NPHP1
MCID: NPH019
MIFTS: 44

Nephronophthisis 1 (NPHP1)

Categories: Genetic diseases, Liver diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Nephronophthisis 1

MalaCards integrated aliases for Nephronophthisis 1:

Name: Nephronophthisis 1 58 12 76 30 6 15
Nphp1 58 12 76 56
Nephronophthisis, Familial Juvenile 58 74
Nephronophthisis 1, Juvenile 58 13
Nph1 58 12
Familial Juvenile Nephronophthisis 1 76
Juvenile Nephronophthisis 1 12

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
medial onset of end stage renal disease 13 years
allelic to senior-loken syndrome 1 and joubert syndrome 4


HPO:

33
nephronophthisis 1:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Nephronophthisis 1

OMIM : 58 Nephronophthisis is an autosomal recessive cystic kidney disease that leads to renal failure in childhood or adolescence. It is the most frequent genetic cause of renal failure in children. NPHP may be combined with extrarenal manifestations, such as liver fibrosis, situs inversus, or cardiac malformations. When nephronophthisis is combined with retinitis pigmentosa, the disorder is known as Senior-Loken syndrome (SLSN1; 266900); when it is combined with cerebellar vermis hypoplasia, the disorder is known as Joubert syndrome (JBTS1; 213300); and when it is combined with multiple developmental and neurologic abnormalities, the disorder is often known as Meckel-Gruber syndrome (MKS1; 249000). Because most NPHP gene products localize to the cilium or its associated structures, nephronophthisis and the related syndromes have been termed 'ciliopathies' (summary by Hoff et al., 2013). Clinical features of familial juvenile nephronophthisis include anemia, polyuria, polydipsia, isosthenuria, and death in uremia. Simms et al. (2009) provided a detailed review of nephronophthisis, including a discussion of clinical features and molecular genetics. (256100)

MalaCards based summary : Nephronophthisis 1, also known as nphp1, is related to apraxia and nephronophthisis 18, and has symptoms including polydipsia and polyuria. An important gene associated with Nephronophthisis 1 is NPHP1 (Nephrocystin 1), and among its related pathways/superpathways is Organelle biogenesis and maintenance. Affiliated tissues include kidney, and related phenotypes are hypertension and polydipsia

Disease Ontology : 12 A nephronophthisis that has material basis in homozygous or compound heterozygous mutation in or deletion of the NPHP1 gene on chromosome 2q13.

UniProtKB/Swiss-Prot : 76 Nephronophthisis 1: An autosomal recessive inherited disease characterized by anemia, polyuria, polydipsia, isosthenuria and death in uremia. Symmetrical destruction of the kidneys involving both tubules and glomeruli occurs. The underlying pathology is a chronic tubulo-interstitial nephropathy with characteristic tubular basement membrane thickening and medullary cyst formation. Associations with extrarenal symptoms, especially ocular lesions, are frequent. The age at death ranges from about 4 to 15 years.

Related Diseases for Nephronophthisis 1

Diseases in the Nephronophthisis family:

Nephronophthisis 1 Nephronophthisis 2
Nephronophthisis 3 Nephronophthisis 4
Nephronophthisis 7 Nephronophthisis 11
Nephronophthisis 12 Nephronophthisis 9
Nephronophthisis 13 Nephronophthisis 14
Nephronophthisis 15 Nephronophthisis 16
Nephronophthisis 18 Nephronophthisis 19
Nephronophthisis 20 Infantile Nephronophthisis
Juvenile Nephronophthisis Late-Onset Nephronophthisis

Diseases related to Nephronophthisis 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 56)
# Related Disease Score Top Affiliating Genes
1 apraxia 32.3 NPHP1 NPHP4
2 nephronophthisis 18 32.1 INVS NPHP1 NPHP3 NPHP4
3 nephronophthisis 9 32.0 INVS NPHP1 NPHP3 NPHP4
4 juvenile nephronophthisis 32.0 INVS NPHP1 NPHP3 NPHP4
5 nephronophthisis 4 31.9 NPHP1 NPHP4
6 nephronophthisis 19 31.8 NPHP1 NPHP4
7 retinal aplasia 31.8 NPHP1 NPHP4
8 joubert syndrome 6 31.8 AHI1 NPHP1
9 nephronophthisis 13 31.7 INVS NPHP1
10 nephronophthisis 3 31.7 NPHP1 NPHP3
11 senior-loken syndrome 1 31.7 AHI1 INVS NPHP1 NPHP3 NPHP4
12 joubert syndrome 2 31.7 APPL1 NPHP1
13 bardet-biedl syndrome 31.6 INVS NPHP1 NPHP4 PKD1
14 nephronophthisis 7 31.6 INVS NPHP1
15 joubert syndrome 3 31.4 AHI1 APPL1 NPHP1
16 polycystic liver disease 1 with or without kidney cysts 31.4 NPHP1 NPHP4 PKD1
17 chronic kidney failure 31.3 INVS NPHP1 PKD1
18 nephronophthisis 2 31.3 INVS NPHP1 NPHP3 NPHP4
19 nephronophthisis 11 31.2 AHI1 NPHP1 NPHP3 NPHP4
20 visceral heterotaxy 31.2 INVS NPHP1 NPHP3
21 leber congenital amaurosis 31.2 AHI1 NPHP1 NPHP3 NPHP4
22 cogan syndrome 31.1 APPL1 NPHP1 NPHP3 NPHP4
23 meckel syndrome, type 6 31.1 AHI1 INVS NPHP1 NPHP4
24 meckel syndrome, type 1 31.1 AHI1 INVS NPHP1 NPHP4
25 retinitis pigmentosa 30.8 AHI1 INVS NPHP1 NPHP3 NPHP4
26 cystic kidney disease 30.1 BCAR1 INVS NPHP1 NPHP3 NPHP4 PKD1
27 joubert syndrome 1 28.6 AHI1 APPL1 INVS NPHP1 NPHP3 NPHP4
28 nephronophthisis 28.0 AHI1 BCAR1 INVS NPHP1 NPHP3 NPHP4
29 joubert syndrome 4 12.0
30 nephronophthisis-like nephropathy 1 11.7
31 ocular motor apraxia 11.4
32 pontine tegmental cap dysplasia 11.4
33 medullary cystic kidney disease 1 11.4
34 kidney disease 11.2
35 nephronophthisis 20 11.1
36 hyperuricemic nephropathy, familial juvenile, 1 11.0
37 meckel syndrome, type 3 11.0
38 joubert syndrome 17 11.0
39 nephronophthisis 16 11.0
40 senior-loken syndrome 3 10.9
41 fundus dystrophy 10.9
42 joubert syndrome with renal anomalies 10.9
43 autism 10.1
44 autism spectrum disorder 10.1
45 infertility 10.1
46 bardet-biedl syndrome 13 10.0 AHI1 NPHP3
47 alacrima, achalasia, and mental retardation syndrome 10.0
48 bardet-biedl syndrome 2 10.0
49 bardet-biedl syndrome 10 10.0
50 bardet-biedl syndrome 11 10.0

Graphical network of the top 20 diseases related to Nephronophthisis 1:



Diseases related to Nephronophthisis 1

Symptoms & Phenotypes for Nephronophthisis 1

Human phenotypes related to Nephronophthisis 1:

33 (show all 12)
# Description HPO Frequency HPO Source Accession
1 hypertension 33 HP:0000822
2 polydipsia 33 HP:0001959
3 anemia 33 HP:0001903
4 growth delay 33 HP:0001510
5 nephronophthisis 33 HP:0000090
6 stage 5 chronic kidney disease 33 HP:0003774
7 tubular atrophy 33 HP:0000092
8 tubulointerstitial fibrosis 33 HP:0005576
9 hyposthenuria 33 HP:0003158
10 polyuria 33 HP:0000103
11 tubular basement membrane disintegration 33 HP:0005583
12 renal corticomedullary cysts 33 HP:0000108

Symptoms via clinical synopsis from OMIM:

58
Metabolic Features:
polydipsia
polyuria
absence of hypertension

Genitourinary Kidneys:
nephronophthisis
tubular atrophy
interstitial fibrosis
end stage renal disease
tubular basement membrane disintegration
more
Laboratory Abnormalities:
hyposthenuria (inability to concentrate urine normally)

Hematology:
anemia

Growth Other:
growth retardation

Clinical features from OMIM:

256100

UMLS symptoms related to Nephronophthisis 1:


polydipsia, polyuria

MGI Mouse Phenotypes related to Nephronophthisis 1:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.76 AHI1 APPL1 BCAR1 INVS NPHP1 NPHP3
2 cardiovascular system MP:0005385 9.73 APPL1 BCAR1 INVS NPHP3 NPHP4 PKD1
3 growth/size/body region MP:0005378 9.43 AHI1 APPL1 BCAR1 INVS NPHP3 PKD1
4 renal/urinary system MP:0005367 9.1 AHI1 INVS NPHP1 NPHP3 NPHP4 PKD1

Drugs & Therapeutics for Nephronophthisis 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome Completed NCT00873678
2 Nephronophthisis : Clinical and Genetic Study Completed NCT01022957 Not Applicable
3 Hereditary Tubulointerstitial Nephritis Completed NCT01312727 Not Applicable

Search NIH Clinical Center for Nephronophthisis 1

Genetic Tests for Nephronophthisis 1

Genetic tests related to Nephronophthisis 1:

# Genetic test Affiliating Genes
1 Nephronophthisis 1 30 NPHP1

Anatomical Context for Nephronophthisis 1

MalaCards organs/tissues related to Nephronophthisis 1:

42
Kidney

Publications for Nephronophthisis 1

Articles related to Nephronophthisis 1:

(show all 34)
# Title Authors Year
1
PKD1 mutation may epistatically ameliorate nephronophthisis progression in patients with NPHP1 deletion. ( 30847201 )
2019
2
Two novel homozygous mutations in NPHP1 lead to late onset end-stage renal disease: a case report of an adult nephronophthisis in a Chinese intermarriage family. ( 31096956 )
2019
3
Fluorescence in situ hybridization for the diagnosis of NPHP1 deletion-related nephronophthisis on renal biopsy. ( 29949740 )
2018
4
NPHP1 (Nephrocystin-1) Gene Deletions Cause Adult-Onset ESRD. ( 29654215 )
2018
5
Recurrent 2q13 microduplication encompassing MALL, NPHP1, RGPD6, and BUB1 associated with autism spectrum disorder, intellectual disability, and liver disorder. ( 28254236 )
2017
6
Whole-exome sequencing and digital PCR identified a novel compound heterozygous mutation in the NPHP1 gene in a case of Joubert syndrome and related disorders. ( 28347285 )
2017
7
QMPSF is sensitive and specific in the detection of NPHP1 heterozygous deletions. ( 28002029 )
2017
8
Identification of an NPHP1 deletion causing adult form of nephronophthisis. ( 26037636 )
2016
9
Copy number analysis of the low-copy repeats at the primate NPHP1 locus by array comparative genomic hybridization. ( 27222811 )
2016
10
Expression profiles of NPHP1 in the germ cells in the semen of men with male factor infertility. ( 26198798 )
2015
11
Comparative Genomic Analyses of the Human NPHP1 Locus Reveal Complex Genomic Architecture and Its Regional Evolution in Primates. ( 26641089 )
2015
12
Recurrent CNVs and SNVs at the NPHP1 locus contribute pathogenic alleles to Bardet-Biedl syndrome. ( 24746959 )
2014
13
Duplication of the NPHP1 gene in patients with autism spectrum disorder and normal intellectual ability: a case series. ( 25126106 )
2014
14
Congenital ocular motor apraxia, the NPHP1 gene, and surveillance for nephronophthisis. ( 23683649 )
2013
15
Clinical characterization and NPHP1 mutations in nephronophthisis and associated ciliopathies: a single center experience. ( 22982934 )
2012
16
Prevalence and incidence estimation of large NPHP1 homozygous deletion in Tunisian population. ( 22743096 )
2012
17
Pseudodominant inheritance of nephronophthisis caused by a homozygous NPHP1 deletion. ( 21258817 )
2011
18
Homozygous NPHP1 deletions in Egyptian children with nephronophthisis including an infantile onset patient. ( 20454808 )
2010
19
Pontine tegmental cap dysplasia with a 2q13 microdeletion involving the NPHP1 gene: insights into malformations of the mid-hindbrain. ( 20434703 )
2010
20
Targeted disruption of Nphp1 causes male infertility due to defects in the later steps of sperm morphogenesis in mice. ( 18684731 )
2008
21
DNA analysis of AHI1, NPHP1 and CYCLIN D1 in Joubert syndrome patients from the Netherlands. ( 18054307 )
2008
22
High NPHP1 and NPHP6 mutation rate in patients with Joubert syndrome and nephronophthisis: potential epistatic effect of NPHP6 and AHI1 mutations in patients with NPHP1 mutations. ( 17409309 )
2007
23
Nephronophthisis related to homozygous NPHP1 gene deletion as a cause of chronic renal failure in adults. ( 16782989 )
2006
24
Identification of a novel polymorphism--the duplication of the NPHP1 (nephronophthisis 1) gene. ( 16892302 )
2006
25
AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome. ( 16155189 )
2006
26
NPHP1 gene deletion is a rare cause of Joubert syndrome related disorders. ( 15689444 )
2005
27
The NPHP1 gene deletion associated with juvenile nephronophthisis is present in a subset of individuals with Joubert syndrome. ( 15138899 )
2004
28
Children with ocular motor apraxia type Cogan carry deletions in the gene (NPHP1) for juvenile nephronophthisis. ( 10839884 )
2000
29
Characterization of the NPHP1 locus: mutational mechanism involved in deletions in familial juvenile nephronophthisis. ( 10712196 )
2000
30
Construction of a gene map of the nephronophthisis type 1 (NPHP1) region on human chromosome 2q12-q13. ( 9479500 )
1998
31
Lack of large, homozygous deletions of the nephronophthisis 1 region in Joubert syndrome type B. APN Study Group. Arbeitsgemeinschaft für Pädiatrische Nephrologie. ( 9502560 )
1998
32
Renal-retinal syndromes: association of retinal anomalies and recessive nephronophthisis in patients with homozygous deletion of the NPH1 locus. ( 9856524 )
1998
33
A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1. ( 9326933 )
1997
34
Large homozygous deletions of the 2q13 region are a major cause of juvenile nephronophthisis. ( 8852662 )
1996

Variations for Nephronophthisis 1

UniProtKB/Swiss-Prot genetic disease variations for Nephronophthisis 1:

76
# Symbol AA change Variation ID SNP ID
1 NPHP1 p.Gly342Arg VAR_012160 rs121907899

ClinVar genetic disease variations for Nephronophthisis 1:

6 (show all 26)
# Gene Variation Type Significance SNP ID Assembly Location
1 NPHP1 NM_000272.3(NPHP1): c.1884+1G> T single nucleotide variant Pathogenic GRCh37 Chromosome 2, 110886762: 110886762
2 NPHP1 NM_000272.3(NPHP1): c.1884+1G> T single nucleotide variant Pathogenic GRCh38 Chromosome 2, 110129185: 110129185
3 NPHP1 NM_000272.3(NPHP1): c.80T> A (p.Leu27Ter) single nucleotide variant Pathogenic rs121907898 GRCh37 Chromosome 2, 110959061: 110959061
4 NPHP1 NM_000272.3(NPHP1): c.80T> A (p.Leu27Ter) single nucleotide variant Pathogenic rs121907898 GRCh38 Chromosome 2, 110201484: 110201484
5 NPHP1 NM_000272.3(NPHP1): c.1027G> A (p.Gly343Arg) single nucleotide variant Pathogenic rs121907899 GRCh37 Chromosome 2, 110920625: 110920625
6 NPHP1 NM_000272.3(NPHP1): c.1027G> A (p.Gly343Arg) single nucleotide variant Pathogenic rs121907899 GRCh38 Chromosome 2, 110163048: 110163048
7 NPHP1 NPHP1, DEL deletion Pathogenic
8 NPHP1 NM_000272.3(NPHP1): c.1184dupC (p.Leu396Serfs) duplication Pathogenic rs398123285 GRCh37 Chromosome 2, 110917771: 110917771
9 NPHP1 NM_000272.3(NPHP1): c.1184dupC (p.Leu396Serfs) duplication Pathogenic rs398123285 GRCh38 Chromosome 2, 110160194: 110160194
10 NPHP1 NM_000272.3(NPHP1): c.625-3dup duplication Conflicting interpretations of pathogenicity rs200118387 GRCh38 Chromosome 2, 110165163: 110165163
11 NPHP1 NM_000272.3(NPHP1): c.625-3dup duplication Conflicting interpretations of pathogenicity rs200118387 GRCh37 Chromosome 2, 110922740: 110922740
12 NPHP1 NM_000272.3(NPHP1): c.232T> C (p.Tyr78His) single nucleotide variant Conflicting interpretations of pathogenicity rs140446520 GRCh37 Chromosome 2, 110936097: 110936097
13 NPHP1 NM_000272.3(NPHP1): c.232T> C (p.Tyr78His) single nucleotide variant Conflicting interpretations of pathogenicity rs140446520 GRCh38 Chromosome 2, 110178520: 110178520
14 NPHP1 NM_000272.3(NPHP1): c.555dupA (p.Pro186Thrfs) duplication Pathogenic rs766524637 GRCh37 Chromosome 2, 110926098: 110926098
15 NPHP1 NM_000272.3(NPHP1): c.555dupA (p.Pro186Thrfs) duplication Pathogenic rs766524637 GRCh38 Chromosome 2, 110168521: 110168521
16 NPHP1 NM_000272.3(NPHP1): c.971T> C (p.Met324Thr) single nucleotide variant Uncertain significance rs114250691 GRCh37 Chromosome 2, 110920681: 110920681
17 NPHP1 NM_000272.3(NPHP1): c.971T> C (p.Met324Thr) single nucleotide variant Uncertain significance rs114250691 GRCh38 Chromosome 2, 110163104: 110163104
18 NPHP1 NM_000272.3(NPHP1): c.1333C> T (p.Arg445Cys) single nucleotide variant Uncertain significance rs375907280 GRCh38 Chromosome 2, 110148020: 110148020
19 NPHP1 NM_000272.3(NPHP1): c.1333C> T (p.Arg445Cys) single nucleotide variant Uncertain significance rs375907280 GRCh37 Chromosome 2, 110905597: 110905597
20 NPHP1 NM_000272.3(NPHP1): c.1529_1530del (p.Glu510Alafs) deletion Pathogenic rs1553484094 GRCh37 Chromosome 2, 110902137: 110902138
21 NPHP1 NM_000272.3(NPHP1): c.1529_1530del (p.Glu510Alafs) deletion Pathogenic rs1553484094 GRCh38 Chromosome 2, 110144560: 110144561
22 NPHP1 NC_000002.12: g.110095383_110217525del122143 deletion Pathogenic GRCh37 Chromosome 2, 110852960: 110975102
23 NPHP1 NC_000002.12: g.110095383_110217525del122143 deletion Pathogenic GRCh38 Chromosome 2, 110095383: 110217525
24 NPHP1 NM_000272.3(NPHP1): c.1520+1delG deletion Pathogenic rs747861275 GRCh38 Chromosome 2, 110146752: 110146752
25 NPHP1 NM_000272.3(NPHP1): c.1520+1delG deletion Pathogenic rs747861275 GRCh37 Chromosome 2, 110904329: 110904329
26 MALL; NPHP1 GRCh37/hg19 2q13(chr2: 110862477-110983703) copy number loss Pathogenic GRCh37 Chromosome 2, 110862477: 110983703

Expression for Nephronophthisis 1

Search GEO for disease gene expression data for Nephronophthisis 1.

Pathways for Nephronophthisis 1

Pathways related to Nephronophthisis 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.75 AHI1 NPHP1 NPHP3 NPHP4 PKD1

GO Terms for Nephronophthisis 1

Cellular components related to Nephronophthisis 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoskeleton GO:0005856 9.73 AHI1 INVS NPHP1 NPHP4
2 cell junction GO:0030054 9.62 AHI1 BCAR1 NPHP1 NPHP4
3 cell projection GO:0042995 9.43 AHI1 INVS NPHP1 NPHP3 NPHP4 PKD1
4 adherens junction GO:0005912 9.4 AHI1 NPHP1
5 photoreceptor connecting cilium GO:0032391 9.37 NPHP1 NPHP4
6 cell-cell junction GO:0005911 9.33 AHI1 NPHP1 NPHP4
7 non-motile cilium GO:0097730 9.26 AHI1 NPHP4
8 cilium GO:0005929 9.1 AHI1 INVS NPHP1 NPHP3 NPHP4 PKD1

Biological processes related to Nephronophthisis 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell-cell adhesion GO:0098609 9.54 NPHP1 NPHP4 PKD1
2 negative regulation of canonical Wnt signaling pathway GO:0090090 9.5 INVS NPHP3 NPHP4
3 insulin receptor signaling pathway GO:0008286 9.48 APPL1 BCAR1
4 retina development in camera-type eye GO:0060041 9.46 NPHP1 NPHP4
5 heart looping GO:0001947 9.43 AHI1 NPHP3
6 photoreceptor cell maintenance GO:0045494 9.4 NPHP3 NPHP4
7 ciliary basal body-plasma membrane docking GO:0097711 9.33 AHI1 NPHP1 NPHP4
8 photoreceptor cell outer segment organization GO:0035845 9.26 AHI1 NPHP4
9 visual behavior GO:0007632 8.96 NPHP1 NPHP4
10 positive regulation of bicellular tight junction assembly GO:1903348 8.62 NPHP1 NPHP4

Molecular functions related to Nephronophthisis 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.23 AHI1 APPL1 BCAR1 INVS NPHP1 NPHP3

Sources for Nephronophthisis 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
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45 MeSH
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47 MGI
50 NCI
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58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
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75 UMLS via Orphanet
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