NPHS2: Podocin and Nephrotic Syndrome
Key gene in steroid-resistant nephrotic syndrome and glomerular filtration barrier integrity
Gene Information Card
| Symbol | NPHS2 |
|---|---|
| Full Name | NPHS2, podocin |
| Gene Type | protein-coding |
| Chromosomal Location | 1q25.2 |
| NCBI Gene ID | 7827 ncbi.nlm.nih.gov/gene/7827 |
| Ensembl ID | ENSG00000116218 |
| UniProt ID | Q9NP85 |
| OMIM ID | 604766 |
| HGNC ID | 7908 |
| Aliases | PDCN, SRN1 |
Description
NPHS2 encodes podocin, a stomatin family protein essential for the structural integrity of the glomerular slit diaphragm. Podocin localizes to the podocyte foot process membrane and interacts with nephrin and CD2AP. Loss-of-function mutations in NPHS2 cause autosomal recessive steroid-resistant nephrotic syndrome (SRNS) and focal segmental glomerulosclerosis (FSGS).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Steroid-resistant nephrotic syndrome (SRNS) | Loss-of-function mutations disrupt slit diaphragm assembly, leading to proteinuria and podocyte effacement. | OMIM #604766; ClinVar |
| Focal segmental glomerulosclerosis (FSGS) | Podocin deficiency impairs glomerular filtration barrier, causing segmental scarring. | OMIM #603278; NCBI Gene |
| Nephrotic syndrome type 2 | Biallelic NPHS2 mutations result in early-onset SRNS with rapid progression to end-stage renal disease. | OMIM #600995 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.8 | High |
| Testis | 0.6 | Low |
| Pancreas | 0.3 | Low |
| Liver | 0.1 | Not detected |
| Brain | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Podocyte (primary) | 15.2 | High expression; key functional cell |
| HEK293 | 0.0 | Not expressed |
| HepG2 | 0.0 | Not expressed |
| A549 | 0.0 | Not expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.413G>A (p.Arg138Gln) | Missense | ~10% in SRNS cohorts | Impaired nephrin binding; loss of function |
| c.467_468del (p.Leu156fs) | Frameshift | ~5% in SRNS | Premature truncation; complete loss of function |
| c.686G>A (p.Arg229Gln) | Missense | ~3% in SRNS | Reduced membrane localization; loss of function |
| c.871C>T (p.Arg291Trp) | Missense | ~2% in SRNS | Dominant-negative effect reported in some families |
Mutation functional classification
Loss of Function (LOF)
Most NPHS2 mutations (e.g., p.Arg138Gln, p.Leu156fs) cause loss of podocin function by disrupting slit diaphragm assembly or protein stability.
Gain of Function (GOF)
No gain-of-function mutations reported for NPHS2.
Dominant Negative (DN)
Rare variants such as p.Arg291Trp may exert dominant-negative effects in heterozygous state, though typical inheritance is recessive.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • plasma membrane (GO:0005886) |
| • integral component of membrane (GO:0016021) | • slit diaphragm (GO:0036057) |
| • filtration diaphragm (GO:0036058) | • identical protein binding (GO:0042802) |
| • transmembrane transport (GO:0055085) |
Pathways
• Slit diaphragm signaling (Reactome: R-HSA-373753)
• Cell junction organization (Reactome: R-HSA-446728)
• Glomerular filtration (KEGG: hsa04964)
Protein Summary
Podocin (UniProt Q9NP85) is a 383-amino-acid integral membrane protein with a hairpin-like topology. It contains a prohibitin (PHB) domain and localizes to the slit diaphragm of podocyte foot processes. Podocin oligomerizes and recruits nephrin and CD2AP to form a signaling complex critical for glomerular permselectivity. Mutations cause proteinuria and nephrotic syndrome.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NPHS2 Knockout HEK293 Cell Line | EDJ-KQ6129 | Human | 7827 | Details Get a Quote |
| NPHS2 Knockout HeLa Cell Line | EDJ-KQ54799 | Human | 7827 | Details Get a Quote |
| NPHS2 Knockout A-549 Cell Line | EDJ-KQ63291 | Human | 7827 | Details Get a Quote |
| NPHS2 Knockout HCT 116 Cell Line | EDJ-KQ71758 | Human | 7827 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
