Nephrin

Nephrosis 1, congenital, Finnish type (nephrin)
Identifiers
Symbols	NPHS1 ; CNF; NPHN; nephrin
External IDs	OMIM: 602716 MGI: 1859637 HomoloGene: 20974 GeneCards: NPHS1 Gene
Gene ontology Molecular function • protein binding • myosin binding Cellular component • intracellular • plasma membrane • integral component of plasma membrane • slit diaphragm • cell projection • extracellular exosome Biological process • cell adhesion • JNK cascade • skeletal muscle tissue development • myoblast fusion • excretion • positive regulation of actin filament polymerization • glomerular basement membrane development • regulation of excretion • glomerular visceral epithelial cell development Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4868	54631
Ensembl	ENSG00000161270	ENSMUSG00000006649
UniProt	O60500	Q9QZS7
RefSeq (mRNA)	NM_004646	NM_019459
RefSeq (protein)	NP_004637	NP_062332
Location (UCSC)	Chr 19: 35.83 – 35.87 Mb	Chr 7: 30.46 – 30.49 Mb
PubMed search

Nephrin is a protein necessary for the proper functioning of the renal filtration barrier. The renal filtration barrier consists of fenestrated endothelial cells, the glomerular basement membrane, and the podocytes of epithelial cells. Nephrin is a transmembrane protein that is a structural component of the slit diaphragm.^[1] They are present on the tips of the podocytes and maintain the normal relationship between the basement membrane and the podocytes of the epithelial cells.

A defect in the gene for nephrin, NPHS1, is associated with congenital nephrotic syndrome of the Finnish type and causes massive amounts of protein to be leaked into the urine, or proteinuria. Nephrin is also required for cardiovascular development.^[2]

Interactions

Nephrin has been shown to interact with:

• CASK,^[3]
• CD2AP,^[3]
• CDH3^[3] and
• CTNND1,^[3]
• FYN,^[4][5]
• KIRREL,^[6][7] and
• NPHS2.^[8]

See also

• Podocyte

References

1. "Entrez Gene: NPHS1 nephrosis 1, congenital, Finnish type (nephrin)".
2. Wagner N, Morrison H, Pagnotta S, Michiels JF, Schwab Y, Tryggvason K, Schedl A, Wagner KD (2011-03-29). "The podocyte protein nephrin is required for cardiac vessel formation.". Human Molecular Genetics 20 (11): 2182–94. doi:10.1093/hmg/ddr106. PMID 21402589.
3. Lehtonen S, Lehtonen E, Kudlicka K, Holthöfer H, Farquhar MG (Sep 2004). "Nephrin forms a complex with adherens junction proteins and CASK in podocytes and in Madin-Darby canine kidney cells expressing nephrin". Am. J. Pathol. 165 (3): 923–36. doi:10.1016/S0002-9440(10)63354-8. PMC 1618613. PMID 15331416.
4. Lahdenperä J, Kilpeläinen P, Liu XL, Pikkarainen T, Reponen P, Ruotsalainen V, Tryggvason K (Aug 2003). "Clustering-induced tyrosine phosphorylation of nephrin by Src family kinases". Kidney Int. 64 (2): 404–13. doi:10.1046/j.1523-1755.2003.00097.x. PMID 12846735.
5. Verma R, Wharram B, Kovari I, Kunkel R, Nihalani D, Wary KK, Wiggins RC, Killen P, Holzman LB (Jun 2003). "Fyn binds to and phosphorylates the kidney slit diaphragm component Nephrin". J. Biol. Chem. 278 (23): 20716–23. doi:10.1074/jbc.M301689200. PMID 12668668.
6. Liu G, Kaw B, Kurfis J, Rahmanuddin S, Kanwar YS, Chugh SS (Jul 2003). "Neph1 and nephrin interaction in the slit diaphragm is an important determinant of glomerular permeability". J. Clin. Invest. 112 (2): 209–21. doi:10.1172/JCI18242. PMC 164293. PMID 12865409.
7. Gerke P, Huber TB, Sellin L, Benzing T, Walz G (Apr 2003). "Homodimerization and heterodimerization of the glomerular podocyte proteins nephrin and NEPH1". J. Am. Soc. Nephrol. 14 (4): 918–26. doi:10.1097/01.ASN.0000057853.05686.89. PMID 12660326.
8. Schwarz K, Simons M, Reiser J, Saleem MA, Faul C, Kriz W, Shaw AS, Holzman LB, Mundel P (Dec 2001). "Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin". J. Clin. Invest. 108 (11): 1621–9. doi:10.1172/JCI12849. PMC 200981. PMID 11733557.

Further reading

• Tryggvason K (2002). "Nephrin: role in normal kidney and in disease.". Adv. Nephrol. Necker Hosp. 31: 221–34. PMID 11692461.
• Kestilä M, Lenkkeri U, Männikkö M, Lamerdin J, McCready P, Putaala H, Ruotsalainen V, Morita T, Nissinen M, Herva R, Kashtan CE, Peltonen L, Holmberg C, Olsen A, Tryggvason K (1998). "Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome.". Mol. Cell 1 (4): 575–82. doi:10.1016/S1097-2765(00)80057-X. PMID 9660941.
• Lenkkeri U, Männikkö M, McCready P, Lamerdin J, Gribouval O, Niaudet PM, Antignac CK, Kashtan CE, Homberg C, Olsen A, Kestilä M, Tryggvason K (1999). "Structure of the gene for congenital nephrotic syndrome of the finnish type (NPHS1) and characterization of mutations.". Am. J. Hum. Genet. 64 (1): 51–61. doi:10.1086/302182. PMC 1377702. PMID 9915943.
• Ruotsalainen V, Ljungberg P, Wartiovaara J, Lenkkeri U, Kestilä M, Jalanko H, Holmberg C, Tryggvason K (1999). "Nephrin is specifically located at the slit diaphragm of glomerular podocytes.". Proc. Natl. Acad. Sci. U.S.A. 96 (14): 7962–7. doi:10.1073/pnas.96.14.7962. PMC 22170. PMID 10393930.
• Holthöfer H, Ahola H, Solin ML, Wang S, Palmen T, Luimula P, Miettinen A, Kerjaschki D (1999). "Nephrin localizes at the podocyte filtration slit area and is characteristically spliced in the human kidney.". Am. J. Pathol. 155 (5): 1681–7. doi:10.1016/S0002-9440(10)65483-1. PMC 1866978. PMID 10550324.
• Bolk S, Puffenberger EG, Hudson J, Morton DH, Chakravarti A (2000). "Elevated frequency and allelic heterogeneity of congenital nephrotic syndrome, Finnish type, in the old order Mennonites.". Am. J. Hum. Genet. 65 (6): 1785–90. doi:10.1086/302687. PMC 1288392. PMID 10577936.
• Aya K, Tanaka H, Seino Y (2000). "Novel mutation in the nephrin gene of a Japanese patient with congenital nephrotic syndrome of the Finnish type.". Kidney Int. 57 (2): 401–4. doi:10.1046/j.1523-1755.2000.00859.x. PMID 10652016.
• Li C, Ruotsalainen V, Tryggvason K, Shaw AS, Miner JH (2000). "CD2AP is expressed with nephrin in developing podocytes and is found widely in mature kidney and elsewhere.". Am. J. Physiol. Renal Physiol. 279 (4): F785–92. PMID 10997929.
• Huber TB, Kottgen M, Schilling B, Walz G, Benzing T (2001). "Interaction with podocin facilitates nephrin signaling.". J. Biol. Chem. 276 (45): 41543–6. doi:10.1074/jbc.C100452200. PMID 11562357.
• Palmén T, Ahola H, Palgi J, Aaltonen P, Luimula P, Wang S, Jaakkola I, Knip M, Otonkoski T, Holthöfer H (2002). "Nephrin is expressed in the pancreatic beta cells.". Diabetologia 44 (10): 1274–80. doi:10.1007/s001250100641. PMID 11692176.
• Schwarz K, Simons M, Reiser J, Saleem MA, Faul C, Kriz W, Shaw AS, Holzman LB, Mundel P (2002). "Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin.". J. Clin. Invest. 108 (11): 1621–9. doi:10.1172/JCI12849. PMC 200981. PMID 11733557.
• Koziell A, Grech V, Hussain S, Lee G, Lenkkeri U, Tryggvason K, Scambler P (2002). "Genotype/phenotype correlations of NPHS1 and NPHS2 mutations in nephrotic syndrome advocate a functional inter-relationship in glomerular filtration.". Hum. Mol. Genet. 11 (4): 379–88. doi:10.1093/hmg/11.4.379. PMID 11854170.
• Yan K, Khoshnoodi J, Ruotsalainen V, Tryggvason K (2002). "N-linked glycosylation is critical for the plasma membrane localization of nephrin.". J. Am. Soc. Nephrol. 13 (5): 1385–9. doi:10.1097/01.ASN.0000013297.11876.5B. PMID 11961028.
• Shimizu J, Tanaka H, Aya K, Ito S, Sado Y, Seino Y (2002). "A missense mutation in the nephrin gene impairs membrane targeting.". Am. J. Kidney Dis. 40 (4): 697–703. doi:10.1053/ajkd.2002.35676. PMID 12324903.
• Saleem MA, Ni L, Witherden I, Tryggvason K, Ruotsalainen V, Mundel P, Mathieson PW (2002). "Co-localization of nephrin, podocin, and the actin cytoskeleton: evidence for a role in podocyte foot process formation.". Am. J. Pathol. 161 (4): 1459–66. doi:10.1016/S0002-9440(10)64421-5. PMC 1867300. PMID 12368218.
• Kim BK, Hong HK, Kim JH, Lee HS (2002). "Differential expression of nephrin in acquired human proteinuric diseases.". Am. J. Kidney Dis. 40 (5): 964–73. doi:10.1053/ajkd.2002.36328. PMID 12407641.
• Langham RG, Kelly DJ, Cox AJ, Thomson NM, Holthöfer H, Zaoui P, Pinel N, Cordonnier DJ, Gilbert RE (2003). "Proteinuria and the expression of the podocyte slit diaphragm protein, nephrin, in diabetic nephropathy: effects of angiotensin converting enzyme inhibition.". Diabetologia 45 (11): 1572–6. doi:10.1007/s00125-002-0946-y. PMID 12436341.
• Gigante M, Monno F, Roberto R, Laforgia N, Assael MB, Livolti S, Caringella A, La Manna A, Masella L, Iolascon A (2003). "Congenital nephrotic syndrome of the Finnish type in Italy: a molecular approach.". J. Nephrol. 15 (6): 696–702. PMID 12495287.
• Pettersson-Fernholm K, Forsblom C, Perola M, Groop PH (2003). "Polymorphisms in the nephrin gene and diabetic nephropathy in type 1 diabetic patients.". Kidney Int. 63 (4): 1205–10. doi:10.1046/j.1523-1755.2003.00855.x. PMID 12631336.

External links

• nephrin at the US National Library of Medicine Medical Subject Headings (MeSH)