NPHS4
MCID: NPH047
MIFTS: 25

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 58 13 41 74
Nphs4 58 76
Isolated Diffuse Mesangial Sclerosis 76
Nephrotic Syndrome Type 4 12
Nephrotic Syndrome 4 76

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
onset in early childhood


HPO:

33
nephrotic syndrome, type 4:
Onset and clinical course childhood onset progressive
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Nephrotic Syndrome, Type 4

UniProtKB/Swiss-Prot : 76 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). 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 : 58 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

Symptoms & Phenotypes for Nephrotic Syndrome, Type 4

Human phenotypes related to Nephrotic Syndrome, Type 4:

33
# Description HPO Frequency HPO Source Accession
1 focal segmental glomerulosclerosis 33 occasional (7.5%) HP:0000097
2 renal insufficiency 33 HP:0000083
3 nephrotic syndrome 33 HP:0000100
4 nephroblastoma 33 HP:0002667
5 diffuse mesangial sclerosis 33 HP:0001967

Symptoms via clinical synopsis from OMIM:

58
Genitourinary Kidneys:
nephrotic syndrome
renal failure
diffuse mesangial sclerosis
focal segmental glomerulosclerosis (less common)

Clinical features from OMIM:

256370

Drugs & Therapeutics for Nephrotic Syndrome, Type 4

Search Clinical Trials , 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:

42
Kidney

Publications for Nephrotic Syndrome, Type 4

Articles related to Nephrotic Syndrome, Type 4:

# Title Authors Year
1
Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS). ( 18065803 )
2008
2
Two cases of isolated diffuse mesangial sclerosis with WT1 mutations. ( 16479084 )
2006
3
Isolated diffuse mesangial sclerosis and Wilms tumor suppressor gene. ( 11241056 )
2001
4
WT1 and PAX-2 podocyte expression in Denys-Drash syndrome and isolated diffuse mesangial sclerosis. ( 9916932 )
1999
5
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. ( 9529364 )
1998
6
Isolated diffuse mesangial sclerosis in three siblings. ( 9546709 )
1998

Variations for Nephrotic Syndrome, Type 4

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

76
# 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

ClinVar genetic disease variations for Nephrotic Syndrome, Type 4:

6 (show top 50) (show all 200)
# Gene Variation Type Significance SNP ID Assembly Location
1 WT1 NM_024426.5(WT1): c.123G> C (p.Pro41=) single nucleotide variant Benign/Likely benign rs555140661 GRCh37 Chromosome 11, 32456784: 32456784
2 WT1 NM_024426.5(WT1): c.123G> C (p.Pro41=) single nucleotide variant Benign/Likely benign rs555140661 GRCh38 Chromosome 11, 32435238: 32435238
3 WT1 NM_024426.5(WT1): c.345C> T (p.Pro115=) single nucleotide variant Benign rs1799925 GRCh37 Chromosome 11, 32456562: 32456562
4 WT1 NM_024426.5(WT1): c.345C> T (p.Pro115=) single nucleotide variant Benign rs1799925 GRCh38 Chromosome 11, 32435016: 32435016
5 WT1 NM_024426.5(WT1): c.1122A> G (p.Arg374=) single nucleotide variant Benign rs16754 GRCh37 Chromosome 11, 32417945: 32417945
6 WT1 NM_024426.5(WT1): c.1122A> G (p.Arg374=) single nucleotide variant Benign rs16754 GRCh38 Chromosome 11, 32396399: 32396399
7 WT1 NM_024426.4(WT1): c.1384C> T (p.Arg462Trp) single nucleotide variant Pathogenic rs121907900 GRCh37 Chromosome 11, 32413566: 32413566
8 WT1 NM_024426.4(WT1): c.1384C> T (p.Arg462Trp) single nucleotide variant Pathogenic rs121907900 GRCh38 Chromosome 11, 32392020: 32392020
9 WT1 NM_024426.4(WT1): c.1390G> A (p.Asp464Asn) single nucleotide variant Pathogenic rs28941778 GRCh37 Chromosome 11, 32413560: 32413560
10 WT1 NM_024426.4(WT1): c.1390G> A (p.Asp464Asn) single nucleotide variant Pathogenic rs28941778 GRCh38 Chromosome 11, 32392014: 32392014
11 WT1 NM_024426.5(WT1): c.1447+5G> A single nucleotide variant Pathogenic rs587776576 GRCh38 Chromosome 11, 32391967: 32391967
12 WT1 NM_024426.5(WT1): c.1447+5G> A single nucleotide variant Pathogenic rs587776576 GRCh37 Chromosome 11, 32413513: 32413513
13 WT1 NM_024426.4(WT1): c.1333C> T (p.His445Tyr) single nucleotide variant Pathogenic rs28942089 GRCh37 Chromosome 11, 32414218: 32414218
14 WT1 NM_024426.4(WT1): c.1333C> T (p.His445Tyr) single nucleotide variant Pathogenic rs28942089 GRCh38 Chromosome 11, 32392672: 32392672
15 WT1 NM_024426.4(WT1): c.1432+4C> T single nucleotide variant Pathogenic rs587776577 GRCh38 Chromosome 11, 32391968: 32391968
16 WT1 NM_024426.4(WT1): c.1432+4C> T single nucleotide variant Pathogenic rs587776577 GRCh37 Chromosome 11, 32413514: 32413514
17 WT1 NM_024426.4(WT1): c.1351T> C (p.Phe451Leu) single nucleotide variant Pathogenic rs28941777 GRCh37 Chromosome 11, 32413599: 32413599
18 WT1 NM_024426.4(WT1): c.1351T> C (p.Phe451Leu) single nucleotide variant Pathogenic rs28941777 GRCh38 Chromosome 11, 32392053: 32392053
19 WT1 NM_024426.5(WT1): c.1114-9T> C single nucleotide variant Benign/Likely benign rs5030274 GRCh38 Chromosome 11, 32396416: 32396416
20 WT1 NM_024426.5(WT1): c.1114-9T> C single nucleotide variant Benign/Likely benign rs5030274 GRCh37 Chromosome 11, 32417962: 32417962
21 WT1 NM_024426.5(WT1): c.375C> T (p.Gly125=) single nucleotide variant Conflicting interpretations of pathogenicity rs776209354 GRCh38 Chromosome 11, 32434986: 32434986
22 WT1 NM_024426.5(WT1): c.375C> T (p.Gly125=) single nucleotide variant Conflicting interpretations of pathogenicity rs776209354 GRCh37 Chromosome 11, 32456532: 32456532
23 WT1 NM_024426.5(WT1): c.309C> A (p.Gly103=) single nucleotide variant Benign/Likely benign rs547333427 GRCh38 Chromosome 11, 32435052: 32435052
24 WT1 NM_024426.5(WT1): c.309C> A (p.Gly103=) single nucleotide variant Benign/Likely benign rs547333427 GRCh37 Chromosome 11, 32456598: 32456598
25 WT1 NM_024426.5(WT1): c.216G> T (p.Gln72His) single nucleotide variant Benign/Likely benign rs5030135 GRCh38 Chromosome 11, 32435145: 32435145
26 WT1 NM_024426.5(WT1): c.216G> T (p.Gln72His) single nucleotide variant Benign/Likely benign rs5030135 GRCh37 Chromosome 11, 32456691: 32456691
27 WT1 NM_024426.5(WT1): c.181C> A (p.Arg61=) single nucleotide variant Benign/Likely benign rs2234581 GRCh38 Chromosome 11, 32435180: 32435180
28 WT1 NM_024426.5(WT1): c.181C> A (p.Arg61=) single nucleotide variant Benign/Likely benign rs2234581 GRCh37 Chromosome 11, 32456726: 32456726
29 WT1 NM_024426.5(WT1): c.83G> A (p.Gly28Glu) single nucleotide variant Uncertain significance rs751641518 GRCh38 Chromosome 11, 32435278: 32435278
30 WT1 NM_024426.5(WT1): c.83G> A (p.Gly28Glu) single nucleotide variant Uncertain significance rs751641518 GRCh37 Chromosome 11, 32456824: 32456824
31 WT1 NM_024426.5(WT1): c.1074A> G (p.Gln358=) single nucleotide variant Benign/Likely benign rs2234590 GRCh37 Chromosome 11, 32421533: 32421533
32 WT1 NM_024426.5(WT1): c.1074A> G (p.Gln358=) single nucleotide variant Benign/Likely benign rs2234590 GRCh38 Chromosome 11, 32399987: 32399987
33 WT1 NM_024426.5(WT1): c.696C> T (p.Ser232=) single nucleotide variant Benign/Likely benign rs9332974 GRCh38 Chromosome 11, 32428585: 32428585
34 WT1 NM_024426.5(WT1): c.696C> T (p.Ser232=) single nucleotide variant Benign/Likely benign rs9332974 GRCh37 Chromosome 11, 32450131: 32450131
35 WT1 NM_024426.5(WT1): c.609C> T (p.Asn203=) single nucleotide variant Benign/Likely benign rs2234583 GRCh37 Chromosome 11, 32456298: 32456298
36 WT1 NM_024426.5(WT1): c.609C> T (p.Asn203=) single nucleotide variant Benign/Likely benign rs2234583 GRCh38 Chromosome 11, 32434752: 32434752
37 WT1 NM_024426.5(WT1): c.513C> A (p.Gly171=) single nucleotide variant Benign/Likely benign rs536728682 GRCh38 Chromosome 11, 32434848: 32434848
38 WT1 NM_024426.5(WT1): c.513C> A (p.Gly171=) single nucleotide variant Benign/Likely benign rs536728682 GRCh37 Chromosome 11, 32456394: 32456394
39 WT1 NM_024426.5(WT1): c.381C> G (p.Pro127=) single nucleotide variant Conflicting interpretations of pathogenicity rs771681406 GRCh38 Chromosome 11, 32434980: 32434980
40 WT1 NM_024426.5(WT1): c.381C> G (p.Pro127=) single nucleotide variant Conflicting interpretations of pathogenicity rs771681406 GRCh37 Chromosome 11, 32456526: 32456526
41 WT1 NM_024426.5(WT1): c.213G> T (p.Pro71=) single nucleotide variant Benign rs2234582 GRCh37 Chromosome 11, 32456694: 32456694
42 WT1 NM_024426.5(WT1): c.213G> T (p.Pro71=) single nucleotide variant Benign rs2234582 GRCh38 Chromosome 11, 32435148: 32435148
43 WT1 NM_024426.5(WT1): c.*1132A> T single nucleotide variant Likely benign rs5030328 GRCh38 Chromosome 11, 32387926: 32387926
44 WT1 NM_024426.5(WT1): c.*1132A> T single nucleotide variant Likely benign rs5030328 GRCh37 Chromosome 11, 32409472: 32409472
45 WT1 NM_024426.5(WT1): c.*1098C> T single nucleotide variant Likely benign rs5030327 GRCh38 Chromosome 11, 32387960: 32387960
46 WT1 NM_024426.5(WT1): c.*1098C> T single nucleotide variant Likely benign rs5030327 GRCh37 Chromosome 11, 32409506: 32409506
47 WT1 NM_024426.5(WT1): c.*1058G> T single nucleotide variant Uncertain significance rs886048211 GRCh38 Chromosome 11, 32388000: 32388000
48 WT1 NM_024426.5(WT1): c.*1058G> T single nucleotide variant Uncertain significance rs886048211 GRCh37 Chromosome 11, 32409546: 32409546
49 WT1 NM_024426.5(WT1): c.*1053_*1054dup duplication Uncertain significance rs58549495 GRCh38 Chromosome 11, 32388004: 32388005
50 WT1 NM_024426.5(WT1): c.*1053_*1054dup duplication Uncertain significance rs58549495 GRCh37 Chromosome 11, 32409550: 32409551

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

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