GeneBe

NPHS2

NPHS2 stomatin family member, podocin, the group of Stomatin family

Basic information

Region (hg38): 1:179550539-179575952

Links

ENSG00000116218 ∙ NCBI:7827 ∙ OMIM:604766 ∙ HGNC:13394 ∙ Uniprot:Q9NP85 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • nephrotic syndrome, type 2 (Definitive), mode of inheritance: AR
  • nephrotic syndrome, type 2 (Definitive), mode of inheritance: AR
  • nephrotic syndrome, type 2 (Strong), mode of inheritance: AR
  • nephrotic syndrome, type 2 (Definitive), mode of inheritance: AR
  • familial idiopathic steroid-resistant nephrotic syndrome (Supportive), mode of inheritance: AD
  • nephrotic syndrome, type 2 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Nephrotic syndrome, type 2ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingRenal8589695; 8606597; 10742096; 11729243; 12464671; 12707396; 17109732; 22036940; 22080622; 22228437; 22565185; 23013956
The disease is steroid resistant; Partially steroid-responsive AD forms have been described; Renal transplant has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NPHS2 gene.

  • not_provided (373 variants)
  • Nephrotic_syndrome,_type_2 (224 variants)
  • Steroid-resistant_nephrotic_syndrome (76 variants)
  • Inborn_genetic_diseases (29 variants)
  • not_specified (23 variants)
  • NPHS2-related_disorder (20 variants)
  • Nephrotic_syndrome (13 variants)
  • Focal_segmental_glomerulosclerosis (9 variants)
  • Idiopathic_nephrotic_syndrome (9 variants)
  • Prednisolone_response (5 variants)
  • Kidney_disorder (3 variants)
  • Finnish_congenital_nephrotic_syndrome (2 variants)
  • Chronic_kidney_disease (2 variants)
  • Nephrotic_range_proteinuria (2 variants)
  • Proteinuria (2 variants)
  • Corticosteroids_response (1 variants)
  • . (1 variants)
  • See_cases (1 variants)
  • Familial_idiopathic_steroid-resistant_nephrotic_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NPHS2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014625.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
7
clinvar
157
clinvar
 165
missense
6
clinvar
37
clinvar
125
clinvar
6
clinvar
1
clinvar
 175
nonsense
11
clinvar
15
clinvar
 26
start loss
3
1
 4
frameshift
18
clinvar
41
clinvar
1
clinvar
 60
splice donor/acceptor (+/-2bp)
4
clinvar
21
clinvar
1
clinvar
 26
Total 42 116 134 163 1

Highest pathogenic variant AF is 0.0007972158

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
NPHS2protein_codingprotein_codingENST00000367615 825414
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
7.22e-90.4571256890591257480.000235
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.6861742010.8640.00001002415
Missense in Polyphen6675.2440.87715934
Synonymous-0.08117877.11.010.00000365800
Loss of Function0.9741519.70.7630.00000116201

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004290.000420
Ashkenazi Jewish0.000.00
East Asian0.0002740.000272
Finnish0.000.00
European (Non-Finnish)0.0002650.000264
Middle Eastern0.0002740.000272
South Asian0.0003980.000392
Other0.0001860.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Plays a role in the regulation of glomerular permeability, acting probably as a linker between the plasma membrane and the cytoskeleton.;
Disease
DISEASE: Nephrotic syndrome 2 (NPHS2) [MIM:600995]: 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. The disorder is resistant to steroid treatment and progresses to end- stage renal failure in the first or second decades. Some patients show later onset of the disorder. {ECO:0000269|PubMed:10742096, ECO:0000269|PubMed:12464671, ECO:0000269|PubMed:15253708, ECO:0000269|PubMed:17899208, ECO:0000269|PubMed:20798252, ECO:0000269|PubMed:20947785, ECO:0000269|PubMed:22565185, ECO:0000269|PubMed:22578956, ECO:0000269|PubMed:23242530, ECO:0000269|PubMed:23800802, ECO:0000269|PubMed:23913389, ECO:0000269|PubMed:24072147, ECO:0000269|PubMed:24227627, ECO:0000269|PubMed:26420286}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Primary Focal Segmental Glomerulosclerosis FSGS;Nephrin/Neph1 signaling in the kidney podocyte (Consensus)

Recessive Scores

pRec
0.267

Intolerance Scores

loftool
0.251
rvis_EVS
0.02
rvis_percentile_EVS
55.22

Haploinsufficiency Scores

pHI
0.266
hipred
Y
hipred_score
0.661
ghis

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.632

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Nphs2
Phenotype
cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); renal/urinary system phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype;

Zebrafish Information Network

Gene name
nphs2
Affected structure
podocyte
Phenotype tag
abnormal
Phenotype quality
morphology

Gene ontology

Biological process
excretion;actin cytoskeleton reorganization;metanephric glomerular visceral epithelial cell development
Cellular component
endoplasmic reticulum;plasma membrane;integral component of plasma membrane;cell-cell junction;intrinsic component of the cytoplasmic side of the plasma membrane;protein-containing complex;slit diaphragm;membrane raft;extracellular exosome
Molecular function
protein binding