Zinc transporter 8

Protein found in humans

SLC30A8

Identifiers

Aliases

SLC30A8, ZNT8, ZnT-8, solute carrier family 30 member 8

External IDs

OMIM: 611145 MGI: 2442682 HomoloGene: 13795 GeneCards: SLC30A8

Gene location (Human)

Chr.	Chromosome 8 (human)^[1]

Band	8q24.11	Start	116,950,273 bp^[1]
Band	8q24.11	End	117,176,714 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 15 (mouse)^[2]

Band	15\|15 C	Start	52,158,949 bp^[2]
Band	15\|15 C	End	52,199,194 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

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

BioGPS


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

Species

Human

Mouse

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 Mb

Chr 15: 52.16 – 52.2 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/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

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.