NPHS1 Gene: Nephrin, Key to Kidney Filtration
Comprehensive guide to NPHS1, its role in congenital nephrotic syndrome, and molecular mechanisms.
Gene Information Card
| Symbol | NPHS1 |
|---|---|
| Full Name | NPHS1, nephrin |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.12 |
| NCBI Gene ID | 4868 ncbi.nlm.nih.gov/gene/4868 |
| Ensembl ID | ENSG00000161270 |
| UniProt ID | O60500 |
| OMIM ID | 602716 |
| HGNC ID | 7908 |
| Aliases | NPHN, CNF, nephrin |
Description
The NPHS1 gene encodes nephrin, a transmembrane protein of the immunoglobulin superfamily, which is a critical component of the slit diaphragm between podocyte foot processes in the kidney glomerulus. Nephrin maintains the selective permeability of the glomerular filtration barrier, preventing protein loss into urine. Mutations in NPHS1 cause congenital nephrotic syndrome of the Finnish type (NPHS1), characterized by massive proteinuria, edema, and renal failure in infancy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital nephrotic syndrome, Finnish type (NPHS1) | Loss-of-function mutations in NPHS1 disrupt slit diaphragm integrity, leading to proteinuria and nephrotic syndrome. | OMIM #256300; ClinVar; multiple case studies |
| Nephrotic syndrome, type 1 | Biallelic NPHS1 mutations cause early-onset nephrotic syndrome with steroid resistance. | OMIM; PubMed PMID: 10631141 |
| Focal segmental glomerulosclerosis (FSGS) | Rare NPHS1 missense variants may contribute to FSGS in older children and adults. | ClinVar; PMID: 19056937 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 146.3 | High |
| Pancreas | 0.8 | Low |
| Testis | 0.5 | Low |
| Lung | 0.3 | Low |
| Brain | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Podocyte (primary) | 146.3 | High expression; key cell type |
| HEK 293 | 0.0 | No endogenous expression |
| HK-2 (proximal tubule) | 0.0 | Not expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3325C>T (p.Arg1109*) | Nonsense | ~50% in Finnish population | Loss of function; truncated protein |
| c.3478C>T (p.Arg1160*) | Nonsense | Common in Finnish patients | Loss of function |
| c.3250G>A (p.Gly1084Arg) | Missense | Rare | Impaired trafficking to cell membrane |
| c.274G>A (p.Gly92Arg) | Missense | Rare | Disrupts slit diaphragm assembly |
Mutation functional classification
Loss of Function (LOF)
Most NPHS1 mutations are loss-of-function, leading to absence or non-functional nephrin, causing slit diaphragm breakdown and proteinuria.
Gain of Function (GOF)
No gain-of-function mutations reported for NPHS1.
Dominant Negative (DN)
Rare missense variants may exert dominant-negative effects by interfering with wild-type nephrin multimerization, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • plasma membrane (GO:0005886) |
| • cell adhesion (GO:0007155) | • slit diaphragm (GO:0036057) |
| • filtration diaphragm (GO:0036058) | • slit diaphragm assembly (GO:0060088) |
| • endocytosis (GO:0006897) | • actin cytoskeleton organization (GO:0030036) |
Pathways
• Slit diaphragm signaling (Reactome: R-HSA-373753)
• Cell junction organization (Reactome: R-HSA-446728)
• Cell-cell communication (Reactome: R-HSA-1500931)
Protein Summary
Nephrin (UniProt O60500) is a 1241-amino acid transmembrane protein with eight extracellular immunoglobulin-like domains and a fibronectin type III domain. It localizes to the slit diaphragm of podocytes, where it homodimerizes and interacts with other slit diaphragm proteins (e.g., podocin, CD2AP) to form a size- and charge-selective barrier. Intracellularly, nephrin signals via phosphorylation of its cytoplasmic tail, regulating actin dynamics and podocyte survival. Loss of nephrin function leads to congenital nephrotic syndrome.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NPHS1 Knockout HEK293 Cell Line | EDJ-KQ3876 | Human | 4868 | Details Get a Quote |
| NPHS1 Knockout HeLa Cell Line | EDJ-KQ54012 | Human | 4868 | Details Get a Quote |
| NPHS1 Knockout A-549 Cell Line | EDJ-KQ62503 | Human | 4868 | Details Get a Quote |
| NPHS1 Knockout HCT 116 Cell Line | EDJ-KQ70971 | Human | 4868 | Details Get a Quote |
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