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View Ontology Report


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 FKBP prolyl isomerase 4 JBrowse link 4 161,748,993 161,757,447 RGD:5144125
G Fkbp5 FKBP prolyl isomerase 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 (Hsp70) 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
acute myeloid leukemiaCrebbp , Ncoa2
Acute-Phase ReactionNcor1
adenoid cystic carcinomaCrebbp , Ep300
adult respiratory distress syndromeHspa4
Alzheimer's diseaseCrebbp , Ep300 , Hsp90aa1
amyotrophic lateral sclerosis type 1Crebbp
anaplastic large cell lymphomaHsp90aa1
androgen insensitivity syndromeFkbp4
anorexia nervosaNr3c1
anxiety disorderNcor1
asthmaFkbp5 , Nr3c1
atrial fibrillationNr3c1
atrial heart septal defectCrebbp
attention deficit hyperactivity disorderCrebbp
autism spectrum disorderCrebbp
autistic disorderMed14
bipolar disorderNr3c1
bladder urothelial carcinomaCrebbp , Ep300
Bone NeoplasmsNcoa3
Brain HypoxiaEp300
Brain InjuriesHspa4
brain ischemiaNr3c1
breast cancerNcoa3 , Ncor2 , Ptges3 , Smarca4
Breast Cancer, FamilialNcor1
breast carcinomaEp300 , Ncoa1 , Ncoa3
Breast NeoplasmsEp300 , Hsp90aa1 , Ncoa1 , Ncoa2 , Ncoa3 , Ncor1
Burkitt lymphomaSmarca4
cardiac arrestEp300
central nervous system diseaseCrebbp
Chagas diseaseHspa4
Chemical and Drug Induced Liver InjuryMed1
chronic obstructive pulmonary diseaseHspa4 , Nr3c1
clear cell renal cell carcinomaEp300
Cocaine-Related DisordersNr3c1 , Smarca4
Coffin-Siris syndromeSmarca4
Coffin-Siris syndrome 1Smarca4
Coffin-Siris syndrome 4Smarca4
Cognitive DysfunctionHsp90aa1
colon carcinomaEp300
colorectal cancerEp300
Colorectal NeoplasmsCrebbp , Ep300
congenital diaphragmatic herniaEp300
congestive heart failureEp300 , Med1 , Nr3c1
contact dermatitisHsp90aa1
coronary artery diseaseNr3c1
Craniofacial AbnormalitiesEp300
Cushing SyndromeNr3c1
Developmental DisabilitiesCrebbp , Ep300 , Ncor1 , Smarca4
Diabetes Mellitus, Experimental Ep300 , Hsp90aa1 , Nr3c1 , Smarca4
Diabetic NephropathiesEp300
diabetic retinopathyEp300
dilated cardiomyopathyMed1
Drug-Related Side Effects and Adverse ReactionsNr3c1
dry eye syndromeHspa4
Ductal CarcinomaHsp90aa1
end stage renal failureNr3c1
endogenous depressionFkbp5
endometrial carcinomaNcoa1 , Ncor2
Endometrial NeoplasmsEp300
endometriosisFkbp5 , Med1 , Med14 , Ncoa1 , Ncor1 , Nr3c1
EndotoxemiaEp300 , Nr3c1
esophageal carcinomaEp300
Experimental ArthritisPtges3
Experimental Autoimmune EncephalomyelitisNr3c1
Experimental Liver CirrhosisNcor2
facioscapulohumeral muscular dystrophyHspa4
familial hypercholesterolemiaSmarca4
Female InfertilityHsp90ab1
Fetal Growth RetardationNr3c1
FG syndromeMed14
follicular lymphomaCrebbp
Frontotemporal Lobar DegenerationHsp90aa1
gastric adenocarcinomaCrebbp
genetic diseaseCrebbp , Ep300 , Smarca4
glioblastoma multiformeCrebbp , Ncor1
Glucocorticoid Receptor DeficiencyNr3c1
glucose metabolism diseaseNr3c1
head and neck squamous cell carcinomaCrebbp , Ep300
heart diseaseEp300
Heat StrokeHspa4
hepatocellular carcinomaCrebbp , Ep300 , Med1
Hereditary Neoplastic SyndromesHspa4 , Nr3c1 , Smarca4
Hirschsprung Disease 1Crebbp
human immunodeficiency virus infectious diseaseHsp90aa1 , Hsp90ab1
Huntington's diseaseCrebbp , Ep300 , Ncor1
HyperalgesiaEp300 , Ptges3
hyperphosphatemic familial tumoral calcinosisFkbp4
hypertensionEp300 , Nr3c1
hypothyroidismNcoa1 , Ncor1
Infant, Newborn, DiseasesFkbp5
intellectual disabilityEp300
interstitial lung diseaseNr3c1
Kidney Reperfusion InjuryEp300
Knee OsteoarthritisHsp90aa1
Lead Poisoning, Nervous SystemEp300
Left Ventricular HypertrophySmarca4
lipoid nephrosisNr3c1
liver benign neoplasmHspa4 , Ncor1
liver cancerCrebbp
liver diseaseDnaja2
lung diseaseNr3c1
lung non-small cell carcinomaNcoa3 , Smarca4
lung small cell carcinomaCrebbp , Ep300 , Smarca4
lung squamous cell carcinomaCrebbp , Ep300
lupus nephritisNr3c1
major depressive disorderFkbp5 , Nr3c1
malignant gliomaStip1
Mammary Neoplasms, ExperimentalNcoa1
medulloblastomaCrebbp , Ep300 , Smarca4
melanomaCrebbp , Ep300 , Stip1
membranoproliferative glomerulonephritisEp300
Menke-Hennekam Syndrome 1Crebbp
Menke-Hennekam Syndrome 2Ep300
mental depressionNr3c1
middle cerebral artery infarctionHspa4
mitochondrial complex III deficiencyNcor1
mood disorderNr3c1
Multiple AbnormalitiesCrebbp , Ep300 , Smarca4
multiple sclerosisHsp90ab1
Muscle SpasticityCrebbp
muscular atrophyHsp90ab1 , Nr3c1
myelodysplastic syndromeCrebbp
Neonatal HyperbilirubinemiaNcor1
Neoplasm MetastasisHsp90aa1 , Ncoa1
nephronophthisis-like nephropathy 1Ep300
nephrotic syndromeNr3c1
nephrotic syndrome type 2Nr3c1
Neurobehavioral ManifestationsFkbp5
neurodegenerative diseaseHspa4
Neurodevelopmental DisordersHsp90aa1 , Hspa4 , Med14 , Nr3c1
obesityEp300 , Ncoa1 , Ncoa3 , Nr3c1 , Smarca4
obstructive lung diseaseNr3c1
obstructive sleep apneaNr3c1
ocular hypertensionNr3c1
Optic Nerve InjuriesEp300
Ovarian NeoplasmsSmarca4
Painful NeuropathyEp300
pancreatic cancerSmarca4
Parkinson's diseaseHspa4
Perennial Allergic RhinitisNr3c1
polycystic ovary syndromeNcor1 , Nr3c1
portal hypertensionHsp90aa1
post-traumatic stress disorderNr3c1
precursor lymphoblastic lymphoma/leukemiaCrebbp
precursor T-lymphoblastic lymphoma/leukemiaSmarca4
Pregnancy ComplicationsNcoa2
primary biliary cirrhosisNr3c1
primary hyperaldosteronismNr3c1
prostate cancerEp300 , Med1 , Ncoa1 , Ncoa2 , Ncoa3 , Nr3c1 , Smarca4
Prostatic NeoplasmsCrebbp , Hsp90ab1 , Ncoa1 , Ncoa2 , Ncoa3 , Ncor1 , Ncor2 , Nr3c1 , Smarca4
psychotic disorderNr3c1
pulmonary fibrosisHsp90ab1
pulmonary sarcoidosisNr3c1
renal cell carcinomaNr3c1
Reperfusion InjuryEp300
Rhabdoid Tumor Predisposition Syndrome 2Smarca4
rheumatoid arthritisFkbp5 , Hsp90aa1 , Hspa4 , Nr3c1
Rubinstein-Taybi syndromeCrebbp , Ep300
SepsisEp300 , Nr3c1
Sezary's diseaseCrebbp , Smarca4
small cell carcinomaSmarca4
spina bifidaCrebbp
Spinal Cord CompressionHspa4
Spinal Cord InjuriesHsp90ab1
squamous cell carcinomaCrebbp , Ep300 , Ncoa3
status epilepticusNr3c1
Stevens-Johnson syndromeEp300
syndromic X-linked intellectual disability Hedera typeMed14
syndromic X-linked intellectual disability Lubs typeMed14
systemic lupus erythematosusEp300
T-Cell LymphomaEp300
Thoracic NeoplasmsSmarca4
Thumb DeformityCrebbp , Ep300
thyroid hormone resistance syndromeNcoa1
toxic encephalopathyPtges3
transient cerebral ischemiaEp300
transitional cell carcinomaCrebbp , Ep300 , Ncor1
Transplant RejectionNr3c1
type 2 diabetes mellitusEp300 , Hspa4 , Nr3c1
ulcerative colitisHspa4
urinary bladder cancerCrebbp , Ep300 , Ncor1
Uterine Cervical NeoplasmsCrebbp , Ep300
ventricular septal defectSmarca4
visual epilepsyNr3c1
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's disease pathwayCrebbp , Ep300
hypoxia inducible factor pathwayCrebbp , Ep300 , Ncoa1 , Ncoa2
influenza A pathwayCrebbp , Ep300
Jak-Stat signaling pathwayCrebbp , Ep300
long term potentiationCrebbp , 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 disease pathwayStip1
prostaglandin biosynthetic pathwayPtges3
prostate cancer pathwayCrebbp , Ep300 , Hsp90aa1 , Hsp90ab1 , Ncoa2 , Ncor2
protein kinase C (PKC) signaling pathwayHsp90aa1
renal cell carcinoma 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
tuberculosis 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:

paths to the root

Import into Pathway Studio:


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.