NPHP4
MCID: NPH032
MIFTS: 38

Nephronophthisis 4 (NPHP4)

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

Aliases & Classifications for Nephronophthisis 4

MalaCards integrated aliases for Nephronophthisis 4:

Name: Nephronophthisis 4 58 12 76 30 13 6 15 74
Nphp4 58 12 76
Juvenile Nephronophthisis 4 12 76
Nephronophthisis 4, Juvenile 58
Nephronophthisis, Type 4 41

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
allelic to senior-loken syndrome 4


HPO:

33
nephronophthisis 4:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Nephronophthisis 4

UniProtKB/Swiss-Prot : 76 Nephronophthisis 4: An autosomal recessive inherited disease resulting in end-stage renal disease at age ranging between 6 and 35 years. It is a progressive tubulo-interstitial kidney disorder characterized by polydipsia, polyuria, anemia and growth retardation. The most prominent histological features are modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts.

MalaCards based summary : Nephronophthisis 4, also known as nphp4, is related to nephronophthisis 1 and juvenile nephronophthisis, and has symptoms including polydipsia and polyuria. An important gene associated with Nephronophthisis 4 is NPHP4 (Nephrocystin 4). Affiliated tissues include kidney, and related phenotypes are polydipsia and anemia

Disease Ontology : 12 A nephronophthisis that has material basis in mutation in the NPHP4 gene on chromosome 1p36.31.

Description from OMIM: 606966

Related Diseases for Nephronophthisis 4

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

(show all 32)
# Related Disease Score Top Affiliating Genes
1 nephronophthisis 1 31.9 NPHP1 NPHP4
2 juvenile nephronophthisis 31.9 NPHP1 NPHP4
3 nephronophthisis 2 31.8 NPHP1 NPHP4
4 cogan syndrome 31.8 NPHP1 NPHP4
5 nephronophthisis 19 31.8 NPHP1 NPHP4
6 senior-loken syndrome 1 31.8 NPHP1 NPHP4
7 retinal aplasia 31.7 NPHP1 NPHP4
8 nephronophthisis 18 31.7 NPHP1 NPHP4
9 nephronophthisis 11 31.7 NPHP1 NPHP4
10 nephronophthisis 9 31.7 NPHP1 NPHP4
11 meckel syndrome, type 6 31.6 NPHP1 NPHP4
12 cystic kidney disease 31.6 NPHP1 NPHP4
13 meckel syndrome, type 1 31.5 NPHP1 NPHP4
14 polycystic liver disease 1 with or without kidney cysts 31.4 NPHP1 NPHP4
15 joubert syndrome 1 31.2 NPHP1 NPHP4
16 infertility 11.6
17 senior-loken syndrome 4 11.4
18 retinitis pigmentosa 11.2
19 leber congenital amaurosis 11.2
20 renal fibrosis 11.2
21 joubert syndrome 14 11.1
22 nephronophthisis 14 11.1
23 joubert syndrome 20 11.1
24 bardet-biedl syndrome 11.1
25 renal dysplasia 11.1
26 infantile nephronophthisis 11.1
27 nephronophthisis 10.2
28 focal segmental glomerulosclerosis 1 10.1
29 focal segmental glomerulosclerosis 10.1
30 male infertility 10.1
31 apraxia 10.0 NPHP1 NPHP4
32 cone-rod dystrophy 2 9.9

Graphical network of the top 20 diseases related to Nephronophthisis 4:



Diseases related to Nephronophthisis 4

Symptoms & Phenotypes for Nephronophthisis 4

Human phenotypes related to Nephronophthisis 4:

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

Symptoms via clinical synopsis from OMIM:

58
Metabolic Features:
polydipsia
polyuria

Genitourinary Kidneys:
nephronophthisis
end stage renal disease (age 6-35 years)
interstitial cell infiltrate
renal tubular cell atrophy with corticomedullary cysts
renal interstitial fibrosis

Hematology:
anemia

Growth Other:
growth retardation

Clinical features from OMIM:

606966

UMLS symptoms related to Nephronophthisis 4:


polydipsia, polyuria

MGI Mouse Phenotypes related to Nephronophthisis 4:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 vision/eye MP:0005391 8.92 AQP3 NPHP1 NPHP4 PLXNA1

Drugs & Therapeutics for Nephronophthisis 4

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Nephronophthisis : Clinical and Genetic Study Completed NCT01022957 Not Applicable
2 Somatosensory Modulation of Salivary Gene Expression and Oral Feeding in Preterm Infants Recruiting NCT02696343 Not Applicable

Search NIH Clinical Center for Nephronophthisis 4

Genetic Tests for Nephronophthisis 4

Genetic tests related to Nephronophthisis 4:

# Genetic test Affiliating Genes
1 Nephronophthisis 4 30 NPHP4

Anatomical Context for Nephronophthisis 4

MalaCards organs/tissues related to Nephronophthisis 4:

42
Kidney

Publications for Nephronophthisis 4

Articles related to Nephronophthisis 4:

(show all 17)
# Title Authors Year
1
Renal histology and MRI in a 25-year-old Japanese man with nephronophthisis 4
. ( 29162218 )
2018
2
The polarity protein Inturned links NPHP4 to Daam1 to control the subapical actin network in multiciliated cells. ( 26644512 )
2015
3
NPHP4 mutation is linked to cerebello-oculo-renal syndrome and male infertility. ( 23574405 )
2014
4
Analysis of a deletion in the nephronophthisis 4 gene in different dog breeds. ( 23998563 )
2014
5
NPHP4 controls ciliary trafficking of membrane proteins and large soluble proteins at the transition zone. ( 25150219 )
2014
6
Diverse phenotypic expression of NPHP4 mutations in four siblings. ( 25818963 )
2014
7
NPHP4 variants are associated with pleiotropic heart malformations. ( 22550138 )
2012
8
Selective loss of RPGRIP1-dependent ciliary targeting of NPHP4, RPGR and SDCCAG8 underlies the degeneration of photoreceptor neurons. ( 22825473 )
2012
9
NPHP4 is necessary for normal photoreceptor ribbon synapse maintenance and outer segment formation, and for sperm development. ( 21078623 )
2011
10
NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway. ( 21555462 )
2011
11
The novel and independent association between single-point SNP of NPHP4 gene and renal function in non-diabetic Japanese population: the Takahata study. ( 20844548 )
2010
12
A deletion in nephronophthisis 4 (NPHP4) is associated with recessive cone-rod dystrophy in standard wire-haired dachshund. ( 18687878 )
2008
13
Novel mutations in NPHP4 in a consanguineous family with histological findings of focal segmental glomerulosclerosis. ( 17954299 )
2007
14
Mutational analysis of the NPHP4 gene in 250 patients with nephronophthisis. ( 15776426 )
2005
15
Effect of splice-site polymorphisms of the TMPRSS4, NPHP4 and ORCTL4 genes on their mRNA expression. ( 16131712 )
2005
16
Clinical and histological presentation of 3 siblings with mutations in the NPHP4 gene. ( 14750102 )
2004
17
The gene mutated in juvenile nephronophthisis type 4 encodes a novel protein that interacts with nephrocystin. ( 12244321 )
2002

Variations for Nephronophthisis 4

UniProtKB/Swiss-Prot genetic disease variations for Nephronophthisis 4:

76 (show all 14)
# Symbol AA change Variation ID SNP ID
1 NPHP4 p.Phe991Ser VAR_015186 rs28940891
2 NPHP4 p.Gly754Arg VAR_015214 rs373962831
3 NPHP4 p.Arg342Cys VAR_022529 rs190940697
4 NPHP4 p.Arg469Trp VAR_022530 rs758253306
5 NPHP4 p.Ala654Gly VAR_022534
6 NPHP4 p.Arg735Trp VAR_022535 rs191913664
7 NPHP4 p.Gln766Arg VAR_022538
8 NPHP4 p.Pro776Arg VAR_022539 rs201527181
9 NPHP4 p.His782Gln VAR_022540 rs143385204
10 NPHP4 p.Arg961His VAR_022543 rs183885357
11 NPHP4 p.Ala1098Thr VAR_022544 rs41280798
12 NPHP4 p.Arg1192Trp VAR_022545 rs139022622
13 NPHP4 p.Arg1284Cys VAR_022547 rs779755743
14 NPHP4 p.Gln1287Glu VAR_022548 rs201779243

ClinVar genetic disease variations for Nephronophthisis 4:

6 (show all 40)
# Gene Variation Type Significance SNP ID Assembly Location
1 NPHP4 NM_015102.4(NPHP4): c.2368G> T (p.Glu790Ter) single nucleotide variant Pathogenic rs137852918 GRCh37 Chromosome 1, 5947463: 5947463
2 NPHP4 NM_015102.4(NPHP4): c.2368G> T (p.Glu790Ter) single nucleotide variant Pathogenic rs137852918 GRCh38 Chromosome 1, 5887403: 5887403
3 NPHP4 NM_015102.4(NPHP4): c.2377C> T (p.Gln793Ter) single nucleotide variant Pathogenic rs137852919 GRCh37 Chromosome 1, 5947454: 5947454
4 NPHP4 NM_015102.4(NPHP4): c.2377C> T (p.Gln793Ter) single nucleotide variant Pathogenic rs137852919 GRCh38 Chromosome 1, 5887394: 5887394
5 NPHP4 NM_015102.4(NPHP4): c.2044C> T (p.Arg682Ter) single nucleotide variant Pathogenic/Likely pathogenic rs137852920 GRCh37 Chromosome 1, 5964776: 5964776
6 NPHP4 NM_015102.4(NPHP4): c.2044C> T (p.Arg682Ter) single nucleotide variant Pathogenic/Likely pathogenic rs137852920 GRCh38 Chromosome 1, 5904716: 5904716
7 NPHP4 NM_015102.4(NPHP4): c.2972T> C (p.Phe991Ser) single nucleotide variant Pathogenic rs28940891 GRCh37 Chromosome 1, 5935006: 5935006
8 NPHP4 NM_015102.4(NPHP4): c.2972T> C (p.Phe991Ser) single nucleotide variant Pathogenic rs28940891 GRCh38 Chromosome 1, 5874946: 5874946
9 NPHP4 NM_015102.4(NPHP4): c.3272delT (p.Val1091Glyfs) deletion Pathogenic GRCh38 Chromosome 1, 5873295: 5873295
10 NPHP4 NM_015102.4(NPHP4): c.3272delT (p.Val1091Glyfs) deletion Pathogenic GRCh37 Chromosome 1, 5933355: 5933355
11 NPHP4 NM_015102.4(NPHP4): c.1972C> T (p.Arg658Ter) single nucleotide variant Pathogenic rs137852923 GRCh37 Chromosome 1, 5964848: 5964848
12 NPHP4 NM_015102.4(NPHP4): c.1972C> T (p.Arg658Ter) single nucleotide variant Pathogenic rs137852923 GRCh38 Chromosome 1, 5904788: 5904788
13 NPHP4 NM_015102.4(NPHP4): c.3181G> A (p.Val1061Ile) single nucleotide variant Uncertain significance rs143020939 GRCh37 Chromosome 1, 5934581: 5934581
14 NPHP4 NM_015102.4(NPHP4): c.3181G> A (p.Val1061Ile) single nucleotide variant Uncertain significance rs143020939 GRCh38 Chromosome 1, 5874521: 5874521
15 NPHP4 NM_015102.3(NPHP4): c.271T> C (p.Phe91Leu) single nucleotide variant Uncertain significance rs201065230 GRCh37 Chromosome 1, 6038338: 6038338
16 NPHP4 NM_015102.3(NPHP4): c.271T> C (p.Phe91Leu) single nucleotide variant Uncertain significance rs201065230 GRCh38 Chromosome 1, 5978278: 5978278
17 NPHP4 NM_015102.4(NPHP4): c.4145G> A (p.Gly1382Glu) single nucleotide variant Uncertain significance rs773368924 GRCh37 Chromosome 1, 5923461: 5923461
18 NPHP4 NM_015102.4(NPHP4): c.4145G> A (p.Gly1382Glu) single nucleotide variant Uncertain significance rs773368924 GRCh38 Chromosome 1, 5863401: 5863401
19 NPHP4 NM_001291593.1(NPHP4): c.249_252delCTCC (p.Ser84Trpfs) deletion Likely pathogenic rs747699128 GRCh37 Chromosome 1, 5965516: 5965519
20 NPHP4 NM_001291593.1(NPHP4): c.249_252delCTCC (p.Ser84Trpfs) deletion Likely pathogenic rs747699128 GRCh38 Chromosome 1, 5905456: 5905459
21 NPHP4 NM_015102.4(NPHP4): c.1852G> A (p.Glu618Lys) single nucleotide variant Benign rs571655 GRCh37 Chromosome 1, 5965455: 5965455
22 NPHP4 NM_015102.4(NPHP4): c.1852G> A (p.Glu618Lys) single nucleotide variant Benign rs571655 GRCh38 Chromosome 1, 5905395: 5905395
23 NPHP4 NM_015102.4(NPHP4): c.2051A> G (p.Gln684Arg) single nucleotide variant Uncertain significance rs200667197 GRCh37 Chromosome 1, 5964769: 5964769
24 NPHP4 NM_015102.4(NPHP4): c.2051A> G (p.Gln684Arg) single nucleotide variant Uncertain significance rs200667197 GRCh38 Chromosome 1, 5904709: 5904709
25 NPHP4 NM_015102.4(NPHP4): c.2653A> C (p.Ser885Arg) single nucleotide variant Uncertain significance rs112206586 GRCh37 Chromosome 1, 5937317: 5937317
26 NPHP4 NM_015102.4(NPHP4): c.2653A> C (p.Ser885Arg) single nucleotide variant Uncertain significance rs112206586 GRCh38 Chromosome 1, 5877257: 5877257
27 NPHP4 NM_015102.4(NPHP4): c.4034G> A (p.Gly1345Asp) single nucleotide variant Uncertain significance rs200407553 GRCh37 Chromosome 1, 5924056: 5924056
28 NPHP4 NM_015102.4(NPHP4): c.4034G> A (p.Gly1345Asp) single nucleotide variant Uncertain significance rs200407553 GRCh38 Chromosome 1, 5863996: 5863996
29 NPHP4 NM_015102.4(NPHP4): c.257C> T (p.Pro86Leu) single nucleotide variant Uncertain significance rs201998215 GRCh37 Chromosome 1, 6038352: 6038352
30 NPHP4 NM_015102.4(NPHP4): c.257C> T (p.Pro86Leu) single nucleotide variant Uncertain significance rs201998215 GRCh38 Chromosome 1, 5978292: 5978292
31 NPHP4 NM_015102.4(NPHP4): c.2306A> T (p.His769Leu) single nucleotide variant Uncertain significance rs200821373 GRCh38 Chromosome 1, 5887465: 5887465
32 NPHP4 NM_015102.4(NPHP4): c.2306A> T (p.His769Leu) single nucleotide variant Uncertain significance rs200821373 GRCh37 Chromosome 1, 5947525: 5947525
33 NPHP4 NM_015102.4(NPHP4): c.3292G> A (p.Ala1098Thr) single nucleotide variant Uncertain significance rs41280798 GRCh37 Chromosome 1, 5933335: 5933335
34 NPHP4 NM_015102.4(NPHP4): c.3292G> A (p.Ala1098Thr) single nucleotide variant Uncertain significance rs41280798 GRCh38 Chromosome 1, 5873275: 5873275
35 NPHP4 NM_015102.4(NPHP4): c.254C> T (p.Pro85Leu) single nucleotide variant Uncertain significance rs200272048 GRCh37 Chromosome 1, 6038355: 6038355
36 NPHP4 NM_015102.4(NPHP4): c.254C> T (p.Pro85Leu) single nucleotide variant Uncertain significance rs200272048 GRCh38 Chromosome 1, 5978295: 5978295
37 NPHP4 NM_015102.4(NPHP4): c.3175G> A (p.Ala1059Thr) single nucleotide variant Uncertain significance rs202004152 GRCh37 Chromosome 1, 5934587: 5934587
38 NPHP4 NM_015102.4(NPHP4): c.3175G> A (p.Ala1059Thr) single nucleotide variant Uncertain significance rs202004152 GRCh38 Chromosome 1, 5874527: 5874527
39 NPHP4 NM_015102.4(NPHP4): c.946C> T (p.Arg316Cys) single nucleotide variant Uncertain significance rs761345213 GRCh38 Chromosome 1, 5948116: 5948116
40 NPHP4 NM_015102.4(NPHP4): c.946C> T (p.Arg316Cys) single nucleotide variant Uncertain significance rs761345213 GRCh37 Chromosome 1, 6008176: 6008176

Expression for Nephronophthisis 4

Search GEO for disease gene expression data for Nephronophthisis 4.

Pathways for Nephronophthisis 4

GO Terms for Nephronophthisis 4

Cellular components related to Nephronophthisis 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 bicellular tight junction GO:0005923 9.16 NPHP1 NPHP4
2 photoreceptor connecting cilium GO:0032391 8.96 NPHP1 NPHP4
3 cell-cell junction GO:0005911 8.8 AQP3 NPHP1 NPHP4

Biological processes related to Nephronophthisis 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 actin cytoskeleton organization GO:0030036 9.4 NPHP1 NPHP4
2 cell-cell adhesion GO:0098609 9.37 NPHP1 NPHP4
3 ciliary basal body-plasma membrane docking GO:0097711 9.32 NPHP1 NPHP4
4 retina development in camera-type eye GO:0060041 9.26 NPHP1 NPHP4
5 excretion GO:0007588 9.16 AQP3 NPHP1
6 visual behavior GO:0007632 8.96 NPHP1 NPHP4
7 positive regulation of bicellular tight junction assembly GO:1903348 8.62 NPHP1 NPHP4

Sources for Nephronophthisis 4

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
43 MedGen
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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