NPHP2
MCID: NPH030
MIFTS: 45

Nephronophthisis 2 (NPHP2)

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

Aliases & Classifications for Nephronophthisis 2

MalaCards integrated aliases for Nephronophthisis 2:

Name: Nephronophthisis 2 58 12 76 15 74
Nphp2 58 12 76 56
Nephronophthisis 2, Infantile 58 13
Nph2 58 12
Infantile Nephronophthisis 2 12
Infantile Nephronophthisis 76
Nephronophthisis, Type 2 41

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
neonatal death secondary to pulmonary insufficiency


HPO:

33
nephronophthisis 2:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Nephronophthisis 2

UniProtKB/Swiss-Prot : 76 Nephronophthisis 2: An autosomal recessive disorder resulting in end-stage renal disease. It is characterized by early onset and rapid progression. Phenotypic manifestations include enlarged kidneys, chronic tubulo-interstitial nephritis, anemia, hyperkalemic metabolic acidosis. Some patients also display situs inversus. Pathologically, it differs from later-onset nephronophthisis by the absence of medullary cysts and thickened tubular basement membranes, and by the presence of cortical microcysts.

MalaCards based summary : Nephronophthisis 2, also known as nphp2, is related to infantile nephronophthisis and juvenile nephronophthisis. An important gene associated with Nephronophthisis 2 is INVS (Inversin), and among its related pathways/superpathways are Regulation of PLK1 Activity at G2/M Transition and Organelle biogenesis and maintenance. The drugs Zinc and Benzoyl peroxide have been mentioned in the context of this disorder. Affiliated tissues include kidney, and related phenotypes are situs inversus totalis and hypertension

Disease Ontology : 12 A nephronophthisis that has material basis in homozygous or compound heterozygous mutation in the INVS gene on chromosome 9q31.

Description from OMIM: 602088

Related Diseases for Nephronophthisis 2

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 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 39)
# Related Disease Score Top Affiliating Genes
1 infantile nephronophthisis 31.3 INVS NEK8 NPHP3 NPHP4
2 juvenile nephronophthisis 31.2 INVS IQCB1 NPHP1 NPHP3 NPHP4
3 nephronophthisis 3 30.3 NPHP1 NPHP3
4 nephronophthisis 30.1 INVS IQCB1 MKS1 NEK8 NEK9 NPHP1
5 nephronophthisis 18 28.6 INVS IQCB1 NEK8 NEK9 NPHP1 NPHP3
6 joubert syndrome 1 28.4 B9D2 INVS IQCB1 MKS1 NPHP1 NPHP3
7 nephronophthisis 13 10.3 INVS NPHP1
8 nephrotic syndrome 10.2
9 nephronophthisis 19 10.2 NPHP1 NPHP4
10 nephronophthisis 7 10.1 INVS NPHP1
11 nephronophthisis 4 10.1 NPHP1 NPHP4
12 joubert syndrome 14 10.1 B9D2 NPHP4
13 visceral heterotaxy 10.1 INVS NPHP1 NPHP3
14 meckel syndrome, type 5 10.1 B9D2 NPHP4
15 cogan syndrome 10.0 NPHP1 NPHP3 NPHP4
16 renal fibrosis 10.0
17 situs inversus 10.0
18 nephronophthisis 16 10.0 IQCB1 NPHP1
19 alacrima, achalasia, and mental retardation syndrome 10.0
20 polycystic liver disease 1 with or without kidney cysts 10.0 NPHP1 NPHP4
21 retinal aplasia 10.0 IQCB1 NPHP1 NPHP4
22 meckel syndrome, type 7 10.0 MKS1 NPHP3
23 joubert syndrome 6 9.9 MKS1 NPHP1
24 nephronophthisis 1 9.9 INVS NPHP1 NPHP3 NPHP4
25 apraxia 9.9 NPHP1 NPHP4
26 meckel syndrome, type 2 9.8 B9D2 MKS1
27 nephronophthisis 11 9.8 IQCB1 NPHP1 NPHP3 NPHP4
28 bardet-biedl syndrome 13 9.8 MKS1 NPHP3
29 leber congenital amaurosis 9.8 IQCB1 NPHP1 NPHP3 NPHP4
30 chronic kidney failure 9.7 INVS MKS1 NPHP1
31 meckel syndrome, type 3 9.7 B9D2 MKS1 NPHP1
32 renal-hepatic-pancreatic dysplasia 9.7 INVS IQCB1 NEK8 NPHP3
33 bardet-biedl syndrome 9.6 INVS MKS1 NPHP1 NPHP4
34 retinitis pigmentosa 9.5 INVS IQCB1 NPHP1 NPHP3 NPHP4
35 nephronophthisis 9 9.3 INVS NEK8 NEK9 NPHP1 NPHP3 NPHP4
36 meckel syndrome, type 6 9.3 B9D2 INVS MKS1 NPHP1 NPHP4
37 cystic kidney disease 9.3 INVS NEK8 NEK9 NPHP1 NPHP3 NPHP4
38 meckel syndrome, type 1 9.0 B9D2 INVS IQCB1 MKS1 NPHP1 NPHP4
39 senior-loken syndrome 1 8.9 INVS IQCB1 MKS1 NEK9 NPHP1 NPHP3

Graphical network of the top 20 diseases related to Nephronophthisis 2:



Diseases related to Nephronophthisis 2

Symptoms & Phenotypes for Nephronophthisis 2

Human phenotypes related to Nephronophthisis 2:

33 (show all 17)
# Description HPO Frequency HPO Source Accession
1 situs inversus totalis 33 occasional (7.5%) HP:0001696
2 hypertension 33 HP:0000822
3 respiratory insufficiency 33 HP:0002093
4 respiratory failure 33 HP:0002878
5 elevated serum creatinine 33 HP:0003259
6 oligohydramnios 33 HP:0001562
7 nephronophthisis 33 HP:0000090
8 enlarged kidney 33 HP:0000105
9 pulmonary hypoplasia 33 HP:0002089
10 hyperkalemia 33 HP:0002153
11 stage 5 chronic kidney disease 33 HP:0003774
12 pulmonary insufficiency 33 HP:0010444
13 hyperechogenic kidneys 33 HP:0004719
14 hyperkalemic metabolic acidosis 33 HP:0005976
15 renal cortical microcysts 33 HP:0004734
16 chronic tubulointerstitial nephritis 33 HP:0004743
17 absence of renal corticomedullary differentiation 33 HP:0005564

Symptoms via clinical synopsis from OMIM:

58
Cardiovascular Vascular:
hypertension

Laboratory Abnormalities:
elevated serum creatinine
hyperkalemia

Metabolic Features:
hyperkalemic metabolic acidosis

Abdomen:
situs inversus (in some patients)

Respiratory Lung:
respiratory failure
pulmonary hypoplasia

Prenatal Manifestations Amniotic Fluid:
oligohydramnios

Genitourinary Kidneys:
cortical microcysts
renal failure by age 3
enlarged, hyperechogenic kidneys (ultrasound)
chronic tubulointerstitial nephritis
absence of corticomedullary differentiation (ultrasound)
more

Clinical features from OMIM:

602088

MGI Mouse Phenotypes related to Nephronophthisis 2:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.43 B9D2 INVS MKS1 NEK8 NPHP3 NPHP4
2 renal/urinary system MP:0005367 9.23 B9D2 HAL INVS MKS1 NEK8 NPHP1

Drugs & Therapeutics for Nephronophthisis 2

Drugs for Nephronophthisis 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 11)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Zinc Approved, Investigational Not Applicable 7440-66-6 32051
2
Benzoyl peroxide Approved Not Applicable 94-36-0 7187
3
Insulin glargine Approved Not Applicable 160337-95-1
4
Insulin Aspart Approved Not Applicable 116094-23-6 16132418
5 Protamines Not Applicable
6 Isophane insulin, beef Not Applicable
7 Isophane Insulin, Human Not Applicable
8 insulin Not Applicable
9 Insulin, Isophane Not Applicable
10 Hypoglycemic Agents Not Applicable
11 Insulin, Globin Zinc Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of The Association of Mutations in The NPHS2 Gene and Nephrotic Syndrome in Children and Adults in Middle East Active, not recruiting NCT03326037
2 Urinary Aquaporin 2 and Expression of the NPHS2 Gene in Adults Suffering From Nephrotic Syndrome Completed NCT00286910
3 Nephronophthisis : Clinical and Genetic Study Completed NCT01022957 Not Applicable
4 The Inova Type 2 Diabetes Mellitus Study Withdrawn NCT02222623 Not Applicable Glargine;NPH
5 Cardiomyopathy in Steroid-resistant Nephrotic Syndrome: Impact of Focal Segmental Glomerulosclerosis Terminated NCT00883636

Search NIH Clinical Center for Nephronophthisis 2

Genetic Tests for Nephronophthisis 2

Anatomical Context for Nephronophthisis 2

MalaCards organs/tissues related to Nephronophthisis 2:

42
Kidney

Publications for Nephronophthisis 2

Articles related to Nephronophthisis 2:

(show all 16)
# Title Authors Year
1
Transplantation for infantile nephronophthisis with loss-of-function mutation in NPHP3: Lesson from a case. ( 29869359 )
2018
2
Tubular cell loss in early inv/nphp2 mutant kidneys represents a possible homeostatic mechanism in cortical tubular formation. ( 29889867 )
2018
3
A familial case of severe infantile nephronophthisis explained by oligogenic inheritance. ( 28392475 )
2017
4
High mutation rate of NPHP3 in 18 Chinese infantile nephronophthisis patients. ( 26184788 )
2016
5
Structural basis of the Inv compartment and ciliary abnormalities in Inv/nphp2 mutant mice. ( 26615802 )
2016
6
Mutations of CEP83 cause infantile nephronophthisis and intellectual disability. ( 24882706 )
2014
7
Broadening the ciliopathy spectrum: motile cilia dyskinesia, and nephronophthisis associated with a previously unreported homozygous mutation in the INVS/NPHP2 gene. ( 23713026 )
2013
8
The nephronophthisis gene product NPHP2/Inversin interacts with Aurora A and interferes with HDAC6-mediated cilia disassembly. ( 24026243 )
2013
9
Inhibition of the p38 MAPK pathway ameliorates renal fibrosis in an NPHP2 mouse model. ( 22076433 )
2012
10
The ciliary protein Nek8/Nphp9 acts downstream of Inv/Nphp2 during pronephros morphogenesis and left-right establishment in zebrafish. ( 22687244 )
2012
11
Mutations of NPHP2 and NPHP3 in infantile nephronophthisis. ( 19177160 )
2009
12
Association of INVS (NPHP2) mutation in an adolescent exhibiting nephronophthisis (NPH) and complete situs inversus. ( 18218308 )
2008
13
Lack of NPHP2 mutations in a newborn infant with Joubert syndrome-related disorder presenting as end-stage renal disease. ( 17216245 )
2007
14
Renal cysts of inv/inv mice resemble early infantile nephronophthisis. ( 15213262 )
2004
15
A Bedouin kindred with infantile nephronophthisis demonstrates linkage to chromosome 9 by homozygosity mapping. ( 9792867 )
1998
16
Infantile nephronophthisis. ( 3449470 )
1987

Variations for Nephronophthisis 2

UniProtKB/Swiss-Prot genetic disease variations for Nephronophthisis 2:

76
# Symbol AA change Variation ID SNP ID
1 INVS p.Pro482Arg VAR_022822
2 INVS p.Leu493Ser VAR_022823 rs121964995

ClinVar genetic disease variations for Nephronophthisis 2:

6 (show all 27)
# Gene Variation Type Significance SNP ID Assembly Location
1 INVS NM_014425.4(INVS): c.1807C> T (p.Arg603Ter) single nucleotide variant Pathogenic rs121964994 GRCh37 Chromosome 9, 103046624: 103046624
2 INVS NM_014425.4(INVS): c.1807C> T (p.Arg603Ter) single nucleotide variant Pathogenic rs121964994 GRCh38 Chromosome 9, 100284342: 100284342
3 INVS NM_014425.4(INVS): c.1478T> C (p.Leu493Ser) single nucleotide variant Pathogenic rs121964995 GRCh37 Chromosome 9, 103027117: 103027117
4 INVS NM_014425.4(INVS): c.1478T> C (p.Leu493Ser) single nucleotide variant Pathogenic rs121964995 GRCh38 Chromosome 9, 100264835: 100264835
5 INVS NM_014425.4(INVS): c.2719C> T (p.Arg907Ter) single nucleotide variant Pathogenic rs267607185 GRCh37 Chromosome 9, 103055258: 103055258
6 INVS NM_014425.4(INVS): c.2719C> T (p.Arg907Ter) single nucleotide variant Pathogenic rs267607185 GRCh38 Chromosome 9, 100292976: 100292976
7 INVS NM_014425.4(INVS): c.2695C> T (p.Arg899Ter) single nucleotide variant Pathogenic rs200844390 GRCh37 Chromosome 9, 103055234: 103055234
8 INVS NM_014425.4(INVS): c.2695C> T (p.Arg899Ter) single nucleotide variant Pathogenic rs200844390 GRCh38 Chromosome 9, 100292952: 100292952
9 INVS NM_014425.5(INVS): c.1453del (p.Gln485Lysfs) deletion Pathogenic GRCh37 Chromosome 9, 103015407: 103015407
10 INVS NM_014425.5(INVS): c.1453del (p.Gln485Lysfs) deletion Pathogenic GRCh38 Chromosome 9, 100253125: 100253125
11 INVS NM_014425.4(INVS): c.1235-5T> C single nucleotide variant Benign rs2245216 GRCh37 Chromosome 9, 103015184: 103015184
12 INVS NM_014425.4(INVS): c.1235-5T> C single nucleotide variant Benign rs2245216 GRCh38 Chromosome 9, 100252902: 100252902
13 INVS NM_014425.4(INVS): c.2412T> C (p.Ser804=) single nucleotide variant Benign rs2787374 GRCh37 Chromosome 9, 103054951: 103054951
14 INVS NM_014425.4(INVS): c.2412T> C (p.Ser804=) single nucleotide variant Benign rs2787374 GRCh38 Chromosome 9, 100292669: 100292669
15 INVS NM_014425.4(INVS): c.2776G> A (p.Ala926Thr) single nucleotide variant Uncertain significance rs374891838 GRCh37 Chromosome 9, 103055315: 103055315
16 INVS NM_014425.4(INVS): c.2776G> A (p.Ala926Thr) single nucleotide variant Uncertain significance rs374891838 GRCh38 Chromosome 9, 100293033: 100293033
17 INVS NM_014425.4(INVS): c.2310C> T (p.His770=) single nucleotide variant Conflicting interpretations of pathogenicity rs116606949 GRCh37 Chromosome 9, 103054849: 103054849
18 INVS NM_014425.4(INVS): c.2310C> T (p.His770=) single nucleotide variant Conflicting interpretations of pathogenicity rs116606949 GRCh38 Chromosome 9, 100292567: 100292567
19 INVS NM_014425.4(INVS): c.3017-5T> G single nucleotide variant Benign/Likely benign rs201018893 GRCh37 Chromosome 9, 103060213: 103060213
20 INVS NM_014425.4(INVS): c.3017-5T> G single nucleotide variant Benign/Likely benign rs201018893 GRCh38 Chromosome 9, 100297931: 100297931
21 INVS NM_014425.4(INVS): c.662dupG (p.Arg222Serfs) duplication Pathogenic rs769739938 GRCh37 Chromosome 9, 103002388: 103002388
22 INVS NM_014425.4(INVS): c.662dupG (p.Arg222Serfs) duplication Pathogenic rs769739938 GRCh38 Chromosome 9, 100240106: 100240106
23 INVS NC_000009.11 deletion Likely pathogenic GRCh37 Chromosome 9, 102814578: 102968415
24 INVS NM_014425.4(INVS): c.2386C> G (p.Gln796Glu) single nucleotide variant Uncertain significance rs147731667 GRCh38 Chromosome 9, 100292643: 100292643
25 INVS NM_014425.4(INVS): c.2386C> G (p.Gln796Glu) single nucleotide variant Uncertain significance rs147731667 GRCh37 Chromosome 9, 103054925: 103054925
26 INVS NM_014425.4(INVS): c.284G> A (p.Arg95His) single nucleotide variant Uncertain significance rs372088206 GRCh37 Chromosome 9, 102988354: 102988354
27 INVS NM_014425.4(INVS): c.284G> A (p.Arg95His) single nucleotide variant Uncertain significance rs372088206 GRCh38 Chromosome 9, 100226072: 100226072

Expression for Nephronophthisis 2

Search GEO for disease gene expression data for Nephronophthisis 2.

Pathways for Nephronophthisis 2

GO Terms for Nephronophthisis 2

Cellular components related to Nephronophthisis 2 according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 centrosome GO:0005813 9.77 B9D2 IQCB1 MKS1 NEK9 NPHP4
2 cytoskeleton GO:0005856 9.7 B9D2 INVS IQCB1 MKS1 NEK8 NPHP1
3 ciliary basal body GO:0036064 9.61 B9D2 MKS1 NPHP4
4 photoreceptor connecting cilium GO:0032391 9.5 IQCB1 NPHP1 NPHP4
5 cell projection GO:0042995 9.5 B9D2 INVS MKS1 NEK8 NPHP1 NPHP3
6 ciliary base GO:0097546 9.49 NEK8 NPHP4
7 ciliary transition zone GO:0035869 9.43 B9D2 MKS1 NPHP4
8 MKS complex GO:0036038 9.4 B9D2 MKS1
9 cilium GO:0005929 9.17 B9D2 INVS MKS1 NEK8 NPHP1 NPHP3
10 cytoplasm GO:0005737 10.11 B9D2 HAL INVS IQCB1 MKS1 NEK8
11 cytosol GO:0005829 10.08 B9D2 HAL IQCB1 MKS1 NEK9 NPHP1

Biological processes related to Nephronophthisis 2 according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of canonical Wnt signaling pathway GO:0090090 9.65 INVS NPHP3 NPHP4
2 determination of left/right symmetry GO:0007368 9.63 MKS1 NEK8 NPHP3
3 cilium assembly GO:0060271 9.62 B9D2 IQCB1 MKS1 NPHP3
4 retina development in camera-type eye GO:0060041 9.49 NPHP1 NPHP4
5 cell projection organization GO:0030030 9.46 B9D2 IQCB1 MKS1 NPHP1
6 maintenance of animal organ identity GO:0048496 9.43 IQCB1 NPHP3
7 regulation of Wnt signaling pathway, planar cell polarity pathway GO:2000095 9.4 MKS1 NPHP3
8 visual behavior GO:0007632 9.37 NPHP1 NPHP4
9 positive regulation of bicellular tight junction assembly GO:1903348 9.26 NPHP1 NPHP4
10 photoreceptor cell maintenance GO:0045494 9.13 IQCB1 NPHP3 NPHP4
11 ciliary basal body-plasma membrane docking GO:0097711 9.02 B9D2 IQCB1 MKS1 NPHP1 NPHP4

Sources for Nephronophthisis 2

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
39 LifeMap
41 LOVD
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45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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