Zinc transporter 8

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]

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)[1] Band 8q24.11 Start 116,950,273 bp[1] End 117,176,714 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15|15 C Start 52,158,949 bp[2] End 52,199,194 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in islet of Langerhans pancreatic epithelial cell testicle body of pancreas tibialis anterior muscle mucosa of ileum gonad right testis left testis deltoid muscle Top expressed in islet of Langerhans embryo right kidney 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
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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]

See also

• Solute carrier family