KEGG   PATHWAY: mmu04934Help
Entry
mmu04934                    Pathway                                

Name
Cushing syndrome - Mus musculus (mouse)
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 disease
BRITE hierarchy
Pathway map
mmu04934  Cushing syndrome
mmu04934

Ortholog table
Organism
Mus musculus (mouse) [GN:mmu]
Gene
12918  Crh; corticotropin releasing hormone [KO:K05256]
12921  Crhr1; corticotropin releasing hormone receptor 1 [KO:K04578]
12922  Crhr2; corticotropin releasing hormone receptor 2 [KO:K04579]
14683  Gnas; GNAS (guanine nucleotide binding protein, alpha stimulating) complex locus [KO:K04632]
432530  Adcy1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
210044  Adcy2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
104111  Adcy3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
104110  Adcy4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
224129  Adcy5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
11512  Adcy6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
11513  Adcy7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
11514  Adcy8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
11515  Adcy9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
18747  Prkaca; protein kinase, cAMP dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
18749  Prkacb; protein kinase, cAMP dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
12912  Creb1; cAMP responsive element binding protein 1 [KO:K05870]
11909  Atf2; activating transcription factor 2 [KO:K04450]
11911  Atf4; activating transcription factor 4 [KO:K04374]
12913  Creb3; cAMP responsive element binding protein 3 [KO:K09048]
26427  Creb3l1; cAMP responsive element binding protein 3-like 1 [KO:K09048]
208647  Creb3l2; cAMP responsive element binding protein 3-like 2 [KO:K09048]
208677  Creb3l3; cAMP responsive element binding protein 3-like 3 [KO:K09048]
78284  Creb3l4; cAMP responsive element binding protein 3-like 4 [KO:K09048]
231991  Creb5; cAMP responsive element binding protein 5 [KO:K09047]
12915  Atf6b; activating transcription factor 6 beta [KO:K09049]
17283  Men1; multiple endocrine neoplasia 1 [KO:K14970]
23808  Ash2l; ASH2 like histone lysine methyltransferase complex subunit [KO:K14964]
213464  Rbbp5; retinoblastoma binding protein 5, histone lysine methyltransferase complex subunit [KO:K14961]
69544  Wdr5b; WD repeat domain 5B [KO:K14963]
140858  Wdr5; WD repeat domain 5 [KO:K14963]
214162  Kmt2a; lysine (K)-specific methyltransferase 2A [KO:K09186] [EC:2.1.1.354]
381022  Kmt2d; lysine (K)-specific methyltransferase 2D [KO:K09187] [EC:2.1.1.354]
12580  Cdkn2c; cyclin dependent kinase inhibitor 2C [KO:K06622]
12579  Cdkn2b; cyclin dependent kinase inhibitor 2B [KO:K04685]
12578  Cdkn2a; cyclin dependent kinase inhibitor 2A [KO:K06621]
12567  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
12571  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
12443  Ccnd1; cyclin D1 [KO:K04503]
19645  Rb1; RB transcriptional corepressor 1 [KO:K06618]
13555  E2f1; E2F transcription factor 1 [KO:K17454]
242705  E2f2; E2F transcription factor 2 [KO:K09389]
13557  E2f3; E2F transcription factor 3 [KO:K06620]
19416  Rasd1; RAS, dexamethasone-induced 1 [KO:K07843]
14677  Gnai1; guanine nucleotide binding protein (G protein), alpha inhibiting 1 [KO:K04630]
14679  Gnai3; guanine nucleotide binding protein (G protein), alpha inhibiting 3 [KO:K04630]
14678  Gnai2; guanine nucleotide binding protein (G protein), alpha inhibiting 2 [KO:K04630]
11622  Ahr; aryl-hydrocarbon receptor [KO:K09093]
114230  Aipl1; aryl hydrocarbon receptor-interacting protein-like 1 [KO:K17767]
11632  Aip; aryl-hydrocarbon receptor-interacting protein [KO:K17767]
11863  Arnt; aryl hydrocarbon receptor nuclear translocator [KO:K09097]
12576  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
12566  Cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
12447  Ccne1; cyclin E1 [KO:K06626]
12448  Ccne2; cyclin E2 [KO:K06626]
12575  Cdkn1a; cyclin-dependent kinase inhibitor 1A (P21) [KO:K06625]
12288  Cacna1c; calcium channel, voltage-dependent, L type, alpha 1C subunit [KO:K04850]
12289  Cacna1d; calcium channel, voltage-dependent, L type, alpha 1D subunit [KO:K04851]
54652  Cacna1f; calcium channel, voltage-dependent, alpha 1F subunit [KO:K04853]
12292  Cacna1s; calcium channel, voltage-dependent, L type, alpha 1S subunit [KO:K04857]
108058  Camk2d; calcium/calmodulin-dependent protein kinase II, delta [KO:K04515] [EC:2.7.11.17]
12325  Camk2g; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
12323  Camk2b; calcium/calmodulin-dependent protein kinase II, beta [KO:K04515] [EC:2.7.11.17]
12322  Camk2a; calcium/calmodulin-dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
109905  Rap1a; RAS-related protein 1a [KO:K04353]
215449  Rap1b; RAS related protein 1b [KO:K07836]
109880  Braf; Braf transforming gene [KO:K04365] [EC:2.7.11.1]
26395  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
15370  Nr4a1; nuclear receptor subfamily 4, group A, member 1 [KO:K04465]
13649  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
84092  Usp8; ubiquitin specific peptidase 8 [KO:K11839] [EC:3.4.19.12]
18976  Pomc; pro-opiomelanocortin-alpha [KO:K05228]
17200  Mc2r; melanocortin 2 receptor [KO:K04200]
77037  Mrap; melanocortin 2 receptor accessory protein [KO:K22398]
218461  Pde8b; phosphodiesterase 8B [KO:K18437] [EC:3.1.4.53]
18584  Pde8a; phosphodiesterase 8A [KO:K18437] [EC:3.1.4.53]
241489  Pde11a; phosphodiesterase 11A [KO:K13298] [EC:3.1.4.17 3.1.4.35]
26423  Nr5a1; nuclear receptor subfamily 5, group A, member 1 [KO:K08560]
20683  Sp1; trans-acting transcription factor 1 [KO:K04684]
18514  Pbx1; pre B cell leukemia homeobox 1 [KO:K09355]
13072  Cyp11b2; cytochrome P450, family 11, subfamily b, polypeptide 2 [KO:K00497] [EC:1.14.15.4]
13074  Cyp17a1; cytochrome P450, family 17, subfamily a, polypeptide 1 [KO:K00512] [EC:1.14.14.19 1.14.14.32]
20845  Star; steroidogenic acute regulatory protein [KO:K16931]
320024  Nceh1; neutral cholesterol ester hydrolase 1 [KO:K14349] [EC:3.1.1.-]
233912  Armc5; armadillo repeat containing 5 [KO:K22499]
11606  Agt; angiotensinogen (serpin peptidase inhibitor, clade A, member 8) [KO:K09821]
11607  Agtr1a; angiotensin II receptor, type 1a [KO:K04166]
11608  Agtr1b; angiotensin II receptor, type 1b [KO:K04166]
14682  Gnaq; guanine nucleotide binding protein, alpha q polypeptide [KO:K04634]
14672  Gna11; guanine nucleotide binding protein, alpha 11 [KO:K04635]
18795  Plcb1; phospholipase C, beta 1 [KO:K05858] [EC:3.1.4.11]
18797  Plcb3; phospholipase C, beta 3 [KO:K05858] [EC:3.1.4.11]
18798  Plcb4; phospholipase C, beta 4 [KO:K05858] [EC:3.1.4.11]
18796  Plcb2; phospholipase C, beta 2 [KO:K05858] [EC:3.1.4.11]
16438  Itpr1; inositol 1,4,5-trisphosphate receptor 1 [KO:K04958]
16439  Itpr2; inositol 1,4,5-triphosphate receptor 2 [KO:K04959]
16440  Itpr3; inositol 1,4,5-triphosphate receptor 3 [KO:K04960]
16526  Kcnk2; potassium channel, subfamily K, member 2 [KO:K04913]
12291  Cacna1g; calcium channel, voltage-dependent, T type, alpha 1G subunit [KO:K04854]
58226  Cacna1h; calcium channel, voltage-dependent, T type, alpha 1H subunit [KO:K04855]
239556  Cacna1i; calcium channel, voltage-dependent, alpha 1I subunit [KO:K04856]
109305  Orai1; ORAI calcium release-activated calcium modulator 1 [KO:K16056]
16492  Kcna4; potassium voltage-gated channel, shaker-related subfamily, member 4 [KO:K04877]
16527  Kcnk3; potassium channel, subfamily K, member 3 [KO:K04914]
16835  Ldlr; low density lipoprotein receptor [KO:K12473]
20778  Scarb1; scavenger receptor class B, member 1 [KO:K13885]
13070  Cyp11a1; cytochrome P450, family 11, subfamily a, polypeptide 1 [KO:K00498] [EC:1.14.15.6]
15495  Hsd3b4; hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 4 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
15496  Hsd3b5; hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 5 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
15493  Hsd3b2; hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
15492  Hsd3b1; hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
15497  Hsd3b6; hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 6 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
100043456  Gm10681; predicted gene 10681 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
13079  Cyp21a1; cytochrome P450, family 21, subfamily a, polypeptide 1 [KO:K00513] [EC:1.14.14.16]
14194  Fh1; fumarate hydratase 1 [KO:K01679] [EC:4.2.1.2]
22408  Wnt1; wingless-type MMTV integration site family, member 1 [KO:K03209]
22413  Wnt2; wingless-type MMTV integration site family, member 2 [KO:K00182]
22414  Wnt2b; wingless-type MMTV integration site family, member 2B [KO:K00182]
22415  Wnt3; wingless-type MMTV integration site family, member 3 [KO:K00312]
22416  Wnt3a; wingless-type MMTV integration site family, member 3A [KO:K00312]
22417  Wnt4; wingless-type MMTV integration site family, member 4 [KO:K00408]
22418  Wnt5a; wingless-type MMTV integration site family, member 5A [KO:K00444]
22419  Wnt5b; wingless-type MMTV integration site family, member 5B [KO:K00444]
22420  Wnt6; wingless-type MMTV integration site family, member 6 [KO:K00445]
22421  Wnt7a; wingless-type MMTV integration site family, member 7A [KO:K00572]
22422  Wnt7b; wingless-type MMTV integration site family, member 7B [KO:K00572]
20890  Wnt8a; wingless-type MMTV integration site family, member 8A [KO:K00714]
22423  Wnt8b; wingless-type MMTV integration site family, member 8B [KO:K00714]
216795  Wnt9a; wingless-type MMTV integration site family, member 9A [KO:K01064]
22412  Wnt9b; wingless-type MMTV integration site family, member 9B [KO:K01064]
22410  Wnt10b; wingless-type MMTV integration site family, member 10B [KO:K01357]
22409  Wnt10a; wingless-type MMTV integration site family, member 10A [KO:K01357]
22411  Wnt11; wingless-type MMTV integration site family, member 11 [KO:K01384]
93735  Wnt16; wingless-type MMTV integration site family, member 16 [KO:K01558]
14362  Fzd1; frizzled class receptor 1 [KO:K02432]
14369  Fzd7; frizzled class receptor 7 [KO:K02432]
57265  Fzd2; frizzled class receptor 2 [KO:K02235]
14365  Fzd3; frizzled class receptor 3 [KO:K02329]
14366  Fzd4; frizzled class receptor 4 [KO:K02354]
14367  Fzd5; frizzled class receptor 5 [KO:K02375]
14370  Fzd8; frizzled class receptor 8 [KO:K02375]
14368  Fzd6; frizzled class receptor 6 [KO:K02376]
93897  Fzd10; frizzled class receptor 10 [KO:K02842]
14371  Fzd9; frizzled class receptor 9 [KO:K02842]
13544  Dvl3; dishevelled segment polarity protein 3 [KO:K02353]
13542  Dvl1; dishevelled segment polarity protein 1 [KO:K02353]
13543  Dvl2; dishevelled segment polarity protein 2 [KO:K02353]
56637  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
12005  Axin1; axin 1 [KO:K02157]
12006  Axin2; axin 2 [KO:K04385]
12387  Ctnnb1; catenin (cadherin associated protein), beta 1 [KO:K02105]
11789  Apc; APC, WNT signaling pathway regulator [KO:K02085]
23805  Apc2; adenomatosis polyposis coli 2 [KO:K02085]
21414  Tcf7; transcription factor 7, T cell specific [KO:K02620]
21415  Tcf7l1; transcription factor 7 like 1 (T cell specific, HMG box) [KO:K04490]
21416  Tcf7l2; transcription factor 7 like 2, T cell specific, HMG box [KO:K04491]
16842  Lef1; lymphoid enhancer binding factor 1 [KO:K04492]
Compound
C00020  AMP
C00076  Calcium cation
C00187  Cholesterol
C00238  Potassium cation
C00410  Progesterone
C00575  3',5'-Cyclic AMP
C00735  Cortisol
C01176  17alpha-Hydroxyprogesterone
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01953  Pregnenolone
C05138  17alpha-Hydroxypregnenolone
C05488  11-Deoxycortisol
C07557  2,3,7,8-Tetrachlorodibenzodioxin
Reference
  Authors
Lacroix A, Feelders RA, Stratakis CA, Nieman LK
  Title
Cushing's syndrome.
  Journal
Lancet 386:913-27 (2015)
DOI:10.1016/S0140-6736(14)61375-1
Reference
  Authors
Xiong Q, Ge W
  Title
Gene mutations in Cushing's disease.
  Journal
Biomed Rep 5:277-282 (2016)
DOI:10.3892/br.2016.729
Reference
  Authors
Fukuoka H, Takahashi Y
  Title
The role of genetic and epigenetic changes in pituitary tumorigenesis.
  Journal
Neurol Med Chir (Tokyo) 54 Suppl 3:943-57 (2014)
DOI:10.2176/nmc.suppl.2014-3
Reference
  Authors
Quereda V, Malumbres M
  Title
Cell cycle control of pituitary development and disease.
  Journal
J Mol Endocrinol 42:75-86 (2009)
DOI:10.1677/JME-08-0146
Reference
  Authors
Caimari F, Korbonits M
  Title
Novel Genetic Causes of Pituitary Adenomas.
  Journal
Clin Cancer Res 22:5030-5042 (2016)
DOI:10.1158/1078-0432.CCR-16-0452
Reference
  Authors
Lecoq AL, Kamenicky P, Guiochon-Mantel A, Chanson P
  Title
Genetic mutations in sporadic pituitary adenomas--what to screen for?
  Journal
Nat Rev Endocrinol 11:43-54 (2015)
DOI:10.1038/nrendo.2014.181
Reference
  Authors
Hannah-Shmouni F, Faucz FR, Stratakis CA
  Title
Alterations of Phosphodiesterases in Adrenocortical Tumors.
  Journal
Front Endocrinol (Lausanne) 7:111 (2016)
DOI:10.3389/fendo.2016.00111
Reference
  Authors
Melmed S
  Title
Pathogenesis of pituitary tumors.
  Journal
Nat Rev Endocrinol 7:257-66 (2011)
DOI:10.1038/nrendo.2011.40
Reference
  Authors
Daly AF, Tichomirowa MA, Beckers A
  Title
Genetic, molecular and clinical features of familial isolated pituitary adenomas.
  Journal
Horm Res 71 Suppl 2:116-22 (2009)
DOI:10.1159/000192448
Reference
  Authors
Albani A, Theodoropoulou M, Reincke M
  Title
Genetics of Cushing's disease.
  Journal
Clin Endocrinol (Oxf) 88:3-12 (2018)
DOI:10.1111/cen.13457
Reference
  Authors
Duan K, Hernandez KG, Mete O
  Title
Clinicopathological correlates of adrenal Cushing's syndrome.
  Journal
Postgrad Med J 91:331-42 (2015)
DOI:10.1136/postgradmedj-2014-202612rep
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
Eur J Endocrinol 173:M121-31 (2015)
DOI:10.1530/EJE-15-0532
Reference
  Authors
Stratakis CA, Boikos SA
  Title
Genetics of adrenal tumors associated with Cushing's syndrome: a new classification for bilateral adrenocortical hyperplasias.
  Journal
Nat Clin Pract Endocrinol Metab 3:748-57 (2007)
DOI:10.1038/ncpendmet0648
Reference
  Authors
Refojo D, Holsboer F
  Title
CRH signaling. Molecular specificity for drug targeting in the CNS.
  Journal
Ann N Y Acad Sci 1179:106-19 (2009)
DOI:10.1111/j.1749-6632.2009.04983.x
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
Mol Endocrinol 16:1638-51 (2002)
DOI:10.1210/mend.16.7.0863
Reference
  Authors
Lacroix A, Baldacchino V, Bourdeau I, Hamet P, Tremblay J
  Title
Cushing's syndrome variants secondary to aberrant hormone receptors.
  Journal
Trends Endocrinol Metab 15:375-82 (2004)
DOI:10.1016/j.tem.2004.08.007
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
Nat Genet 47:31-8 (2015)
DOI:10.1038/ng.3166
Reference
  Authors
Kaiser UB
  Title
Cushing's disease: towards precision medicine.
  Journal
Cell Res 25:649-50 (2015)
DOI:10.1038/cr.2015.53
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
Cold Spring Harb Mol Case Stud 3:a001602 (2017)
DOI:10.1101/mcs.a001602
Reference
  Authors
Huang C, Shi Y, Zhao Y
  Title
USP8 mutation in Cushing's disease.
  Journal
Oncotarget 6:18240-1 (2015)
DOI:10.18632/oncotarget.4856
Reference
  Authors
Theodoropoulou M, Reincke M, Fassnacht M, Komada M
  Title
Decoding the genetic basis of Cushing's disease: USP8 in the spotlight.
  Journal
Eur J Endocrinol 173:M73-83 (2015)
DOI:10.1530/EJE-15-0320
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
PLoS One 13:e0191602 (2018)
DOI:10.1371/journal.pone.0191602
Reference
  Authors
Wu X, Hua X
  Title
Menin, histone h3 methyltransferases, and regulation of cell proliferation: current knowledge and perspective.
  Journal
Curr Mol Med 8:805-15 (2008)
DOI:10.2174/156652408786733702
Reference
  Authors
Ozfirat Z, Korbonits M
  Title
AIP gene and familial isolated pituitary adenomas.
  Journal
Mol Cell Endocrinol 326:71-9 (2010)
DOI:10.1016/j.mce.2010.05.001
Related
pathway
mmu00020  Citrate cycle (TCA cycle)
mmu00140  Steroid hormone biosynthesis
mmu04020  Calcium signaling pathway
mmu04024  cAMP signaling pathway
mmu04110  Cell cycle
mmu04310  Wnt signaling pathway
mmu04927  Cortisol synthesis and secretion
mmu04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04934   
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