Details of Disease

Disease Name

Nephronophthisis

nephronophthisis; nephronophthisis (disease); medullary cystic kidney; medullary cystic disease

Definition

Progressive tubulointerstitial injury, inherited in an autosomal recessive pattern, caused by mutations in genes involved in ciliary function, which may result in an end stage renal failure.

Disease Hierarchy

DISZ75RJ: Inherited renal tubular disease

DISCPWH9: Autosomal recessive disease

DISXU4HY: Nephronophthisis

Disease Identifiers

MONDO ID

MONDO_0019005

UMLS CUI

C0687120

MedGen ID

146912

HPO ID

HP:0000090

Orphanet ID

655

SNOMED CT ID

204958008

General Information of Disease (ID: DISXU4HY)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 44 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ZNF423	OTU8QKMT	Limited	Autosomal recessive	[1]
AHI1	OT8K2YWY	Limited	Altered Expression	[9]
ATXN10	OTKRDUNN	Limited	Biomarker	[10]
CEP164	OTLNRPAR	Limited	Biomarker	[11]
CC2D2A	OTFGRGFR	moderate	Altered Expression	[9]
GLIS2	OTOUUV1X	moderate	Biomarker	[12]
GLIS3	OTBC960E	moderate	Genetic Variation	[13]
IFT140	OT6KO5FH	moderate	Genetic Variation	[14]
MAPKBP1	OTMLEJ67	moderate	Genetic Variation	[15]
PKHD1	OTAH8SMF	moderate	CausalMutation	[16]
TMEM67	OTME92T5	moderate	Genetic Variation	[17]
TRAF3IP1	OTLCC64B	moderate	Genetic Variation	[18]
AATF	OT1QOKLD	Strong	Altered Expression	[19]
ACTN4	OTCNZAJ5	Strong	Biomarker	[20]
ADAMTS9	OTV3Q0DS	Strong	Genetic Variation	[21]
ANKS3	OTFXNRZD	Strong	Biomarker	[22]
ANKS6	OT6DXD3Q	Strong	Genetic Variation	[23]
CSPP1	OTNX7GD4	Strong	Biomarker	[24]
CYS1	OTUXN7CO	Strong	Genetic Variation	[25]
DCDC2	OTSUFH1H	Strong	Genetic Variation	[26]
FAM186B	OTU3B9X5	Strong	Genetic Variation	[27]
INCENP	OT9HFRYK	Strong	Genetic Variation	[27]
INVS	OT8KPESR	Strong	Biomarker	[28]
IQCB1	OTYQ28V9	Strong	Genetic Variation	[29]
KIF3A	OTMUBSSK	Strong	Biomarker	[30]
MALL	OTKGZ89D	Strong	Genetic Variation	[31]
MKKS	OTLF5T11	Strong	Biomarker	[32]
MKS1	OT83W5PB	Strong	Biomarker	[32]
NPHP4	OTBNOA7U	Strong	Biomarker	[33]
NXPH1	OTGKX860	Strong	Biomarker	[34]
PACRG	OT1NYNNW	Strong	Biomarker	[35]
PIAS1	OTZVAHZI	Strong	Genetic Variation	[27]
PRPF40B	OTBPUXVD	Strong	Genetic Variation	[27]
RBM48	OTUTO9NZ	Strong	Genetic Variation	[27]
RCC1	OT25AGMB	Strong	Genetic Variation	[36]
RPGRIP1	OTABESO9	Strong	Biomarker	[37]
RPGRIP1L	OT6Z069I	Strong	Genetic Variation	[38]
SCLT1	OT2ZSSP4	Strong	Biomarker	[39]
SDCCAG8	OTV2ZGV9	Strong	Genetic Variation	[40]
TCTN2	OTKR3I3L	Strong	Biomarker	[10]
TINAG	OTY7BSD7	Strong	Biomarker	[41]
TMEM218	OTM46L89	Strong	Biomarker	[42]
TTC21B	OTXXA87U	Strong	Biomarker	[43]
NPHP3	OT8U8ELA	Definitive	Autosomal recessive	[1]
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⏷ Show the Full List of 44 DOT(s)

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CEP290	TT3XBOV	moderate	CausalMutation	[2]
MLYCD	TT9Z4YD	moderate	Genetic Variation	[3]
AGXT	TTF5NVW	Strong	Biomarker	[4]
ALDH3A2	TTB6UM0	Strong	Biomarker	[5]
AVPR2	TTK8R02	Strong	Genetic Variation	[6]
NEK8	TT8AH9I	Strong	Genetic Variation	[7]
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⏷ Show the Full List of 6 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC41A1	DTB37ZE	Limited	Biomarker	[8]
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References

1	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.
2	Combining targeted panel-based resequencing and copy-number variation analysis for the diagnosis of inherited syndromic retinopathies and associated ciliopathies.Sci Rep. 2018 Mar 27;8(1):5285. doi: 10.1038/s41598-018-23520-1.
3	Autosomal dominant medullary cystic kidney disease: evidence of gene locus heterogeneity.Nephrol Dial Transplant. 1998 Aug;13(8):1955-7. doi: 10.1093/ndt/13.8.1955.
4	Whole-exome resequencing distinguishes cystic kidney diseases from phenocopies in renal ciliopathies.Kidney Int. 2014 Apr;85(4):880-7. doi: 10.1038/ki.2013.450. Epub 2013 Nov 20.
5	Mutation analysis in nephronophthisis using a combined approach of homozygosity mapping, CEL I endonuclease cleavage, and direct sequencing. Hum Mutat. 2008 Mar;29(3):418-26. doi: 10.1002/humu.20669.
6	A 4-year-old boy presenting with persistent urinary incontinence: Questions.Pediatr Nephrol. 2017 May;32(5):767-768. doi: 10.1007/s00467-016-3441-2. Epub 2016 Jun 27.
7	Untargeted gas chromatography-mass spectrometry-based metabolomics analysis of kidney and liver tissue from the Lewis Polycystic Kidney rat.J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Jun 15;1118-1119:25-32. doi: 10.1016/j.jchromb.2019.04.021. Epub 2019 Apr 12.
8	Mutation of the Mg2+ transporter SLC41A1 results in a nephronophthisis-like phenotype. J Am Soc Nephrol. 2013 May;24(6):967-77. doi: 10.1681/ASN.2012101034. Epub 2013 May 9.
9	Genotype-phenotype correlation in 440 patients with NPHP-related ciliopathies.Kidney Int. 2011 Dec;80(11):1239-45. doi: 10.1038/ki.2011.284. Epub 2011 Aug 24.
10	Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell. 2011 May 13;145(4):513-28. doi: 10.1016/j.cell.2011.04.019.
11	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.
12	Innate Immune Signaling Contributes to Tubular Cell Senescence in the Glis2 Knockout Mouse Model of Nephronophthisis.Am J Pathol. 2020 Jan;190(1):176-189. doi: 10.1016/j.ajpath.2019.09.013. Epub 2019 Oct 30.
13	Gli-similar proteins: their mechanisms of action, physiological functions, and roles in disease.Vitam Horm. 2012;88:141-71. doi: 10.1016/B978-0-12-394622-5.00007-9.
14	Patient-iPSC-Derived Kidney Organoids Show Functional Validation of a Ciliopathic Renal Phenotype and Reveal Underlying Pathogenetic Mechanisms.Am J Hum Genet. 2018 May 3;102(5):816-831. doi: 10.1016/j.ajhg.2018.03.014. Epub 2018 Apr 26.
15	Mutations in MAPKBP1 Cause Juvenile or Late-Onset Cilia-Independent Nephronophthisis. Am J Hum Genet. 2017 Feb 2;100(2):323-333. doi: 10.1016/j.ajhg.2016.12.011. Epub 2017 Jan 12.
16	PKHD1 sequence variations in 78 children and adults with autosomal recessive polycystic kidney disease and congenital hepatic fibrosis. Mol Genet Metab. 2010 Feb;99(2):160-73. doi: 10.1016/j.ymgme.2009.10.010. Epub 2009 Oct 20.
17	High-throughput mutation analysis in patients with a nephronophthisis-associated ciliopathy applying multiplexed barcoded array-based PCR amplification and next-generation sequencing.J Med Genet. 2012 Dec;49(12):756-67. doi: 10.1136/jmedgenet-2012-100973.
18	Mutations in TRAF3IP1/IFT54 reveal a new role for IFT proteins in microtubule stabilization. Nat Commun. 2015 Oct 21;6:8666. doi: 10.1038/ncomms9666.
19	Inactivation of Apoptosis Antagonizing Transcription Factor in tubular epithelial cells induces accumulation of DNA damage and nephronophthisis.Kidney Int. 2019 Apr;95(4):846-858. doi: 10.1016/j.kint.2018.10.034. Epub 2019 Feb 13.
20	Integration of Genetic Testing and Pathology for the Diagnosis of Adults with FSGS.Clin J Am Soc Nephrol. 2019 Feb 7;14(2):213-223. doi: 10.2215/CJN.08750718. Epub 2019 Jan 15.
21	Mutations of ADAMTS9 Cause Nephronophthisis-Related Ciliopathy. Am J Hum Genet. 2019 Jan 3;104(1):45-54. doi: 10.1016/j.ajhg.2018.11.003.
22	Metabolic Phenotyping of Anks3 Depletion in mIMCD-3 cells - a Putative Nephronophthisis Candidate.Sci Rep. 2018 Jun 13;8(1):9022. doi: 10.1038/s41598-018-27389-y.
23	Whole-exome sequencing identifies a novel compound heterozygous mutation of ANKS6 gene in a Chinese nephronophthisis patient.Clin Chim Acta. 2020 Feb;501:131-135. doi: 10.1016/j.cca.2019.10.030. Epub 2019 Oct 31.
24	Mutations in CSPP1 lead to classical Joubert syndrome. Am J Hum Genet. 2014 Jan 2;94(1):80-6. doi: 10.1016/j.ajhg.2013.11.015. Epub 2013 Dec 19.
25	Mutational analysis in 119 families with nephronophthisis.Pediatr Nephrol. 2007 Mar;22(3):366-70. doi: 10.1007/s00467-006-0334-9. Epub 2006 Oct 24.
26	Nephronophthisis due to a novel DCDC2 variant in a patient from African-Caribbean descent: A case report.Am J Med Genet A. 2020 Mar;182(3):527-531. doi: 10.1002/ajmg.a.61440. Epub 2019 Dec 10.
27	Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity.Kidney Int. 2016 Feb;89(2):468-475. doi: 10.1038/ki.2015.317.
28	Tubular cell loss in early inv/nphp2 mutant kidneys represents a possible homeostatic mechanism in cortical tubular formation.PLoS One. 2018 Jun 11;13(6):e0198580. doi: 10.1371/journal.pone.0198580. eCollection 2018.
29	Rescue of cone function in cone-only Nphp5 knockout mouse model with Leber congenital amaurosis phenotype.Mol Vis. 2018 Dec 30;24:834-846. eCollection 2018.
30	Loss of Glis2/NPHP7 causes kidney epithelial cell senescence and suppresses cyst growth in the Kif3a mouse model of cystic kidney disease.Kidney Int. 2016 Jun;89(6):1307-23. doi: 10.1016/j.kint.2016.03.006.
31	Atypical retinopathy in patients with nephronophthisis type 1: an uncommon ophthalmological finding.Clin Exp Ophthalmol. 2015 Jul;43(5):437-42. doi: 10.1111/ceo.12469. Epub 2015 Jan 14.
32	MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.PLoS Biol. 2016 Mar 16;14(3):e1002416. doi: 10.1371/journal.pbio.1002416. eCollection 2016 Mar.
33	Adult-Diagnosed Nonsyndromic Nephronophthisis in Australian Families Caused by Biallelic NPHP4 Variants.Am J Kidney Dis. 2020 Aug;76(2):282-287. doi: 10.1053/j.ajkd.2019.08.031. Epub 2019 Dec 4.
34	The genes and proteins associated with poly-cystic kidney diseases.Minerva Urol Nefrol. 2002 Dec;54(4):201-11.
35	Proteomic analysis of isolated chlamydomonas centrioles reveals orthologs of ciliary-disease genes.Curr Biol. 2005 Jun 21;15(12):1090-8. doi: 10.1016/j.cub.2005.05.024.
36	A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8.BMC Genomics. 2012 Aug 16;13:393. doi: 10.1186/1471-2164-13-393.
37	Interaction of nephrocystin-4 and RPGRIP1 is disrupted by nephronophthisis or Leber congenital amaurosis-associated mutations.Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18520-5. doi: 10.1073/pnas.0505774102. Epub 2005 Dec 9.
38	Expanding Phenotype of Nephronophthisis-Related Ciliopathy: an Elderly Patient with Homozygous RPGRIP1L Mutation.Nephron. 2018;140(1):74-78. doi: 10.1159/000490770. Epub 2018 Jul 10.
39	Mutations of CEP83 cause infantile nephronophthisis and intellectual disability. Am J Hum Genet. 2014 Jun 5;94(6):905-14. doi: 10.1016/j.ajhg.2014.05.002. Epub 2014 May 29.
40	Rapidly Progressive Nephronophthisis in a 2-Year-Old Boy with a Homozygous SDCCAG8 Mutation.Tohoku J Exp Med. 2019 Sep;249(1):29-32. doi: 10.1620/tjem.249.29.
41	Molecular cloning, expression, and chromosomal localization of a human tubulointerstitial nephritis antigen.Biochem Biophys Res Commun. 2000 Feb 5;268(1):225-30. doi: 10.1006/bbrc.2000.2103.
42	Nephronophthisis and retinal degeneration in tmem218-/- mice: a novel mouse model for Senior-L?ken syndrome?. Vet Pathol. 2015 May;52(3):580-95. doi: 10.1177/0300985814547392. Epub 2014 Aug 26.
43	Mutations in TTC21B cause different phenotypes in two childhood cases in China.Nephrology (Carlton). 2018 Apr;23(4):371-376. doi: 10.1111/nep.13008.