NPHS1 gene
The NPHS1 gene provides instructions for making nephrin, a protein essential for the kidney's filtration barrier, and mutations in this gene cause congenital nephrotic syndrome.
Normal Function
The NPHS1 gene provides instructions for making a protein called nephrin. Nephrin is primarily found in the kidneys within cells called podocytes, located in specialized structures called glomeruli. Nephrin is located at the cell surface in the area between two podocytes called the slit diaphragm.
The slit diaphragm acts as a filtration barrier, capturing proteins in the blood so they remain in the body while allowing molecules like sugars and salts to be excreted in urine. Nephrin proteins on adjacent podocytes interact to form a zipper-like structure that facilitates this filtration. Additionally, nephrin is involved in cell signaling, relaying information from outside the cell to the inside and allowing podocytes to communicate with one another.
Health Conditions Related to Genetic Changes
Congenital nephrotic syndrome
At least 250 mutations in the NPHS1 gene have been found to cause congenital nephrotic syndrome, a kidney disorder that begins in infancy and typically leads to end-stage renal disease by early childhood.
- Congenital nephrotic syndrome of the Finnish type: Caused by two specific mutations (Finnmajor and Finnminor) that result in an abnormally short, nonfunctional nephrin protein.
- Non-Finnish cases: Most mutations result in an abnormal nephrin protein that is trapped inside the cell and cannot reach the podocyte surface.
A shortage of functional nephrin at the podocyte surface impairs the formation of normal slit diaphragms. Without this functional barrier, molecules pass through the kidneys abnormally and are excreted in urine, leading to progressive kidney damage.
Other Names for This Gene
- CNF
- nephrin
- nephrin precursor
- nephrosis 1, congenital, Finnish type (nephrin)
- NPHN
- NPHS1 nephrin
- renal glomerulus-specific cell adhesion receptor