Details of Disease

General Information of Disease (ID: DISPUS40)

• Disease Name: Autosomal recessive polycystic kidney disease
• Synonyms: PKHD1; polycystic kidney and hepatic disease 1; polycystic kidney disease, infantile, type I; AR-PKD; polycystic kidney disease, infantile type; polycystic kidney disease, autosomal recessive; autosomal recessive polycystic kidney; ARPKD
• Definition: An inherited disorder characterized by the development of cysts affecting the collecting ducts. It is frequently associated with hepatic involvement.
• Disease Hierarchy:
  DISWS3UY: Polycystic kidney disease
  DISCPWH9: Autosomal recessive disease
  DISPUS40: Autosomal recessive polycystic kidney disease
• Disease Identifiers:
  MONDO ID: MONDO_0009889
  MESH ID: D017044
  UMLS CUI: C0085548
  OMIM ID: 263200
  MedGen ID: 39076
  Orphanet ID: 731
  SNOMED CT ID: 28770003

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
DAAM2	TTN0Z6H	Limited	Altered Expression	[1]
AQP1	TTSF1KH	Strong	Altered Expression	[2]
AVPR2	TTK8R02	Strong	Biomarker	[3]
CDC25A	TTLZS4Q	Strong	Altered Expression	[4]
MTOR	TTCJG29	Strong	Biomarker	[5]
NEK1	TTO5QT2	Strong	Biomarker	[6]
NEK8	TT8AH9I	Strong	Biomarker	[7]
SRC	TT6PKBN	Strong	Biomarker	[8]
TST	TT51OTS	Strong	Genetic Variation	[9]
CFTR	TTRLZHP	Definitive	Biomarker	[2]
P2RX1	TTJW7B3	Definitive	Altered Expression	[10]
P2RX3	TT2THBD	Definitive	Altered Expression	[10]
P2RX4	TT1NLOA	Definitive	Altered Expression	[10]
P2RY1	TTA93TL	Definitive	Altered Expression	[10]
P2RY2	TTOZHQC	Definitive	Altered Expression	[10]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC4A2	DTF7GAL	Definitive	Biomarker	[2]

This Disease Is Related to 25 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ATMIN	OTEADE76	Limited	Altered Expression	[1]
SCRIB	OTW4N3FV	Limited	Altered Expression	[1]
ARL3	OT3OGOMX	Strong	Biomarker	[11]
BICC1	OTYRKIJ1	Strong	Biomarker	[12]
CEP164	OTLNRPAR	Strong	Biomarker	[13]
CYP4A22	OTHO7KC4	Strong	Biomarker	[14]
CYS1	OTUXN7CO	Strong	Biomarker	[15]
ELN	OTFSO7PG	Strong	Biomarker	[16]
IFT88	OTDR3VBD	Strong	Biomarker	[17]
MCM3	OTOOHQPM	Strong	Biomarker	[18]
MEP1A	OTY2Z48T	Strong	Biomarker	[19]
NPHP3	OT8U8ELA	Strong	Biomarker	[20]
PANX1	OTXPEDOK	Strong	Biomarker	[21]
PRPH2	OTNH2G5H	Strong	Genetic Variation	[9]
SCLT1	OT2ZSSP4	Strong	Biomarker	[22]
STATH	OTQHBHM9	Strong	Genetic Variation	[23]
TMEM67	OTME92T5	Strong	Biomarker	[24]
TSC1	OTFF4YZ7	Strong	Biomarker	[25]
DZIP1L	OT0XRDV6	Definitive	Autosomal recessive	[26]
P2RX2	OT0LF34A	Definitive	Altered Expression	[10]
P2RX5	OTLBR20R	Definitive	Altered Expression	[10]
P2RX6	OT1FNTXA	Definitive	Altered Expression	[10]
PKD1	OT5ALRZ5	Definitive	Autosomal recessive	[26]
PKHD1	OTAH8SMF	Definitive	Autosomal recessive	[26]
PKHD1L1	OTREFCAA	Definitive	Biomarker	[27]

References

• [1] Atmin modulates Pkhd1 expression and may mediate Autosomal Recessive Polycystic Kidney Disease (ARPKD) through altered non-canonical Wnt/Planar Cell Polarity (PCP) signalling.Biochim Biophys Acta Mol Basis Dis. 2019 Feb 1;1865(2):378-390. doi: 10.1016/j.bbadis.2018.11.003. Epub 2018 Nov 7.
• [2] Hepatic cystogenesis is associated with abnormal expression and location of ion transporters and water channels in an animal model of autosomal recessive polycystic kidney disease.Am J Pathol. 2008 Dec;173(6):1637-46. doi: 10.2353/ajpath.2008.080125. Epub 2008 Nov 6.
• [3] Molecular and cellular pathogenesis of autosomal recessive polycystic kidney disease.Braz J Med Biol Res. 2006 Dec;39(12):1537-48. doi: 10.1590/s0100-879x2006001200004.
• [4] Inhibition of Cdc25A suppresses hepato-renal cystogenesis in rodent models of polycystic kidney and liver disease.Gastroenterology. 2012 Mar;142(3):622-633.e4. doi: 10.1053/j.gastro.2011.11.036. Epub 2011 Dec 7.
• [5] Activation of the PI3K/mTOR pathway is involved in cystic proliferation of cholangiocytes of the PCK rat.PLoS One. 2014 Jan 30;9(1):e87660. doi: 10.1371/journal.pone.0087660. eCollection 2014.
• [6] The mammalian Nek1 kinase is involved in primary cilium formation.FEBS Lett. 2008 Apr 30;582(10):1465-70. doi: 10.1016/j.febslet.2008.03.036. Epub 2008 Apr 1.
• [7] Downregulating hedgehog signaling reduces renal cystogenic potential of mouse models.J Am Soc Nephrol. 2014 Oct;25(10):2201-12. doi: 10.1681/ASN.2013070735. Epub 2014 Apr 3.
• [8] Src inhibition ameliorates polycystic kidney disease.J Am Soc Nephrol. 2008 Jul;19(7):1331-41. doi: 10.1681/ASN.2007060665. Epub 2008 Apr 2.
• [9] Fine mapping of the autosomal recessive polycystic kidney disease locus (PKHD1) and the genes MUT, RDS, CSNK2 beta, and GSTA1 at 6p21.1-p12.Genomics. 1998 Feb 15;48(1):40-5. doi: 10.1006/geno.1997.5145.
• [10] Characterization of purinergic receptor expression in ARPKD cystic epithelia.Purinergic Signal. 2018 Dec;14(4):485-497. doi: 10.1007/s11302-018-9632-5. Epub 2018 Nov 11.
• [11] ADP-ribosylation factor-like 3 is involved in kidney and photoreceptor development. Am J Pathol. 2006 Apr;168(4):1288-98. doi: 10.2353/ajpath.2006.050941.
• [12] Evidence that two phenotypically distinct mouse PKD mutations, bpk and jcpk, are allelic.Kidney Int. 1996 Oct;50(4):1158-65. doi: 10.1038/ki.1996.423.
• [13] Nephronophthisis-associated CEP164 regulates cell cycle progression, apoptosis and epithelial-to-mesenchymal transition.PLoS Genet. 2014 Oct 23;10(10):e1004594. doi: 10.1371/journal.pgen.1004594. eCollection 2014 Oct.
• [14] Chronic blockade of 20-HETE synthesis reduces polycystic kidney disease in an orthologous rat model of ARPKD.Am J Physiol Renal Physiol. 2009 Mar;296(3):F575-82. doi: 10.1152/ajprenal.90705.2008. Epub 2009 Jan 7.
• [15] Cystin localizes to primary cilia via membrane microdomains and a targeting motif.J Am Soc Nephrol. 2009 Dec;20(12):2570-80. doi: 10.1681/ASN.2009020188. Epub 2009 Oct 22.
• [16] Aortic stiffness is associated with vascular calcification and remodeling in a chronic kidney disease rat model.Am J Physiol Renal Physiol. 2011 Jun;300(6):F1431-6. doi: 10.1152/ajprenal.00079.2011. Epub 2011 Apr 6.
• [17] Primary cilia and signaling pathways in mammalian development, health and disease.Nephron Physiol. 2009;111(3):p39-53. doi: 10.1159/000208212. Epub 2009 Mar 10.
• [18] Genomic structure of the gene for the human P1 protein (MCM3) and its exclusion as a candidate for autosomal recessive polycystic kidney disease.Eur J Hum Genet. 2000 Mar;8(3):163-6. doi: 10.1038/sj.ejhg.5200426.
• [19] Fine mapping of MEP1A, the gene encoding the alpha subunit of the metalloendopeptidase meprin, to human chromosome 6P21.Biochem Biophys Res Commun. 1995 Nov 13;216(2):630-5. doi: 10.1006/bbrc.1995.2668.
• [20] Altered expression pattern of polycystin-2 in acute and chronic renal tubular diseases.J Am Soc Nephrol. 2002 Jul;13(7):1855-64. doi: 10.1097/01.asn.0000018402.33620.c7.
• [21] Knockout of P2rx7 purinergic receptor attenuates cyst growth in a rat model of ARPKD.Am J Physiol Renal Physiol. 2019 Dec 1;317(6):F1649-F1655. doi: 10.1152/ajprenal.00395.2019. Epub 2019 Oct 21.
• [22] Sclt1 deficiency causes cystic kidney by activating ERK and STAT3 signaling.Hum Mol Genet. 2017 Aug 1;26(15):2949-2960. doi: 10.1093/hmg/ddx183.
• [23] Birth of a healthy infant following preimplantation PKHD1 haplotyping for autosomal recessive polycystic kidney disease using multiple displacement amplification.J Assist Reprod Genet. 2010 Jul;27(7):397-407. doi: 10.1007/s10815-010-9432-5. Epub 2010 May 20.
• [24] Hydrocephalus in a rat model of Meckel Gruber syndrome with a TMEM67 mutation.Sci Rep. 2019 Jan 31;9(1):1069. doi: 10.1038/s41598-018-37620-5.
• [25] Autosomal recessive and dominant polycystic kidney diseases.Minerva Urol Nefrol. 2004 Dec;56(4):329-38.
• [26] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [27] PKHD1L1 is a coat protein of hair-cell stereocilia and is required for normal hearing.Nat Commun. 2019 Aug 23;10(1):3801. doi: 10.1038/s41467-019-11712-w.