NPHS3
MCID: NPH054
MIFTS: 39

Nephrotic Syndrome, Type 3 (NPHS3)

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

Aliases & Classifications for Nephrotic Syndrome, Type 3

MalaCards integrated aliases for Nephrotic Syndrome, Type 3:

Name: Nephrotic Syndrome, Type 3 56 29 13 6 39 71
Nephrotic Syndrome Type 3 12 15
Nphs3 56 73
Nephrotic Syndrome, Early-Onset, Type 3 56
Early Onset Nephrotic Syndrome Type 3 12
Early-Onset Nephrotic Syndrome Type 3 73
Nephrotic Syndrome 3 73

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset in infancy or childhood


HPO:

31
nephrotic syndrome, type 3:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive childhood onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0080382
OMIM 56 610725
OMIM Phenotypic Series 56 PS256300
MeSH 43 D009404
MedGen 41 C1853124
UMLS 71 C1853124

Summaries for Nephrotic Syndrome, Type 3

OMIM : 56 Nephrotic syndrome, a malfunction of the glomerular filter, is characterized clinically by proteinuria, edema, and end-stage renal disease (ESRD). Renal histopathology may show diffuse mesangial sclerosis (DMS) or focal segmental glomerulosclerosis (FSGS) (Hinkes et al., 2006). Most patients with NPHS3 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 (Gbadegesin et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome and FSGS, see NPHS1 (256300). (610725)

MalaCards based summary : Nephrotic Syndrome, Type 3, also known as nephrotic syndrome type 3, is related to diffuse mesangial sclerosis and sensorineural hearing loss, and has symptoms including edema An important gene associated with Nephrotic Syndrome, Type 3 is PLCE1 (Phospholipase C Epsilon 1), and among its related pathways/superpathways are G-protein signaling RAC1 in cellular process and cAMP signaling pathway. The drugs Dalteparin and Valsartan have been mentioned in the context of this disorder. Affiliated tissues include kidney, and related phenotypes are proteinuria and edema

Disease Ontology : 12 A familial nephrotic syndrome characterized by early childhood onset, steroid restance and diffuse mesangial sclerosis in most patients that has material basis in homozygous or compound heterozygous mutation in the PLCE1 gene on chromosome 10q23.

UniProtKB/Swiss-Prot : 73 Nephrotic syndrome 3: 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 NPHS3 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.

Related Diseases for Nephrotic Syndrome, Type 3

Graphical network of the top 20 diseases related to Nephrotic Syndrome, Type 3:



Diseases related to Nephrotic Syndrome, Type 3

Symptoms & Phenotypes for Nephrotic Syndrome, Type 3

Human phenotypes related to Nephrotic Syndrome, Type 3:

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 proteinuria 31 HP:0000093
2 edema 31 HP:0000969
3 nephrotic syndrome 31 HP:0000100
4 stage 5 chronic kidney disease 31 HP:0003774
5 hypoalbuminemia 31 HP:0003073
6 focal segmental glomerulosclerosis 31 HP:0000097
7 diffuse mesangial sclerosis 31 HP:0001967

Symptoms via clinical synopsis from OMIM:

56
Laboratory Abnormalities:
proteinuria
hypoalbuminemia

Genitourinary Kidneys:
nephrotic syndrome
focal segmental glomerulosclerosis
diffuse mesangial sclerosis

Muscle Soft Tissue:
edema

Clinical features from OMIM:

610725

UMLS symptoms related to Nephrotic Syndrome, Type 3:


edema

Drugs & Therapeutics for Nephrotic Syndrome, Type 3

Drugs for Nephrotic Syndrome, Type 3 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 20)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dalteparin Approved Phase 2 9005-49-6
2
Valsartan Approved, Investigational Phase 2 137862-53-4 60846
3
Amlodipine Approved Phase 2 88150-42-9 2162
4
Heparin Approved, Investigational Phase 2 9005-49-6 772 46507594
5
rituximab Approved Phase 2 174722-31-7 10201696
6
Terazosin Approved Phase 2 63590-64-7 5401
7
Metoprolol Approved, Investigational Phase 2 51384-51-1, 37350-58-6 4171
8 Antineoplastic Agents, Immunological Phase 2
9 Antibodies, Monoclonal Phase 2
10 Antirheumatic Agents Phase 2
11 Heparin, Low-Molecular-Weight Phase 2
12 calcium heparin Phase 2
13 Immunologic Factors Phase 2
14 Antibodies Phase 2
15 Immunoglobulins Phase 2
16
Angiotensin II Approved, Investigational 68521-88-0, 4474-91-3, 11128-99-7 172198
17 Hormone Antagonists
18 Giapreza
19 Hormones
20 Angiotensinogen

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 The Clinical Study of Rituximab Combined With Mesenchymal Stem Cells in the Treatment of Primary Nephrotic Syndrome (3-4 Stage of Chronic Kidney Disease) Active, not recruiting NCT02966717 Phase 2 Rituximab;conventional therapy;Mesenchymal stem cells
2 Assessment of the Educational Experience for Patients With Newly Diagnosed Nephrotic Syndrome Completed NCT02190955
3 Fluid Balance, Hormones and Urine Proteomics in Nephrotic Syndrome in Childhood Completed NCT00690586

Search NIH Clinical Center for Nephrotic Syndrome, Type 3

Genetic Tests for Nephrotic Syndrome, Type 3

Genetic tests related to Nephrotic Syndrome, Type 3:

# Genetic test Affiliating Genes
1 Nephrotic Syndrome, Type 3 29 PLCE1

Anatomical Context for Nephrotic Syndrome, Type 3

MalaCards organs/tissues related to Nephrotic Syndrome, Type 3:

40
Kidney

Publications for Nephrotic Syndrome, Type 3

Articles related to Nephrotic Syndrome, Type 3:

(show all 11)
# Title Authors PMID Year
1
Mutational analysis of the PLCE1 gene in steroid resistant nephrotic syndrome. 56 6
20591883 2010
2
Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. 56 6
17086182 2006
3
NPHS3: new clues for understanding idiopathic nephrotic syndrome. 61 56
18270750 2008
4
Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS). 61 56
18065803 2008
5
The Role of p.Ser1105Ser (in NPHS1 Gene) and p.Arg548Leu (in PLCE1 Gene) with Disease Status of Vietnamese Patients with Congenital Nephrotic Syndrome: Benign or Pathogenic? 61
31013750 2019
6
Cyclosporine A responsive congenital nephrotic syndrome with single heterozygous variants in NPHS1, NPHS2, and PLCE1. 61
29663071 2018
7
The etiology of congenital nephrotic syndrome: current status and challenges. 61
26961288 2016
8
Respiratory-chain deficiency presenting as diffuse mesangial sclerosis with NPHS3 mutation. 61
21365190 2011
9
Exclusion of homozygous PLCE1 (NPHS3) mutations in 69 families with idiopathic and hereditary FSGS. 61
18975016 2009
10
Mutations in phospholipase C epsilon 1 are not sufficient to cause diffuse mesangial sclerosis. 61
19037252 2009
11
Identification of BRAF as a new interactor of PLCepsilon1, the protein mutated in nephrotic syndrome type 3. 61
17942568 2008

Variations for Nephrotic Syndrome, Type 3

ClinVar genetic disease variations for Nephrotic Syndrome, Type 3:

6 (show all 28) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PLCE1 NM_016341.4(PLCE1):c.1146del (p.Ser383fs)deletion Pathogenic 2344 rs876657369 10:95791949-95791949 10:94032192-94032192
2 PLCE1 NM_016341.4(PLCE1):c.1477C>T (p.Arg493Ter)SNV Pathogenic 2345 rs121912601 10:95892201-95892201 10:94132444-94132444
3 PLCE1 NM_016341.4(PLCE1):c.3346C>T (p.Arg1116Ter)SNV Pathogenic 2346 rs121912602 10:96014013-96014013 10:94254256-94254256
4 PLCE1 NM_016341.4(PLCE1):c.3846del (p.Leu1283fs)deletion Pathogenic 2347 rs876657370 10:96022279-96022279 10:94262522-94262522
5 PLCE1 NM_016341.4(PLCE1):c.4846C>T (p.Gln1616Ter)SNV Pathogenic 2348 rs121912603 10:96043597-96043597 10:94283840-94283840
6 PLCE1 NM_016341.4(PLCE1):c.5560C>T (p.Gln1854Ter)SNV Pathogenic 2349 rs121912604 10:96064340-96064340 10:94304583-94304583
7 PLCE1 NM_016341.4(PLCE1):c.4451C>T (p.Ser1484Leu)SNV Pathogenic 2350 rs121912605 10:96030304-96030304 10:94270547-94270547
8 PLCE1 NM_016341.4(PLCE1):c.6448C>T (p.Arg2150Ter)SNV Pathogenic 18422 rs267606953 10:96081763-96081763 10:94322006-94322006
9 PLCE1 NM_016341.4(PLCE1):c.961C>T (p.Arg321Ter)SNV Pathogenic 18423 rs267606954 10:95791764-95791764 10:94032007-94032007
10 PLCE1 NM_016341.4(PLCE1):c.3736C>T (p.Arg1246Ter)SNV Pathogenic 18424 rs267606955 10:96018829-96018829 10:94259072-94259072
11 PLCE1 NM_016341.4(PLCE1):c.3065G>A (p.Trp1022Ter)SNV Pathogenic 635315 10:96006347-96006347 10:94246590-94246590
12 PLCE1 NM_016341.4(PLCE1):c.3058C>T (p.Gln1020Ter)SNV Pathogenic 800845 10:96006340-96006340 10:94246583-94246583
13 PLCE1 NM_016341.4(PLCE1):c.1223G>T (p.Arg408Ile)SNV Likely pathogenic 635446 10:95891947-95891947 10:94132190-94132190
14 PLCE1 NM_016341.4(PLCE1):c.4974_4977CAGA[1] (p.Gln1660fs)short repeat Likely pathogenic 635085 10:96044661-96044664 10:94284904-94284907
15 PLCE1 NM_016341.4(PLCE1):c.3698T>C (p.Leu1233Pro)SNV Likely pathogenic 802623 10:96018791-96018791 10:94259034-94259034
16 PLCE1 NM_016341.4(PLCE1):c.5559T>G (p.Tyr1853Ter)SNV Likely pathogenic 804417 10:96064339-96064339 10:94304582-94304582
17 PLCE1 NM_016341.4(PLCE1):c.6377_6378del (p.Lys2126fs)deletion Uncertain significance 631642 rs773902333 10:96081691-96081692 10:94321934-94321935
18 PLCE1 NM_016341.4(PLCE1):c.5549G>A (p.Cys1850Tyr)SNV Uncertain significance 266011 rs776276690 10:96064329-96064329 10:94304572-94304572
19 PLCE1 NM_016341.4(PLCE1):c.6757G>A (p.Ala2253Thr)SNV Uncertain significance 800752 10:96084685-96084685 10:94324928-94324928
20 PLCE1 NM_016341.4(PLCE1):c.810T>C (p.Cys270=)SNV Benign 260733 rs17109671 10:95791613-95791613 10:94031856-94031856
21 PLCE1 NM_016341.4(PLCE1):c.960G>A (p.Glu320=)SNV Benign 260734 rs17109674 10:95791763-95791763 10:94032006-94032006
22 PLCE1 NM_016341.4(PLCE1):c.1643G>T (p.Arg548Leu)SNV Benign 260712 rs17417407 10:95931087-95931087 10:94171330-94171330
23 PLCE1 NM_016341.4(PLCE1):c.4724G>C (p.Arg1575Pro)SNV Benign 260720 rs2274224 10:96039597-96039597 10:94279840-94279840
24 PLCE1 NM_016341.4(PLCE1):c.5035+12C>ASNV Benign 260722 rs3736901 10:96044734-96044734 10:94284977-94284977
25 PLCE1 NM_016341.4(PLCE1):c.5330C>T (p.Thr1777Ile)SNV Benign 260724 rs3765524 10:96058298-96058298 10:94298541-94298541
26 PLCE1 NM_016341.4(PLCE1):c.5780A>G (p.His1927Arg)SNV Benign 260728 rs2274223 10:96066341-96066341 10:94306584-94306584
27 PLCE1 NM_016341.4(PLCE1):c.6093T>C (p.Thr2031=)SNV no interpretation for the single variant 267284 rs886039891 10:96073100-96073100 10:94313343-94313343
28 PLCE1 NM_016341.4(PLCE1):c.6800G>A (p.Arg2267Gln)SNV no interpretation for the single variant 267283 rs886039892 10:96084728-96084728 10:94324971-94324971

UniProtKB/Swiss-Prot genetic disease variations for Nephrotic Syndrome, Type 3:

73
# Symbol AA change Variation ID SNP ID
1 PLCE1 p.Ser1484Leu VAR_029883 rs121912605

Expression for Nephrotic Syndrome, Type 3

Search GEO for disease gene expression data for Nephrotic Syndrome, Type 3.

Pathways for Nephrotic Syndrome, Type 3

Pathways related to Nephrotic Syndrome, Type 3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.73 PLCE1 IQGAP1 BRAF
2 11.67 PLCE1 BRAF ATP2B1
3
Show member pathways
11.57 IQGAP1 BRAF
4 11.45 PLCE1 BRAF
5 11.44 PLCE1 IQGAP1 BRAF
6 11.38 IQGAP1 BRAF
7 11.21 IQGAP1 ATP2B1
8 11.01 PLCE1 IQGAP1 BRAF

GO Terms for Nephrotic Syndrome, Type 3

Biological processes related to Nephrotic Syndrome, Type 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to calcium ion GO:0071277 8.96 IQGAP1 BRAF
2 epidermal growth factor receptor signaling pathway GO:0007173 8.62 PLCE1 IQGAP1

Molecular functions related to Nephrotic Syndrome, Type 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 small GTPase binding GO:0031267 8.96 IQGAP1 BRAF
2 Ras GTPase binding GO:0017016 8.62 PLCE1 BRAF

Sources for Nephrotic Syndrome, Type 3

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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