Zinc transporter 8 (ZNT8) is a protein that in humans is encoded by the SLC30A8gene.[5] ZNT8 is a zinc transporter related to insulin secretion in humans. In particular, ZNT8 is critical for the accumulation of zinc into beta cell secretory granules and the maintenance of stored insulin as tightly packaged hexamers. Certain alleles of the SLC30A8 gene may increase the risk for developing type 2 diabetes, but a loss-of-function mutation appears to greatly reduce the risk of diabetes.[6]
Twelve rare variants in SLC30A8 have been identified through the sequencing or genotyping of approximately 150,000 individuals from 5 different ancestry groups. SLC30A8 contains a common variant (p.Trp325Arg), which is associated with T2D risk and levels of glucose and proinsulin.[7][8][9] Individuals carrying protein-truncating variants collectively had 65% reduced risk of T2D. Additionally, non-diabetic individuals from Iceland harboring a frameshift variant p. Lys34Serfs*50 demonstrated reduced glucose levels.[6] Earlier functional studies of SLC30A8 suggested that reduced zinc transport increased T2D risk.[10][11] Conversely, loss-of-function mutations in humans indicate that SLC30A8 haploinsufficiency protects against T2D. Therefore, ZnT8 inhibition can serve as a therapeutic strategy in preventing T2D.[6]
^ abcGRCh38: Ensembl release 89: ENSG00000164756 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000022315 - 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.
^"Entrez Gene: SLC30A8 solute carrier family 30 (zinc transporter), member 8".
^ abcFlannick, Jason; et al. (2014). "Loss-of-function mutations in SLC30A8 protect against type 2 diabetes". Nature Genetics. 46 (4): 357–363. doi:10.1038/ng.2915. PMC4051628. PMID 24584071.
^Dupis, J.; et al. (Feb 2010). "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk". Nature Genetics. 42 (2): 105–16. doi:10.1038/ng.520. PMC3018764. PMID 20081858.
^Strawbridge, R.J.; et al. (October 2011). "Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes". Diabetes. 60 (10): 2624–34. doi:10.2337/db11-0415. PMC3178302. PMID 21873549.
^Morris, A.P.; et al. (Sep 2012). "Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes". Nature Genetics. 44 (9): 981–90. doi:10.1038/ng.2383. PMC3442244. PMID 22885922.
^Nicolson, T.J.; et al. (Sep 2009). "Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes–associated variants". Diabetes. 58 (9): 2070–83. doi:10.2337/db09-0551. PMC2731533. PMID 19542200.
^Rutter, G.A.; et al. (2010). "Think zinc: new roles for zinc in the control of insulin secretion". Islets. 2 (1): 49–50. doi:10.4161/isl.2.1.10259. PMID 21099294.
Further readingEdit
Chimienti F, Favier A, Seve M (2006). "ZnT-8, a pancreatic beta-cell-specific zinc transporter". Biometals. 18 (4): 313–7. doi:10.1007/s10534-005-3687-9. PMID 16158222. S2CID 25680038.
Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC310948. PMID 11076863.
Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC311072. PMID 11230166.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. PMID 12477932.
Seve M, Chimienti F, Devergnas S, Favier A (2004). "In silico identification and expression of SLC30 family genes: an expressed sequence tag data mining strategy for the characterization of zinc transporters' tissue expression". BMC Genomics. 5 (1): 32. doi:10.1186/1471-2164-5-32. PMC428573. PMID 15154973.
Chimienti F, Devergnas S, Favier A, Seve M (2004). "Identification and cloning of a beta-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules". Diabetes. 53 (9): 2330–7. doi:10.2337/diabetes.53.9.2330. PMID 15331542.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC528928. PMID 15489334.
Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to biology: a functional genomics pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC528930. PMID 15489336.
Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC1347501. PMID 16381901.
Sladek R, Rocheleau G, Rung J, et al. (2007). "A genome-wide association study identifies novel risk loci for type 2 diabetes". Nature. 445 (7130): 881–5. Bibcode:2007Natur.445..881S. doi:10.1038/nature05616. PMID 17293876. S2CID 4302932.
Wenzlau JM, Juhl K, Yu L, et al. (2007). "The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes". Proc. Natl. Acad. Sci. U.S.A. 104 (43): 17040–5. Bibcode:2007PNAS..10417040W. doi:10.1073/pnas.0705894104. PMC2040407. PMID 17942684.
External linksEdit
Type 2 diabetes genes mapped out, BBC News article
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zinc, transporter, znt8, protein, that, humans, encoded, slc30a8, gene, znt8, zinc, transporter, related, insulin, secretion, humans, particular, znt8, critical, accumulation, zinc, into, beta, cell, secretory, granules, maintenance, stored, insulin, tightly, . Zinc transporter 8 ZNT8 is a protein that in humans is encoded by the SLC30A8 gene 5 ZNT8 is a zinc transporter related to insulin secretion in humans In particular ZNT8 is critical for the accumulation of zinc into beta cell secretory granules and the maintenance of stored insulin as tightly packaged hexamers Certain alleles of the SLC30A8 gene may increase the risk for developing type 2 diabetes but a loss of function mutation appears to greatly reduce the risk of diabetes 6 SLC30A8IdentifiersAliasesSLC30A8 ZNT8 ZnT 8 solute carrier family 30 member 8External IDsOMIM 611145 MGI 2442682 HomoloGene 13795 GeneCards SLC30A8Gene location Human Chr Chromosome 8 human 1 Band8q24 11Start116 950 273 bp 1 End117 176 714 bp 1 Gene location Mouse Chr Chromosome 15 mouse 2 Band15 15 CStart52 158 949 bp 2 End52 199 194 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inislet of Langerhanspancreatic epithelial cellbody of pancreastibialis anterior muscletesticledeltoid musclekidneykidneyfundusduodenumTop expressed inislet of LangerhansforegutstomachMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionprotein homodimerization activity cation transmembrane transporter activity zinc ion binding protein binding zinc ion transmembrane transporter activityCellular componentintegral component of membrane Golgi apparatus secretory granule membrane membrane plasma membrane transport vesicle membrane secretory granule cytoplasmic vesicleBiological processresponse to interleukin 1 response to interferon gamma glucose homeostasis regulation of vesicle mediated transport zinc ion transport response to zinc ion cation transport insulin secretion ion transport response to glucose cation transmembrane transport sequestering of zinc ion cellular zinc ion homeostasis regulation of sequestering of zinc ion positive regulation of insulin secretion zinc ion transmembrane transport transmembrane transportSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez169026239436EnsemblENSG00000164756ENSMUSG00000022315UniProtQ8IWU4Q8BGG0RefSeq mRNA NM 001172811NM 001172813NM 001172814NM 001172815NM 173851NM 172816RefSeq protein NP 001166282NP 001166284NP 001166285NP 001166286NP 776250NP 766404Location UCSC Chr 8 116 95 117 18 MbChr 15 52 16 52 2 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Clinical significance 1 1 Association with type 2 diabetes T2D 2 See also 3 References 4 Further reading 5 External linksClinical significance EditAssociation with type 2 diabetes T2D Edit Twelve rare variants in SLC30A8 have been identified through the sequencing or genotyping of approximately 150 000 individuals from 5 different ancestry groups SLC30A8 contains a common variant p Trp325Arg which is associated with T2D risk and levels of glucose and proinsulin 7 8 9 Individuals carrying protein truncating variants collectively had 65 reduced risk of T2D Additionally non diabetic individuals from Iceland harboring a frameshift variant p Lys34Serfs 50 demonstrated reduced glucose levels 6 Earlier functional studies of SLC30A8 suggested that reduced zinc transport increased T2D risk 10 11 Conversely loss of function mutations in humans indicate that SLC30A8 haploinsufficiency protects against T2D Therefore ZnT8 inhibition can serve as a therapeutic strategy in preventing T2D 6 See also EditSolute carrier familyReferences Edit a b c GRCh38 Ensembl release 89 ENSG00000164756 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000022315 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 Entrez Gene SLC30A8 solute carrier family 30 zinc transporter member 8 a b c Flannick Jason et al 2014 Loss of function mutations in SLC30A8 protect against type 2 diabetes Nature Genetics 46 4 357 363 doi 10 1038 ng 2915 PMC 4051628 PMID 24584071 Dupis J et al Feb 2010 New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk Nature Genetics 42 2 105 16 doi 10 1038 ng 520 PMC 3018764 PMID 20081858 Strawbridge R J et al October 2011 Genome wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes Diabetes 60 10 2624 34 doi 10 2337 db11 0415 PMC 3178302 PMID 21873549 Morris A P et al Sep 2012 Large scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes Nature Genetics 44 9 981 90 doi 10 1038 ng 2383 PMC 3442244 PMID 22885922 Nicolson T J et al Sep 2009 Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes associated variants Diabetes 58 9 2070 83 doi 10 2337 db09 0551 PMC 2731533 PMID 19542200 Rutter G A et al 2010 Think zinc new roles for zinc in the control of insulin secretion Islets 2 1 49 50 doi 10 4161 isl 2 1 10259 PMID 21099294 Further reading EditChimienti F Favier A Seve M 2006 ZnT 8 a pancreatic beta cell specific zinc transporter Biometals 18 4 313 7 doi 10 1007 s10534 005 3687 9 PMID 16158222 S2CID 25680038 Hartley JL Temple GF Brasch MA 2001 DNA cloning using in vitro site specific recombination Genome Res 10 11 1788 95 doi 10 1101 gr 143000 PMC 310948 PMID 11076863 Wiemann S Weil B Wellenreuther R et al 2001 Toward a catalog of human genes and proteins sequencing and analysis of 500 novel complete protein coding human cDNAs Genome Res 11 3 422 35 doi 10 1101 gr GR1547R PMC 311072 PMID 11230166 Strausberg RL Feingold EA Grouse LH et al 2003 Generation and initial analysis of more than 15 000 full length human and mouse cDNA sequences Proc Natl Acad Sci U S A 99 26 16899 903 Bibcode 2002PNAS 9916899M doi 10 1073 pnas 242603899 PMC 139241 PMID 12477932 Seve M Chimienti F Devergnas S Favier A 2004 In silico identification and expression of SLC30 family genes an expressed sequence tag data mining strategy for the characterization of zinc transporters tissue expression BMC Genomics 5 1 32 doi 10 1186 1471 2164 5 32 PMC 428573 PMID 15154973 Chimienti F Devergnas S Favier A Seve M 2004 Identification and cloning of a beta cell specific zinc transporter ZnT 8 localized into insulin secretory granules Diabetes 53 9 2330 7 doi 10 2337 diabetes 53 9 2330 PMID 15331542 Gerhard DS Wagner L Feingold EA et al 2004 The status quality and expansion of the NIH full length cDNA project the Mammalian Gene Collection MGC Genome Res 14 10B 2121 7 doi 10 1101 gr 2596504 PMC 528928 PMID 15489334 Wiemann S Arlt D Huber W et al 2004 From ORFeome to biology a functional genomics pipeline Genome Res 14 10B 2136 44 doi 10 1101 gr 2576704 PMC 528930 PMID 15489336 Mehrle A Rosenfelder H Schupp I et al 2006 The LIFEdb database in 2006 Nucleic Acids Res 34 Database issue D415 8 doi 10 1093 nar gkj139 PMC 1347501 PMID 16381901 Sladek R Rocheleau G Rung J et al 2007 A genome wide association study identifies novel risk loci for type 2 diabetes Nature 445 7130 881 5 Bibcode 2007Natur 445 881S doi 10 1038 nature05616 PMID 17293876 S2CID 4302932 Wenzlau JM Juhl K Yu L et al 2007 The cation efflux transporter ZnT8 Slc30A8 is a major autoantigen in human type 1 diabetes Proc Natl Acad Sci U S A 104 43 17040 5 Bibcode 2007PNAS 10417040W doi 10 1073 pnas 0705894104 PMC 2040407 PMID 17942684 External links EditType 2 diabetes genes mapped out BBC News article This genetics article is a stub You can help Wikipedia by expanding it vte This membrane protein related article is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Zinc transporter 8 amp oldid 1168361766, wikipedia, wiki, book, books, library,
