NPHS4
MCID: NPH047
MIFTS: 32

Nephrotic Syndrome, Type 4 (NPHS4)

Categories: Blood diseases, Endocrine diseases, Genetic diseases, Immune diseases, Metabolic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Nephrotic Syndrome, Type 4

MalaCards integrated aliases for Nephrotic Syndrome, Type 4:

Name: Nephrotic Syndrome, Type 4 56 13 39 71
Nphs4 56 73
Isolated Diffuse Mesangial Sclerosis 73
Nephrotic Syndrome Type 4 12
Nephrotic Syndrome 4 73

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
onset in early childhood


HPO:

31
nephrotic syndrome, type 4:
Inheritance autosomal dominant inheritance autosomal recessive inheritance
Onset and clinical course progressive childhood onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0080383
OMIM 56 256370
OMIM Phenotypic Series 56 PS256300
MeSH 43 D009404
UMLS 71 C3151568

Summaries for Nephrotic Syndrome, Type 4

UniProtKB/Swiss-Prot : 73 Nephrotic syndrome 4: A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non- specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. Most patients with NPHS4 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen.

MalaCards based summary : Nephrotic Syndrome, Type 4, also known as nphs4, is related to diffuse mesangial sclerosis and denys-drash syndrome. An important gene associated with Nephrotic Syndrome, Type 4 is WT1 (WT1 Transcription Factor). The drugs Angiotensin II and Irbesartan have been mentioned in the context of this disorder. Affiliated tissues include kidney, and related phenotypes are focal segmental glomerulosclerosis and renal insufficiency

Disease Ontology : 12 A familial nephrotic syndrome that has material basis in heterozygous mutation in the WT1 gene on chromosome 11p13.

OMIM : 56 Nephrotic syndrome, a malfunction of the glomerular filter, leads to proteinuria, edema, and, in steroid-resistant nephrotic syndrome, end-stage renal disease (ESRD). Renal histopathology in NPHS4 due to WT1 mutations most often shows diffuse mesangial sclerosis (DMS), but can also show focal segmental glomerulosclerosis (FSGS). Both of these terms refer to pathologic findings and may be associated with the same clinical phenotype, namely nephrotic syndrome (review by Schumacher et al., 1998). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300). (256370)

Related Diseases for Nephrotic Syndrome, Type 4

Graphical network of the top 20 diseases related to Nephrotic Syndrome, Type 4:



Diseases related to Nephrotic Syndrome, Type 4

Symptoms & Phenotypes for Nephrotic Syndrome, Type 4

Human phenotypes related to Nephrotic Syndrome, Type 4:

31
# Description HPO Frequency HPO Source Accession
1 focal segmental glomerulosclerosis 31 occasional (7.5%) HP:0000097
2 renal insufficiency 31 HP:0000083
3 nephrotic syndrome 31 HP:0000100
4 nephroblastoma 31 HP:0002667
5 diffuse mesangial sclerosis 31 HP:0001967

Symptoms via clinical synopsis from OMIM:

56
Genitourinary Kidneys:
nephrotic syndrome
diffuse mesangial sclerosis
renal failure
focal segmental glomerulosclerosis (less common)

Clinical features from OMIM:

256370

Drugs & Therapeutics for Nephrotic Syndrome, Type 4

Drugs for Nephrotic Syndrome, Type 4 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Angiotensin II Approved, Investigational Early Phase 1 68521-88-0, 4474-91-3, 11128-99-7 172198
2
Irbesartan Approved, Investigational Early Phase 1 138402-11-6 3749
3 Antihypertensive Agents Early Phase 1
4 Angiotensin II Type 1 Receptor Blockers Early Phase 1
5 Angiotensin Receptor Antagonists Early Phase 1
6 Giapreza Early Phase 1
7 Angiotensinogen Early Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Randomized, Double-blind, Parallel-controlled, Multi-center Clinical Trial of HuangKui Capsule to Treat Diabetic Kidney Disease Unknown status NCT03016832 Early Phase 1 Placebo drug that simulates Irbesartan tablets;irbesartan tablets;Placebo drug that simulates HuangKui capsule;HuangKui Capsule
2 Assessment of the Educational Experience for Patients With Newly Diagnosed Nephrotic Syndrome Completed NCT02190955

Search NIH Clinical Center for Nephrotic Syndrome, Type 4

Genetic Tests for Nephrotic Syndrome, Type 4

Anatomical Context for Nephrotic Syndrome, Type 4

MalaCards organs/tissues related to Nephrotic Syndrome, Type 4:

40
Kidney

Publications for Nephrotic Syndrome, Type 4

Articles related to Nephrotic Syndrome, Type 4:

(show all 19)
# Title Authors PMID Year
1
Spectrum of early onset nephrotic syndrome associated with WT1 missense mutations. 56 6
9607189 1998
2
Identification of constitutional WT1 mutations, in patients with isolated diffuse mesangial sclerosis, and analysis of genotype/phenotype correlations by use of a computerized mutation database. 56 6
9529364 1998
3
WT1 mutations in Meacham syndrome suggest a coelomic mesothelial origin of the cardiac and diaphragmatic malformations. 6
17853480 2007
4
An unusual phenotype of Frasier syndrome due to IVS9 +4C>T mutation in the WT1 gene: predominantly male ambiguous genitalia and absence of gonadal dysgenesis. 6
12050205 2002
5
Isolated diffuse mesangial sclerosis and Wilms tumor suppressor gene. 56
11241056 2001
6
The same mutation affecting the splicing of WT1 gene is present on Frasier syndrome patients with or without Wilms' tumor. 6
10094551 1999
7
Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms. 6
9499425 1998
8
Donor splice-site mutations in WT1 are responsible for Frasier syndrome. 6
9398852 1997
9
A clinical overview of WT1 gene mutations. 6
9090524 1997
10
Inherited WT1 mutation in Denys-Drash syndrome. 6
1327525 1992
11
Constitutional mutations in the WT1 gene in patients with Denys-Drash syndrome. 6
1338906 1992
12
Germline intronic and exonic mutations in the Wilms' tumour gene (WT1) affecting urogenital development. 6
1302008 1992
13
Alternative splicing and genomic structure of the Wilms tumor gene WT1. 6
1658787 1991
14
Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. 6
1655284 1991
15
Glomerulonephritis associated with male pseudohermaphroditism and nephroblastoma. 6
6307071 1983
16
Familial early-onset nephrotic syndrome: diffuse mesangial sclerosis. Clinico-pathological study of a kindred. 56
7180443 1982
17
[Heterogeneity of early onset nephrotic syndromes in infants (nephrotic syndrome "in infants"). Anatomical, clinical and genetic study of 37 cases]. 56
4706144 1973
18
Urinary proteome signature of Renal Cysts and Diabetes syndrome in children. 61
30778115 2019
19
Expansion of phenotype and genotypic data in CRB2-related syndrome. 61
27004616 2016

Variations for Nephrotic Syndrome, Type 4

ClinVar genetic disease variations for Nephrotic Syndrome, Type 4:

6 (show top 50) (show all 103) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 WT1 NM_024426.6(WT1):c.1399C>T (p.Arg467Trp)SNV Pathogenic 3487 rs121907900 11:32413566-32413566 11:32392020-32392020
2 WT1 NM_024426.6(WT1):c.1405G>A (p.Asp469Asn)SNV Pathogenic 3490 rs28941778 11:32413560-32413560 11:32392014-32392014
3 WT1 NM_024426.6(WT1):c.1447+5G>ASNV Pathogenic 3493 rs587776576 11:32413513-32413513 11:32391967-32391967
4 WT1 NM_024426.6(WT1):c.1348C>T (p.His450Tyr)SNV Pathogenic 3495 rs28942089 11:32414218-32414218 11:32392672-32392672
5 WT1 NM_024426.6(WT1):c.1303C>T (p.Arg435Ter)SNV Pathogenic 3497 rs121907906 11:32414263-32414263 11:32392717-32392717
6 WT1 NM_024426.6(WT1):c.1447+4C>TSNV Pathogenic 3500 rs587776577 11:32413514-32413514 11:32391968-32391968
7 WT1 NM_024426.6(WT1):c.1366T>C (p.Phe456Leu)SNV Pathogenic 3502 rs28941777 11:32413599-32413599 11:32392053-32392053
8 WT1 NM_024426.6(WT1):c.1388G>A (p.Arg463Gln)SNV Pathogenic 599100 rs1037084691 11:32413577-32413577 11:32392031-32392031
9 WT1 NM_024426.6(WT1):c.1405G>T (p.Asp469Tyr)SNV Likely pathogenic 547167 rs28941778 11:32413560-32413560 11:32392014-32392014
10 WT1 NM_024426.6(WT1):c.1259A>C (p.His420Pro)SNV Likely pathogenic 522401 rs1554939785 11:32417808-32417808 11:32396262-32396262
11 WT1 NM_024426.6(WT1):c.-106C>TSNV Conflicting interpretations of pathogenicity 304438 rs867975105 11:32457012-32457012 11:32435466-32435466
12 WT1 NM_024426.6(WT1):c.375C>T (p.Gly125=)SNV Conflicting interpretations of pathogenicity 241481 rs776209354 11:32456532-32456532 11:32434986-32434986
13 WT1 NM_024426.6(WT1):c.123G>C (p.Pro41=)SNV Conflicting interpretations of pathogenicity 193453 rs555140661 11:32456784-32456784 11:32435238-32435238
14 WT1 NM_024426.6(WT1):c.381C>G (p.Pro127=)SNV Conflicting interpretations of pathogenicity 261711 rs771681406 11:32456526-32456526 11:32434980-32434980
15 WT1 NM_024426.6(WT1):c.390A>G (p.Pro130=)SNV Conflicting interpretations of pathogenicity 304424 rs886048228 11:32456517-32456517 11:32434971-32434971
16 WT1 NM_024426.6(WT1):c.1200C>T (p.Tyr400=)SNV Conflicting interpretations of pathogenicity 304418 rs886048227 11:32417867-32417867 11:32396321-32396321
17 WT1 NM_024426.6(WT1):c.247G>T (p.Ala83Ser)SNV Uncertain significance 304427 rs886048231 11:32456660-32456660 11:32435114-32435114
18 WT1 NM_024426.6(WT1):c.174C>G (p.Leu58=)SNV Uncertain significance 304428 rs886048232 11:32456733-32456733 11:32435187-32435187
19 WT1 NM_024426.6(WT1):c.136G>T (p.Ala46Ser)SNV Uncertain significance 304430 rs886048233 11:32456771-32456771 11:32435225-32435225
20 WT1 NM_024426.6(WT1):c.-76T>CSNV Uncertain significance 304432 rs886048235 11:32456982-32456982 11:32435436-32435436
21 WT1 NM_024426.6(WT1):c.-86T>CSNV Uncertain significance 304434 rs886048237 11:32456992-32456992 11:32435446-32435446
22 WT1 NM_024426.6(WT1):c.-94G>CSNV Uncertain significance 304436 rs886048239 11:32457000-32457000 11:32435454-32435454
23 WT1 NM_024426.6(WT1):c.*1225T>CSNV Uncertain significance 304371 rs886048210 11:32409379-32409379 11:32387833-32387833
24 WT1 NM_024426.6(WT1):c.*1021_*1022GT[15]short repeat Uncertain significance 304379 rs58549495 11:32409550-32409553 11:32388004-32388007
25 WT1 NM_024426.6(WT1):c.*1021_*1022GT[19]short repeat Uncertain significance 304377 rs58549495 11:32409549-32409550 11:32388003-32388004
26 WT1 NM_024426.6(WT1):c.*741G>TSNV Uncertain significance 304393 rs886048216 11:32409863-32409863 11:32388317-32388317
27 WT1 NM_024426.6(WT1):c.*534C>TSNV Uncertain significance 304402 rs868546165 11:32410070-32410070 11:32388524-32388524
28 WT1 NM_024426.6(WT1):c.*366C>ASNV Uncertain significance 304406 rs886048223 11:32410238-32410238 11:32388692-32388692
29 WT1 NM_024426.6(WT1):c.*354G>TSNV Uncertain significance 304407 rs886048224 11:32410250-32410250 11:32388704-32388704
30 WT1 NM_024426.6(WT1):c.*841C>ASNV Uncertain significance 304388 rs886048213 11:32409763-32409763 11:32388217-32388217
31 WT1 NM_024426.6(WT1):c.*269G>TSNV Uncertain significance 304409 rs886048225 11:32410335-32410335 11:32388789-32388789
32 WT1 NM_024426.6(WT1):c.*685G>TSNV Uncertain significance 304395 rs886048218 11:32409919-32409919 11:32388373-32388373
33 WT1 NM_024426.6(WT1):c.*614A>CSNV Uncertain significance 304397 rs886048219 11:32409990-32409990 11:32388444-32388444
34 WT1 NM_024426.6(WT1):c.*110C>TSNV Uncertain significance 304415 rs757474299 11:32410494-32410494 11:32388948-32388948
35 WT1 NM_024426.6(WT1):c.887+4G>ASNV Uncertain significance 304421 rs778673400 11:32449498-32449498 11:32427952-32427952
36 WT1 NM_024426.6(WT1):c.*1021_*1022GT[14]short repeat Uncertain significance 304381 rs58549495 11:32409550-32409555 11:32388004-32388009
37 WT1 NM_024426.6(WT1):c.*1021_*1022GT[20]short repeat Uncertain significance 304378 rs58549495 11:32409549-32409550 11:32388003-32388004
38 WT1 NM_024426.6(WT1):c.*785C>ASNV Uncertain significance 304391 rs886048214 11:32409819-32409819 11:32388273-32388273
39 WT1 NM_024426.6(WT1):c.*707C>ASNV Uncertain significance 304394 rs886048217 11:32409897-32409897 11:32388351-32388351
40 WT1 NM_024426.6(WT1):c.*574deldeletion Uncertain significance 304400 rs5030319 11:32410030-32410030 11:32388484-32388484
41 WT1 NM_024426.6(WT1):c.*460C>ASNV Uncertain significance 304404 rs886048221 11:32410144-32410144 11:32388598-32388598
42 WT1 NM_024426.6(WT1):c.*393G>TSNV Uncertain significance 304405 rs886048222 11:32410211-32410211 11:32388665-32388665
43 WT1 NM_024426.6(WT1):c.*159G>CSNV Uncertain significance 304413 rs746218880 11:32410445-32410445 11:32388899-32388899
44 WT1 NM_024426.6(WT1):c.162C>G (p.Ser54Arg)SNV Uncertain significance 304429 rs776954184 11:32456745-32456745 11:32435199-32435199
45 WT1 NM_024426.6(WT1):c.-82A>CSNV Uncertain significance 304433 rs886048236 11:32456988-32456988 11:32435442-32435442
46 WT1 NM_024426.6(WT1):c.-102C>ASNV Uncertain significance 304437 rs886048240 11:32457008-32457008 11:32435462-32435462
47 WT1 NM_024426.6(WT1):c.-110C>TSNV Uncertain significance 304439 rs886048241 11:32457016-32457016 11:32435470-32435470
48 WT1 NM_024426.6(WT1):c.-114T>ASNV Uncertain significance 304440 rs886048242 11:32457020-32457020 11:32435474-32435474
49 WT1 NM_024426.6(WT1):c.-135G>ASNV Uncertain significance 304441 rs886048243 11:32457041-32457041 11:32435495-32435495
50 WT1 NM_024426.6(WT1):c.*1058G>TSNV Uncertain significance 304376 rs886048211 11:32409546-32409546 11:32388000-32388000

UniProtKB/Swiss-Prot genetic disease variations for Nephrotic Syndrome, Type 4:

73
# Symbol AA change Variation ID SNP ID
1 WT1 p.His377Tyr VAR_007748
2 WT1 p.Phe383Leu VAR_007749
3 WT1 p.Arg394Trp VAR_007750
4 WT1 p.Asp396Asn VAR_007751
5 WT1 p.Arg312Gln VAR_015053
6 WT1 p.Arg394Gln VAR_015061
7 WT1 p.Phe364Leu VAR_043801
8 WT1 p.Gly379Cys VAR_043804
9 WT1 p.Cys388Arg VAR_043805
10 WT1 p.His397Pro VAR_043810

Expression for Nephrotic Syndrome, Type 4

Search GEO for disease gene expression data for Nephrotic Syndrome, Type 4.

Pathways for Nephrotic Syndrome, Type 4

GO Terms for Nephrotic Syndrome, Type 4

Sources for Nephrotic Syndrome, Type 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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