Details of Disease

General Information of Disease (ID: DISKNSJK)

• Disease Name: Nephrogenic diabetes insipidus
• Synonyms: diabetes insipidus nephrogenic X-linked; vasopressin-resistant diabetes insipidus; ADH resistant diabetes insipidus; diabetes insipidus nephrogenic type 1; diabetes insipidus nephrogenic
• Definition: Nephrogenic diabetes insipidus (NDI) is characterized by polyuria with polydipsia, recurrent bouts of fever, constipation, and acute hypernatremic dehydration after birth that may cause neurological sequelae. Polyuria may exceed 10 liters in children.
• Disease Hierarchy:
  DISZ75RJ: Inherited renal tubular disease
  DISK7GAB: Kidney disease
  DIS0U6CJ: Diabetes insipidus
  DISKNSJK: Nephrogenic diabetes insipidus
• Disease Identifiers:
  MONDO ID: MONDO_0016383
  MESH ID: D018500
  UMLS CUI: C0162283
  MedGen ID: 57876
  HPO ID: HP:0009806
  Orphanet ID: 223
  SNOMED CT ID: 111395007

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 16 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
AVPR2	TTK8R02	Supportive	Autosomal dominant	[1]
AQP3	TTLDNMQ	Strong	Biomarker	[2]
AVP	TTJ8EWH	Strong	Biomarker	[3]
AVPR2	TTK8R02	Strong	Genetic Variation	[4]
CLCNKA	TT823N1	Strong	Genetic Variation	[5]
CLCNKB	TTR68GQ	Strong	Genetic Variation	[5]
GPRC6A	TTI1PRE	Strong	Biomarker	[6]
GRN	TT0LWE3	Strong	Biomarker	[7]
L1CAM	TTC9D3K	Strong	Genetic Variation	[8]
LPAR3	TTE2YJR	Strong	Biomarker	[6]
MRGPRX1	TTIX6PK	Strong	Biomarker	[6]
OXER1	TT7WBSV	Strong	Biomarker	[6]
PRKCA	TTFJ8Q1	Strong	Biomarker	[9]
SCT	TTOBVIN	Strong	Biomarker	[6]
SIRT1	TTUF2HO	Strong	Biomarker	[10]
SLC12A1	TTS087L	Strong	Genetic Variation	[11]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC4A4	DTWDEIL	Strong	Biomarker	[12]

This Disease Is Related to 14 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
AQP2	OTQLBKK6	Supportive	Autosomal dominant	[1]
AVPR2	OTJ2GUB1	Supportive	Autosomal dominant	[1]
ADCY6	OTFOY4WW	Strong	Biomarker	[13]
AQP8	OT99JKME	Strong	Genetic Variation	[14]
ARHGAP1	OT0H2ZBZ	Strong	Genetic Variation	[15]
ARHGAP4	OTXV053R	Strong	Genetic Variation	[16]
CANX	OTYP1F6J	Strong	Genetic Variation	[17]
FZD4	OTGLZIE0	Strong	Biomarker	[6]
GPR151	OT7EACU6	Strong	Biomarker	[6]
LGR6	OTPZ1PWR	Strong	Biomarker	[6]
MRGPRX3	OTRKCCDS	Strong	Biomarker	[6]
MRGPRX4	OTOBHZVA	Strong	Biomarker	[6]
PDZD4	OTEBJTOU	Strong	Genetic Variation	[8]
RNF40	OTC8SDA3	Strong	Biomarker	[18]

References

• [1] Hereditary Nephrogenic Diabetes Insipidus. 2000 Feb 12 [updated 2020 Feb 27]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [2] Nephrogenic diabetes insipidus in mice lacking aquaporin-3 water channels.Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4386-91. doi: 10.1073/pnas.080499597.
• [3] Copeptin in the differential diagnosis of hypotonic polyuria.J Endocrinol Invest. 2020 Jan;43(1):21-30. doi: 10.1007/s40618-019-01087-6. Epub 2019 Jul 31.
• [4] A novel AVPR2 missense mutation in an Asian family with inherited nephrogenic diabetes insipidus: A case report.Medicine (Baltimore). 2019 Apr;98(17):e15348. doi: 10.1097/MD.0000000000015348.
• [5] Functional and structural analysis of ClC-K chloride channels involved in renal disease.J Biol Chem. 2000 Aug 11;275(32):24527-33. doi: 10.1074/jbc.M001987200.
• [6] Signaling Modification by GPCR Heteromer and Its Implication on X-Linked Nephrogenic Diabetes Insipidus.PLoS One. 2016 Sep 20;11(9):e0163086. doi: 10.1371/journal.pone.0163086. eCollection 2016.
• [7] Progranulin Deficient Mice Develop Nephrogenic Diabetes Insipidus.Aging Dis. 2018 Oct 1;9(5):817-830. doi: 10.14336/AD.2017.1127. eCollection 2018 Oct.
• [8] L1CAM whole gene deletion in a child with L1 syndrome.Am J Med Genet A. 2014 Jun;164A(6):1555-8. doi: 10.1002/ajmg.a.36474. Epub 2014 Mar 25.
• [9] Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.PLoS One. 2014 Jul 9;9(7):e101753. doi: 10.1371/journal.pone.0101753. eCollection 2014.
• [10] SirT1 regulates energy metabolism and response to caloric restriction in mice.PLoS One. 2008 Mar 12;3(3):e1759. doi: 10.1371/journal.pone.0001759.
• [11] A novel SLC12A1 gene mutation associated with hyperparathyroidism, hypercalcemia, nephrogenic diabetes insipidus, and nephrocalcinosis in four patients.Bone. 2017 Apr;97:121-125. doi: 10.1016/j.bone.2017.01.011. Epub 2017 Jan 14.
• [12] Altered expression of renal acid-base transporters in rats with lithium-induced NDI.Am J Physiol Renal Physiol. 2003 Dec;285(6):F1244-57. doi: 10.1152/ajprenal.00176.2003. Epub 2003 Aug 26.
• [13] Role of adenylyl cyclase 6 in the development of lithium-induced nephrogenic diabetes insipidus.JCI Insight. 2017 Apr 6;2(7):e91042. doi: 10.1172/jci.insight.91042.
• [14] Structural Basis for Mutations of Human Aquaporins Associated to Genetic Diseases.Int J Mol Sci. 2018 May 25;19(6):1577. doi: 10.3390/ijms19061577.
• [15] Two novel types of contiguous gene deletion of the AVPR2 and ARHGAP4 genes in unrelated Japanese kindreds with nephrogenic diabetes insipidus.Hum Mutat. 2002 Jan;19(1):23-9. doi: 10.1002/humu.10011.
• [16] Contiguous 22.1-kb deletion embracing AVPR2 and ARHGAP4 genes at novel breakpoints leads to nephrogenic diabetes insipidus in a Chinese pedigree.BMC Nephrol. 2018 Feb 2;19(1):26. doi: 10.1186/s12882-018-0825-5.
• [17] Association of calnexin with wild type and mutant AVPR2 that causes nephrogenic diabetes insipidus.Biochemistry. 2001 Jun 12;40(23):6766-75. doi: 10.1021/bi002699r.
• [18] E3 ubiquitin-protein ligases in rat kidney collecting duct: response to vasopressin stimulation and withdrawal.Am J Physiol Renal Physiol. 2011 Oct;301(4):F883-96. doi: 10.1152/ajprenal.00117.2011. Epub 2011 Jul 6.