NPHS3
MCID: NPH054
MIFTS: 42

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 57 29 13 6 40 72
Nephrotic Syndrome Type 3 12 15
Nphs3 57 74
Nephrotic Syndrome, Early-Onset, Type 3 57
Early Onset Nephrotic Syndrome Type 3 12
Early-Onset Nephrotic Syndrome Type 3 74
Nephrotic Syndrome 3 74

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset in infancy or childhood


HPO:

32
nephrotic syndrome, type 3:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive childhood onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0080382
MeSH 44 D009404
MedGen 42 C1853124
UMLS 72 C1853124

Summaries for Nephrotic Syndrome, Type 3

OMIM : 57 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 NFAT and Cardiac Hypertrophy and Ras signaling pathway. The drugs Heparin and Metoprolol 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 : 74 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:

32 (show all 7)
# Description HPO Frequency HPO Source Accession
1 proteinuria 32 HP:0000093
2 edema 32 HP:0000969
3 nephrotic syndrome 32 HP:0000100
4 stage 5 chronic kidney disease 32 HP:0003774
5 hypoalbuminemia 32 HP:0003073
6 focal segmental glomerulosclerosis 32 HP:0000097
7 diffuse mesangial sclerosis 32 HP:0001967

Symptoms via clinical synopsis from OMIM:

57
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 23)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Heparin Approved, Investigational Phase 2 9005-49-6 46507594 772
2
Metoprolol Approved, Investigational Phase 2 37350-58-6, 51384-51-1 4171
3
Amlodipine Approved Phase 2 88150-42-9 2162
4
rituximab Approved Phase 2 174722-31-7 10201696
5
Dalteparin Approved Phase 2 9005-49-6
6
Terazosin Approved Phase 2 63590-64-7 5401
7
Valsartan Approved, Investigational Phase 2 137862-53-4 60846
8 Fibrinolytic Agents Phase 2
9 Immunologic Factors Phase 2
10 Heparin, Low-Molecular-Weight Phase 2
11 Antineoplastic Agents, Immunological Phase 2
12 Antibodies Phase 2
13 Immunoglobulins Phase 2
14 Anticoagulants Phase 2
15 calcium heparin Phase 2
16 Antibodies, Monoclonal Phase 2
17 Antirheumatic Agents Phase 2
18
Angiotensin II Approved, Investigational 11128-99-7, 68521-88-0, 4474-91-3 172198
19 Angiotensinogen
20 Hormones
21 Giapreza
22 Hormone Antagonists
23 Hormones, Hormone Substitutes, and Hormone Antagonists

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:

41
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. 8 71
20591883 2010
2
Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. 8 71
17086182 2006
3
NPHS3: new clues for understanding idiopathic nephrotic syndrome. 38 8
18270750 2008
4
Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS). 38 8
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? 38
31013750 2019
6
Cyclosporine A responsive congenital nephrotic syndrome with single heterozygous variants in NPHS1, NPHS2, and PLCE1. 38
29663071 2018
7
The etiology of congenital nephrotic syndrome: current status and challenges. 38
26961288 2016
8
Respiratory-chain deficiency presenting as diffuse mesangial sclerosis with NPHS3 mutation. 38
21365190 2011
9
Mutations in phospholipase C epsilon 1 are not sufficient to cause diffuse mesangial sclerosis. 38
19037252 2009
10
Exclusion of homozygous PLCE1 (NPHS3) mutations in 69 families with idiopathic and hereditary FSGS. 38
18975016 2009
11
Identification of BRAF as a new interactor of PLCepsilon1, the protein mutated in nephrotic syndrome type 3. 38
17942568 2008

Variations for Nephrotic Syndrome, Type 3

ClinVar genetic disease variations for Nephrotic Syndrome, Type 3:

6 (show all 24)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 PLCE1 NM_016341.4(PLCE1): c.5560C> T (p.Gln1854Ter) single nucleotide variant Pathogenic rs121912604 10:96064340-96064340 10:94304583-94304583
2 PLCE1 NM_016341.4(PLCE1): c.1146del (p.Ser383fs) deletion Pathogenic rs876657369 10:95791949-95791949 10:94032192-94032192
3 PLCE1 NM_016341.4(PLCE1): c.1477C> T (p.Arg493Ter) single nucleotide variant Pathogenic rs121912601 10:95892201-95892201 10:94132444-94132444
4 PLCE1 NM_016341.4(PLCE1): c.3346C> T (p.Arg1116Ter) single nucleotide variant Pathogenic rs121912602 10:96014013-96014013 10:94254256-94254256
5 PLCE1 NM_016341.4(PLCE1): c.3846del (p.Leu1283fs) deletion Pathogenic rs876657370 10:96022282-96022282 10:94262525-94262525
6 PLCE1 NM_016341.4(PLCE1): c.4846C> T (p.Gln1616Ter) single nucleotide variant Pathogenic rs121912603 10:96043597-96043597 10:94283840-94283840
7 PLCE1 NM_016341.4(PLCE1): c.4451C> T (p.Ser1484Leu) single nucleotide variant Pathogenic rs121912605 10:96030304-96030304 10:94270547-94270547
8 PLCE1 NM_016341.4(PLCE1): c.3736C> T (p.Arg1246Ter) single nucleotide variant Pathogenic rs267606955 10:96018829-96018829 10:94259072-94259072
9 PLCE1 NM_016341.4(PLCE1): c.6448C> T (p.Arg2150Ter) single nucleotide variant Pathogenic rs267606953 10:96081763-96081763 10:94322006-94322006
10 PLCE1 NM_016341.4(PLCE1): c.961C> T (p.Arg321Ter) single nucleotide variant Pathogenic rs267606954 10:95791764-95791764 10:94032007-94032007
11 PLCE1 NM_016341.4(PLCE1): c.3065G> A (p.Trp1022Ter) single nucleotide variant Pathogenic 10:96006347-96006347 10:94246590-94246590
12 PLCE1 NM_016341.4(PLCE1): c.1223G> T (p.Arg408Ile) single nucleotide variant Likely pathogenic 10:95891947-95891947 10:94132190-94132190
13 PLCE1 NM_016341.4(PLCE1): c.4974_4977CAGA[1] (p.Gln1660fs) short repeat Likely pathogenic 10:96044660-96044664 10:94284904-94284907
14 PLCE1 NM_016341.4(PLCE1): c.6377_6378del (p.Lys2126fs) deletion Uncertain significance 10:96081690-96081692 10:94321935-94321936
15 PLCE1 NM_016341.4(PLCE1): c.5549G> A (p.Cys1850Tyr) single nucleotide variant Uncertain significance rs776276690 10:96064329-96064329 10:94304572-94304572
16 PLCE1 NM_016341.4(PLCE1): c.810T> C (p.Cys270=) single nucleotide variant Benign rs17109671 10:95791613-95791613 10:94031856-94031856
17 PLCE1 NM_016341.4(PLCE1): c.960G> A (p.Glu320=) single nucleotide variant Benign rs17109674 10:95791763-95791763 10:94032006-94032006
18 PLCE1 NM_016341.4(PLCE1): c.1643G> T (p.Arg548Leu) single nucleotide variant Benign rs17417407 10:95931087-95931087 10:94171330-94171330
19 PLCE1 NM_016341.4(PLCE1): c.4724G> C (p.Arg1575Pro) single nucleotide variant Benign rs2274224 10:96039597-96039597 10:94279840-94279840
20 PLCE1 NM_016341.4(PLCE1): c.5035+12C> A single nucleotide variant Benign rs3736901 10:96044734-96044734 10:94284977-94284977
21 PLCE1 NM_016341.4(PLCE1): c.5330C> T (p.Thr1777Ile) single nucleotide variant Benign rs3765524 10:96058298-96058298 10:94298541-94298541
22 PLCE1 NM_016341.4(PLCE1): c.5780A> G (p.His1927Arg) single nucleotide variant Benign rs2274223 10:96066341-96066341 10:94306584-94306584
23 PLCE1 NM_016341.4(PLCE1): c.6093T> C (p.Thr2031=) single nucleotide variant no interpretation for the single variant rs886039891 10:96073100-96073100 10:94313343-94313343
24 PLCE1 NM_016341.4(PLCE1): c.6800G> A (p.Arg2267Gln) single nucleotide variant no interpretation for the single variant rs886039892 10:96084728-96084728 10:94324971-94324971

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

74
# 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:

(show all 28)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.53 PLCG1 PLCE1 BRAF
2
Show member pathways
12.38 PLCG1 PLCE1 BRAF
3
Show member pathways
12.31 PLCG1 PLCE1 BRAF
4
Show member pathways
12.3 PLCG1 PLCE1 BRAF
5
Show member pathways
12.04 PLCE1 IQGAP1 BRAF
6
Show member pathways
11.97 PLCG1 IQGAP1 BRAF
7
Show member pathways
11.91 PLCG1 PLCE1 BRAF
8
Show member pathways
11.9 PLCG1 PLCE1 BRAF
9 11.71 PLCG1 PLCE1
10
Show member pathways
11.69 PLCG1 PLCE1
11 11.64 IQGAP1 BRAF
12 11.62 PLCG1 PLCE1
13 11.57 PLCG1 BRAF
14 11.57 PLCG1 PLCE1 IQGAP1 BRAF
15
Show member pathways
11.56 PLCG1 IQGAP1
16 11.51 PLCG1 PLCE1
17
Show member pathways
11.46 PLCG1 PLCE1 BRAF
18 11.45 PLCG1 PLCE1
19 11.42 PLCG1 PLCE1 BRAF
20 11.38 PLCG1 PLCE1 BRAF
21 11.34 PLCG1 PLCE1 BRAF
22 11.26 PLCG1 BRAF
23
Show member pathways
11.21 PLCG1 PLCE1
24 11.16 PLCG1 PLCE1
25 11.14 PLCG1 PLCE1 IQGAP1 BRAF
26 11.01 PLCG1 PLCE1
27 10.99 PLCG1 PLCE1 BRAF
28 10.98 PLCG1 BRAF

GO Terms for Nephrotic Syndrome, Type 3

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

# Name GO ID Score Top Affiliating Genes
1 ruffle GO:0001726 8.62 PLCG1 IQGAP1

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

# Name GO ID Score Top Affiliating Genes
1 T cell receptor signaling pathway GO:0050852 9.43 PLCG1 BRAF
2 intracellular signal transduction GO:0035556 9.43 PLCG1 PLCE1 BRAF
3 lipid catabolic process GO:0016042 9.4 PLCG1 PLCE1
4 calcium-mediated signaling GO:0019722 9.37 PLCG1 PLCE1
5 cellular response to calcium ion GO:0071277 9.32 IQGAP1 BRAF
6 inositol phosphate metabolic process GO:0043647 9.16 PLCG1 PLCE1
7 cellular response to epidermal growth factor stimulus GO:0071364 8.96 PLCG1 IQGAP1
8 epidermal growth factor receptor signaling pathway GO:0007173 8.8 PLCG1 PLCE1 IQGAP1

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

# Name GO ID Score Top Affiliating Genes
1 phosphoric diester hydrolase activity GO:0008081 9.26 PLCG1 PLCE1
2 phosphatidylinositol phospholipase C activity GO:0004435 9.16 PLCG1 PLCE1
3 small GTPase binding GO:0031267 8.96 IQGAP1 BRAF
4 phospholipase C activity GO:0004629 8.62 PLCG1 PLCE1

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 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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