Zinc transporter 8: Difference between revisions

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{{Short description|Protein found in humans}}
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{{Infobox_gene}}
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Solute carrier family 30 (zinc transporter), member 8
| HGNCid = 20303
| Symbol = SLC30A8
| AltSymbols =; ZnT-8
| OMIM =
| ECnumber =
| Homologene = 13795
| MGIid = 2442682
| GeneAtlas_image1 = PBB_GE_SLC30A8_gnf1h06210_at_tn.png
| Function = {{GNF_GO|id=GO:0008324 |text = cation transmembrane transporter activity}}
| Component = {{GNF_GO|id=GO:0016020 |text = membrane}}
| Process = {{GNF_GO|id=GO:0006812 |text = cation transport}}
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 169026
| Hs_Ensembl = ENSG00000164756
| Hs_RefseqProtein = NP_776250
| Hs_RefseqmRNA = NM_173851
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 8
| Hs_GenLoc_start = 118032399
| Hs_GenLoc_end = 118258131
| Hs_Uniprot =
| Mm_EntrezGene = 239436
| Mm_Ensembl = ENSMUSG00000022315
| Mm_RefseqmRNA = NM_172816
| Mm_RefseqProtein = NP_766404
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 15
| Mm_GenLoc_start = 52125636
| Mm_GenLoc_end = 52165816
| Mm_Uniprot =
}}
}}


'''Solute carrier family 30 (zinc transporter), member 8''', also known as '''SLC30A8''', is a human [[gene]]<ref name="entrez">{{cite web | title = Entrez Gene: SLC30A8 solute carrier family 30 (zinc transporter), member 8| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=169026| accessdate = }}</ref> that codes for a [[zinc]] [[Transport protein|transporter]] related to [[insulin]] secretion in humans. Certain [[Allele|alleles]] of this gene may be responsible for a large percentage of [[Diabetes mellitus type 2|type 2 diabetes]] cases.
'''Zinc transporter 8''' ('''ZNT8''') is a [[protein]] that in humans is encoded by the ''SLC30A8'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: SLC30A8 solute carrier family 30 (zinc transporter), member 8| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=169026}}</ref> 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 [[allele]]s of the SLC30A8 gene may increase the risk for developing [[Diabetes mellitus type 2|type 2 diabetes]], but a loss-of-function mutation appears to greatly reduce the risk of diabetes.<ref name="Loss-of-function">{{cite journal|last=Flannick|first=Jason|title=Loss-of-function mutations in SLC30A8 protect against type 2 diabetes|journal=Nature Genetics|year=2014|doi=10.1038/ng.2915|display-authors=etal|volume=46|issue=4|pages=357–363|pmid=24584071|pmc=4051628}}</ref>


== Clinical significance ==
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->

{{PBB_Summary
=== Association with type 2 diabetes (T2D)===
| section_title =
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.<ref>{{cite journal|last1=Dupis|first1=J.|title=New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.|journal=Nature Genetics|doi=10.1038/ng.520|pmid=20081858|volume=42|issue=2|date=Feb 2010|pages=105–16|display-authors=etal|pmc=3018764}}</ref><ref>{{cite journal|last1=Strawbridge|first1=R.J.|title=Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.|journal=Diabetes|doi=10.2337/db11-0415|pmid=21873549|url=http://diabetes.diabetesjournals.org/content/60/10/2624|volume=60|issue=10|pmc=3178302|date=October 2011|pages=2624–34|display-authors=etal}}</ref><ref>{{cite journal|last1=Morris|first1=A.P.|title=Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes.|journal=Nature Genetics|doi=10.1038/ng.2383|pmid=22885922|volume=44|issue=9|date=Sep 2012|pages=981–90|display-authors=etal|pmc=3442244}}</ref> Individuals carrying protein-truncating variants collectively had 65% reduced risk of T2D. Additionally, non-diabetic individuals from Iceland harboring a frameshift variant p.&nbsp;Lys34Serfs*50 demonstrated reduced glucose levels.<ref name="Loss-of-function" /> Earlier functional studies of SLC30A8 suggested that reduced zinc transport increased T2D risk.<ref>{{cite journal|last1=Nicolson|first1=T.J.|title=Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes–associated variants.|journal=Diabetes|doi=10.2337/db09-0551|pmid=19542200|url=http://diabetes.diabetesjournals.org/content/58/9/2070|volume=58|issue=9|date=Sep 2009|pages=2070–83|display-authors=etal|pmc=2731533}}</ref><ref>{{cite journal|last1=Rutter|first1=G.A.|title=Think zinc: new roles for zinc in the control of insulin secretion.|journal=Islets|doi=10.4161/isl.2.1.10259|pmid=21099294|volume=2|issue=1|pages=49–50|display-authors=etal|year=2010|doi-access=free}}</ref> 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.<ref name="Loss-of-function" />
| summary_text =
}}


==See also==
==See also==
Line 62: Line 17:
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
*{{cite journal |vauthors=Chimienti F, Favier A, Seve M |title=ZnT-8, a pancreatic beta-cell-specific zinc transporter. |journal=Biometals |volume=18 |issue= 4 |pages= 313–7 |year= 2006 |pmid= 16158222 |doi= 10.1007/s10534-005-3687-9 |s2cid=25680038 }}
{{PBB_Further_reading
*{{cite journal |vauthors=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination. |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788–95 |year= 2001 |pmid= 11076863 |doi=10.1101/gr.143000 | pmc=310948 }}
| citations =
*{{cite journal | author=Chimienti F, Favier A, Seve M |title=ZnT-8, a pancreatic beta-cell-specific zinc transporter. |journal=Biometals |volume=18 |issue= 4 |pages= 313–7 |year= 2006 |pmid= 16158222 |doi= 10.1007/s10534-005-3687-9 }}
*{{cite journal |vauthors=Wiemann S, Weil B, Wellenreuther R, etal |title=Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. |journal=Genome Res. |volume=11 |issue= 3 |pages= 422–35 |year= 2001 |pmid= 11230166 |doi= 10.1101/gr.GR1547R | pmc=311072 }}
*{{cite journal | author=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination. |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788–95 |year= 2001 |pmid= 11076863 |doi= }}
*{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }}
*{{cite journal | author=Wiemann S, Weil B, Wellenreuther R, ''et al.'' |title=Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. |journal=Genome Res. |volume=11 |issue= 3 |pages= 422–35 |year= 2001 |pmid= 11230166 |doi= 10.1101/gr.154701 }}
*{{cite journal |vauthors=Seve M, Chimienti F, Devergnas S, Favier A |title=In silico identification and expression of SLC30 family genes: an expressed sequence tag data mining strategy for the characterization of zinc transporters' tissue expression. |journal=BMC Genomics |volume=5 |pages= 32 |year= 2004 |pmid= 15154973 |doi= 10.1186/1471-2164-5-32 | pmc=428573 |issue=1 |doi-access=free }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal |vauthors=Chimienti F, Devergnas S, Favier A, Seve M |title=Identification and cloning of a beta-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules. |journal=Diabetes |volume=53 |issue= 9 |pages= 2330–7 |year= 2004 |pmid= 15331542 |doi=10.2337/diabetes.53.9.2330 |doi-access=free }}
*{{cite journal | author=Seve M, Chimienti F, Devergnas S, Favier A |title=In silico identification and expression of SLC30 family genes: an expressed sequence tag data mining strategy for the characterization of zinc transporters' tissue expression. |journal=BMC Genomics |volume=5 |issue= 1 |pages= 32 |year= 2004 |pmid= 15154973 |doi= 10.1186/1471-2164-5-32 }}
*{{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
*{{cite journal | author=Chimienti F, Devergnas S, Favier A, Seve M |title=Identification and cloning of a beta-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules. |journal=Diabetes |volume=53 |issue= 9 |pages= 2330–7 |year= 2004 |pmid= 15331542 |doi= }}
*{{cite journal |vauthors=Wiemann S, Arlt D, Huber W, etal |title=From ORFeome to biology: a functional genomics pipeline. |journal=Genome Res. |volume=14 |issue= 10B |pages= 2136–44 |year= 2004 |pmid= 15489336 |doi= 10.1101/gr.2576704 | pmc=528930 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal |vauthors=Mehrle A, Rosenfelder H, Schupp I, etal |title=The LIFEdb database in 2006. |journal=Nucleic Acids Res. |volume=34 |issue= Database issue |pages= D415–8 |year= 2006 |pmid= 16381901 |doi= 10.1093/nar/gkj139 | pmc=1347501 }}
*{{cite journal | author=Wiemann S, Arlt D, Huber W, ''et al.'' |title=From ORFeome to biology: a functional genomics pipeline. |journal=Genome Res. |volume=14 |issue= 10B |pages= 2136–44 |year= 2004 |pmid= 15489336 |doi= 10.1101/gr.2576704 }}
*{{cite journal |vauthors=Sladek R, Rocheleau G, Rung J, etal |title=A genome-wide association study identifies novel risk loci for type 2 diabetes. |journal=Nature |volume=445 |issue= 7130 |pages= 881–5 |year= 2007 |pmid= 17293876 |doi= 10.1038/nature05616 |bibcode=2007Natur.445..881S |s2cid=4302932 }}
*{{cite journal | author=Mehrle A, Rosenfelder H, Schupp I, ''et al.'' |title=The LIFEdb database in 2006. |journal=Nucleic Acids Res. |volume=34 |issue= Database issue |pages= D415–8 |year= 2006 |pmid= 16381901 |doi= 10.1093/nar/gkj139 }}
*{{cite journal |vauthors=Wenzlau JM, Juhl K, Yu L, etal |title=The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=104 |issue= 43 |pages= 17040–5 |year= 2007 |pmid= 17942684 |doi= 10.1073/pnas.0705894104 | pmc=2040407 |bibcode=2007PNAS..10417040W |doi-access=free }}
*{{cite journal | author=Sladek R, Rocheleau G, Rung J, ''et al.'' |title=A genome-wide association study identifies novel risk loci for type 2 diabetes. |journal=Nature |volume=445 |issue= 7130 |pages= 881–5 |year= 2007 |pmid= 17293876 |doi= 10.1038/nature05616 }}
*{{cite journal | author=Wenzlau JM, Juhl K, Yu L, ''et al.'' |title=The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=104 |issue= 43 |pages= 17040–5 |year= 2007 |pmid= 17942684 |doi= 10.1073/pnas.0705894104 }}
}}
{{refend}}
{{refend}}


==External links==
==External links==
*[http://news.bbc.co.uk/2/hi/health/6342855.stm Type 2 diabetes genes mapped out], BBC News article
*[http://news.bbc.co.uk/2/hi/health/6342855.stm Type 2 diabetes genes mapped out], BBC News article

⚫
[[Category:Solute carrier family]]



{{genetics-stub}}
{{genetics-stub}}
{{membrane-protein-stub}}
{{membrane-protein-stub}}
{{Membrane transport proteins}}
⚫
[[Category:Solute carrier family]]

Latest revision as of 16:23, 26 November 2023

SLC30A8
Identifiers
AliasesSLC30A8, ZNT8, ZnT-8, solute carrier family 30 member 8
External IDsOMIM: 611145 MGI: 2442682 HomoloGene: 13795 GeneCards: SLC30A8
Orthologs
SpeciesHumanMouse
Entrez

169026

239436

Ensembl

ENSG00000164756

ENSMUSG00000022315

UniProt

Q8IWU4

Q8BGG0

RefSeq (mRNA)

NM_001172811
NM_001172813
NM_001172814
NM_001172815
NM_173851

NM_172816

RefSeq (protein)

NP_001166282
NP_001166284
NP_001166285
NP_001166286
NP_776250

NP_766404

Location (UCSC)Chr 8: 116.95 – 117.18 MbChr 15: 52.16 – 52.2 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Clinical significance[edit]

Association 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[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164756 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022315 – 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.
  5. ^ "Entrez Gene: SLC30A8 solute carrier family 30 (zinc transporter), member 8".
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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[edit]

External links[edit]


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