Zinc transporter 8: Difference between revisions

SLC30A8
Identifiers
Aliases	SLC30A8, ZNT8, ZnT-8, solute carrier family 30 member 8
External IDs	OMIM: 611145; MGI: 2442682; HomoloGene: 13795; GeneCards: SLC30A8; OMA:SLC30A8 - orthologs
Gene location (Human)
Chr.	Chromosome 8 (human)
End	117,176,714 bp
Gene location (Mouse)
Chr.	Chromosome 15 (mouse)
End	52,199,194 bp
RNA expression pattern
	Top expressed in
	islet of Langerhans; ; pancreatic epithelial cell; ; body of pancreas; ; tibialis anterior muscle; ; testicle; ; deltoid muscle; ; kidney; ; kidney; ; fundus; ; duodenum;
	Top expressed in
	islet of Langerhans; ; foregut; ; stomach;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	protein homodimerization activity; cation transmembrane transporter activity; zinc ion binding; protein binding; zinc ion transmembrane transporter activity;
Cellular component	integral component of membrane; Golgi apparatus; secretory granule membrane; membrane; plasma membrane; transport vesicle membrane; secretory granule; cytoplasmic vesicle;
Biological process	response 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 transport;
	Sources:Amigo / QuickGO
Orthologs
	169026
	239436
	ENSG00000164756
	ENSMUSG00000022315
	Q8IWU4
	Q8BGG0
	NM_001172811; NM_001172813; NM_001172814; NM_001172815; NM_173851
	NM_172816
	NP_001166282; NP_001166284; NP_001166285; NP_001166286; NP_776250
	NP_766404
	Wikidata
View/Edit Human	View/Edit Mouse

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Revision as of 02:17, 17 October 2022

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. 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

Association with type 2 diabetes (T2D)

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]

References

^ ^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.

External links

Type 2 diabetes genes mapped out, BBC News article

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000164756 – Ensembl, May 2017

[refGRCm38Ensembl-2] 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.

[entrez-5] "Entrez Gene: SLC30A8 solute carrier family 30 (zinc transporter), member 8".

[Loss-of-function-6] 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.

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@@ Line 19: / Line 19: @@
 *{{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  }}
 *{{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   |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 |doi-access=free }}
+*{{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  |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}}
 *{{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 }}