Details of Disease

General Information of Disease (ID: DISP6CYE)

• Disease Name: Distal renal tubular acidosis
• Synonyms: renal tubular acidosis, distal; Primary Distal Renal Tubular Acidosis; distal renal tubular acidosis; classic RTA; familial distal primary acidosis; renal tubular acidosis type 1; dRTA; distal renal tubular acidosis (disease)
• Disease Class: GB90: kidney/ureter disorder
• Definition: Distal renal tubular acidosis (dRTA) is a disorder of impaired net acid secretion by the distal tubule characterized by hyperchloremic metabolic acidosis. The classic form is often associated with hypokalemia whereas other forms of acquired dRTA may be associated with hypokalemia, hyperkalemia or normokalemia.
• Disease Hierarchy:
  DISNCQLA: Inherited kidney disorder
  DISP6CYE: Distal renal tubular acidosis
• ICD Code: ICD-11: ICD-11: GB90.44
• Disease Identifiers:
  MONDO ID: MONDO_0015827
  MESH ID: D000141
  UMLS CUI: C1704380
  OMIM ID: 179800
  MedGen ID: 853429
  HPO ID: HP:0008341
  Orphanet ID: 18
  SNOMED CT ID: 236461000

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
ADV7103	DM1MDMQ	Phase 3	Small molecule	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ATP6AP1	TTWDM4U	Strong	Genetic Variation	[2]
CA2	TTANPDJ	Strong	Genetic Variation	[3]
EPHA3	TTHS2LR	Strong	Genetic Variation	[4]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC26A7	DTOTME4	Strong	Biomarker	[5]
SLC4A4	DTWDEIL	Strong	Biomarker	[6]

This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ATP6V0A4	OT149Z7Q	Strong	Genetic Variation	[7]
ATP6V1B1	OT8FQ7MN	Strong	Genetic Variation	[8]
FOXI1	OT2UFOE2	Strong	Genetic Variation	[3]
GYPB	OTESHUIX	Strong	Genetic Variation	[9]
MRGPRF	OT74OZ2Z	Strong	Genetic Variation	[10]
NCOA7	OT2CNBOG	Strong	Genetic Variation	[11]

References

• [1] ClinicalTrials.gov (NCT03644706) A Phase 3 Multicenter, Randomized, Double-Blinded, Placebo-Controlled Withdrawal Study Evaluating ADV7103 In Pediatric and Adult Subjects With Distal Renal Tubular Acidosis (dRTA). U.S.National Institutes of Health.
• [2] Localization and regulation of the ATP6V0A4 (a4) vacuolar H+-ATPase subunit defective in an inherited form of distal renal tubular acidosis.J Am Soc Nephrol. 2003 Dec;14(12):3027-38. doi: 10.1097/01.asn.0000099375.74789.ab.
• [3] Molecular Pathophysiology of Acid-Base Disorders.Semin Nephrol. 2019 Jul;39(4):340-352. doi: 10.1016/j.semnephrol.2019.04.004.
• [4] Trafficking defects of a novel autosomal recessive distal renal tubular acidosis mutant (S773P) of the human kidney anion exchanger (kAE1).J Biol Chem. 2004 Sep 24;279(39):40960-71. doi: 10.1074/jbc.M405356200. Epub 2004 Jul 13.
• [5] Deletion of the chloride transporter slc26a7 causes distal renal tubular acidosis and impairs gastric acid secretion.J Biol Chem. 2009 Oct 23;284(43):29470-9. doi: 10.1074/jbc.M109.044396. Epub 2009 Sep 1.
• [6] G418-mediated ribosomal read-through of a nonsense mutation causing autosomal recessive proximal renal tubular acidosis. Am J Physiol Renal Physiol. 2008 Sep;295(3):F633-41. doi: 10.1152/ajprenal.00015.2008. Epub 2008 Jul 9.
• [7] A Family with Autosomal Dominant Distal Renal Tubular Acidosis Presents with Atypical Phenotype Caused by a Missence Mutation (R388C) of the Human Kidney Anion Exchanger.Nephron. 2019;141(3):207-212. doi: 10.1159/000495763. Epub 2018 Dec 14.
• [8] ATP6V1B1 recurrent mutations in Algerian deaf patients associated with renal tubular acidosis.Int J Pediatr Otorhinolaryngol. 2020 Feb;129:109772. doi: 10.1016/j.ijporl.2019.109772. Epub 2019 Nov 9.
• [9] Novel AE1 mutations in recessive distal renal tubular acidosis. Loss-of-function is rescued by glycophorin A.J Clin Invest. 1998 Dec 15;102(12):2173-9. doi: 10.1172/JCI4836.
• [10] Hereditary renal tubular disorders in Turkey: demographic, clinical, and laboratory features.Clin Exp Nephrol. 2011 Feb;15(1):108-13. doi: 10.1007/s10157-010-0367-z. Epub 2010 Nov 20.
• [11] Targeted deletion of the Ncoa7 gene results in incomplete distal renal tubular acidosis in mice.Am J Physiol Renal Physiol. 2018 Jul 1;315(1):F173-F185. doi: 10.1152/ajprenal.00407.2017. Epub 2018 Jan 31.