The NPHS2 gene provides instructions for making a protein called podocin. Podocin is primarily found in the kidneys, which are organs that filter waste products from the blood and remove them in urine. Specifically, podocin is found in cells called podocytes, which are located in specialized kidney structures called glomeruli. Podocin is located at the cell surface in the area between two podocytes called the slit diaphragm. The slit diaphragm is known as a filtration barrier because it captures proteins in blood so that they remain in the body while allowing other molecules like sugars and salts to be excreted in urine. Podocin likely helps bring other proteins that are needed for a functional slit diaphragm to the podocyte cell surface. The protein also is involved with podocyte cell signaling, helping the cell adapt to changes that occur during the filtration process.
2. Health Conditions Related to Genetic Changes
2.1. Congenital nephrotic syndrome
At least 170 mutations in the NPHS2 gene have been found to cause congenital nephrotic syndrome. This condition is a kidney disorder that begins in infancy and typically leads to irreversible kidney failure (end-stage renal disease) by early childhood. Mutations in this gene appear to be the most frequent cause of congenital nephrotic syndrome. Most NPHS2 gene mutations change single protein building blocks (amino acids) in the podocin protein. These mutations result in a reduction or absence of functional protein, which impairs the formation of normal slit diaphragms. Without a functional slit diaphragm, molecules pass through the kidneys abnormally and are excreted in urine. The filtering ability of the kidneys worsens from birth, eventually leading to end-stage renal disease.
2.2. Other disorders
NPHS2 gene mutations can cause other forms of nephrotic syndrome that develop later in life. In one form, called infantile nephrotic syndrome, signs and symptoms of the condition appear between 4 and 12 months of age. The features of this condition are similar to congenital nephrotic syndrome (described above), but they are often less severe. It is likely that NPHS2 gene mutations that cause infantile nephrotic syndrome have less effect on podocin function than those that cause congenital nephrotic syndrome, accounting for the later onset of the disorder.
3. Other Names for This Gene
- nephrosis 2, idiopathic, steroid-resistant (podocin)
- NPHS2 podocin
- podocin isoform 1
- podocin isoform 2
The entry is from https://medlineplus.gov/genetics/gene/nphs2
- Grahammer F, Schell C, Huber TB. The podocyte slit diaphragm--from a thin greyline to a complex signalling hub. Nat Rev Nephrol. 2013 Oct;9(10):587-98. doi:10.1038/nrneph.2013.169.
- Machuca E, Benoit G, Nevo F, Tête MJ, Gribouval O, Pawtowski A, Brandström P, Loirat C, Niaudet P, Gubler MC, Antignac C. Genotype-phenotype correlations innon-Finnish congenital nephrotic syndrome. J Am Soc Nephrol. 2010Jul;21(7):1209-17. doi: 10.1681/ASN.2009121309.
- Sadowski CE, Lovric S, Ashraf S, Pabst WL, Gee HY, Kohl S, Engelmann S,Vega-Warner V, Fang H, Halbritter J, Somers MJ, Tan W, Shril S, Fessi I, LiftonRP, Bockenhauer D, El-Desoky S, Kari JA, Zenker M, Kemper MJ, Mueller D, FathyHM, Soliman NA; SRNS Study Group, Hildebrandt F. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2015Jun;26(6):1279-89. doi: 10.1681/ASN.2014050489.
- Wang JJ, Mao JH. The etiology of congenital nephrotic syndrome: current statusand challenges. World J Pediatr. 2016 May;12(2):149-58. doi:10.1007/s12519-016-0009-y.