eRAM
encyclopedia of Rare Disease Annotation for Precision Medicine
| glucocorticoid resistance | ||||
| Disease ID | 1077 |
|---|---|
| Disease | glucocorticoid resistance |
| Definition | An autosomal dominant condition due to mutation(s) in the NR3C1 gene, encoding the glucocorticoid receptor, resulting in decreased receptor affinity to glucocorticoids. Compensatory activation of the hypothalamic- pituitary-adrenal (HPA) axis results in increased mineralocorticoid and androgen production; clinical manifestations of glucocorticoid deficiency are rare. |
| Synonym | cortisol resistance from glucocorticoid receptor defect gccr deficiency gcr deficiency glucocorticoid receptor deficiency glucocorticoid resistance, generalized grl deficiency |
| Orphanet | |
| OMIM | |
| UMLS | C1841972 |
| Comorbidity | UMLS | Disease | Sentences' Count(Total Sentences:18) C0023449 | acute lymphoblastic leukemia | 2 C0004096 | asthma | 2 C0021390 | inflammatory bowel disease | 2 C0023448 | lymphoblastic leukemia | 2 C0004096 | bronchial asthma | 2 C0011570 | depression | 1 C0041696 | major depression | 1 C0023418 | leukemia | 1 C0272286 | immune thrombocytopenia | 1 C0023434 | chronic lymphocytic leukemia | 1 C0040034 | thrombocytopenia | 1 C0206667 | adrenocortical adenoma | 1 C0010346 | crohn's disease | 1 C0001430 | adenoma | 1 C0023434 | chronic lymphocytic leukaemia | 1 C0011615 | atopic dermatitis | 1 C0024141 | systemic lupus erythematosus | 1 C0001622 | hypercortisolism | 1 |
| Curated Gene | Entrez_id | Symbol | Resource(Total Genes:1) |
| Inferring Gene | Entrez_id | Symbol | Resource(Total Genes:1) |
| Text Mined Gene | (Waiting for update.) |
| Locus | Symbol | Locus(Total Locus:1) NR3C1 | 5q31.3 |
| Disease ID | 1077 |
|---|---|
| Disease | glucocorticoid resistance |
| Integrated Phenotype | HPO | Name(Total Integrated Phenotypes:22) HP:0001297 | Stroke HP:0001061 | Acne HP:0008221 | Adrenal hyperplasia HP:0012378 | Fatigue HP:0000798 | Oligospermia HP:0000826 | Precocious puberty HP:0002924 | Decreased circulating aldosterone level HP:0000876 | Oligomenorrhea HP:0012030 | Increased urinary cortisol level HP:0030087 | Abnormal testosterone level HP:0000822 | Hypertension HP:0001943 | Hypoglycemia HP:0000062 | Ambiguous genitalia HP:0003154 | Increased circulating ACTH level HP:0002900 | Hypokalemia HP:0200114 | Metabolic alkalosis HP:0001578 | Hypercortisolism HP:0003118 | Increased circulating cortisol level HP:0010458 | Female pseudohermaphroditism HP:0000789 | Infertility HP:0002292 | Frontal balding HP:0001007 | Hirsutism |
| Text Mined Phenotype | HPO | Name | Sentences' Count(Total Phenotypes:14) HP:0002099 | Asthma | 4 HP:0006721 | Acute lymphocytic leukemia | 2 HP:0000716 | Depression | 1 HP:0001047 | Atopic dermatitis | 1 HP:0001578 | Hypercortisolism | 1 HP:0001973 | Autoimmune thrombocytopenia | 1 HP:0005550 | Chronic lymphatic leukemia | 1 HP:0001873 | Low platelet count | 1 HP:0100280 | Morbus Crohn | 1 HP:0002725 | Systemic lupus erythematosus | 1 HP:0000855 | Insulin resistance | 1 HP:0008256 | Adrenocortical adenomas | 1 HP:0002664 | Neoplasia | 1 HP:0001909 | Leukemia | 1 |
| Disease ID | 1077 |
|---|---|
| Disease | glucocorticoid resistance |
| Manually Symptom | UMLS | Name(Total Manually Symptoms:1) C0221406 | cushing's disease |
| Text Mined Symptom | (Waiting for update.) |
Manually Genotype(Total Text Mining Genotypes:0) |
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| (Waiting for update.) |
Text Mining Genotype(Total Genotypes:0) | |
|---|---|
| (Waiting for update.) | |
All Snps(Total Genotypes:4) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| snpId | pubmedId | geneId | geneSymbol | diseaseId | sourceId | sentence | score | Year | geneSymbol_dbSNP | CHROMOSOME | POS | REF | ALT |
| rs104893913 | 23391271 | 2908 | NR3C1 | umls:C1841972 | BeFree | Further characterization of human glucocorticoid receptor mutants, R477H and G679S, associated with primary generalized glucocorticoid resistance. | 0.255743629 | 2013 | NR3C1 | 5 | 143310135 | C | T |
| rs104893914 | 23391271 | 2908 | NR3C1 | umls:C1841972 | BeFree | Further characterization of human glucocorticoid receptor mutants, R477H and G679S, associated with primary generalized glucocorticoid resistance. | 0.255743629 | 2013 | NR3C1;LOC105378206 | 5 | 143282714 | C | T |
| rs28451617 | 22445700 | 115 | ADCY9 | umls:C1841972 | BeFree | Multivariable analysis revealed that respiratory distress syndrome was associated with maternal single nucleotide polymorphisms in CYP3A5 (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.16-2.30) and the glucocorticoid resistance (OR, 0.28; 95% CI, 0.08-0.95) and fetal single nucleotide polymorphisms in ADCY9 (OR, 0.17; 95% CI, 0.03-0.80) and CYP3A7*1E (rs28451617; OR, 23.68; 95% CI, 1.33-420.6). | 0.000271442 | 2012 | CYP3A7;ZSCAN25;CYP3A7-CYP3A51P | 7 | 99735142 | C | T |
| rs28451617 | 22445700 | 1577 | CYP3A5 | umls:C1841972 | BeFree | Multivariable analysis revealed that respiratory distress syndrome was associated with maternal single nucleotide polymorphisms in CYP3A5 (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.16-2.30) and the glucocorticoid resistance (OR, 0.28; 95% CI, 0.08-0.95) and fetal single nucleotide polymorphisms in ADCY9 (OR, 0.17; 95% CI, 0.03-0.80) and CYP3A7*1E (rs28451617; OR, 23.68; 95% CI, 1.33-420.6). | 0.000271442 | 2012 | CYP3A7;ZSCAN25;CYP3A7-CYP3A51P | 7 | 99735142 | C | T |
GWASdb Annotation(Total Genotypes:0) | |
|---|---|
| (Waiting for update.) | |
GWASdb Snp Trait(Total Genotypes:0) | |
|---|---|
| (Waiting for update.) | |
Mapped by lexical matching(Total Items:6) | ||||
|---|---|---|---|---|
| HP ID | HP Name | MP ID | MP Name | Annotation |
| HP:0003154 | Increased circulating ACTH level | MP:0005661 | decreased circulating adrenaline level | less than the normal concentration in the blood of a catecholamine hormone that stimulates the adrenergic receptors and that causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels |
| HP:0008221 | Adrenal hyperplasia | MP:0009092 | endometrium hyperplasia | overdevelopment or increased size, usually due an increased number of cells, of the glandular mucous membrane lining of the uterine cavity that is hormonally responsive during the estrous/menstrual cycle and during pregnancy |
| HP:0000062 | Ambiguous genitalia | MP:0009202 | small external male genitalia | reduced size of the external masculine genital organs |
| HP:0002924 | Decreased circulating aldosterone level | MP:0011553 | increased urine deoxycorticosterone level | an increased amount of deoxycorticosterone in the urine compared to the normal state |
| HP:0003118 | Increased circulating cortisol level | MP:0011549 | increased urine corticosterone level | an increased amount of corticosterone in the urine compared to the normal state |
| HP:0012030 | Increased urinary cortisol level | MP:0009355 | increased liver triglyceride level | greater concentration of naturally occurring esters of three fatty acids and glycerol in the liver; triglycerides are widespread in adipose tissue, commonly circulate in the blood in the form of lipoproteins, and are involved in the process of bidirection |
Mapped by homologous gene(Total Items:21) | ||||
|---|---|---|---|---|
| HP ID | HP Name | MP ID | MP Name | Annotation |
| HP:0001578 | Hypercortisolism | MP:0020220 | decreased tear production | decreased production of the amount of fluid produced in the eye |
| HP:0002900 | Hypokalemia | MP:0014206 | decreased intestinal epithelial sodium ion transmembrane transport | |
| HP:0000822 | Hypertension | MP:0020216 | decreased circulating complement protein level | less than normal levels of the serum proteins that act sequentially to allow for the direct killing of microbes, the disposal of immune complexes, and the regulation of other immune processes |
| HP:0002924 | Decreased circulating aldosterone level | MP:0011942 | decreased fluid intake | reduction in the total amount of fluid taken in over time when compared to the normal state |
| HP:0001943 | Hypoglycemia | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0010458 | Female pseudohermaphroditism | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0003154 | Increased circulating ACTH level | MP:0013565 | abnormal adrenal gland capsule morphology | any structural anomaly of the thick capsule of dense irregular connective tissue that surrounds each adrenal gland and contains scattered elastic fibers; the capsule contains a rich plexus of blood vessels (mainly small arteries) and numerous nerve fibers |
| HP:0000826 | Precocious puberty | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0012030 | Increased urinary cortisol level | MP:0011090 | perinatal lethality, incomplete penetrance | the appearance of lower than Mendelian ratios of organisms of a given genotype due to death of some, but not all of the organisms within the perinatal period (Mus: E18.5 through postnatal day 1) |
| HP:0000789 | Infertility | MP:0020254 | decreased collagen level | decreased level of the main structural protein of the various connective tissues in animals |
| HP:0001007 | Hirsutism | MP:0020254 | decreased collagen level | decreased level of the main structural protein of the various connective tissues in animals |
| HP:0003118 | Increased circulating cortisol level | MP:0014167 | ectopic bone | the appearance of an extra bone structure at an atypical location |
| HP:0001297 | Stroke | MP:0020329 | decreased capillary density | reduction in the number of capillaries in a given cross-sectional area of a tissue |
| HP:0002292 | Frontal balding | MP:0013505 | decreased embryonic tissue cell apoptosis | decrease in the timing or the number of cells in embryonic tissue undergoing programmed cell death |
| HP:0000798 | Oligospermia | MP:0013505 | decreased embryonic tissue cell apoptosis | decrease in the timing or the number of cells in embryonic tissue undergoing programmed cell death |
| HP:0000876 | Oligomenorrhea | MP:0020254 | decreased collagen level | decreased level of the main structural protein of the various connective tissues in animals |
| HP:0200114 | Metabolic alkalosis | MP:0011967 | increased or absent threshold for auditory brainstem response | increase in the value at which one or more sound frequencies or broadband clicks first elicits a recordable response generated by electrical activity of neurons in the ascending auditory system, or complete lack of a recordable response at any frequency o |
| HP:0001061 | Acne | MP:0020254 | decreased collagen level | decreased level of the main structural protein of the various connective tissues in animals |
| HP:0012378 | Fatigue | MP:0013659 | abnormal erythroid lineage cell morphology | any structural anomaly of an immature or mature cell in the lineage leading to and including erythrocytes |
| HP:0008221 | Adrenal hyperplasia | MP:0012498 | abnormal cardiogenic plate morphology | any structural anomaly of the splanchnic mesodermal thickening which forms cranial and lateral to the developing neural plate; angiogenic cell clusters (aka angioblastic cords) located in a horse-shoe shape configuration in the cardiogenic plate coalesce |
| HP:0000062 | Ambiguous genitalia | MP:0014198 | absent pituitary infundibular stalk | absence of the apical portion of the tubular structure extending from the hypothalamus to the posterior lobe of the pituitary gland |
| Disease ID | 1077 |
|---|---|
| Disease | glucocorticoid resistance |
| Case | (Waiting for update.) |