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Gene Review

NPHS1  -  nephrosis 1, congenital, Finnish type...

Homo sapiens

Synonyms: CNF, NPHN, Nephrin, Renal glomerulus-specific cell adhesion receptor, nephrin
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Disease relevance of NPHS1


Psychiatry related information on NPHS1

  • Gait disturbance and dementia were quantified by an NPH scale (NPHS) and handicap by the modified Rankin scale (MRS) [6].

High impact information on NPHS1

  • Congenital nephrotic syndrome of the Finnish type (NPHS1) is an autosomal-recessive disorder, characterized by massive proteinuria in utero and nephrosis at birth [7].
  • The NPHS1 gene product, termed nephrin, is a 1241-residue putative transmembrane protein of the immunoglobulin family of cell adhesion molecules, which by Northern and in situ hybridization was shown to be specifically expressed in renal glomeruli [7].
  • Structure of the gene for congenital nephrotic syndrome of the finnish type (NPHS1) and characterization of mutations [8].
  • 1. In the present study, the genomic structure of the nephrin gene was analyzed, and 35 NPHS1 patients were screened for the presence of mutations in the gene [8].
  • CNF represents a unique, apparently specific dysfunction of the renal basement membranes, and the estimated incidence of CNF in the isolated population of Finland is 1 in 8,000 newborns [9].

Chemical compound and disease context of NPHS1


Biological context of NPHS1


Anatomical context of NPHS1


Associations of NPHS1 with chemical compounds

  • Mutations in the nephrin gene (NPHS1) lead to congenital Finnish nephropathy, whereas alterations in the level of nephrin expression have been identified in a wide range of acquired glomerular diseases [15].
  • We conclude that renal transplantation substantially improves the triglyceride and cholesterol abnormalities in CNF but significant abnormalities still persist [24].
  • The HN Ca value (2.80 +/- 0.18 mmol/L) was similar to those in PHP and NPHN subjects [25].
  • Increases of lipoperoxidation products MDA and 4-HNE were constantly found in the glomeruli of CNF [26].
  • Chemotherapy consisted of three presurgical cycles of CNF [cyclophosphamide at 600 mg/m2, mitoxantrone (Novantrone) at 10 mg/m2 and 5-fluorouracil at 600 mg/m2] administered every 2 weeks, plus G-CSF (5 microg/kg s.c./day on days 7-12) [27].

Other interactions of NPHS1

  • In mutant kidneys, NPHS1 and NPHS2 were only moderately downregulated (25 to 30%) at birth but not at 2 or 4 months [28].
  • Taken together, these results suggest that WT1 may be required for regulation of the NPHS1 gene in vivo [15].
  • In addition, mice lacking NEPH1 develop a nephrotic syndrome that resembles NPHS mutations, suggesting that all three proteins are essential for the integrity of glomerular podocytes [29].
  • The remaining five S/MARs were found within intronic sequences of APLP1, HSPOX1, MAG, and NPHS1 genes, and can be tentatively characterized as regulatory S/MARs [30].
  • BACKGROUND: Congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessive disorder mainly caused by mutations in the nephrin gene (NPHS1) [31].

Analytical, diagnostic and therapeutic context of NPHS1

  • Our findings provide the first evidence for a functional inter-relationship between NPHS1 and NPHS2 in human nephrotic disease, thus underscoring their critical role in the regulation of glomerular filtration [1].
  • A total of 464 Japanese subjects, including 267 patients with histologically proven IgAN and 197 healthy controls with normal urinalysis, were genotyped for the NPHS1 G349A, G2289A, and T3315C polymorphisms [18].
  • METHODS: The pathologic lesions and expression of profibrotic and proinflammatory factors in nephrectomized NPHS1 kidneys were studied by immunohistochemistry, Western blotting, and cytokine antibody array [32].
  • Methods and Results: We describe two different molecular methods for the detection of the NPHS1 mutations: a PCR-restriction fragment length polymorphism (PCR-RFLP) and a dual-color oligonucleotide ligation assay (OLA) [33].
  • Direct sequencing was performed after PCR amplification of all 29 and 8 exons of the NPHS1 and NPHS2 genes, respectively [34].


  1. Genotype/phenotype correlations of NPHS1 and NPHS2 mutations in nephrotic syndrome advocate a functional inter-relationship in glomerular filtration. Koziell, A., Grech, V., Hussain, S., Lee, G., Lenkkeri, U., Tryggvason, K., Scambler, P. Hum. Mol. Genet. (2002) [Pubmed]
  2. Molecular basis of the functional podocin-nephrin complex: mutations in the NPHS2 gene disrupt nephrin targeting to lipid raft microdomains. Huber, T.B., Simons, M., Hartleben, B., Sernetz, L., Schmidts, M., Gundlach, E., Saleem, M.A., Walz, G., Benzing, T. Hum. Mol. Genet. (2003) [Pubmed]
  3. The genetic basis of FSGS and steroid-resistant nephrosis. Pollak, M.R. Semin. Nephrol. (2003) [Pubmed]
  4. Muscular dystonia and athetosis in six patients with congenital nephrotic syndrome of the Finnish type (NPHS1). Laakkonen, H., Lönnqvist, T., Uusimaa, J., Qvist, E., Valanne, L., Nuutinen, M., Ala-Houhala, M., Majamaa, K., Jalanko, H., Holmberg, C. Pediatr. Nephrol. (2006) [Pubmed]
  5. Prenatal findings in four consecutive pregnancies with fetal Pierson syndrome, a newly defined congenital nephrosis syndrome. Mark, K., Reis, A., Zenker, M. Prenat. Diagn. (2006) [Pubmed]
  6. How to select patients with normal pressure hydrocephalus for shunting. Tans, J.T., Boon, A.J. Acta Neurochir. Suppl. (2002) [Pubmed]
  7. Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome. Kestilä, M., Lenkkeri, U., Männikkö, M., Lamerdin, J., McCready, P., Putaala, H., Ruotsalainen, V., Morita, T., Nissinen, M., Herva, R., Kashtan, C.E., Peltonen, L., Holmberg, C., Olsen, A., Tryggvason, K. Mol. Cell (1998) [Pubmed]
  8. Structure of the gene for congenital nephrotic syndrome of the finnish type (NPHS1) and characterization of mutations. Lenkkeri, U., Männikkö, M., McCready, P., Lamerdin, J., Gribouval, O., Niaudet, P.M., Antignac C, K., Kashtan, C.E., Homberg, C., Olsen, A., Kestilä, M., Tryggvason, K. Am. J. Hum. Genet. (1999) [Pubmed]
  9. Congenital nephrotic syndrome of the Finnish type maps to the long arm of chromosome 19. Kestilä, M., Männikkö, M., Holmberg, C., Gyapay, G., Weissenbach, J., Savolainen, E.R., Peltonen, L., Tryggvason, K. Am. J. Hum. Genet. (1994) [Pubmed]
  10. Genetic basis of nephrotic syndrome--review. Obeidová, H., Merta, M., Reiterová, J., Maixnerová, D., Stekrová, J., Rysavá, R., Tesar, V. Prague medical report. (2006) [Pubmed]
  11. A randomized multicenter trial comparing mitoxantrone, cyclophosphamide, and fluorouracil with doxorubicin, cyclophosphamide, and fluorouracil in the therapy of metastatic breast carcinoma. Bennett, J.M., Muss, H.B., Doroshow, J.H., Wolff, S., Krementz, E.T., Cartwright, K., Dukart, G., Reisman, A., Schoch, I. J. Clin. Oncol. (1988) [Pubmed]
  12. A randomized multicenter trial of cyclophosphamide, Novantrone and 5-fluorouracil (CNF) versus cyclophosphamide, Adriamycin and 5-fluorouracil (CAF) in patients with metastatic breast cancer. Bennett, J.M., Byrne, P., Desai, A., White, C., DeConti, R., Vogel, C., Krementz, E., Muggia, F., Doroshow, J., Plotkin, D. Investigational new drugs. (1985) [Pubmed]
  13. Growth, serum lipoproteins and apoproteins in infants with congenital nephrosis. Antikainen, M., Holmberg, C., Taskinen, M.R. Clin. Nephrol. (1992) [Pubmed]
  14. Phase III trial of cyclophosphamide, epirubicin, fluorouracil (CEF) versus cyclophosphamide, mitoxantrone, fluorouracil (CNF) in women with metastatic breast cancer. Estaban, E., Lacave, A.J., Fernández, J.L., Corral, N., Buesa, J.M., Estrada, E., Palacio, I., Vieitez, J.M., Muñiz, I., Alvarez, E. Breast Cancer Res. Treat. (1999) [Pubmed]
  15. WT1 activates a glomerular-specific enhancer identified from the human nephrin gene. Guo, G., Morrison, D.J., Licht, J.D., Quaggin, S.E. J. Am. Soc. Nephrol. (2004) [Pubmed]
  16. Genetic kidney diseases disclose the pathogenesis of proteinuria. Jalanko, H., Patrakka, J., Tryggvason, K., Holmberg, C. Ann. Med. (2001) [Pubmed]
  17. Nephrin gene (NPHS1) in patients with minimal change nephrotic syndrome (MCNS). Lahdenkari, A.T., Kestilä, M., Holmberg, C., Koskimies, O., Jalanko, H. Kidney Int. (2004) [Pubmed]
  18. Genetic polymorphism of NPHS1 modifies the clinical manifestations of Ig A nephropathy. Narita, I., Goto, S., Saito, N., Song, J., Kondo, D., Omori, K., Kawachi, H., Shimizu, F., Sakatsume, M., Ueno, M., Gejyo, F. Lab. Invest. (2003) [Pubmed]
  19. Interaction with podocin facilitates nephrin signaling. Huber, T.B., Kottgen, M., Schilling, B., Walz, G., Benzing, T. J. Biol. Chem. (2001) [Pubmed]
  20. Filtrin is a novel member of nephrin-like proteins. Ihalmo, P., Palmén, T., Ahola, H., Valtonen, E., Holthöfer, H. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  21. Nck adaptor proteins link nephrin to the actin cytoskeleton of kidney podocytes. Jones, N., Blasutig, I.M., Eremina, V., Ruston, J.M., Bladt, F., Li, H., Huang, H., Larose, L., Li, S.S., Takano, T., Quaggin, S.E., Pawson, T. Nature (2006) [Pubmed]
  22. Structure of the human amyloid-precursor-like protein gene APLP1 at 19q13.1. Lenkkeri, U., Kestilä, M., Lamerdin, J., McCready, P., Adamson, A., Olsen, A., Tryggvason, K. Hum. Genet. (1998) [Pubmed]
  23. Altered gene expression and functions of mitochondria in human nephrotic syndrome. Holthöfer, H., Kretzler, M., Haltia, A., Solin, M.L., Taanman, J.W., Schägger, H., Kriz, W., Kerjaschki, D., Schlöndorff, D. FASEB J. (1999) [Pubmed]
  24. Short-term effects of renal transplantation on plasma lipids and lipoprotein lipase in children with congenital nephrosis. Antikainen, M., Holmberg, C., Taskinen, M.R. Clin. Nephrol. (1994) [Pubmed]
  25. Carboxyl-terminal fragments of parathyroid hormone are not secreted preferentially in primary hyperparathyroidism as they are in other hypercalcemic conditions. Brossard, J.H., Whittom, S., Lepage, R., D'Amour, P. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
  26. Lipid peroxidation in human proteinuric disease. Solin, M.L., Ahola, H., Haltia, A., Ursini, F., Montine, T., Roveri, A., Kerjaschki, D., Holthöfer, H. Kidney Int. (2001) [Pubmed]
  27. Neoadjuvant chemotherapy with accelerated CNF plus G-CSF in patients with breast cancer tumors larger than three centimeters: a pilot study. Lorusso, V., Catino, A., Schittulli, F., Longo, S., Racanelli, A., Timurian, A., Marzullo, F., Simone, G., Brandi, M., De Lena, M. Int. J. Oncol. (1998) [Pubmed]
  28. The Wt1+/R394W mouse displays glomerulosclerosis and early-onset renal failure characteristic of human Denys-Drash syndrome. Gao, F., Maiti, S., Sun, G., Ordonez, N.G., Udtha, M., Deng, J.M., Behringer, R.R., Huff, V. Mol. Cell. Biol. (2004) [Pubmed]
  29. NEPH1 defines a novel family of podocin interacting proteins. Sellin, L., Huber, T.B., Gerke, P., Quack, I., Pavenstädt, H., Walz, G. FASEB J. (2003) [Pubmed]
  30. Identification and mapping of nuclear matrix-attachment regions in a one megabase locus of human chromosome 19q13.12: long-range correlation of S/MARs and gene positions. Chernov, I.P., Akopov, S.B., Nikolaev, L.G., Sverdlov, E.D. J. Cell. Biochem. (2002) [Pubmed]
  31. Congenital nephrotic syndrome of the Finnish type in Italy: a molecular approach. Gigante, M., Monno, F., Roberto, R., Laforgia, N., Assael, M.B., Livolti, S., Caringella, A., La Manna, A., Masella, L., Iolascon, A. J. Nephrol. (2002) [Pubmed]
  32. Kidneys with heavy proteinuria show fibrosis, inflammation, and oxidative stress, but no tubular phenotypic change. Kuusniemi, A.M., Lapatto, R., Holmberg, C., Karikoski, R., Rapola, J., Jalanko, H. Kidney Int. (2005) [Pubmed]
  33. Detection of the Finnish-type congenital nephrotic syndrome by restriction fragment length polymorphism and dual-color oligonucleotide ligation assays. Romppanen, E.L., Mononen, I. Clin. Chem. (2000) [Pubmed]
  34. NPHS1 and NPHS2 gene mutations in Chinese children with sporadic nephrotic syndrome. Mao, J., Zhang, Y., Du, L., Dai, Y., Gu, W., Liu, A., Shang, S., Liang, L. Pediatr. Res. (2007) [Pubmed]
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