MCID: NPH047
MIFTS: 25

Nephrotic Syndrome, Type 4

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

Aliases & Classifications for Nephrotic Syndrome, Type 4

MalaCards integrated aliases for Nephrotic Syndrome, Type 4:

Name: Nephrotic Syndrome, Type 4 54 13 69
Isolated Diffuse Mesangial Sclerosis 71
Nephrotic Syndrome 4 71
Nphs4 71

Characteristics:

OMIM:

54
Miscellaneous:
progressive disorder
onset in early childhood

Inheritance:
autosomal dominant


HPO:

32
nephrotic syndrome, type 4:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive childhood onset


Classifications:



Summaries for Nephrotic Syndrome, Type 4

UniProtKB/Swiss-Prot : 71 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 isolated diffuse mesangial sclerosis, is related to diffuse mesangial sclerosis and denys-drash syndrome, and has symptoms including renal insufficiency, nephrotic syndrome and focal segmental glomerulosclerosis. An important gene associated with Nephrotic Syndrome, Type 4 is WT1 (Wilms Tumor 1). The drugs Mycophenolate mofetil and Mycophenolic acid have been mentioned in the context of this disorder. Affiliated tissues include kidney.

OMIM : 54
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

Symptoms via clinical synopsis from OMIM:

54

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


Clinical features from OMIM:

256370

Human phenotypes related to Nephrotic Syndrome, Type 4:

32
id Description HPO Frequency HPO Source Accession
1 renal insufficiency 32 HP:0000083
2 nephrotic syndrome 32 HP:0000100
3 focal segmental glomerulosclerosis 32 occasional (7.5%) HP:0000097
4 diffuse mesangial sclerosis 32 HP:0001967
5 nephroblastoma 32 HP:0002667

Drugs & Therapeutics for Nephrotic Syndrome, Type 4

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

(show all 50)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Mycophenolate mofetil Approved, Investigational Phase 4 128794-94-5 5281078
2
Mycophenolic acid Approved Phase 4 24280-93-1 446541
3
Tacrolimus Approved, Investigational Phase 4 104987-11-3 445643 439492
4 Adrenocorticotropic Hormone Phase 4,Phase 2
5 beta-endorphin Phase 4,Phase 2
6 Endorphins Phase 4
7 Hormone Antagonists Phase 4,Phase 3,Phase 2
8 Hormones Phase 4,Phase 3,Phase 2
9 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 4,Phase 3,Phase 2
10 Melanocyte-Stimulating Hormones Phase 4,Phase 2
11 Mitogens Phase 4
12 Neurotransmitter Agents Phase 4
13 Immunosuppressive Agents Phase 4,Phase 3
14 Anti-Bacterial Agents Phase 4
15 Antibiotics, Antitubercular Phase 4
16 Calcineurin Inhibitors Phase 4
17
Cyclophosphamide Approved, Investigational Phase 3 50-18-0, 6055-19-2 2907
18
Methylprednisolone Approved, Vet_approved Phase 3 83-43-2 6741
19
Prednisolone Approved, Vet_approved Phase 3 50-24-8 5755
20
Prednisone Approved, Vet_approved Phase 3 53-03-2 5865
21
rituximab Approved Phase 3,Phase 2 174722-31-7 10201696
22 Alkylating Agents Phase 3
23 Antiemetics Phase 3
24 Anti-Inflammatory Agents Phase 3
25 Antineoplastic Agents, Hormonal Phase 3
26 Antirheumatic Agents Phase 3,Phase 2
27 Autonomic Agents Phase 3
28 Gastrointestinal Agents Phase 3
29 glucocorticoids Phase 3
30 Methylprednisolone acetate Phase 3
31 Methylprednisolone Hemisuccinate Phase 3
32 Neuroprotective Agents Phase 3
33 Peripheral Nervous System Agents Phase 3
34 Prednisolone acetate Phase 3
35 Prednisolone hemisuccinate Phase 3
36 Prednisolone phosphate Phase 3
37 Protective Agents Phase 3
38
Amlodipine Approved Phase 2 88150-42-9 2162
39
Dalteparin Approved Phase 2 9005-49-6
40
Heparin Approved, Investigational Phase 2 9005-49-6 772 46507594
41
Metoprolol Approved, Investigational Phase 2 37350-58-6, 51384-51-1 4171
42
Terazosin Approved Phase 2 63590-64-7 5401
43
Valsartan Approved, Investigational Phase 2 137862-53-4 60846
44 Antibodies Phase 2
45 Antibodies, Monoclonal Phase 2
46 Anticoagulants Phase 2
47 calcium heparin Phase 2
48 Fibrinolytic Agents Phase 2
49 Heparin, Low-Molecular-Weight Phase 2
50 Immunoglobulins Phase 2

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Adrenocorticotropic Hormone (ACTH) Treatment of Nephrotic Range Proteinuria in Diabetic Nephropathy (NRDN) Completed NCT01028287 Phase 4 ACTH;ACTH
2 Mycophenolate Mofetil and Tacrolimus Versus Tacrolimus for the Treatment of Idiopathic Membranous Glomerulonephritis (IMG) Active, not recruiting NCT00843856 Phase 4 tacrolimus;tacrolimus and mycophenolate mofetil
3 Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy Recruiting NCT03018535 Phase 3 Rituximab;Methylprednisolone;Cyclophosphamide
4 Acthar for Treatment of Proteinuria in Diabetic Nephropathy Patients Completed NCT01601236 Phase 2 Repository Corticotropin Injection;Placebo
5 Rituximab Combined With MSCs in the Treatment of PNS (3-4 Stage of CKD) Active, not recruiting NCT02966717 Phase 2 Rituximab;conventional therapy;Mesenchymal stem cells
6 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

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:

39
Kidney

Publications for Nephrotic Syndrome, Type 4

Variations for Nephrotic Syndrome, Type 4

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

71
id Symbol AA change Variation ID SNP ID
1 WT1 p.His377Tyr VAR_007748
2 WT1 p.Phe383Leu VAR_007749
3 WT1 p.Asp396Asn VAR_007751
4 WT1 p.Arg312Gln VAR_015053
5 WT1 p.Phe364Leu VAR_043801
6 WT1 p.Gly379Cys VAR_043804
7 WT1 p.Cys388Arg VAR_043805
8 WT1 p.His397Pro VAR_043810

ClinVar genetic disease variations for Nephrotic Syndrome, Type 4:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 WT1 NM_024426.4(WT1): c.1384C> T (p.Arg462Trp) single nucleotide variant Pathogenic rs121907900 GRCh37 Chromosome 11, 32413566: 32413566
2 WT1 NM_024426.4(WT1): c.1390G> A (p.Asp464Asn) single nucleotide variant Pathogenic rs28941778 GRCh37 Chromosome 11, 32413560: 32413560
3 WT1 NM_024426.4(WT1): c.1333C> T (p.His445Tyr) single nucleotide variant Pathogenic rs28942089 GRCh37 Chromosome 11, 32414218: 32414218
4 WT1 NM_024426.4(WT1): c.1432+4C> T single nucleotide variant Pathogenic rs587776577 GRCh38 Chromosome 11, 32391968: 32391968
5 WT1 NM_024426.4(WT1): c.1351T> C (p.Phe451Leu) single nucleotide variant Pathogenic rs28941777 GRCh37 Chromosome 11, 32413599: 32413599

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
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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