Nephrin

Nephrin forms the slit diaphragm between podocytes' foot processes. Mutations of the gene cause an autosomal recessive disease, the congenital steroid resistant nephrotic syndrome of the Finnish type.

Protein Structure

Nephrin consists of 3 domains. Intracellular and transmembrane domains are only short. The 35nm-long extracellular domain contains a proximal fibronectin type III-like motif and 8 distal IgG-like motifs. Extracellular protein chains from adjacent foot processes are stretched out towards each other, interact in the middle, and form the slits, so important to the filtering function of the glomeruli.

With a tyrosine residue phosphorylated by tyrosine kinases (Src, Fyn), the intracellular domain plays an important role in signal transduction.

Genetests:

Related Diseases:

Congenital nephrotic syndrome type 01 (Finnish type)
	NPHS1

Glomerulosclerosis
	Familial partial lipodystrophy type 2
		LMNA
	Focal, segmental glomerulosclerosis (FSGS)
		ALG13
		ARHGAP24
		CLU
		Hereditary FSGS type 1
			ACTN4
		Hereditary FSGS type 2
			TRPC6
		Hereditary FSGS type 3
			CD2AP
		Hereditary FSGS type 4
			APOL1
		Hereditary FSGS type 5
			INF2
		Hereditary FSGS type 6
			MYO1E
		Hereditary FSGS type 7
			PAX2
		Hereditary FSGS type 8
			ANLN
		Hereditary FSGS type 9
			CRB2
		ITGA9
		LAMA5
		NXF5
	Frasier syndrome
		WT1
	Glycogen storage disease 1A
		G6PC
	Norum disease
		LCAT

References:

1.	Koziell A et al. (2002) Genotype/phenotype correlations of NPHS1 and NPHS2 mutations in nephrotic syndrome advocate a functional inter-relationship in glomerular filtration.

2.	Philippe A et al. (2008) Nephrin mutations can cause childhood-onset steroid-resistant nephrotic syndrome.

3.	Santín S et al. (2009) Nephrin mutations cause childhood- and adult-onset focal segmental glomerulosclerosis.

4.	Orphanet article Orphanet ID 123889

5.	NCBI article NCBI 4868

6.	OMIM.ORG article Omim 602716

7.	Wikipedia article Wikipedia EN (Nephrin)