CORTISOL SIGNALING PATHWAY (PW:0000569)
Description
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 stresses, the hypothalamus releases corticotropin-releasing hormone (CRH) whose signaling results in activation of protein kinase A (PKA) pathway and the expression and release of pro-opiomelanocortin (POMC) gene from the pituitary. Processing of POMC gives rise to several peptides of which adrenocorticotropin (ACTH), specifically binding to melanocortin receptor type 2 (Mc2r) also setting in motion PKA, prompts the expression of steroidogenic genes and the secretion of cortisol from the adrenal cortex. Cortisol binds the glucocorticoid receptor Nr3c1, a nuclear hormone receptor. In the absence of ligand Nr3c1 is predominantly cytoplasmic and dynamically complexed with a chaperone/co-chaperone machinery that is critical for its function and turnover. Like the other members of the nuclear receptor superfamily, Nr3c1 is modular consisting of trans-activation, DNA-binding (DBD) and ligand-binding (LBD) domains. The N-terminal trans-activation domain 1 (AF-1) is ligand independent whereas a second domain (AF-2), embedded in the LBD, is ligand dependent. The DBD, which contains two zinc fingers motifs, is the most conserved domain within the family. Two main receptor isoforms are generated through alternative splicing of which the alpha represents the classic glucocorticoid receptor. The beta isoform, thought to be largely disordered, does not bind glucocorticoids and while residing in the nucleus does not regulate gene expression. Yet, if co-expressed with the alpha isoform, it can act as an inhibitor of the classic receptor, suggesting a possible modulator role. Additional splice and translational isoforms have been reported. Upon ligand binding, Nr3c1 translocates to the nucleus where it binds as a homodimer to specific glucocorticoids response elements (GRE) or, possibly as a monomer, to other transcription factors to enhance or downregulate the transcription of many genes. The receptor may bind negative GRE as another mechanism of repression. In addition, Nr3c1 interacts with many coactivators and corepressors that modulate the outcomes of its function. Nr3c1is a substrate for many post-translational modifications that affect in various ways its function and fate. The receptor plays important roles in the negative feedback loop the pathway provides for the upstream components of the HPA axis. A notable example is the repression of POMC gene expression. While POMC, and also CRH genes appear to harbor negative GREs, Nr3c1 has been reported to bind to and antagonize the function of Nr4a1, an orphan nuclear receptor and transcriptional mediator of POMC expression. The Nr3c1 coactivator Brg1 is crucial for the interaction; the complex can then recruit Hdac2 and silence gene expression. Glucocorticoid deficiency or excess has been associated with several pathophysiological conditions.
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Pathway Diagram:
Genes in Pathway:
G
Crebbp
CREB binding protein
ISO
RGD
PMID:11306337
RGD:5147892
NCBI chr10:11,335,551...11,461,888
Ensembl chr10:11,335,953...11,461,888
G
Dnaja2
DnaJ heat shock protein family (Hsp40) member A2
ISO
RGD
PMID:16610357
RGD:5144125
NCBI chr19:21,497,792...21,516,904
Ensembl chr19:21,497,729...21,516,901
G
Ep300
E1A binding protein p300
ISO
RGD
PMID:11306337
RGD:5147892
NCBI chr 7:113,108,476...113,178,529
Ensembl chr 7:113,106,247...113,136,088 Ensembl chr 7:113,106,247...113,136,088
G
Fkbp4
FKBP prolyl isomerase 4
ISO
RGD
PMID:16610357
RGD:5144125
NCBI chr 4:161,703,379...161,711,833
Ensembl chr 4:161,703,379...161,711,833
G
Fkbp5
FKBP prolyl isomerase 5
ISO
RGD
PMID:16610357
RGD:5144125
NCBI chr20:6,457,207...6,575,404
Ensembl chr20:6,457,216...6,541,674
G
Hsp90aa1
heat shock protein 90 alpha family class A member 1
ISO
RGD
PMID:16610357
RGD:5144125
NCBI chr 6:129,702,376...129,707,907
Ensembl chr 6:129,702,383...129,707,268
G
Hsp90ab1
heat shock protein 90 alpha family class B member 1
ISO
RGD
PMID:16610357
RGD:5144125
NCBI chr 9:15,432,986...15,438,358
Ensembl chr 9:15,433,691...15,438,488
G
Hspa4
heat shock protein family A (Hsp70) member 4
ISO
RGD
PMID:16610357
RGD:5144125
NCBI chr10:37,408,025...37,449,080
Ensembl chr10:37,408,025...37,449,001
G
Kat2b
lysine acetyltransferase 2B
ISO
RGD
PMID:11306337
RGD:5147892
NCBI chr 9:6,562,525...6,667,064
Ensembl chr 9:6,562,288...6,667,064
G
Med1
mediator complex subunit 1
TAS ISO
RGD
PMID:11306337 PMID:11306337
RGD:5147892 , RGD:5147892
NCBI chr10:83,145,538...83,189,260
Ensembl chr10:83,145,568...83,189,299
G
Med14
mediator complex subunit 14
ISO
RGD
PMID:11306337
RGD:5147892
NCBI chr X:10,036,749...10,127,910
Ensembl chr X:10,036,805...10,126,240
G
Ncoa1
nuclear receptor coactivator 1
ISO
RGD
PMID:19818358 PMID:11306337
RGD:5144138 , RGD:5147892
NCBI chr 6:27,232,609...27,507,992
Ensembl chr 6:27,232,611...27,475,664
G
Ncoa2
nuclear receptor coactivator 2
ISO
RGD
PMID:19818358 PMID:11306337
RGD:5144138 , RGD:5147892
NCBI chr 5:5,835,642...6,069,693
Ensembl chr 5:5,835,706...6,067,451
G
Ncoa3
nuclear receptor coactivator 3
ISO
RGD
PMID:19818358 PMID:11306337
RGD:5144138 , RGD:5147892
NCBI chr 3:154,738,566...154,821,395
Ensembl chr 3:154,738,581...154,818,594
G
Ncor1
nuclear receptor co-repressor 1
ISO
RGD
PMID:20801081
RGD:5147413
NCBI chr10:46,999,536...47,142,294
Ensembl chr10:46,999,536...47,141,032
G
Ncor2
nuclear receptor co-repressor 2
ISO
RGD
PMID:20801081
RGD:5147413
NCBI chr12:31,466,418...31,628,319
Ensembl chr12:31,466,412...31,628,319
G
Nr3c1
nuclear receptor subfamily 3, group C, member 1
ISO
RGD
PMID:16610357
RGD:5144125
NCBI chr18:31,271,681...31,393,320
Ensembl chr18:31,271,681...31,393,375
G
Ptges3
prostaglandin E synthase 3
ISO
RGD
PMID:16610357
RGD:5144125
NCBI chr 7:490,698...507,759
Ensembl chr 7:490,656...508,084
G
Smarca4
SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4
ISO
RGD
PMID:11306337
RGD:5147892
NCBI chr 8:20,167,717...20,258,975
Ensembl chr 8:20,167,717...20,258,975
G
Stip1
stress-induced phosphoprotein 1
ISO
RGD
PMID:16610357
RGD:5144125
NCBI chr 1:204,209,433...204,228,452
Ensembl chr 1:204,178,932...204,228,476
Pathway Gene Annotations
Disease Annotations Associated with Genes in the cortisol signaling pathway
Crebbp acute lymphoblastic leukemia , acute myeloid leukemia , adenoid cystic carcinoma , Agenesis of Corpus Callosum , alcohol use disorder , Alzheimer's disease , amyotrophic lateral sclerosis type 1 , atrial heart septal defect , Au-Kline Syndrome , autism spectrum disorder , cardiac amyloidosis , Colorectal Neoplasms , Developmental Disabilities , diffuse large B-cell lymphoma , epilepsy , esophagus squamous cell carcinoma , Familial Amyloid Polyneuropathies , follicular lymphoma , gastric adenocarcinoma , genetic disease , glaucoma , glioblastoma , head and neck squamous cell carcinoma , hepatocellular carcinoma , Hirschsprung Disease 1 , Hirschsprung's disease , Huntington's disease , idiopathic generalized epilepsy , intellectual disability , Kohlschutter-Tonz syndrome , lung adenocarcinoma , Lung Reperfusion Injury , lung small cell carcinoma , lung squamous cell carcinoma , Marfanoid Mental Retardation Syndrome, Autosomal , medulloblastoma , melanoma , Menke-Hennekam Syndrome , Menke-Hennekam Syndrome 1 , multiple myeloma , myelodysplastic syndrome , Myocardial Reperfusion Injury , Nervous System Malformations , NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, ARTHROGRYPOSIS, AND STRUCTURAL BRAIN ANOMALIES , Neurodevelopmental Disorders , pre-eclampsia , Prostatic Neoplasms , Rubinstein-Taybi syndrome , scoliosis , Sezary's disease , short-rib thoracic dysplasia 9 with or without polydactyly , skin melanoma , squamous cell carcinoma , teratoma , Thumb Deformity , transitional cell carcinoma , transthyretin amyloidosis , urinary bladder cancer , Uterine Cervical Neoplasms Dnaja2 genetic disease , glycogen storage disease IXB , liver disease Ep300 adenoid cystic carcinoma , adenylosuccinase lyase deficiency , Agenesis of Corpus Callosum , alcohol use disorder , Alzheimer's disease , autosomal dominant cerebellar ataxia , Brain Hypoxia , breast carcinoma , Breast Neoplasms , cardiac arrest , Cardiomegaly , cardiomyopathy , CHARGE syndrome , clear cell renal cell carcinoma , colon carcinoma , colorectal cancer , colorectal carcinoma , Colorectal Neoplasms , common variable immunodeficiency 4 , congenital diaphragmatic hernia , congestive heart failure , Craniofacial Abnormalities , developmental and epileptic encephalopathy 18 , Diabetic Nephropathies , diabetic retinopathy , Dwarfism , Endometrial Neoplasms , Endotoxemia , esophageal carcinoma , esophagus squamous cell carcinoma , Experimental Diabetes Mellitus , genetic disease , glomerulonephritis , head and neck squamous cell carcinoma , heart disease , hepatoblastoma , hepatocellular carcinoma , hereditary breast ovarian cancer syndrome , Hittner Hirsch Kreh Syndrome , Huntington's disease , Hyperalgesia , hypertension , idiopathic pulmonary fibrosis , intellectual disability , Kidney Reperfusion Injury , lung adenocarcinoma , lung small cell carcinoma , lung squamous cell carcinoma , medulloblastoma , melanoma , membranoproliferative glomerulonephritis , Menke-Hennekam Syndrome 2 , microcephaly , Multicystic Dysplastic Kidney , Multiple Abnormalities , nephronophthisis-like nephropathy 1 , Nervous System Lead Poisoning , Neurodevelopmental Disorders , obesity , Optic Nerve Injuries , Painful Neuropathy , prostate cancer , Reperfusion Injury , Rubinstein-Taybi syndrome , Sepsis , Spinocerebellar Ataxias , squamous cell carcinoma , Stevens-Johnson syndrome , systemic lupus erythematosus , T-cell non-Hodgkin lymphoma , Thumb Deformity , transient cerebral ischemia , transitional cell carcinoma , type 2 diabetes mellitus , urinary bladder cancer , Uterine Cervical Neoplasms Fkbp4 androgen insensitivity syndrome , genetic disease , Hyperphosphatemic Familial Tumoral Calcinosis 1 Fkbp5 alcohol dependence , alcohol withdrawal syndrome , Alcoholic Fatty Liver , Alcoholic Liver Diseases , asthma , cocaine abuse , COVID-19 , endometriosis , genetic disease , heroin dependence , Infant, Newborn, Diseases , major depressive disorder , Neurobehavioral Manifestations , post-traumatic stress disorder , proteasome-associated autoinflammatory syndrome 1 , rheumatoid arthritis Hsp90aa1 Alzheimer's disease , anaplastic large cell lymphoma , Breast Neoplasms , Charcot-Marie-Tooth disease axonal type 2O , Cognitive Dysfunction , colon cancer , contact dermatitis , Ductal Carcinoma , Experimental Diabetes Mellitus , Frontotemporal Lobar Degeneration , genetic disease , human immunodeficiency virus infectious disease , intrahepatic cholangiocarcinoma , Knee Osteoarthritis , Neoplasm Metastasis , Neurodevelopmental Disorders , portal hypertension , rheumatoid arthritis Hsp90ab1 Female Infertility , genetic disease , human immunodeficiency virus infectious disease , intrahepatic cholangiocarcinoma , multiple sclerosis , muscular atrophy , pancreatitis , Prostatic Neoplasms , pulmonary fibrosis , Spinal Cord Injuries Hspa4 adult respiratory distress syndrome , Brain Injuries , Chagas disease , chronic obstructive pulmonary disease , dry eye syndrome , facioscapulohumeral muscular dystrophy , familial adenomatous polyposis 1 , genetic disease , Heat Stroke , Hereditary Neoplastic Syndromes , liver benign neoplasm , middle cerebral artery infarction , neurodegenerative disease , Neurodevelopmental Disorders , Parkinson's disease , rheumatoid arthritis , Spinal Cord Compression , type 2 diabetes mellitus , ulcerative colitis Kat2b 3p deletion syndrome , breast cancer , Coronary Disease , esophagus squamous cell carcinoma , genetic disease , hepatocellular carcinoma , rheumatoid arthritis Med1 Chemical and Drug Induced Liver Injury , congestive heart failure , dilated cardiomyopathy , endometriosis , genetic disease , hepatocellular carcinoma , intellectual disability , prostate cancer Med14 autistic disorder , endometriosis , genetic disease , intellectual disability , Neurodevelopmental Disorders , ornithine carbamoyltransferase deficiency , syndromic X-linked intellectual disability Hedera type , syndromic X-linked intellectual disability Lubs type , syndromic X-linked intellectual disability Najm type Ncoa1 breast carcinoma , Breast Neoplasms , endometrial carcinoma , endometriosis , Experimental Mammary Neoplasms , genetic disease , hypothyroidism , Neoplasm Metastasis , obesity , prostate cancer , Prostatic Neoplasms , Tatton-Brown-Rahman syndrome , thyroid hormone resistance syndrome Ncoa2 acute myeloid leukemia , Breast Neoplasms , Chronobiology Disorders , colorectal adenocarcinoma , colorectal carcinoma , genetic disease , hepatocellular carcinoma , lung non-small cell carcinoma , malignant pleural mesothelioma , polycystic ovary syndrome , Pregnancy Complications , prostate adenocarcinoma , prostate cancer , Prostatic Neoplasms , stomach cancer Ncoa3 adenocarcinoma , Bone Neoplasms , breast cancer , breast carcinoma , Breast Neoplasms , focal epilepsy , genetic disease , leukemia , lung non-small cell carcinoma , malignant astrocytoma , obesity , prostate cancer , Prostatic Neoplasms , sensorineural hearing loss , squamous cell carcinoma Ncor1 Acute-Phase Reaction , anxiety disorder , autistic disorder , Breast Cancer, Familial , Breast Neoplasms , Developmental Disabilities , endometriosis , genetic disease , glioblastoma , Huntington's disease , hypothyroidism , Liver Neoplasms , mitochondrial complex III deficiency nuclear type 1 , mitochondrial complex III deficiency nuclear type 2 , Neonatal Hyperbilirubinemia , polycystic ovary syndrome , Prostatic Neoplasms , transitional cell carcinoma , urinary bladder cancer Ncor2 breast cancer , endometrial carcinoma , Experimental Liver Cirrhosis , genetic disease , multiple myeloma , myelofibrosis , osteoarthritis , Prostatic Neoplasms Nr3c1 46, XX Disorders of Sex Development , anorexia nervosa , asthma , atrial fibrillation , bipolar disorder , brain ischemia , Burns , cataract , chronic obstructive pulmonary disease , cocaine abuse , Cocaine-Related Disorders , congestive heart failure , coronary artery disease , Cushing Syndrome , depressive disorder , Drug-Related Side Effects and Adverse Reactions , Edema , end stage renal disease , endometriosis , Endotoxemia , Experimental Autoimmune Encephalomyelitis , Experimental Diabetes Mellitus , familial adenomatous polyposis 1 , fetal alcohol spectrum disorder , Fetal Growth Retardation , genetic disease , Glucocorticoid Receptor Deficiency , glucose metabolism disease , Hereditary Neoplastic Syndromes , hypertension , hypokalemia , interstitial lung disease , lipoid nephrosis , lung disease , lung non-small cell carcinoma , lupus nephritis , major depressive disorder , Malocclusion , mood disorder , muscular atrophy , nephrotic syndrome , nephrotic syndrome type 2 , Neurodevelopmental Disorders , obesity , obstructive lung disease , obstructive sleep apnea , ocular hypertension , opioid abuse , Perennial Allergic Rhinitis , polycystic ovary syndrome , post-traumatic stress disorder , Prenatal Exposure Delayed Effects , primary biliary cholangitis , primary hyperaldosteronism , prostate cancer , Prostatic Neoplasms , psychotic disorder , pulmonary sarcoidosis , renal cell carcinoma , rheumatoid arthritis , schizophrenia , Sepsis , sinusitis , status epilepticus , stress-related disorder , Stroke , Transplant Rejection , type 2 diabetes mellitus , uveitis , visual epilepsy Ptges3 atherosclerosis , autism spectrum disorder , breast cancer , Experimental Arthritis , genetic disease , Hyperalgesia , oligodendroglioma , toxic encephalopathy Smarca4 adrenocortical carcinoma , alpha-mannosidosis , amyotrophic lateral sclerosis , atrial heart septal defect , autistic disorder , bilateral breast cancer , breast cancer , Burkitt lymphoma , cerebral palsy , Charcot-Marie-Tooth disease dominant intermediate B , cleft palate , Cocaine-Related Disorders , Coffin-Siris syndrome , Coffin-Siris syndrome 1 , Coffin-Siris syndrome 4 , Developmental Disabilities , epilepsy , episodic ataxia type 2 , Experimental Diabetes Mellitus , Facial Asymmetry , familial hypercholesterolemia , genetic disease , glutaric acidemia I , hepatocellular carcinoma , Hereditary Neoplastic Syndromes , intellectual disability , Left Ventricular Hypertrophy , lung non-small cell carcinoma , lung small cell carcinoma , medulloblastoma , microcephaly , neuroblastoma , Neurodevelopmental Disorders , obesity , Ovarian Neoplasms , ovarian small cell carcinoma , pancreatic cancer , prostate cancer , Prostatic Neoplasms , Rhabdoid Tumor Predisposition Syndrome 2 , sarcoma , Sezary's disease , small cell carcinoma , strabismus , T-cell acute lymphoblastic leukemia , Thoracic Neoplasms , ventricular septal defect Stip1 Colorectal Neoplasms , genetic disease , high grade glioma , intellectual disability , leukocyte adhesion deficiency 3 , melanoma
3p deletion syndrome Kat2b 46, XX Disorders of Sex Development Nr3c1 acute lymphoblastic leukemia Crebbp acute myeloid leukemia Crebbp , Ncoa2 Acute-Phase Reaction Ncor1 adenocarcinoma Ncoa3 adenoid cystic carcinoma Crebbp , Ep300 adenylosuccinase lyase deficiency Ep300 adrenocortical carcinoma Smarca4 adult respiratory distress syndrome Hspa4 Agenesis of Corpus Callosum Crebbp , Ep300 alcohol dependence Fkbp5 alcohol use disorder Crebbp , Ep300 alcohol withdrawal syndrome Fkbp5 Alcoholic Fatty Liver Fkbp5 Alcoholic Liver Diseases Fkbp5 alpha-mannosidosis Smarca4 Alzheimer's disease Crebbp , Ep300 , Hsp90aa1 amyotrophic lateral sclerosis Smarca4 amyotrophic lateral sclerosis type 1 Crebbp anaplastic large cell lymphoma Hsp90aa1 androgen insensitivity syndrome Fkbp4 anorexia nervosa Nr3c1 anxiety disorder Ncor1 asthma Fkbp5 , Nr3c1 atherosclerosis Ptges3 atrial fibrillation Nr3c1 atrial heart septal defect Crebbp , Smarca4 Au-Kline Syndrome Crebbp autism spectrum disorder Crebbp , Ptges3 autistic disorder Med14 , Ncor1 , Smarca4 autosomal dominant cerebellar ataxia Ep300 bilateral breast cancer Smarca4 bipolar disorder Nr3c1 Bone Neoplasms Ncoa3 Brain Hypoxia Ep300 Brain Injuries Hspa4 brain ischemia Nr3c1 breast cancer Kat2b , Ncoa3 , Ncor2 , Ptges3 , Smarca4 Breast Cancer, Familial Ncor1 breast carcinoma Ep300 , Ncoa1 , Ncoa3 Breast Neoplasms Ep300 , Hsp90aa1 , Ncoa1 , Ncoa2 , Ncoa3 , Ncor1 Burkitt lymphoma Smarca4 Burns Nr3c1 cardiac amyloidosis Crebbp cardiac arrest Ep300 Cardiomegaly Ep300 cardiomyopathy Ep300 cataract Nr3c1 cerebral palsy Smarca4 Chagas disease Hspa4 Charcot-Marie-Tooth disease axonal type 2O Hsp90aa1 Charcot-Marie-Tooth disease dominant intermediate B Smarca4 CHARGE syndrome Ep300 Chemical and Drug Induced Liver Injury Med1 chronic obstructive pulmonary disease Hspa4 , Nr3c1 Chronobiology Disorders Ncoa2 clear cell renal cell carcinoma Ep300 cleft palate Smarca4 cocaine abuse Fkbp5 , Nr3c1 Cocaine-Related Disorders Nr3c1 , Smarca4 Coffin-Siris syndrome Smarca4 Coffin-Siris syndrome 1 Smarca4 Coffin-Siris syndrome 4 Smarca4 Cognitive Dysfunction Hsp90aa1 colon cancer Hsp90aa1 colon carcinoma Ep300 colorectal adenocarcinoma Ncoa2 colorectal cancer Ep300 colorectal carcinoma Ep300 , Ncoa2 Colorectal Neoplasms Crebbp , Ep300 , Stip1 common variable immunodeficiency 4 Ep300 congenital diaphragmatic hernia Ep300 congestive heart failure Ep300 , Med1 , Nr3c1 contact dermatitis Hsp90aa1 coronary artery disease Nr3c1 Coronary Disease Kat2b COVID-19 Fkbp5 Craniofacial Abnormalities Ep300 Cushing Syndrome Nr3c1 depressive disorder Nr3c1 developmental and epileptic encephalopathy 18 Ep300 Developmental Disabilities Crebbp , Ncor1 , Smarca4 Diabetic Nephropathies Ep300 diabetic retinopathy Ep300 diffuse large B-cell lymphoma Crebbp dilated cardiomyopathy Med1 Drug-Related Side Effects and Adverse Reactions Nr3c1 dry eye syndrome Hspa4 Ductal Carcinoma Hsp90aa1 Dwarfism Ep300 Edema Nr3c1 end stage renal disease Nr3c1 endometrial carcinoma Ncoa1 , Ncor2 Endometrial Neoplasms Ep300 endometriosis Fkbp5 , Med1 , Med14 , Ncoa1 , Ncor1 , Nr3c1 Endotoxemia Ep300 , Nr3c1 epilepsy Crebbp , Smarca4 episodic ataxia type 2 Smarca4 esophageal carcinoma Ep300 esophagus squamous cell carcinoma Crebbp , Ep300 , Kat2b Experimental Arthritis Ptges3 Experimental Autoimmune Encephalomyelitis Nr3c1 Experimental Diabetes Mellitus Ep300 , Hsp90aa1 , Nr3c1 , Smarca4 Experimental Liver Cirrhosis Ncor2 Experimental Mammary Neoplasms Ncoa1 Facial Asymmetry Smarca4 facioscapulohumeral muscular dystrophy Hspa4 familial adenomatous polyposis 1 Hspa4 , Nr3c1 Familial Amyloid Polyneuropathies Crebbp familial hypercholesterolemia Smarca4 Female Infertility Hsp90ab1 fetal alcohol spectrum disorder Nr3c1 Fetal Growth Retardation Nr3c1 focal epilepsy Ncoa3 follicular lymphoma Crebbp Frontotemporal Lobar Degeneration Hsp90aa1 gastric adenocarcinoma Crebbp genetic disease Crebbp , Dnaja2 , Ep300 , Fkbp4 , Fkbp5 , Hsp90aa1 , Hsp90ab1 , Hspa4 , Kat2b , Med1 , Med14 , Ncoa1 , Ncoa2 , Ncoa3 , Ncor1 , Ncor2 , Nr3c1 , Ptges3 , Smarca4 , Stip1 glaucoma Crebbp glioblastoma Crebbp , Ncor1 glomerulonephritis Ep300 Glucocorticoid Receptor Deficiency Nr3c1 glucose metabolism disease Nr3c1 glutaric acidemia I Smarca4 glycogen storage disease IXB Dnaja2 head and neck squamous cell carcinoma Crebbp , Ep300 heart disease Ep300 Heat Stroke Hspa4 hepatoblastoma Ep300 hepatocellular carcinoma Crebbp , Ep300 , Kat2b , Med1 , Ncoa2 , Smarca4 hereditary breast ovarian cancer syndrome Ep300 Hereditary Neoplastic Syndromes Hspa4 , Nr3c1 , Smarca4 heroin dependence Fkbp5 high grade glioma Stip1 Hirschsprung Disease 1 Crebbp Hirschsprung's disease Crebbp Hittner Hirsch Kreh Syndrome Ep300 human immunodeficiency virus infectious disease Hsp90aa1 , Hsp90ab1 Huntington's disease Crebbp , Ep300 , Ncor1 Hyperalgesia Ep300 , Ptges3 Hyperphosphatemic Familial Tumoral Calcinosis 1 Fkbp4 hypertension Ep300 , Nr3c1 hypokalemia Nr3c1 hypothyroidism Ncoa1 , Ncor1 idiopathic generalized epilepsy Crebbp idiopathic pulmonary fibrosis Ep300 Infant, Newborn, Diseases Fkbp5 intellectual disability Crebbp , Ep300 , Med1 , Med14 , Smarca4 , Stip1 interstitial lung disease Nr3c1 intrahepatic cholangiocarcinoma Hsp90aa1 , Hsp90ab1 Kidney Reperfusion Injury Ep300 Knee Osteoarthritis Hsp90aa1 Kohlschutter-Tonz syndrome Crebbp Left Ventricular Hypertrophy Smarca4 leukemia Ncoa3 leukocyte adhesion deficiency 3 Stip1 lipoid nephrosis Nr3c1 liver benign neoplasm Hspa4 liver disease Dnaja2 Liver Neoplasms Ncor1 lung adenocarcinoma Crebbp , Ep300 lung disease Nr3c1 lung non-small cell carcinoma Ncoa2 , Ncoa3 , Nr3c1 , Smarca4 Lung Reperfusion Injury Crebbp lung small cell carcinoma Crebbp , Ep300 , Smarca4 lung squamous cell carcinoma Crebbp , Ep300 lupus nephritis Nr3c1 major depressive disorder Fkbp5 , Nr3c1 malignant astrocytoma Ncoa3 malignant pleural mesothelioma Ncoa2 Malocclusion Nr3c1 Marfanoid Mental Retardation Syndrome, Autosomal Crebbp medulloblastoma Crebbp , Ep300 , Smarca4 melanoma Crebbp , Ep300 , Stip1 membranoproliferative glomerulonephritis Ep300 Menke-Hennekam Syndrome Crebbp Menke-Hennekam Syndrome 1 Crebbp Menke-Hennekam Syndrome 2 Ep300 microcephaly Ep300 , Smarca4 middle cerebral artery infarction Hspa4 mitochondrial complex III deficiency nuclear type 1 Ncor1 mitochondrial complex III deficiency nuclear type 2 Ncor1 mood disorder Nr3c1 Multicystic Dysplastic Kidney Ep300 Multiple Abnormalities Ep300 multiple myeloma Crebbp , Ncor2 multiple sclerosis Hsp90ab1 muscular atrophy Hsp90ab1 , Nr3c1 myelodysplastic syndrome Crebbp myelofibrosis Ncor2 Myocardial Reperfusion Injury Crebbp Neonatal Hyperbilirubinemia Ncor1 Neoplasm Metastasis Hsp90aa1 , Ncoa1 nephronophthisis-like nephropathy 1 Ep300 nephrotic syndrome Nr3c1 nephrotic syndrome type 2 Nr3c1 Nervous System Lead Poisoning Ep300 Nervous System Malformations Crebbp Neurobehavioral Manifestations Fkbp5 neuroblastoma Smarca4 neurodegenerative disease Hspa4 NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, ARTHROGRYPOSIS, AND STRUCTURAL BRAIN ANOMALIES Crebbp Neurodevelopmental Disorders Crebbp , Ep300 , Hsp90aa1 , Hspa4 , Med14 , Nr3c1 , Smarca4 obesity Ep300 , Ncoa1 , Ncoa3 , Nr3c1 , Smarca4 obstructive lung disease Nr3c1 obstructive sleep apnea Nr3c1 ocular hypertension Nr3c1 oligodendroglioma Ptges3 opioid abuse Nr3c1 Optic Nerve Injuries Ep300 ornithine carbamoyltransferase deficiency Med14 osteoarthritis Ncor2 Ovarian Neoplasms Smarca4 ovarian small cell carcinoma Smarca4 Painful Neuropathy Ep300 pancreatic cancer Smarca4 pancreatitis Hsp90ab1 Parkinson's disease Hspa4 Perennial Allergic Rhinitis Nr3c1 polycystic ovary syndrome Ncoa2 , Ncor1 , Nr3c1 portal hypertension Hsp90aa1 post-traumatic stress disorder Fkbp5 , Nr3c1 pre-eclampsia Crebbp Pregnancy Complications Ncoa2 Prenatal Exposure Delayed Effects Nr3c1 primary biliary cholangitis Nr3c1 primary hyperaldosteronism Nr3c1 prostate adenocarcinoma Ncoa2 prostate cancer Ep300 , Med1 , Ncoa1 , Ncoa2 , Ncoa3 , Nr3c1 , Smarca4 Prostatic Neoplasms Crebbp , Hsp90ab1 , Ncoa1 , Ncoa2 , Ncoa3 , Ncor1 , Ncor2 , Nr3c1 , Smarca4 proteasome-associated autoinflammatory syndrome 1 Fkbp5 psychotic disorder Nr3c1 pulmonary fibrosis Hsp90ab1 pulmonary sarcoidosis Nr3c1 renal cell carcinoma Nr3c1 Reperfusion Injury Ep300 Rhabdoid Tumor Predisposition Syndrome 2 Smarca4 rheumatoid arthritis Fkbp5 , Hsp90aa1 , Hspa4 , Kat2b , Nr3c1 Rubinstein-Taybi syndrome Crebbp , Ep300 sarcoma Smarca4 schizophrenia Nr3c1 scoliosis Crebbp sensorineural hearing loss Ncoa3 Sepsis Ep300 , Nr3c1 Sezary's disease Crebbp , Smarca4 short-rib thoracic dysplasia 9 with or without polydactyly Crebbp sinusitis Nr3c1 skin melanoma Crebbp small cell carcinoma Smarca4 Spinal Cord Compression Hspa4 Spinal Cord Injuries Hsp90ab1 Spinocerebellar Ataxias Ep300 squamous cell carcinoma Crebbp , Ep300 , Ncoa3 status epilepticus Nr3c1 Stevens-Johnson syndrome Ep300 stomach cancer Ncoa2 strabismus Smarca4 stress-related disorder Nr3c1 Stroke Nr3c1 syndromic X-linked intellectual disability Hedera type Med14 syndromic X-linked intellectual disability Lubs type Med14 syndromic X-linked intellectual disability Najm type Med14 systemic lupus erythematosus Ep300 T-cell acute lymphoblastic leukemia Smarca4 T-cell non-Hodgkin lymphoma Ep300 Tatton-Brown-Rahman syndrome Ncoa1 teratoma Crebbp Thoracic Neoplasms Smarca4 Thumb Deformity Crebbp , Ep300 thyroid hormone resistance syndrome Ncoa1 toxic encephalopathy Ptges3 transient cerebral ischemia Ep300 transitional cell carcinoma Crebbp , Ep300 , Ncor1 Transplant Rejection Nr3c1 transthyretin amyloidosis Crebbp type 2 diabetes mellitus Ep300 , Hspa4 , Nr3c1 ulcerative colitis Hspa4 urinary bladder cancer Crebbp , Ep300 , Ncor1 Uterine Cervical Neoplasms Crebbp , Ep300 uveitis Nr3c1 ventricular septal defect Smarca4 visual epilepsy Nr3c1