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NPHS1

NPHS1 adhesion molecule, nephrin, the group of Fibronectin type III domain containing|V-set domain containing|C2-set domain containing

Basic information

Region (hg38): 19:35825372-35869287

Links

ENSG00000161270 ∙ NCBI:4868 ∙ OMIM:602716 ∙ HGNC:7908 ∙ Uniprot:O60500 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 8.

Transcript IDProtein IDCoding exonsMANE SelectMANE Plus Clinical
NM_004646.4NP_004637.129yes-
ENST00000378910.10ENSP00000368190.429yes-
ENST00000353632.6ENSP00000343634.528--
ENST00000353632.7ENSP00000343634.528--

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Nephrotic syndrome, type 1ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingRenal6384451; 9660941; 10577936; 17413422; 17290294; 20650908; 20798252; 21125408; 22009864; 22565185; 22584503; 22653594
Medical therapy to control bacterial infections, along with renal transplantation, can be beneficial
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ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NPHS1 gene.

  • not_provided (1463 variants)
  • Finnish_congenital_nephrotic_syndrome (852 variants)
  • Inborn_genetic_diseases (163 variants)
  • Congenital_nephrotic_syndrome (99 variants)
  • not_specified (82 variants)
  • NPHS1-related_disorder (52 variants)
  • Focal_segmental_glomerulosclerosis (42 variants)
  • Nephrotic_syndrome (25 variants)
  • Kidney_disorder (7 variants)
  • Corticosteroids_response (3 variants)
  • Infantile_Nephrotic_syndrome (3 variants)
  • Microscopic_hematuria (2 variants)
  • Familial_idiopathic_steroid-resistant_nephrotic_syndrome (2 variants)
  • Proteinuria (2 variants)
  • Atypical_hemolytic-uremic_syndrome (1 variants)
  • Glomerulonephritis (1 variants)
  • See_cases (1 variants)
  • Steroid-resistant_nephrotic_syndrome (1 variants)
  • Unexplained_young_onset_end-stage_renal_disease (1 variants)
  • Congenital_and_infantile_nephrotic_syndrome (1 variants)
  • Nephrotic_range_proteinuria (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NPHS1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_004646.4. 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
2
clinvar
20
clinvar
602
clinvar
8
clinvar
 632
missense
15
clinvar
96
clinvar
392
clinvar
100
clinvar
2
clinvar
 605
nonsense
44
clinvar
39
clinvar
3
clinvar
 86
start loss
3
3
frameshift
72
clinvar
131
clinvar
3
clinvar
 206
splice donor/acceptor (+/-2bp)
12
clinvar
79
clinvar
1
clinvar
 92
Total 143 350 419 702 10

Highest pathogenic variant AF is 0.0004398987

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
NPHS1protein_codingprotein_codingENST00000378910 2943324
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
12525404941257480.00197
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.4086987290.9570.00004367848
Missense in Polyphen198224.960.880162563
Synonymous-1.043463221.070.00002092677
Loss of Function3.533363.40.5210.00000335677

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001430.00141
Ashkenazi Jewish0.0001020.0000992
East Asian0.0004930.000489
Finnish0.01220.0121
European (Non-Finnish)0.001300.00128
Middle Eastern0.0004930.000489
South Asian0.001150.000980
Other0.001640.00163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoskeleton. Plays a role in skeletal muscle formation through regulation of myoblast fusion (By similarity). {ECO:0000250|UniProtKB:Q9QZS7, ECO:0000250|UniProtKB:Q9R044}.;
Disease
DISEASE: Nephrotic syndrome 1 (NPHS1) [MIM:256300]: 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. {ECO:0000269|PubMed:10652016, ECO:0000269|PubMed:11317351, ECO:0000269|PubMed:11726550, ECO:0000269|PubMed:17290294, ECO:0000269|PubMed:18503012, ECO:0000269|PubMed:18614772, ECO:0000269|PubMed:20172850, ECO:0000269|PubMed:20798252, ECO:0000269|PubMed:22009864, ECO:0000269|PubMed:22565185, ECO:0000269|PubMed:22732337, ECO:0000269|PubMed:25804400, ECO:0000269|PubMed:26560236, ECO:0000269|PubMed:9660941, ECO:0000269|PubMed:9915943}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Primary Focal Segmental Glomerulosclerosis FSGS;Nephrin family interactions;Cell-Cell communication;Nephrin/Neph1 signaling in the kidney podocyte (Consensus)

Recessive Scores

pRec
0.535

Intolerance Scores

loftool
0.574
rvis_EVS
0.68
rvis_percentile_EVS
84.95

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.999

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium

Zebrafish Information Network

Gene name
nphs1
Affected structure
skeletal muscle cell
Phenotype tag
abnormal
Phenotype quality
mislocalised

Gene ontology

Biological process
cell adhesion;JNK cascade;skeletal muscle tissue development;myoblast fusion;excretion;positive regulation of actin filament polymerization;glomerular basement membrane development;protein localization to synapse;regulation of excretion;glomerular visceral epithelial cell development
Cellular component
plasma membrane;integral component of plasma membrane;slit diaphragm;cell projection;extracellular exosome
Molecular function
protein binding;myosin binding
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