Entry Name Cushing syndrome - Microcebus murinus (gray mouse lemur)
Description Cushing syndrome (CS) is a rare disorder resulting from prolonged exposure to excess glucocorticoids via exogenous and endogenous sources. The typical clinical features of CS are related to hypercortisolism and include accumulation of central fat, moon facies, neuromuscular weakness, osteoporosis or bone fractures, metabolic complications, and mood changes. Traditionally, endogenous CS is classified as adrenocorticotropic hormone (ACTH)-dependent (about 80%) or ACTH- independent (about 20%). Among ACTH-dependent forms, pituitary corticotroph adenoma (Cushing's disease) is most common. Most pituitary tumors are sporadic, resulting from monoclonal expansion of a single mutated cell. Recently recurrent activating somatic driver mutations in the ubiquitin-specific protease 8 gene (USP8) were identified in almost half of corticotroph adenoma. Germline mutations in MEN1 (encoding menin), AIP (encoding aryl-hydrocarbon receptor-interacting protein), PRKAR1A (encoding cAMP-dependent protein kinase type I alpha regulatory subunit) and CDKN1B (encoding cyclin-dependent kinase inhibitor 1B; also known as p27 Kip1) have been identified in familial forms of pituitary adenomas. However, the frequency of familial pituitary adenomas is less than 5% in patients with pituitary adenomas. Among ACTH-independent CS, adrenal adenoma is most common. Rare adrenal causes of CS include primary bilateral macronodular adrenal hyperplasia (BMAH) or primary pigmented nodular adrenocortical disease (PPNAD).
Class Human Diseases; Endocrine and metabolic diseaseBRITE hierarchy
Pathway map Ortholog table Organism Microcebus murinus (gray mouse lemur) [GN:
mmur ]
Gene 105863672 CRHR1; corticotropin-releasing factor receptor 1 isoform X1 [KO:K04578 ]
105874518 guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632 ]
105864304 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
105865052 ATF2; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2 [KO:K04450 ]
105858535 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
105873936 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
105874305 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
105885209 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
105885942 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048 ]
105859108 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
105855129 cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
105858143 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
105870390 ASH2L; set1/Ash2 histone methyltransferase complex subunit ASH2 isoform X1 [KO:K14964 ]
105861979 RASD1; dexamethasone-induced Ras-related protein 1 isoform X1 [KO:K07843 ]
105874990 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
105864008 GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
105879338 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
105873069 ARNT; LOW QUALITY PROTEIN: aryl hydrocarbon receptor nuclear translocator [KO:K09097 ]
105861596 CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850 ]
105875072 CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851 ]
105856433 CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853 ]
105859992 CACNA1S; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
105868864 CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
105879489 CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515 ] [EC:2.7.11.17 ]
105858406 CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
105880116 MRAP; LOW QUALITY PROTEIN: melanocortin-2 receptor accessory protein [KO:K22398 ]
105870579 PDE8A; high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X1 [KO:K18437 ] [EC:3.1.4.53 ]
105856524 PDE8B; high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B isoform X1 [KO:K18437 ] [EC:3.1.4.53 ]
105868051 PBX1; pre-B-cell leukemia transcription factor 1 isoform X2 [KO:K09355 ]
105870391 STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931 ]
105855431 NCEH1; neutral cholesterol ester hydrolase 1 isoform X2 [KO:K14349 ] [EC:3.1.1.-]
105871031 ARMC5; armadillo repeat-containing protein 5 isoform X1 [KO:K22499 ]
105868697 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
105873966 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
105872433 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
105869384 ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958 ]
105857276 ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959 ]
105880580 KCNK2; potassium channel subfamily K member 2 isoform X1 [KO:K04913 ]
105885120 CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854 ]
105859583 CACNA1H; voltage-dependent T-type calcium channel subunit alpha-1H isoform X1 [KO:K04855 ]
105858532 voltage-dependent T-type calcium channel subunit alpha-1I isoform X1 [KO:K04856 ]
105880911 ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056 ]
105867792 KCNA4; potassium voltage-gated channel subfamily A member 4 [KO:K04877 ]
105884378 KCNK3; potassium channel subfamily K member 3 isoform X1 [KO:K04914 ]
105885441 LDLR; LOW QUALITY PROTEIN: low-density lipoprotein receptor [KO:K12473 ]
105880850 SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885 ]
105877644 DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353 ]
105855775 DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353 ]
105877972 DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353 ]
105860762 APC2; adenomatous polyposis coli protein 2 isoform X1 [KO:K02085 ]
Compound C01176 17alpha-Hydroxyprogesterone
C01245 D-myo-Inositol 1,4,5-trisphosphate
C05138 17alpha-Hydroxypregnenolone
C07557 2,3,7,8-Tetrachlorodibenzodioxin
Reference Authors Lacroix A, Feelders RA, Stratakis CA, Nieman LK
Title Cushing's syndrome.
Journal Reference Authors Xiong Q, Ge W
Title Gene mutations in Cushing's disease.
Journal Reference Authors Fukuoka H, Takahashi Y
Title The role of genetic and epigenetic changes in pituitary tumorigenesis.
Journal Reference Authors Quereda V, Malumbres M
Title Cell cycle control of pituitary development and disease.
Journal Reference Authors Caimari F, Korbonits M
Title Novel Genetic Causes of Pituitary Adenomas.
Journal Reference Authors Lecoq AL, Kamenicky P, Guiochon-Mantel A, Chanson P
Title Genetic mutations in sporadic pituitary adenomas--what to screen for?
Journal Reference Authors Hannah-Shmouni F, Faucz FR, Stratakis CA
Title Alterations of Phosphodiesterases in Adrenocortical Tumors.
Journal Reference Authors Melmed S
Title Pathogenesis of pituitary tumors.
Journal Reference Authors Daly AF, Tichomirowa MA, Beckers A
Title Genetic, molecular and clinical features of familial isolated pituitary adenomas.
Journal Reference Authors Albani A, Theodoropoulou M, Reincke M
Title Genetics of Cushing's disease.
Journal Reference Authors Duan K, Hernandez KG, Mete O
Title Clinicopathological correlates of adrenal Cushing's syndrome.
Journal Reference Authors Drougat L, Espiard S, Bertherat J
Title Genetics of primary bilateral macronodular adrenal hyperplasia: a model for early diagnosis of Cushing's syndrome?
Journal Reference Authors Stratakis CA, Boikos SA
Title Genetics of adrenal tumors associated with Cushing's syndrome: a new classification for bilateral adrenocortical hyperplasias.
Journal Reference Authors Refojo D, Holsboer F
Title CRH signaling. Molecular specificity for drug targeting in the CNS.
Journal Reference Authors Kovalovsky D, Refojo D, Liberman AC, Hochbaum D, Pereda MP, Coso OA, Stalla GK, Holsboer F, Arzt E
Title Activation and induction of NUR77/NURR1 in corticotrophs by CRH/cAMP: involvement of calcium, protein kinase A, and MAPK pathways.
Journal Reference Authors Lacroix A, Baldacchino V, Bourdeau I, Hamet P, Tremblay J
Title Cushing's syndrome variants secondary to aberrant hormone receptors.
Journal Reference Authors Reincke M, Sbiera S, Hayakawa A, Theodoropoulou M, Osswald A, Beuschlein F, Meitinger T, Mizuno-Yamasaki E, Kawaguchi K, Saeki Y, Tanaka K, Wieland T, Graf E, Saeger W, Ronchi CL, Allolio B, Buchfelder M, Strom TM, Fassnacht M, Komada M
Title Mutations in the deubiquitinase gene USP8 cause Cushing's disease.
Journal Reference Authors Kaiser UB
Title Cushing's disease: towards precision medicine.
Journal Reference Authors Uzilov AV, Cheesman KC, Fink MY, Newman LC, Pandya C, Lalazar Y, Hefti M, Fowkes M, Deikus G, Lau CY, Moe AS, Kinoshita Y, Kasai Y, Zweig M, Gupta A, Starcevic D, Mahajan M, Schadt EE, Post KD, Donovan MJ, Sebra R, Chen R, Geer EB
Title Identification of a novel RASD1 somatic mutation in a USP8-mutated corticotroph adenoma.
Journal Reference Authors Huang C, Shi Y, Zhao Y
Title USP8 mutation in Cushing's disease.
Journal Reference Authors Theodoropoulou M, Reincke M, Fassnacht M, Komada M
Title Decoding the genetic basis of Cushing's disease: USP8 in the spotlight.
Journal Reference Authors Yu L, Zhang J, Guo X, Chen X, He Z, He Q
Title ARMC5 mutations in familial and sporadic primary bilateral macronodular adrenal hyperplasia.
Journal Reference Authors Wu X, Hua X
Title Menin, histone h3 methyltransferases, and regulation of cell proliferation: current knowledge and perspective.
Journal Reference Authors Ozfirat Z, Korbonits M
Title AIP gene and familial isolated pituitary adenomas.
Journal Related mmur04960 Aldosterone-regulated sodium reabsorption
KO pathway LinkDB All DBs
