Details of Disease

General Information of Disease (ID: DISE1NDR)

• Disease Name: Renal tubular acidosis
• Definition: A group of genetic disorders of the kidney tubules characterized by the accumulation of metabolically produced acids with elevated plasma chloride, hyperchloremic metabolic acidosis. Defective renal acidification of urine (proximal tubules) or low renal acid excretion (distal tubules) can lead to complications such as hypokalemia, hypercalcinuria with nephrolithiasis and nephrocalcinosis, and rickets.
• Disease Hierarchy:
  DISJQTX1: Acidosis
  DISBGF8S: Renal tubular transport disease
  DISAFXMQ: Renal tubule disorder
  DISE1NDR: Renal tubular acidosis
• Disease Identifiers:
  MONDO ID: MONDO_0001909
  UMLS CUI: C0001126
  MedGen ID: 90
  HPO ID: HP:0001947
  SNOMED CT ID: 1776003

Drug-Interaction Atlas (DIA) of This Disease

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
Potassium Citrate	DMRBUPA	Approved	Small molecular drug	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 13 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
WDR72	OTLMZGTC	Limited	Autosomal recessive	[2]
ATP6V1B1	OT8FQ7MN	Limited	Genetic Variation	[13]
BAMBI	OTCEJ8W5	Disputed	Biomarker	[4]
FOXI1	OT2UFOE2	moderate	Biomarker	[14]
ATP6V0A2	OTJBDX0Y	Strong	Genetic Variation	[15]
ATP6V0A4	OT149Z7Q	Strong	Genetic Variation	[15]
COX10	OTCYIS0L	Strong	Genetic Variation	[16]
COX16	OTEYPTJP	Strong	Genetic Variation	[16]
MRGPRF	OT74OZ2Z	Strong	Altered Expression	[17]
NT5C1A	OTS7UF36	Strong	Biomarker	[18]
PFKM	OT1QY9JM	Strong	Genetic Variation	[19]
PFKP	OTFP7AA8	Strong	Genetic Variation	[19]
RBFOX2	OTXY1WVH	Strong	Altered Expression	[17]

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CA1	TTHQPL7	Strong	Biomarker	[3]
CA2	TTANPDJ	Strong	Genetic Variation	[4]
CLCN7	TTST1AJ	Strong	Genetic Variation	[5]
CLCNKB	TTR68GQ	Strong	Biomarker	[6]
CTSB	TTF2LRI	Strong	Biomarker	[7]
CYP11B1	TTIQUX7	Strong	Biomarker	[8]
SLC12A3	TTP362L	Strong	Biomarker	[9]
SLC12A7	TTU2PCD	Strong	Biomarker	[10]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC4A1	DTB0Q3P	Strong	Biomarker	[11]
SLC4A4	DTWDEIL	Strong	Biomarker	[12]

References

• [1] Potassium Citrate FDA Label
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] Enzymatically inactive red cell carbonic anhydrase B in a family with renal tubular acidosis.J Clin Invest. 1974 Jan;53(1):59-63. doi: 10.1172/JCI107559.
• [4] Molecular modelling and dynamics of CA2 missense mutations causative to carbonic anhydrase 2 deficiency syndrome.J Biomol Struct Dyn. 2020 Sep;38(14):4067-4080. doi: 10.1080/07391102.2019.1671899. Epub 2019 Oct 8.
• [5] Autosomal dominant osteopetrosis associated with renal tubular acidosis is due to a CLCN7 mutation.Am J Med Genet A. 2016 Nov;170(11):2988-2992. doi: 10.1002/ajmg.a.37755. Epub 2016 Aug 19.
• [6] Functional significance of channels and transporters expressed in the inner ear and kidney.Am J Physiol Cell Physiol. 2007 Oct;293(4):C1187-208. doi: 10.1152/ajpcell.00024.2007. Epub 2007 Aug 1.
• [7] Renal tubular cell protein breakdown in uninephrectomized and ammonium chloride-loaded rats.J Am Soc Nephrol. 1994 Nov;5(5):1201-7. doi: 10.1681/ASN.V551201.
• [8] Metabolic acidosis has dual effects on sodium handling by rat kidney.Am J Physiol Renal Physiol. 2006 Aug;291(2):F322-31. doi: 10.1152/ajprenal.00338.2005. Epub 2006 Feb 21.
• [9] Advantages and pitfalls of an extended gene panel for investigating complex neurometabolic phenotypes.Brain. 2016 Nov 1;139(11):2844-2854. doi: 10.1093/brain/aww221.
• [10] Deafness and renal tubular acidosis in mice lacking the K-Cl co-transporter Kcc4.Nature. 2002 Apr 25;416(6883):874-8. doi: 10.1038/416874a.
• [11] Functional rescue of a kidney anion exchanger 1 trafficking mutant in renal epithelial cells.PLoS One. 2013;8(2):e57062. doi: 10.1371/journal.pone.0057062. Epub 2013 Feb 27.
• [12] Severe metabolic acidosis causes early lethality in NBC1 W516X knock-in mice as a model of human isolated proximal renal tubular acidosis.Kidney Int. 2011 Apr;79(7):730-41. doi: 10.1038/ki.2010.523. Epub 2011 Jan 12.
• [13] 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.
• [14] Acidosis and Deafness in Patients with Recessive Mutations in FOXI1. J Am Soc Nephrol. 2018 Mar;29(3):1041-1048. doi: 10.1681/ASN.2017080840. Epub 2017 Dec 14.
• [15] Molecular mechanisms of cutis laxa- and distal renal tubular acidosis-causing mutations in V-ATPase a subunits, ATP6V0A2 and ATP6V0A4.J Biol Chem. 2018 Feb 23;293(8):2787-2800. doi: 10.1074/jbc.M117.818872. Epub 2018 Jan 8.
• [16] Sideroblastic anemia associated with multisystem mitochondrial disorders.Pediatr Blood Cancer. 2019 Apr;66(4):e27591. doi: 10.1002/pbc.27591. Epub 2018 Dec 26.
• [17] Modulation of Kaposi's sarcoma-associated herpesvirus infection and replication by MEK/ERK, JNK, and p38 multiple mitogen-activated protein kinase pathways during primary infection.J Virol. 2006 Jun;80(11):5371-82. doi: 10.1128/JVI.02299-05.
• [18] Clinical analysis of hyperkalemic renal tubular acidosis caused by calcineurin inhibitors in solid organ transplant recipients.J Clin Pharm Ther. 2017 Feb;42(1):122-124. doi: 10.1111/jcpt.12485. Epub 2016 Dec 14.
• [19] Human H+ATPase a4 subunit mutations causing renal tubular acidosis reveal a role for interaction with phosphofructokinase-1.Am J Physiol Renal Physiol. 2008 Oct;295(4):F950-8. doi: 10.1152/ajprenal.90258.2008. Epub 2008 Jul 16.