 47,331,412 RGD:6484113
G Fadd Fas associated via death domain JBrowse link 1 217,746,176 217,748,581 RGD:4143196
RGD:6484113
G Faim2 Fas apoptotic inhibitory molecule 2 JBrowse link 7 141,158,769 141,185,781 RGD:6484113
G Fas Fas cell surface death receptor JBrowse link 1 252,589,785 252,624,790 RGD:2314002
RGD:8662854
RGD:6484113
RGD:4143196
G Faslg Fas ligand JBrowse link 13 79,696,811 79,717,581 RGD:2314002
RGD:6484113
RGD:4143196
G Ikbkb inhibitor of nuclear factor kappa B kinase subunit beta JBrowse link 16 74,177,233 74,230,809 RGD:6484113
G Ikbkg inhibitor of nuclear factor kappa B kinase subunit gamma JBrowse link X 156,254,187 156,280,046 RGD:6484113
G Map2k6 mitogen-activated protein kinase kinase 6 JBrowse link 10 98,707,160 98,823,054 RGD:6484113
G Map2k7 mitogen activated protein kinase kinase 7 JBrowse link 12 2,546,278 2,555,310 RGD:6484113
G Map3k1 mitogen-activated protein kinase kinase kinase 1 JBrowse link 2 43,329,516 43,393,203 RGD:6484113
G Mapk10 mitogen activated protein kinase 10 JBrowse link 14 8,079,955 8,371,508 RGD:6484113
G Mapk11 mitogen-activated protein kinase 11 JBrowse link 7 130,121,678 130,129,199 RGD:6484113
G Mapk14 mitogen activated protein kinase 14 JBrowse link 20 5,933,290 5,995,137 RGD:6484113
G Mapk8 mitogen-activated protein kinase 8 JBrowse link 16 9,620,854 9,709,342 RGD:6484113
G Mapk9 mitogen-activated protein kinase 9 JBrowse link 10 35,333,859 35,374,364 RGD:6484113
G Pdpk1 3-phosphoinositide dependent protein kinase-1 JBrowse link 10 13,446,373 13,525,248 RGD:6484113
G Pik3ca phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha JBrowse link 2 118,831,350 118,861,456 RGD:6484113
G Pik3cb phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta JBrowse link 8 107,275,849 107,381,088 RGD:6484113
G Pik3cd phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta JBrowse link 5 166,602,053 166,628,028 RGD:6484113
G Pik3r1 phosphoinositide-3-kinase regulatory subunit 1 JBrowse link 2 31,742,326 31,826,882 RGD:6484113
G Pik3r2 phosphoinositide-3-kinase regulatory subunit 2 JBrowse link 16 20,415,109 20,424,982 RGD:6484113
G Pik3r3 phosphoinositide-3-kinase regulatory subunit 3 JBrowse link 5 135,069,972 135,145,633 RGD:6484113
G Rfc1 replication factor C subunit 1 JBrowse link 14 44,627,528 44,702,205 RGD:6484113
G Ripk1 receptor interacting serine/threonine kinase 1 JBrowse link 17 31,537,580 31,569,904 RGD:6484113
G Smpd1 sphingomyelin phosphodiesterase 1 JBrowse link 1 170,383,682 170,387,525 RGD:6484113
G Src SRC proto-oncogene, non-receptor tyrosine kinase JBrowse link 3 153,547,807 153,595,643 RGD:6484113
G Syk spleen associated tyrosine kinase JBrowse link 17 12,614,311 12,669,568 RGD:6484113

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Gene GroupCaspase targetscaspage target genes.
Pathwayintrinsic apoptotic pathwayintrinsic apoptotic pathway

Pathway Gene Annotations

Disease Annotations Associated with Genes in the FasL mediated signaling pathway
Disease TermsGene Symbols
46 XY gonadal dysgenesisMap3k1
46,XY Sex Reversal 6Map3k1
abdominal aortic aneurysmMapk8
abdominal obesity-metabolic syndrome 1Fadd , Fas
acute kidney failureFas
Acute Liver FailureCasp3 , Fas , Faslg , Mapk8
Acute Lung InjuryCasp3 , Casp8 , Fadd , Fas , Faslg
acute myeloid leukemiaCasp7 , Cflar , Fadd , Fas
acute myocardial infarctionCasp3 , Casp7
Acute Necrotizing PancreatitisCasp3
acute promyelocytic leukemiaAkt1
Acyl-CoA Dehydrogenase Family, Member 9, Deficiency ofPik3ca
adenocarcinomaCasp8 , Pik3ca
adenoid cystic carcinomaPik3ca
adrenal carcinomaPik3ca
adrenocortical carcinomaPik3ca
adult T-cell leukemiaFas
agammaglobulinemiaBtk , Pik3r1
Agammaglobulinemia 7, Autosomal RecessivePik3r1
Agammaglobulinemia, non-Bruton typeBtk
Alcohol-Related DisordersCasp8
allergic contact dermatitisCasp8
allergic hypersensitivity diseaseMap2k6
Alzheimer's diseaseAkt1 , Casp3 , Casp7 , Casp8 , Fadd , Fas , Ikbkb , Mapk10 , Mapk14 , Mapk8 , Mapk9 , Pik3r1
amphetamine abuseAkt1
amyotrophic lateral sclerosisAkt1 , Bid , Casp3 , Mapk14
AnaphylaxisBtk
Anhidrotic Ectodermal Dysplasia with Immunodeficiency, Osteopetrosis, and LymphedemaIkbkg
Animal Disease ModelsAkt1 , Fas , Mapk8 , Mapk9
Animal Mammary NeoplasmsEzr , Map2k6 , Pik3r1
anti-basement membrane glomerulonephritisMapk14 , Mapk8 , Syk
Anti-Neutrophil Cytoplasmic Antibody-Associated VasculitisFas
Aortic Valve, Calcification ofAkt1
aplastic anemiaFas , Faslg
arteriosclerosisFaslg , Mapk9
arthus reactionBtk
asthmaChuk , Fas
astroblastomaPik3r1
astrocytomaAkt1
atherosclerosisAkt1 , Casp3 , Fas , Faslg
atopic dermatitisCasp8 , Mapk8
Atypical Mycobacteriosis, Familial, X-Linked 1Ikbkg
autism spectrum disorderMapk11
Autoimmune DiseasesCasp8 , Fas
autoimmune lymphoproliferative syndromeCasp8 , Fas , Faslg
autoimmune lymphoproliferative syndrome type 2BCasp8
Autoimmune Lymphoproliferative Syndrome, Type IAFas
autoimmune thrombocytopenic purpuraFas
autosomal dominant mental retardation 56Cltc
autosomal recessive polycystic kidney diseaseAkt1 , Pik3ca , Src
B-Cell Chronic Lymphocytic LeukemiaBtk , Fas
B-cell lymphomaBtk
bacterial infectious diseaseCasp3 , Casp8
bacterial pneumoniaChuk
Bannayan-Riley-Ruvalcaba syndromePik3ca
Barrett's esophagusFas
basal cell carcinomaPik3ca
Behcet's diseaseFas , Ikbkg
biliary tract benign neoplasmFaslg
bipolar disorderAkt1
bladder urothelial carcinomaAkt1 , Pik3ca
Bloch-Sulzberger syndromeIkbkg
bone development diseaseChuk
Brain ContusionCasp3 , Casp8
Brain DeathMap2k6
brain gliomaCasp3 , Fadd , Fas , Faslg
Brain InjuriesAkt1 , Casp3 , Casp8 , Fas
brain ischemiaAkt1 , Casp3 , Fas , Faslg , Mapk8 , Src
Brain NeoplasmsPik3ca , Pik3r1
breast adenocarcinomaAkt1 , Pik3ca
breast cancerAkt1 , Btk , Casp8 , Pik3ca
Breast Cancer, FamilialPik3ca , Pik3r3
Breast NeoplasmsAkt1 , Birc2 , Btk , Casp3 , Casp7 , Casp8 , Fas , Faslg , Ikbkb , Map2k7 , Map3k1 , Pdpk1 , Pik3ca , Pik3r1 , Src
Bronchopulmonary DysplasiaBid , Casp3 , Casp8
Bruton-type agammaglobulinemiaBtk , Pik3r1
Burkitt lymphomaPik3r1
BurnsCasp3
calcinosisCasp3
cancerPik3ca , Pik3r1
cannabis abuseAkt1
Carbon Tetrachloride PoisoningFadd
carcinomaEzr , Pik3r1
cardiac arrestAkt1
CardiomegalyAkt1 , Map2k6 , Mapk8 , Src
cardiomyopathyAkt1 , Fas , Faslg , Mapk11 , Mapk14
carotid artery diseaseFaslg
Carotid Artery InjuriesCflar
carotid stenosisFaslg
cataractCasp3 , Fas
Cell Transformation, NeoplasticMapk8
Cerebral HemorrhageCasp3 , Casp8
cervix uteri carcinoma in situFaslg
Charcot-Marie-Tooth disease dominant intermediate CPik3r3
Chemical and Drug Induced Liver InjuryCasp8 , Fadd , Fas
chemical colitisCasp3 , Casp7
Chest TraumaFas
cholangiocarcinomaFaslg
cholestasisMapk14
chorioamnionitisFas
Choroidal NeovascularizationIkbkb
Chronic Cerebral HypoperfusionMapk14
chronic conjunctivitisFas
Chronic HepatitisCasp3
Chronic Intermittent HypoxiaFadd
chronic lymphocytic leukemiaBtk
chronic myeloid leukemiaAkt1 , Fas , Faslg , Mapk14
chronic obstructive pulmonary diseaseCasp3 , Casp8 , Faim2 , Fas , Faslg , Mapk8
Chronic UveitisFas
cleft palateChuk
clonorchiasisFas , Faslg
CLOVES syndromePik3ca
cocoon syndromeChuk
cognitive disorderMapk14
colitisChuk , Ikbkb , Src
colon adenocarcinomaPik3r3
colon cancerAkt1 , Pik3ca , Src
colon carcinomaAkt1 , Pik3ca
Colonic NeoplasmsCasp3 , Casp7 , Fas , Ikbkb , Map2k6 , Mapk8 , Mapk9 , Pik3ca , Pik3r1 , Pik3r2 , Rfc1 , Src
colorectal adenocarcinomaMapk8
colorectal adenomaMapk8
colorectal cancerAkt1 , Pik3ca , Src
Colorectal NeoplasmsAkt1 , Casp8 , Pik3ca , Pik3cd , Pik3r1 , Pik3r3 , Src
Combined Oxidative Phosphorylation Deficiency 11Ripk1
complex cortical dysplasia with other brain malformationsPik3ca
Congenital Limb DeformitiesChuk
congestive heart failureCasp3 , Cflar , Fas , Faslg , Map2k7 , Pdpk1
contact dermatitisCasp8
Contrast-Induced NephropathyCasp3 , Mapk8
Copper-Overload CirrhosisCasp3
corneal neovascularizationFas
coronary artery diseaseAkt1
Cowden diseaseAkt1 , Pik3ca
Cowden Syndrome 5Pik3ca
Cowden Syndrome 6Akt1
Cowden-Like SyndromePik3ca
Craniofacial AbnormalitiesFadd
cryptorchidismCasp3 , Fas
Currarino TriadPik3ca
cutaneous T cell lymphomaFas
cystic fibrosisFas , Faslg
dermatitisIkbkb
dermatomyositisFas
Developmental DisabilitiesPik3r2
Diabetes Mellitus, Experimental Akt1 , Casp3 , Casp8 , Fas , Faslg , Ikbkb , Map2k6 , Pik3r1 , Smpd1
diabetic angiopathyCasp3 , Fas , Faslg
Diabetic CardiomyopathiesCasp3 , Casp8
Diabetic EmbryopathyFadd
Diabetic NephropathiesCasp3 , Casp7 , Casp8 , Fas , Faslg , Mapk14
diabetic neuropathyCasp3 , Mapk14
diabetic retinopathyCasp3
diffuse large B-cell lymphomaCltc , Fas , Pdpk1 , Pik3ca , Pik3cb , Pik3cd
dilated cardiomyopathyCasp3 , Casp8 , Fas , Faslg
disease of cellular proliferationPik3ca , Pik3r1 , Src
Disease ProgressionPik3ca
drug allergyFaslg
ductal carcinoma in situSrc
EdemaCasp3 , Casp8 , Map2k6
Encephalopathy, Neonatal Severe, due to Mecp2 MutationsIkbkg
endometrial adenocarcinomaPik3r1
endometrial cancerPik3cb , Pik3r1
endometrial carcinomaPik3ca , Pik3r1
Endometrial NeoplasmsPik3ca , Pik3cb , Pik3cd
Endometrioid CarcinomasAkt1 , Pik3r2
endometritisCasp3 , Casp7
endophthalmitisFas
EndotoxemiaCasp3 , Casp7 , Fas , Mapk14
epidermal nevusPik3ca
epilepsyAkt1
esophageal carcinomaPik3ca
Esophageal NeoplasmsCasp8 , Fas , Faslg
esophagus adenocarcinomaFas , Pik3ca
Experimental Allergic AsthmaFas , Faslg
Experimental ArthritisAkt1 , Btk , Faslg , Ikbkb , Ikbkg , Pik3cd
Experimental Autoimmune EncephalomyelitisCasp3 , Casp8 , Faslg
Experimental Autoimmune MyocarditisCasp3 , Casp8
Experimental Autoimmune UveitisFas
Experimental ColitisFas
Experimental Liver CirrhosisBirc3 , Casp7 , Ezr , Fas
Experimental MelanomaIkbkb
Experimental PancreatitisIkbkg
extrahepatic cholestasisMapk14 , Mapk8 , Mapk9
Facial AsymmetryPik3ca
familial adenomatous polyposisAkt1
familial combined hyperlipidemiaFaslg
Familial Prostate CancerCasp8
fatty liver diseaseBirc3 , Ikbkg , Mapk8
favismIkbkg
Fetal DiseasesChuk
Fetal Growth RetardationCasp3 , Fas , Faslg
FibrosisAkt1 , Map2k7
gallbladder carcinomaPik3ca
Gallbladder NeoplasmsFaslg
gastric adenocarcinomaAkt1 , Pik3ca
gastric ulcerCasp3 , Fas , Faslg
Gastrointestinal NeoplasmsPik3ca
Generalized EpilepsyMapk10
genetic diseaseCltc , Fas , Ikbkg , Map3k1 , Pik3ca , Pik3r1 , Pik3r2
glaucomaFas
glioblastoma multiformeAkt1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1
glomerulonephritisFas
glucosephosphate dehydrogenase deficiencyIkbkg
Graft vs Host DiseaseFas , Faslg
Graves' diseaseFas
Growth DisordersPik3ca
Hashimoto DiseaseFas
Head and Neck NeoplasmsPik3ca
head and neck squamous cell carcinomaAkt1 , Pik3ca
heart diseaseCasp3 , Casp8 , Mapk14
heart valve diseaseCasp3
hematopoietic system diseaseFas
HemimegalencephalyPik3ca
Hepatic InsufficiencyMapk14
hepatitisFaslg
hepatocellular carcinomaAkt1 , Bid , Casp3 , Casp8 , Fas , Pik3ca
HepatomegalyMapk14
Hereditary Neoplastic SyndromesPik3ca
heroin dependenceFas
Hodgkin's lymphomaCflar
human immunodeficiency virus infectious diseaseBirc2 , Birc3 , Fas
Huntington's diseaseCasp3 , Casp8 , Fas , Faslg
HyperalgesiaMapk8 , Mapk9
HypercholesterolemiaCasp3
hyperglycemiaCasp8
HyperoxiaCflar , Fadd , Fas
HyperplasiaAkt1 , Ikbkb , Pik3ca
hypersplenismFas
hypertensionAkt1 , Casp3 , Casp8 , Fadd , Ikbkb , Mapk8 , Pik3r1 , Src
hypertrophic cardiomyopathyCasp3
Hypogammaglobulinemia, X-LinkedBtk
hypoglycemiaPik3r1
hypohidrotic ectodermal dysplasiaIkbkg
Hypohidrotic Ectodermal Dysplasia, with Immune DeficiencyIkbkg
hypomelanosis of ItoIkbkg
hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadismPik3r2
HypothermiaFas , Faslg
HypoxiaCasp3
Hypoxia-Ischemia, BrainCasp3 , Casp8 , Fadd , Fas
idiopathic pulmonary fibrosisCflar , Fas , Faslg
IgA glomerulonephritisFas
Immunodeficiency 14Pik3cd
Immunodeficiency 15Ikbkb
Immunodeficiency 36Pik3r1
Immunodeficiency without Anhidrotic Ectodermal DysplasiaIkbkg
impotenceAkt1 , Casp3
in situ carcinomaAkt1
inclusion body myositisFas
infectious mononucleosisFas , Faslg
InflammationAkt1 , Chuk
inflammatory bowel diseaseIkbkb
Insulin ResistanceCasp3 , Casp8 , Fas , Ikbkb , Pik3r1
intermediate coronary syndromeAkt1
intermittent claudicationCasp3
Intervertebral Disc DisplacementAkt1
intestinal diseaseCasp3
Intestinal NeoplasmsMapk8
Intestinal Reperfusion InjuryCasp3 , Faslg
invasive ductal carcinomaAkt1
invasive lobular carcinomaFaslg
Invasive Pneumococcal Disease, Recurrent Isolated, 2Ikbkg
irritable bowel syndromeIkbkg
ischemiaMapk9
isolated growth hormone deficiencyBtk
isolated growth hormone deficiency type IIIBtk
Kashin-Beck DiseaseFas
kidney diseaseCasp3 , Casp8 , Smpd1
Kidney NeoplasmsAkt1
Kidney Reperfusion InjuryCasp3 , Casp7 , Fas , Faslg , Ikbkb , Src
Kuhnt-Junius degenerationMapk8
learning disabilityIkbkg
leiomyomaFaslg
Lennox-Gastaut syndromeMapk10
leukemiaBirc2 , Birc3 , Cflar , Fadd
lichen planusRipk1
limited sclerodermaFas , Faslg
liver benign neoplasmMapk14
liver cancerAkt1 , Casp8 , Pik3ca
liver cirrhosisCasp3 , Casp8
liver diseaseFas , Faslg
Liver Reperfusion InjuryCasp8 , Fadd , Fas , Ikbkg , Mapk8
long QT syndromeSyk
lung adenocarcinomaAkt1 , Pik3ca , Pik3r1
lung cancerCasp8 , Faslg , Pik3ca
Lung NeoplasmsAkt1 , Casp7 , Casp8 , Fas , Faslg , Ikbkg , Map2k7 , Mapk14 , Pik3ca
Lung Reperfusion InjuryCasp3
lung small cell carcinomaAkt1 , Pik3ca , Pik3r1
lung squamous cell carcinomaAkt1 , Pik3ca
Lymphatic MetastasisFas , Pdpk1 , Pik3ca , Pik3cb
Lymphoma, Extranodal NK-T-CellCflar , Fas
lymphoproliferative syndromeFas
macular degenerationFas
male infertilityFas
malignant gliomaFas , Pik3ca , Pik3r3
Mammary Neoplasms, ExperimentalAkt1 , Casp3 , Casp7 , Casp8 , Ezr , Fas , Map2k7 , Pik3r1
mantle cell lymphomaBtk , Pik3cd
medulloblastomaPik3ca
Megalancephaly Polymicrogyria-Polydactyly Hydrocephalus SyndromePik3ca , Pik3r2
Megalencephaly Cutis Marmorata Telangiectatica CongenitaPik3ca , Pik3r2
melanomaAkt1 , Casp8 , Fas , Faslg , Pik3ca , Pik3r1 , Syk
Meningeal NeoplasmsAkt1
meningiomaAkt1
mental depressionFadd
MesotheliomaSyk
Metabolic Brain DiseasesFas
Metabolic SyndromeFadd
Microphthalmia, Syndromic 1Map3k1
middle cerebral artery infarctionCasp3 , Fadd , Ikbkb
mixed connective tissue diseaseFas
morphine dependenceFadd
Mouth NeoplasmsPik3ca
Moyamoya diseaseFas
Multiple AbnormalitiesChuk , Cltc , Pik3r2
Multiple Hamartoma SyndromePik3ca
multiple myelomaFaslg , Pik3ca
multiple sclerosisFas , Faslg
multiple system atrophyFas
Multisystemic Smooth Muscle Dysfunction SyndromeFas
muscular atrophyAkt1 , Chuk , Ikbkb
myasthenia gravisFas
Mycoplasma InfectionsCasp3
myelodysplastic syndromeCflar , Fas , Faslg
myocardial infarctionAkt1 , Casp3
Myocardial IschemiaMapk14
Myocardial Reperfusion InjuryAkt1 , Bid , Casp3 , Casp7 , Casp8 , Cflar , Fadd , Fas , Map2k6 , Mapk14 , Mapk8
Nasal PolypsFas
Nasopharyngeal NeoplasmsPik3ca
NecrosisFas , Faslg
Nematode InfectionsPik3r1
Neonatal HyperbilirubinemiaIkbkb
Neoplasm InvasivenessSmpd1 , Src
Neoplasm MetastasisCasp3 , Chuk , Ezr , Fadd , Fas , Faslg , Mapk9 , Pik3ca , Pik3r3 , Src
nephritisCasp8 , Fas
Nephrosis, Puromycin AminonucleosideFas
Nerve DegenerationCasp3
nervous system diseaseCasp3
neuroblastomaMap2k7 , Pik3ca
neuronal ceroid lipofuscinosis 6Smpd1
Niemann-Pick diseaseSmpd1
Niemann-Pick disease type ASmpd1
Niemann-Pick disease type BSmpd1
Niemann-Pick Disease, Intermediate, Protracted NeurovisceralSmpd1
non-Hodgkin lymphomaPik3ca
non-small cell lung carcinomaAkt1 , Casp3 , Casp7 , Casp8 , Faslg , Pdpk1 , Pik3ca
nonalcoholic fatty liver diseaseFas , Ikbkg , Mapk8
obesityAkt1 , Fadd , Ikbkb , Pik3r1
ocular hypertensionFas
osteoarthritisCasp3 , Ezr
Osteoarthritis, ExperimentalCasp3 , Casp7 , Casp8
Osteoarthritis, Temporomandibular JointFas
osteoporosisMapk14
osteosarcomaAkt1 , Rfc1
ovarian cancerAkt1 , Pik3ca
Ovarian NeoplasmsAkt1 , Fas , Map2k6 , Map2k7 , Pik3ca , Pik3r1
ovarian serous cystadenocarcinomaPik3ca
Oxygen-Induced RetinopathyFas , Faslg , Mapk8
PainAkt1
pancreatic adenocarcinomaPik3ca
pancreatic cancerAkt1 , Bid , Casp8 , Cflar , Faslg
pancreatic ductal carcinomaFaslg
pancreatic intraductal papillary-mucinous neoplasmAkt1
pancreatitisCasp3 , Ikbkb
papillary renal cell carcinomaPik3ca
Papillomavirus InfectionsCasp8
paraplegiaAkt1
Parkinson's diseaseAkt1 , Casp3 , Fas , Faslg
Parkinsonian DisordersCasp3 , Src
penile neoplasmPik3ca
perinatal necrotizing enterocolitisIkbkg
peripheral vascular diseaseFas
Pick's diseaseMap2k6
Plaque, AtheroscleroticCflar
plasmacytomaPik3ca
Plasmodium falciparum malariaFas
pneumoniaIkbkb
portal hypertensionPik3r1
pre-eclampsiaFas
pre-malignant neoplasmAkt1 , Bid , Casp3 , Casp8 , Fas , Map2k7 , Mapk8 , Mapk9
precursor lymphoblastic lymphoma/leukemiaCasp8 , Fas
Pregnancy Complications, CardiovascularFas
primary biliary cirrhosisMapk14
primary immunodeficiency diseaseBtk , Casp8
progressive supranuclear palsyMap2k6
prostate adenocarcinomaAkt1 , Chuk , Ikbkb , Pdpk1 , Pik3ca , Pik3cb
prostate cancerChuk , Ikbkb , Mapk10 , Pdpk1 , Pik3ca , Pik3cb , Pik3r1 , Pik3r2
prostate carcinoma in situMap2k6 , Map2k7
prostatic hypertrophyFadd
Prostatic NeoplasmsAkt1 , Casp3 , Chuk , Ezr , Fas , Faslg , Map2k6 , Map2k7 , Map3k1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Src
proteinuriaFas
Proteus syndromeAkt1
psoriasisIkbkb
PTEN hamartoma tumor syndromePik3ca
pulmonary fibrosisCflar
Radiation Injuries, ExperimentalCasp3 , Casp8 , Fas
rectal neoplasmMapk8 , Pik3ca , Pik3cb
Recurrent Infections, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular MalformationsFadd
relapsing-remitting multiple sclerosisFas
renal carcinomaPik3ca
renal cell carcinomaAkt1 , Birc2 , Birc3 , Casp3 , Fas , Faslg , Pik3ca , Pik3r1
Reperfusion InjuryAkt1 , Bid , Casp3 , Casp8 , Fas , Mapk8 , Mapk9 , Pik3r1 , Src
restrictive cardiomyopathyMap2k6 , Mapk14
Retina Reperfusion InjuryCasp7
retinal detachmentCasp3 , Casp8 , Fas
retinal diseaseCasp3
retinitis pigmentosaCasp7 , Ripk1
retinoblastomaFas
rheumatoid arthritisCasp7 , Fas , Faslg
Right Ventricular HypertrophyAkt1
salivary gland diseaseCasp3
sarcomaPik3ca
schizophreniaAkt1 , Map2k7 , Pik3cb
sciatic neuropathyCasp3 , Casp7 , Casp8 , Fas
scrapieCasp3
seborrheic keratosisPik3ca
seminomaFas , Faslg
sensorineural hearing lossFadd
SepsisCasp3 , Casp8 , Fas , Faslg
Septic PeritonitisPik3r1
Shock, HemorrhagicCasp3 , Casp8
SHORT SyndromePik3r1
Sjogren's syndromeFas
Skin AbnormalitiesChuk
skin cancerChuk
skin melanomaAkt1 , Pik3ca
Skin NeoplasmsAkt1 , Casp8
Smith-Magenis syndromeCltc , Map2k6
spermatic cord torsionCasp3
Spinal Cord CompressionFas , Faslg
Spinal Cord InjuriesAkt1 , Casp3 , Fadd , Fas
Spinocerebellar AtaxiasCasp7
SplenomegalyFas
Sporadic Papillary Renal Cell CarcinomaPik3ca
squamous cell carcinomaAkt1 , Fas , Pik3ca , Ripk1
status epilepticusCasp3 , Casp8 , Src
stomach cancerPik3ca
Stomach NeoplasmsBid , Birc2 , Casp8 , Mapk8 , Pik3ca
Stomatognathic DiseasesFadd
StrokeAkt1 , Casp3 , Mapk8 , Pik3ca , Src
Subarachnoid HemorrhageCasp3
substance-induced psychosisAkt1
substance-related disorderFaslg
systemic lupus erythematosusFas
T-Cell LymphomaAkt1
Taste DisordersFas
testicular diseaseFaslg
Testicular InjuryFas
Testis Reperfusion InjuryCasp3
thoracic aortic aneurysmFas
THROMBOCYTOPENIA 6Src
thrombosisPik3cb
Thyroid NeoplasmsAkt1 , Pik3ca
toxic encephalopathyCasp3
transient cerebral ischemiaCasp3 , Casp7 , Casp8 , Fas , Ikbkb
transitional cell carcinomaAkt1 , Casp3 , Fas , Faslg , Pik3ca
Transplant RejectionIkbkb
trigeminal neuralgiaMapk8 , Mapk9
type 1 diabetes mellitusCasp3 , Casp8 , Fas , Faslg
type 2 diabetes mellitusAkt1 , Casp3 , Casp7 , Casp8 , Fas , Faslg , Ikbkb , Mapk8 , Mapk9 , Pik3cb , Pik3r1 , Src
ulcerative colitisCasp3 , Fas , Faslg
ureteral obstructionAkt1 , Casp3 , Casp7
urinary bladder cancerAkt1 , Birc3 , Casp3 , Fas , Faslg , Src
uterine carcinosarcomaPik3ca , Pik3r1
Uterine Cervical NeoplasmsAkt1 , Birc2 , Casp3 , Casp8 , Faslg , Map2k6 , Pik3ca
Uterine NeoplasmsPik3ca , Pik3r1
varicoceleFas
Vascular MalformationsPik3ca
Ventilator-Induced Lung InjuryAkt1
Ventricular Dysfunction, LeftFas
Viral MyocarditisCasp3 , Casp8
visual epilepsyFas , Pik3ca
vitiligoCasp7 , Pik3r1
Weight GainPik3ca
Williams-Beuren syndromeSrc
Wilson diseaseSmpd1
Pathway Annotations Associated with Genes in the FasL mediated signaling pathway
Pathway TermsGene Symbols
acute myeloid leukemia pathwayAkt1 , Chuk , Ikbkb , Ikbkg , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
adenosine signaling pathwayAkt1 , Chuk , Ikbkb , Map2k6 , Map2k7 , Map3k1 , Mapk11 , Mapk8 , Pdpk1 , Pik3ca
aldosterone signaling pathwayPdpk1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
allograft rejection pathwayFas , Faslg
altered phosphatidylinositol 3-kinase signaling pathwayPik3ca
altered phosphatidylinositol 3-kinase-Akt signaling pathwayAkt1 , Pik3ca
altered Reelin signaling pathwaySrc
Alzheimer's disease pathwayBid , Casp3 , Casp7 , Casp8 , Fadd , Fas
amyotrophic lateral sclerosis pathwayBid , Casp3 , Map2k6 , Mapk11 , Mapk14
angiotensin II signaling pathwayPdpk1
apoptotic cell death pathwayAkt1 , Bid , Birc2 , Birc3 , Casp3 , Casp7 , Casp8 , Cflar , Chuk , Fadd , Fas , Faslg , Ikbkb , Ikbkg , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3 , Ripk1
autoimmune thyroiditis pathwayFas , Faslg
B cell receptor signaling pathwayAkt1 , Btk , Chuk , Ikbkb , Ikbkg , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3 , Syk
c-Jun N-terminal kinases MAPK signaling pathwayMap2k7 , Map3k1 , Mapk10 , Mapk8 , Mapk9
ceramide signaling pathwayAkt1 , Bid , Birc3 , Casp8 , Chuk , Fadd , Ikbkb , Ikbkg , Map3k1 , Mapk10 , Mapk8 , Mapk9 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3 , Ripk1 , Smpd1
Chagas disease pathwayAkt1 , Casp8 , Cflar , Chuk , Fadd , Fas , Faslg , Ikbkb , Ikbkg , Mapk10 , Mapk11 , Mapk14 , Mapk8 , Mapk9 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
chemokine mediated signaling pathwayAkt1 , Chuk , Ikbkb , Ikbkg , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
chronic myeloid leukemia pathwayAkt1 , Chuk , Ikbkb , Ikbkg , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
clathrin-dependent synaptic vesicle endocytosisCltc
colorectal cancer pathwayAkt1 , Casp3 , Mapk10 , Mapk8 , Mapk9 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
cytokine mediated signaling pathwayFas , Faslg
DNA replication pathwayRfc1
dopamine signaling pathwaySrc
E-cadherin signaling pathwayAkt1 , Pik3ca , Pik3r1 , Src
eicosanoid signaling pathwayAkt1 , Mapk11 , Mapk14 , Src , Syk
eicosanoid signaling pathway via peroxisome proliferator-activated receptor gammaPdpk1
endocytosis pathwayCltc , Src
endometrial cancer pathwayAkt1 , Pdpk1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
Endoplasmic Reticulum-associated degradation pathwayMap2k7 , Mapk10 , Mapk8 , Mapk9
endothelin signaling pathwayAkt1 , Mapk14 , Mapk8 , Src
Entamoebiasis pathwayCasp3 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
ephrin - ephrin receptor bidirectional signaling axisMapk8 , Pik3ca , Pik3r1 , Src
epidermal growth factor/neuregulin signaling pathwayAkt1 , Map2k7 , Mapk10 , Mapk8 , Mapk9 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3 , Src
erythropoietin signaling pathwayBtk , Mapk14 , Mapk8 , Pik3r1
estrogen signaling pathwaySrc
extrinsic apoptotic pathwayCasp3 , Casp7 , Casp8 , Fas , Faslg
FasL mediated signaling pathwayAkt1 , Bid , Birc2 , Birc3 , Btk , Casp3 , Casp7 , Casp8 , Cflar , Chuk , Cltc , Ezr , Fadd , Faim2 , Fas , Faslg , Ikbkb , Ikbkg , Map2k6 , Map2k7 , Map3k1 , Mapk10 , Mapk11 , Mapk14 , Mapk8 , Mapk9 , Pdpk1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3 , Rfc1 , Ripk1 , Smpd1 , Src , Syk
Fc epsilon receptor mediated signaling pathwayAkt1 , Btk , Map2k6 , Map2k7 , Mapk10 , Mapk11 , Mapk14 , Mapk8 , Mapk9 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3 , Syk
Fc gamma receptor mediated signaling pathwayAkt1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3 , Syk
fibroblast growth factor signaling pathwayAkt1 , Pdpk1 , Pik3ca , Pik3r1 , Src
forkhead class A signaling pathwayAkt1
glioma pathwayAkt1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
glutathione metabolic pathwayCasp7
glutathione synthase deficiency pathwayCasp7
glutathionuria disease pathwayCasp7
glypican signaling pathwayMapk8 , Mapk9 , Src
gonadotropin-releasing hormone signaling pathwayMap2k6 , Map2k7 , Map3k1 , Mapk10 , Mapk11 , Mapk14 , Mapk8 , Mapk9 , Src
graft-versus-host disease pathwayFas , Faslg
granulocyte-macrophage colony-stimulating factor signaling pathwayIkbkb , Pik3ca , Pik3r1 , Syk
Hedgehog signaling pathwayAkt1 , Pik3ca , Pik3r1
hepatitis C pathwayAkt1 , Chuk , Ikbkb , Ikbkg , Mapk10 , Mapk11 , Mapk14 , Mapk8 , Mapk9 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3 , Ripk1
Huntington's disease pathwayCasp3 , Casp8 , Cltc
hypoxia inducible factor pathwayAkt1
inflammatory response pathwayMapk8
influenza A pathwayAkt1 , Fas , Faslg , Ikbkb , Map2k6 , Map2k7 , Mapk10 , Mapk11 , Mapk14 , Mapk8 , Mapk9 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
inositol metabolic pathwayPik3ca
inositol phosphate metabolic pathwayPik3ca , Pik3cb , Pik3cd
insulin responsive facilitative sugar transporter mediated glucose transport pathwayAkt1
insulin signaling pathwayAkt1 , Ikbkb , Mapk10 , Mapk8 , Mapk9 , Pdpk1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
insulin-like growth factor signaling pathwayAkt1 , Pdpk1 , Pik3ca , Pik3r1
interleukin-1 signaling pathwayChuk , Ikbkb , Ikbkg , Map2k6 , Mapk8 , Pik3ca , Pik3r1
interleukin-12 signaling pathwayFaslg , Map2k6 , Mapk14
interleukin-2 signaling pathwayMapk11 , Mapk14 , Mapk8 , Mapk9 , Pik3ca , Pik3r1 , Syk
interleukin-23 signaling pathwayPik3ca , Pik3r1
interleukin-3 signaling pathwayPik3ca , Pik3r1
interleukin-4 signaling pathwayAkt1 , Mapk14 , Pik3ca , Pik3r1
interleukin-5 signaling pathwayPik3ca , Pik3r1
interleukin-6 signaling pathwayAkt1 , Map2k6 , Mapk11 , Mapk14 , Pik3ca , Pik3r1
intrinsic apoptotic pathwayBid , Casp3 , Casp7 , Fas
Jak-Stat signaling pathwayAkt1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
Leishmaniasis pathwayMapk11 , Mapk14
measles pathwayAkt1 , Chuk , Fas , Faslg , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
melanoma pathwayAkt1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
mismatch repair pathwayRfc1
mitochondrial autophagy pathwaySrc
mitogen activated protein kinase signaling pathwayAkt1 , Casp3 , Chuk , Fas , Faslg , Ikbkb , Ikbkg , Map2k6 , Map2k7 , Map3k1 , Mapk10 , Mapk11 , Mapk14 , Mapk8 , Mapk9
mTOR signaling pathwayAkt1 , Ikbkb , Pdpk1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
myocarditis pathwayBid , Casp3 , Casp8
N-cadherin signaling pathwayMapk8 , Pik3ca , Pik3r1
nerve growth factor signaling pathwaySrc
neurotrophic factor signaling pathwayAkt1 , Faslg , Ikbkb , Map2k7 , Map3k1 , Mapk10 , Mapk11 , Mapk14 , Mapk8 , Mapk9 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
NOD-like receptor signaling pathwayBirc2 , Birc3 , Casp8 , Chuk , Ikbkb , Ikbkg , Mapk10 , Mapk11 , Mapk14 , Mapk8 , Mapk9
non-small cell lung carcinoma pathwayAkt1 , Pdpk1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
nuclear factor kappa B signaling pathwayBirc2 , Chuk , Ikbkb , Ikbkg , Mapk14 , Pik3ca , Pik3r1 , Src , Syk
nuclear factor, erythroid 2 like 2 signaling pathwayIkbkb
nucleotide excision repair pathwayRfc1
p38 MAPK signaling pathwayMap2k6 , Map3k1 , Mapk11 , Mapk14
p53 signaling pathwayAkt1 , Bid , Casp3 , Casp8 , Fas , Mapk14 , Mapk8 , Mapk9
pancreatic cancer pathwayAkt1 , Chuk , Ikbkb , Ikbkg , Mapk10 , Mapk8 , Mapk9 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
parathyroid hormone signaling pathwayEzr
Parkinson's disease pathwayCasp3
phosphatidylinositol 3-kinase class I signaling pathwayBtk , Pdpk1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3 , Src , Syk
phosphatidylinositol 3-kinase signaling pathwayPik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
phosphatidylinositol 3-kinase-Akt signaling pathwayAkt1 , Chuk , Pdpk1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3 , Src
phosphoinositide metabolic pathwayPik3ca , Pik3cd , Pik3r1
platelet-derived growth factor signaling pathwayMap2k7 , Mapk10 , Mapk8 , Mapk9 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3 , Src
primary immunodeficiency pathwayBtk , Ikbkg
prostate cancer pathwayAkt1 , Chuk , Ikbkb , Ikbkg , Pdpk1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
protein kinase A (PKA) signaling pathwayEzr
protein kinase C (PKC) signaling pathwayBtk , Pdpk1
Reelin signaling pathwayAkt1 , Map2k7 , Mapk8 , Pik3ca , Pik3r1 , Src
renal cell carcinoma pathwayAkt1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
Retinoic acid-inducible gene (RIG) I-like receptor signaling pathwayCasp8 , Chuk , Fadd , Ikbkb , Ikbkg , Map3k1 , Mapk10 , Mapk11 , Mapk14 , Mapk8 , Mapk9 , Ripk1
Rho/Rac/Cdc42 mediated signaling pathwayMapk8
scatter factor/hepatocyte growth factor signaling pathwayPik3r1 , Src
signaling pathway pertinent to the brain and nervous systemSrc
sleeping sickness pathwayFas , Faslg
small cell lung carcinoma pathwayAkt1 , Birc2 , Birc3 , Chuk , Ikbkb , Ikbkg , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
somatostatin signaling pathwaySrc
sphingolipid metabolic pathwaySmpd1
sphingosine 1-phosphate signaling pathwayAkt1 , Mapk14 , Mapk8 , Src
syndecan signaling pathwayCasp3 , Ezr , Mapk8 , Src
T cell receptor signaling pathwayAkt1 , Chuk , Ikbkb , Ikbkg , Map2k7 , Mapk11 , Mapk14 , Mapk9 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
the extracellular signal-regulated Raf/Mek/Erk signaling pathwayMap3k1
titanium dioxide nanoparticle response pathwayCasp3 , Casp8 , Fas
Toll-like receptor signaling pathwayAkt1 , Casp8 , Chuk , Fadd , Ikbkb , Ikbkg , Map2k6 , Map2k7 , Mapk10 , Mapk11 , Mapk14 , Mapk8 , Mapk9 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3 , Ripk1
toxoplasmosis pathwayAkt1 , Birc2 , Birc3 , Casp3 , Casp8 , Chuk , Ikbkb , Ikbkg , Map2k6 , Mapk10 , Mapk11 , Mapk14 , Mapk8 , Mapk9 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
Trail mediated signaling pathwayBid , Casp3 , Casp7 , Casp8 , Cflar , Chuk , Fadd , Ikbkb , Ikbkg , Map3k1 , Mapk8 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3 , Ripk1 , Smpd1
transforming growth factor-beta Smad dependent signaling pathwayPdpk1
tuberculosis pathwayAkt1 , Bid , Casp3 , Casp8 , Fadd , Mapk10 , Mapk11 , Mapk14 , Mapk8 , Mapk9 , Src , Syk
tumor necrosis factor mediated signaling pathwayBirc2 , Birc3 , Casp8 , Chuk , Fadd , Ikbkb , Ikbkg , Map2k7 , Map3k1 , Ripk1 , Smpd1
type 1 diabetes mellitus pathwayFas , Faslg
type 2 diabetes mellitus pathwayIkbkb , Mapk10 , Mapk8 , Mapk9 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3
type II interferon signaling pathwayAkt1 , Map3k1 , Pik3ca , Pik3r1
ubiquitin/proteasome degradation pathwayBirc2 , Birc3 , Map3k1 , Src
vascular endothelial growth factor signaling pathwayAkt1 , Map2k6 , Mapk11 , Mapk14 , Pdpk1 , Pik3ca , Pik3cb , Pik3cd , Pik3r1 , Pik3r2 , Pik3r3 , Src
Wnt signaling pathwayMapk10 , Mapk8 , Mapk9
Wnt signaling, non-canonical pathwayMapk10 , Mapk8 , Mapk9
Phenotype Annotations Associated with Genes in the FasL mediated signaling pathway
Phenotype TermsGene Symbols
neurodegenerationFaslg

References Associated with the FasL mediated signaling pathway:

Ontology Path Diagram:

paths to the root

Import into Pathway Studio: