Details of Disease

General Information of Disease (ID: DISEM9V2)

• Disease Name: Gitelman syndrome
• Synonyms: familial hypokalemia-hypomagnesemia; GTLMNS; Potassium and magnesium depletion; Gitelman's syndrome; primary renal tubular hypokalemic hypomagnesemia with hypocalciuria; Gitelman syndrome; hypomagnesemia-hypokalemia, primary renotubular, with hypocalciuria
• Definition: Gitelman syndrome (GS), also referred to as familial hypokalemia-hypomagnesemia, is characterized by hypokalemic metabolic alkalosis in combination with significant hypomagnesemia and low urinary calcium excretion.
• Disease Hierarchy:
  DISZ75RJ: Inherited renal tubular disease
  DIS6SVEE: Syndromic disease
  DISBGF8S: Renal tubular transport disease
  DISEM9V2: Gitelman syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0009904
  MESH ID: D053579
  UMLS CUI: C0268450
  OMIM ID: 263800
  MedGen ID: 75681
  Orphanet ID: 358
  SNOMED CT ID: 707756004

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
SLC12A1	TTS087L	Limited	Genetic Variation	[1]
CLCNKB	TTR68GQ	Disputed	Biomarker	[2]
CLCNKB	TTR68GQ	Supportive	Autosomal recessive	[3]
KCNJ1	TTJ13ST	moderate	Genetic Variation	[4]
SLC12A3	TTP362L	Strong	Genetic Variation	[5]
STK39	TTYQTIU	Strong	Biomarker	[6]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC12A3	DT6MDC9	Strong	Autosomal recessive	[7]

This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ARHGEF25	OT7162TD	Limited	Genetic Variation	[8]
PPP1R12A	OT4AVU95	Limited	Posttranslational Modification	[9]
TESC	OTI8C76M	Limited	Genetic Variation	[10]
TRPV5	OTWF4L0U	Limited	Genetic Variation	[11]
CLCNKB	OTMIG14Q	Supportive	Autosomal recessive	[3]
SLC12A3	OTAO2PG6	Strong	Autosomal recessive	[7]

References

• [1] Analysis of renal tubular electrolyte transporter genes in seven patients with hypokalemic metabolic alkalosis.Kidney Int. 2003 Sep;64(3):808-16. doi: 10.1046/j.1523-1755.2003.00163.x.
• [2] Digenetic inheritance of SLC12A3 and CLCNKB genes in a Chinese girl with Gitelman syndrome.BMC Pediatr. 2019 Apr 18;19(1):114. doi: 10.1186/s12887-019-1498-3.
• [3] Gitelman syndrome due to p.A204T mutation in CLCNKB gene. Int Urol Nephrol. 2010 Dec;42(4):1099-102. doi: 10.1007/s11255-010-9850-4. Epub 2010 Oct 8.
• [4] The pharmacological characteristics of molecular-based inherited salt-losing tubulopathies.J Clin Endocrinol Metab. 2010 Dec;95(12):E511-8. doi: 10.1210/jc.2010-0392. Epub 2010 Sep 1.
• [5] A novel compound heterozygous mutation of SLC12A3 gene in a Chinese pedigree with Gitelman syndrome.Endocrine. 2020 Mar;67(3):673-677. doi: 10.1007/s12020-019-02152-z. Epub 2019 Dec 5.
• [6] Critical role of the SPAK protein kinase CCT domain in controlling blood pressure.Hum Mol Genet. 2015 Aug 15;24(16):4545-58. doi: 10.1093/hmg/ddv185. Epub 2015 May 20.
• [7] Mutations in the Na-Cl cotransporter reduce blood pressure in humans. Hypertension. 2001 Jun;37(6):1458-64. doi: 10.1161/01.hyp.37.6.1458.
• [8] Gq/p63RhoGEF interaction in RhoA/Rho kinase signaling: investigation in Gitelman's syndrome and implications with hypertension.J Endocrinol Invest. 2018 Mar;41(3):351-356. doi: 10.1007/s40618-017-0749-0. Epub 2017 Aug 24.
• [9] Proinflammatory/profibrotic effects of aldosterone in Gitelman's syndrome, a human model opposite to hypertension.J Endocrinol Invest. 2019 May;42(5):521-526. doi: 10.1007/s40618-018-0942-9. Epub 2018 Aug 22.
• [10] Two novel mutations of thiazide-sensitive Na-Cl cotrans porter (TSC) gene in two sporadic Japanese patients with Gitelman syndrome.Endocr J. 2002 Feb;49(1):91-6. doi: 10.1507/endocrj.49.91.
• [11] Generation and analysis of the thiazide-sensitive Na+ -Cl- cotransporter (Ncc/Slc12a3) Ser707X knockin mouse as a model of Gitelman syndrome.Hum Mutat. 2010 Dec;31(12):1304-15. doi: 10.1002/humu.21364. Epub 2010 Oct 14.