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Glucocorticoid steroid hormones, cortisol in humans, play essential roles in the regulation of immune responses, metabolism, development as well as cognitive processes. Cortisol promotes the expression of anti-inflammatory proteins while repressing the expression of pro-inflammatory ones, stimulates gluconeogenesis in liver and the breakdown of fat in the adipose tissue. The synthesis of cortisol is under the control of the hypothalamus-pituitary-adrenal (HPA) axis. In response to various stress

Pathway Diagram:

Ariadne Genomics Inc. stress conditions Nr3c1 target genes Nr3c1 coactivators Nr3c1 corepressors Nr3c1 chaperones cortisol Nr3c1 ---- Nr3c1 chaperones translocated Nr3c1 complex ---> Nr3c1 target genes translocated Nr3c1 complex ---| HPA axis HPA axis HPA axis --+> cortisol biosynthetic pathway cortisol ---- Nr3c1 Nr3c1 Nr3c1 corepressors ---- translocated Nr3c1 complex Nr3c1 coactivators --+> translocated Nr3c1 complex Nr3c1 ---> translocated Nr3c1 complex Nr3c1 corepressors ---| translocated Nr3c1 complex Nr3c1 coactivators ---- translocated Nr3c1 complex direct and indirect target gene expression cortisol biosynthetic pathway translocated Nr3c1 complex stress conditions --+> HPA axis translocated Nr3c1 complex ---> Nr3c1 target genes

Genes in Pathway:

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cortisol signaling pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Crebbp CREB binding protein JBrowse link 10 11,590,994 11,721,039 RGD:5147892
G Dnaja2 DnaJ heat shock protein family (Hsp40) member A2 JBrowse link 19 22,569,999 22,588,143 RGD:5144125
G Ep300 E1A binding protein p300 JBrowse link 7 122,818,194 122,889,055 RGD:5147892
G Fkbp4 FK506 binding protein 4 JBrowse link 4 161,748,993 161,757,447 RGD:5144125
G Fkbp5 FK506 binding protein 5 JBrowse link 20 7,976,704 8,097,290 RGD:5144125
G Hsp90aa1 heat shock protein 90 alpha family class A member 1 JBrowse link 6 135,107,262 135,112,793 RGD:5144125
G Hsp90ab1 heat shock protein 90 alpha family class B member 1 JBrowse link 9 17,817,791 17,823,163 RGD:5144125
G Hspa4 heat shock protein family A member 4 JBrowse link 10 38,601,624 38,642,397 RGD:5144125
G Med1 mediator complex subunit 1 JBrowse link 10 86,101,560 86,145,271 RGD:5147892
G Med14 mediator complex subunit 14 JBrowse link X 10,964,035 11,082,403 RGD:5147892
G Ncoa1 nuclear receptor coactivator 1 JBrowse link 6 28,677,563 28,931,844 RGD:5144138
G Ncoa2 nuclear receptor coactivator 2 JBrowse link 5 5,466,544 5,696,540 RGD:5144138
G Ncoa3 nuclear receptor coactivator 3 JBrowse link 3 162,692,176 162,788,582 RGD:5144138
G Ncor1 nuclear receptor co-repressor 1 JBrowse link 10 48,629,121 48,772,890 RGD:5147413
G Ncor2 nuclear receptor co-repressor 2 JBrowse link 12 36,871,917 37,033,701 RGD:5147413
G Nr3c1 nuclear receptor subfamily 3, group C, member 1 JBrowse link 18 31,728,373 32,704,022 RGD:5144125
G Ptges3 prostaglandin E synthase 3 JBrowse link 7 2,479,267 2,497,024 RGD:5144125
G Smarca4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 JBrowse link 8 22,648,323 22,739,468 RGD:5147892
G Stip1 stress-induced phosphoprotein 1 JBrowse link 1 222,274,133 222,293,139 RGD:5144125

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Pathwaycortisol biosynthetic pathway
Gene GroupNr3c1 target genesseveral genes up- and downregulated by activated Nr3c1
Functional ClassNr3c1 corepressorsthe currently known corepressors of Nr3c1
Functional ClassNr3c1 chaperonesthe set of chaperones and co-chaperones that constitutes the Nr3c1 chaperone machinery essential for the function and turnover of the receptor
Functional ClassNr3c1 coactivatorsthe set of Nr3c1 coactivators

Pathway Gene Annotations

Disease Annotations Associated with Genes in the cortisol signaling pathway
Disease TermsGene Symbols
46, XX Disorders of Sex DevelopmentNr3c1
Abnormalities, MultipleCrebbp , Ep300 , Smarca4
Acute-Phase ReactionNcor1
adult respiratory distress syndromeHspa4
Alzheimer DiseaseCrebbp , Ep300 , Hsp90aa1
amyotrophic lateral sclerosis type 1Crebbp
Anorexia NervosaNr3c1
Anxiety DisordersNcor1
Arthritis, ExperimentalPtges3
Arthritis, RheumatoidFkbp5 , Hsp90aa1 , Hspa4 , Nr3c1
Attention Deficit Disorder with HyperactivityCrebbp
bipolar disorderNr3c1
bladder urothelial carcinomaCrebbp , Ep300
Bone NeoplasmsNcoa3
Brain InjuriesHspa4
Brain IschemiaNr3c1
breast cancer, familialNcor1
Breast NeoplasmsEp300 , Hsp90aa1 , Ncoa1 , Ncoa2 , Ncoa3 , Ncor1 , Ncor2 , Ptges3
Burkitt LymphomaSmarca4
Carcinoma, Adenoid CysticCrebbp , Ep300
Carcinoma, HepatocellularCrebbp , Ep300 , Med1
Carcinoma, Renal CellNr3c1
Carcinoma, Small CellSmarca4
Carcinoma, Squamous CellCrebbp , Ep300 , Ncoa3
Carcinoma, Squamous Cell of Head and NeckCrebbp , Ep300
Carcinoma, Transitional CellCrebbp , Ep300 , Ncor1
Chagas DiseaseHspa4
Chemical and Drug Induced Liver InjuryMed1
Cocaine-Related DisordersNr3c1 , Smarca4
Coffin-Siris syndromeSmarca4
Coffin-Siris syndrome 4Smarca4
Cognitive DysfunctionHsp90aa1
colon cancerEp300
Colonic NeoplasmsEp300
colorectal cancerEp300
Colorectal NeoplasmsCrebbp , Ep300
Coronary Artery DiseaseNr3c1
Craniofacial AbnormalitiesEp300
Cushing syndromeNr3c1
Depressive Disorder, MajorFkbp5 , Nr3c1
Dermatitis, ContactHsp90aa1
Developmental DisabilitiesNcor1
diabetes mellitus, experimentalEp300 , Hsp90aa1 , Nr3c1 , Smarca4
Diabetic NephropathiesEp300
Diabetic RetinopathyEp300
dilated cardiomyopathyMed1
Dry Eye SyndromesHspa4
Endometrial NeoplasmsEp300 , Ncoa1 , Ncor2
EndometriosisFkbp5 , Med1 , Med14 , Ncoa1 , Ncor1 , Nr3c1
EndotoxemiaEp300 , Nr3c1
Esophageal NeoplasmsEp300
Esophageal Squamous Cell CarcinomaCrebbp , Ep300
Experimental Encephalomyelitis, AutoimmuneNr3c1
Fetal Growth RetardationNr3c1
Frontotemporal Lobar DegenerationHsp90aa1
Genetic Diseases, InbornCrebbp , Smarca4
glioblastomaCrebbp , Ncor1
Glomerulonephritis, MembranoproliferativeEp300
Glucocorticoid Receptor DeficiencyNr3c1
Heart ArrestEp300
Heart DiseasesEp300
Heart FailureNr3c1
Heart Septal Defects, VentricularSmarca4
Heat StrokeHspa4
Hernias, Diaphragmatic, CongenitalEp300
Hirschsprung Disease 1Crebbp
HIV InfectionsHsp90aa1 , Hsp90ab1
Huntington DiseaseCrebbp , Ep300 , Ncor1
HyperalgesiaEp300 , Ptges3
Hyperbilirubinemia, NeonatalNcor1
Hypercholesterolemia, FamilialSmarca4
HypertensionEp300 , Nr3c1
Hypertrophy, Left VentricularSmarca4
HypothyroidismNcoa1 , Ncor1
Hypoxia, BrainEp300
Infant, Newborn, DiseasesFkbp5
Infarction, Middle Cerebral ArteryHspa4
Infertility, FemaleHsp90ab1
Intellectual DisabilityEp300
Ischemic Attack, TransientEp300
Kidney Failure, ChronicNr3c1
Kidney Reperfusion InjuryEp300
Lead Poisoning, Nervous SystemEp300
Leukemia, Myeloid, AcuteCrebbp , Ncoa2
liver cancerCrebbp
Liver Cirrhosis, BiliaryNr3c1
Liver Cirrhosis, ExperimentalNcor2
Liver DiseasesDnaja2
Liver NeoplasmsCrebbp , Hspa4 , Ncor1
lung adenocarcinomaCrebbp , Ep300
Lung DiseasesNr3c1
Lung Diseases, InterstitialNr3c1
Lung Diseases, ObstructiveNr3c1
Lung NeoplasmsSmarca4
lung small cell carcinomaCrebbp , Ep300 , Smarca4
lung squamous cell carcinomaCrebbp , Ep300
Lupus NephritisNr3c1
Lymphoma, FollicularCrebbp
Lymphoma, Large-Cell, AnaplasticHsp90aa1
Lymphoma, T-CellEp300
Mammary Neoplasms, ExperimentalNcoa1
medulloblastomaCrebbp , Ep300 , Smarca4
MelanomaCrebbp , Ep300 , Stip1
mental depressionNr3c1
Multiple SclerosisHsp90ab1
Muscle HypotoniaEp300
Muscular AtrophyHsp90ab1 , Nr3c1
Muscular Dystrophy, FacioscapulohumeralHspa4
Neoplasm MetastasisHsp90aa1 , Ncoa1
Neoplastic Syndromes, HereditaryHspa4 , Nr3c1 , Smarca4
Nephronophthisis-Like Nephropathy 1Ep300
Nephrosis, LipoidNr3c1
Nephrotic SyndromeNr3c1
nephrotic syndrome, type 2Nr3c1
Neurobehavioral ManifestationsFkbp5
Neurodegenerative DiseasesHspa4
Neuropathy, PainfulEp300
non-small cell lung carcinomaNcoa3
ObesityEp300 , Ncoa3 , Nr3c1 , Smarca4
Ocular HypertensionNr3c1
Optic Nerve InjuriesEp300
Osteoarthritis, KneeHsp90aa1
Ovarian NeoplasmsSmarca4
Pancreatic NeoplasmsSmarca4
Parkinson DiseaseHspa4
perennial allergic rhinitisNr3c1
Polycystic Ovary SyndromeNcor1 , Nr3c1
portal hypertensionHsp90aa1
Precursor Cell Lymphoblastic Leukemia-LymphomaCrebbp
Precursor T-Cell Lymphoblastic Leukemia-LymphomaSmarca4
Pregnancy ComplicationsNcoa2
prostate cancerMed1 , Nr3c1
Prostatic NeoplasmsCrebbp , Ep300 , Hsp90ab1 , Med1 , Ncoa1 , Ncoa2 , Ncoa3 , Ncor2 , Nr3c1 , Smarca4
Psychotic DisordersNr3c1
Pulmonary Disease, Chronic ObstructiveHspa4 , Nr3c1
Pulmonary FibrosisHsp90ab1
renal clear cell carcinoma Ep300
Reperfusion InjuryEp300
Rhabdoid Tumor Predisposition Syndrome 2Smarca4
Rubinstein-Taybi SyndromeCrebbp , Ep300
Sarcoidosis, PulmonaryNr3c1
SepsisEp300 , Nr3c1
Sezary SyndromeCrebbp , Smarca4
Sleep Apnea, ObstructiveNr3c1
Smith-Magenis SyndromeMed1
Spinal Cord CompressionHspa4
Spinal Cord InjuriesHsp90ab1
Status EpilepticusNr3c1
Stevens-Johnson SyndromeEp300
Stress Disorders, Post-TraumaticNr3c1
Thoracic NeoplasmsSmarca4
Thumb DeformityCrebbp
Transplant RejectionNr3c1
type 2 diabetes mellitusEp300 , Hspa4 , Nr3c1
ulcerative colitisHspa4
urinary bladder cancerCrebbp , Ep300 , Ncor1
uterine cervical neoplasmsCrebbp , Ep300
Pathway Annotations Associated with Genes in the cortisol signaling pathway
Pathway TermsGene Symbols
aldosterone signaling pathwayCrebbp , Fkbp4 , Fkbp5 , Hsp90aa1 , Hsp90ab1 , Ncoa1 , Ncoa2 , Ncor1 , Ncor2 , Ptges3
altered androgen signaling pathwayNcoa2 , Ncor2
altered SWI/SNF family mediated chromatin remodeling pathwaySmarca4
androgen signaling pathwayCrebbp , Dnaja2 , Ep300 , Hsp90aa1 , Hsp90ab1 , Ncoa1 , Ncoa2 , Ncoa3 , Ncor1 , Ncor2 , Stip1
antigen processing and presentation pathwayHsp90aa1 , Hsp90ab1 , Hspa4
cell cycle pathway, mitoticCrebbp , Ep300
chaperone mediated autophagy pathwayHsp90aa1 , Stip1
cortisol signaling pathwayCrebbp , Dnaja2 , Ep300 , Fkbp4 , Fkbp5 , Hsp90aa1 , Hsp90ab1 , Hspa4 , Med1 , Med14 , Ncoa1 , Ncoa2 , Ncoa3 , Ncor1 , Ncor2 , Nr3c1 , Ptges3 , Smarca4 , Stip1
Endoplasmic Reticulum-associated degradation pathwayDnaja2 , Hsp90aa1 , Hsp90ab1
epidermal growth factor/neuregulin signaling pathwayHsp90aa1
estrogen signaling pathwayCrebbp , Dnaja2 , Ep300 , Fkbp4 , Hsp90aa1 , Hsp90ab1 , Hspa4 , Med1 , Ncoa1 , Ncoa2 , Ncoa3 , Ncor1 , Ncor2 , Ptges3 , Stip1
forkhead class A signaling pathwayCrebbp , Ep300 , Ncoa3 , Nr3c1
Hedgehog signaling pathwayCrebbp
histone modification pathwayCrebbp , Ep300 , Smarca4
Huntington disease pathwayCrebbp , Ep300
hypoxia inducible factor pathwayCrebbp , Ep300 , Ncoa1 , Ncoa2
influenza A virus infection pathwayCrebbp , Ep300
Jak-Stat signaling pathwayCrebbp , Ep300
long term potentiationCrebbp , Ep300
Mycobacterium tuberculosis infection pathwayCrebbp , Ep300
NOD-like receptor signaling pathwayHsp90aa1 , Hsp90ab1
Notch signaling pathwayCrebbp , Ep300 , Ncor1 , Ncor2
nuclear factor, erythroid 2 like 2 signaling pathwayCrebbp , Ncoa3
p53 signaling pathwayCrebbp , Ep300
pancreatic cancer pathwaySmarca4
phosphatidylinositol 3-kinase class I signaling pathwayHsp90aa1
phosphatidylinositol 3-kinase-Akt signaling pathwayHsp90aa1
prednisolone pharmacodynamics pathwayHsp90aa1 , Nr3c1
prednisolone pharmacokinetics pathwayHsp90aa1 , Nr3c1
prion diseases pathwayStip1
prostaglandin biosynthetic pathwayPtges3
prostate cancer pathwayCrebbp , Ep300 , Hsp90aa1 , Hsp90ab1 , Ncoa2 , Ncor2
protein kinase C (PKC) signaling pathwayHsp90aa1
renal cell cancer pathwayCrebbp , Ep300
retinoic acid signaling pathwayNcoa1 , Ncoa2 , Ncoa3 , Ncor1 , Ncor2
RNA polymerase I transcription pathwayCrebbp
RNA polymerase II transcription pathwayMed1 , Med14
SWI/SNF family mediated chromatin remodeling pathwaySmarca4
tamoxifen pharmacodynamics pathwayNcoa3 , Ncor1 , Ncor2
transforming growth factor-beta Smad dependent signaling pathwayCrebbp
transforming growth factor-beta superfamily mediated signaling pathwayCrebbp , Ep300
type II interferon signaling pathwayCrebbp , Ep300
vascular endothelial growth factor signaling pathwayHsp90aa1 , Hsp90ab1
Wnt signaling pathwayCrebbp , Ep300
Wnt signaling, canonical pathwayCrebbp , Smarca4
Phenotype Annotations Associated with Genes in the cortisol signaling pathway
Phenotype TermsGene Symbols
cardiac hypertrophyCrebbp , Ep300

References Associated with the cortisol signaling pathway:

Ontology Path Diagram:

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