Podocin

NPHS2
Identifiers
Aliases	NPHS2, PDCN, SRN1, NPHS2 podocin, podocin, NPHS2 stomatin family member, podocin
External IDs	OMIM: 604766; MGI: 2157018; GeneCards: NPHS2
Gene location (Human)
Chr.	Chromosome 1 (human)
End	179,575,952 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	156,155,605 bp
RNA expression pattern
	Top expressed in
	glomerulus; ; metanephric glomerulus; ; human kidney; ; testicle; ; kidney tubule; ; sperm; ; gonad; ; renal medulla; ; right testis; ; left testis;
	Top expressed in
	glomerulus; ; Bowman's capsule; ; right kidney; ; parietal layer of glomerular capsule; ; human kidney; ; morula; ; thymus; ; embryo; ; embryo; ; medullary collecting duct;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	protein binding;
Cellular component	extracellular exosome; slit diaphragm; membrane raft; plasma membrane; membrane; intrinsic component of the cytoplasmic side of the plasma membrane; cell-cell junction; endoplasmic reticulum; integral component of plasma membrane; protein-containing complex;
Biological process	actin cytoskeleton reorganization; metanephric glomerular visceral epithelial cell development; excretion;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	7827
	170484
	ENSG00000116218
	ENSMUSG00000026602
	Q9NP85
	Q91X05
	NM_001297575; NM_014625
	NM_130456
	NP_001284504; NP_055440
	NP_569723
	Wikidata
View/Edit Human	View/Edit Mouse

Podocin is a protein that in humans is encoded by the gene NPHS2 (from "nephrosis 2"). It is a component of the filtration slits of podocytes. Glomerular capillary endothelial cells, the glomerular basement membrane and the filtration slits function as the filtration barrier of the kidney glomerulus. Mutations in the podocin gene NPHS2 can cause nephrotic syndrome, such as focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). Symptoms may develop in the first few months of life (congenital nephrotic syndrome) or later in childhood.

Structure

Podocin is a membrane protein of the band-7-stomatin family, consisting of 383 amino acids. It has a transmembrane domain forming a hairpin structure, with two cytoplasmic ends at the N- and C-terminus, the latter of which interacts with the cytosolic tail of nephrin, with CD2AP serving as an adaptor.

Function

Podocin is localized on the membranes of podocyte foot processes (pedicels) where it oligomerizes in lipid rafts together with nephrin to form the filtration slits.

Interactions

NPHS2 has been shown to interact with Nephrin and CD2AP.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000116218 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026602 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Fuchshuber A, Jean G, Gribouval O, Gubler MC, Broyer M, Beckmann JS, et al. (March 1996). "Mapping a gene (SRN1) to chromosome 1q25-q31 in idiopathic nephrotic syndrome confirms a distinct entity of autosomal recessive nephrosis". Human Molecular Genetics. 4 (11): 2155–2158. doi:10.1093/hmg/4.11.2155. PMID 8589695.
↑ Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A, et al. (May 2000). "NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome". Nature Genetics. 24 (4): 349–354. doi:10.1038/74166. PMID 10742096. S2CID 20737871.
↑ "Entrez Gene: NPHS2 Nephrosis 2, idiopathic, steroid-resistant (podocin)".
↑ Jarad G, Miner JH (May 2009). "Update on the glomerular filtration barrier". Current Opinion in Nephrology and Hypertension. 18 (3): 226–232. doi:10.1097/mnh.0b013e3283296044. PMC 2895306. PMID 19374010.
↑ Mollet G, Ratelade J, Boyer O, Muda AO, Morisset L, Lavin TA, et al. (October 2009). "Podocin inactivation in mature kidneys causes focal segmental glomerulosclerosis and nephrotic syndrome". Journal of the American Society of Nephrology. 20 (10): 2181–2189. doi:10.1681/ASN.2009040379. PMC 2754108. PMID 19713307.
↑ Avner ED, Harmon WE, Niaudet P, Yoshikawa N, Emma F, Goldstein SL (2016). Pediatric Nephrology. Springer. ISBN 978-3-662-43596-0. OCLC 1050008865.
1 2 Tabassum A, Rajeshwari T, Soni N, Raju DS, Yadav M, Nayarisseri A, et al. (March 2014). "Structural characterization and mutational assessment of podocin - a novel drug target to nephrotic syndrome - an in silico approach". Interdisciplinary Sciences, Computational Life Sciences. 6 (1): 32–39. doi:10.1007/s12539-014-0190-4. PMID 24464702. S2CID 17163784.
↑ Saleem MA, Ni L, Witherden I, Tryggvason K, Ruotsalainen V, Mundel P, et al. (October 2002). "Co-localization of nephrin, podocin, and the actin cytoskeleton: evidence for a role in podocyte foot process formation". The American Journal of Pathology. 161 (4): 1459–1466. doi:10.1016/S0002-9440(10)64421-5. PMC 1867300. PMID 12368218.
1 2 Schwarz K, Simons M, Reiser J, Saleem MA, Faul C, Kriz W, et al. (December 2001). "Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin". The Journal of Clinical Investigation. 108 (11): 1621–1629. doi:10.1172/JCI12849. PMC 200981. PMID 11733557.

Caridi G, Perfumo F, Ghiggeri GM (2005). "NPHS2 (Podocin) mutations in nephrotic syndrome. Clinical spectrum and fine mechanisms". Pediatric Research. 57 (5 Pt 2): 54R–61R. doi:10.1203/01.PDR.0000160446.01907.B1. PMID 15817495.
"Correction to "NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome"". Nature Genetics. 25 (1): 125. May 2000. doi:10.1038/75526. PMID 10802674. S2CID 40951671.
Huber TB, Kottgen M, Schilling B, Walz G, Benzing T (2001). "Interaction with podocin facilitates nephrin signaling". The Journal of Biological Chemistry. 276 (45): 41543–41546. doi:10.1074/jbc.C100452200. PMID 11562357.
Caridi G, Bertelli R, Carrea A, Di Duca M, Catarsi P, Artero M, et al. (2002). "Prevalence, genetics, and clinical features of patients carrying podocin mutations in steroid-resistant nonfamilial focal segmental glomerulosclerosis". Journal of the American Society of Nephrology. 12 (12): 2742–2746. doi:10.1681/ASN.V12122742. PMID 11729243.
Karle SM, Uetz B, Ronner V, Glaeser L, Hildebrandt F, Fuchshuber A (2002). "Novel mutations in NPHS2 detected in both familial and sporadic steroid-resistant nephrotic syndrome". Journal of the American Society of Nephrology. 13 (2): 388–393. doi:10.1681/ASN.V132388. PMID 11805166.
Koziell A, Grech V, Hussain S, Lee G, Lenkkeri U, Tryggvason K, et al. (2002). "Genotype/phenotype correlations of NPHS1 and NPHS2 mutations in nephrotic syndrome advocate a functional inter-relationship in glomerular filtration". Human Molecular Genetics. 11 (4): 379–388. doi:10.1093/hmg/11.4.379. PMID 11854170.
Boute N, Roselli S, Gribouval O, Niaudet P, Gubler MC, Antignac C (2002). "[Characterization of the NPH2 gene, coding for the glomerular protein podocin, implicated in a familial form of cortico-resistant nephrotic syndrome transmitted as an autosomal recessive]". Nephrologie. 23 (1): 35–36. PMID 11908478.
Carraro M, Caridi G, Bruschi M, Artero M, Bertelli R, Zennaro C, et al. (2002). "Serum glomerular permeability activity in patients with podocin mutations (NPHS2) and steroid-resistant nephrotic syndrome". Journal of the American Society of Nephrology. 13 (7): 1946–1952. doi:10.1097/01.ASN.0000016445.29513.AB. PMID 12089392.
Sellin L, Huber TB, Gerke P, Quack I, Pavenstädt H, Walz G (2003). "NEPH1 defines a novel family of podocin interacting proteins". FASEB Journal. 17 (1): 115–117. doi:10.1096/fj.02-0242fje. PMID 12424224. S2CID 17732086.
Tsukaguchi H, Sudhakar A, Le TC, Nguyen T, Yao J, Schwimmer JA, et al. (2003). "NPHS2 mutations in late-onset focal segmental glomerulosclerosis: R229Q is a common disease-associated allele". The Journal of Clinical Investigation. 110 (11): 1659–1666. doi:10.1172/JCI16242. PMC 151634. PMID 12464671.
Komatsuda A, Wakui H, Maki N, Kigawa A, Goto H, Ohtani H, et al. (2003). "Analysis of mutations in alpha-actinin 4 and podocin genes of patients with chronic renal failure due to sporadic focal segmental glomerulosclerosis". Renal Failure. 25 (1): 87–93. doi:10.1081/JDI-120017471. PMID 12617336. S2CID 22531807.
Ohashi T, Uchida K, Uchida S, Sasaki S, Nihei H (2004). "Intracellular mislocalization of mutant podocin and correction by chemical chaperones". Histochemistry and Cell Biology. 119 (3): 257–264. doi:10.1007/s00418-003-0511-x. PMID 12649741. S2CID 24927819.
Maruyama K, Iijima K, Ikeda M, Kitamura A, Tsukaguchi H, Yoshiya K, et al. (2004). "NPHS2 mutations in sporadic steroid-resistant nephrotic syndrome in Japanese children". Pediatric Nephrology. 18 (5). Berlin, Germany: 412–416. doi:10.1007/s00467-003-1120-6. PMID 12687458. S2CID 2093444.
Caridi G, Bertelli R, Di Duca M, Dagnino M, Emma F, Onetti Muda A, et al. (2003). "Broadening the spectrum of diseases related to podocin mutations". Journal of the American Society of Nephrology. 14 (5): 1278–1286. doi:10.1097/01.ASN.0000060578.79050.E0. PMID 12707396.
Guan N, Ding J, Zhang J, Yang J (2004). "Expression of nephrin, podocin, alpha-actinin, and WT1 in children with nephrotic syndrome". Pediatric Nephrology. 18 (11). Berlin, Germany: 1122–1127. doi:10.1007/s00467-003-1240-z. PMID 12961083. S2CID 39927513.

This article on a gene on human chromosome 1 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000116218 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026602 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Fuchshuber_1996-5] Fuchshuber A, Jean G, Gribouval O, Gubler MC, Broyer M, Beckmann JS, et al. (March 1996). "Mapping a gene (SRN1) to chromosome 1q25-q31 in idiopathic nephrotic syndrome confirms a distinct entity of autosomal recessive nephrosis". Human Molecular Genetics. 4 (11): 2155–2158. doi:10.1093/hmg/4.11.2155. PMID 8589695.

[Boute_2000-6] Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A, et al. (May 2000). "NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome". Nature Genetics. 24 (4): 349–354. doi:10.1038/74166. PMID 10742096. S2CID 20737871.

[7] "Entrez Gene: NPHS2 Nephrosis 2, idiopathic, steroid-resistant (podocin)".

[8] Jarad G, Miner JH (May 2009). "Update on the glomerular filtration barrier". Current Opinion in Nephrology and Hypertension. 18 (3): 226–232. doi:10.1097/mnh.0b013e3283296044. PMC 2895306. PMID 19374010.

[9] Mollet G, Ratelade J, Boyer O, Muda AO, Morisset L, Lavin TA, et al. (October 2009). "Podocin inactivation in mature kidneys causes focal segmental glomerulosclerosis and nephrotic syndrome". Journal of the American Society of Nephrology. 20 (10): 2181–2189. doi:10.1681/ASN.2009040379. PMC 2754108. PMID 19713307.

[10] Avner ED, Harmon WE, Niaudet P, Yoshikawa N, Emma F, Goldstein SL (2016). Pediatric Nephrology. Springer. ISBN 978-3-662-43596-0. OCLC 1050008865.

[Tabassum_2014-11] 1 2 Tabassum A, Rajeshwari T, Soni N, Raju DS, Yadav M, Nayarisseri A, et al. (March 2014). "Structural characterization and mutational assessment of podocin - a novel drug target to nephrotic syndrome - an in silico approach". Interdisciplinary Sciences, Computational Life Sciences. 6 (1): 32–39. doi:10.1007/s12539-014-0190-4. PMID 24464702. S2CID 17163784.

[Saleem-12] Saleem MA, Ni L, Witherden I, Tryggvason K, Ruotsalainen V, Mundel P, et al. (October 2002). "Co-localization of nephrin, podocin, and the actin cytoskeleton: evidence for a role in podocyte foot process formation". The American Journal of Pathology. 161 (4): 1459–1466. doi:10.1016/S0002-9440(10)64421-5. PMC 1867300. PMID 12368218.

[Schwarz_2001-13] 1 2 Schwarz K, Simons M, Reiser J, Saleem MA, Faul C, Kriz W, et al. (December 2001). "Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin". The Journal of Clinical Investigation. 108 (11): 1621–1629. doi:10.1172/JCI12849. PMC 200981. PMID 11733557.

Podocin

Structure

Function

Interactions

References

Further reading