SLC30A8 (ZnT8): Zinc Transporter 8 in Type 2 Diabetes and Islet Biology
A comprehensive biomedical overview of SLC30A8, encoding the islet-specific zinc transporter ZnT8, with clinical relevance to type 2 diabetes, autoimmunity, and glucose homeostasis.
Gene Information Card
| Symbol | SLC30A8 |
|---|---|
| Full Name | Solute carrier family 30 member 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.11 (GRCh38: chr8:117,172,853-117,233,855) |
| NCBI Gene ID | 169026 ncbi.nlm.nih.gov/gene/169026 |
| Ensembl ID | ENSG00000164756 |
| UniProt ID | Q8IWU4 |
| OMIM ID | 611145 |
| HGNC ID | 20303 |
| Aliases | ZnT-8, ZnT8, DKFZp686M24251 |
Description
SLC30A8 encodes zinc transporter 8 (ZnT8), a member of the SLC30 family of zinc efflux transporters. ZnT8 is predominantly expressed in pancreatic beta cells and, to a lesser extent, in alpha cells, where it facilitates the transport of zinc from the cytoplasm into insulin secretory granules. This zinc transport is critical for insulin crystallization, storage, and secretion. SLC30A8 has been extensively studied for its role in type 2 diabetes (T2D) susceptibility, with common variants modulating risk, and as a major autoantigen in type 1 diabetes (T1D).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 Diabetes | Common variant rs13266634 (Arg325Trp) reduces ZnT8 transport activity, impairing insulin secretion and increasing T2D risk. | Genome-wide association studies (GWAS) and functional studies (e.g., Nicolson et al., 2009; Rutter et al., 2015). |
| Type 1 Diabetes | ZnT8 is a major autoantigen; autoantibodies against ZnT8 are detected in a subset of T1D patients, contributing to beta-cell destruction. | ClinVar and literature (Wenzlau et al., 2007). |
| Maturity-Onset Diabetes of the Young (MODY)-like phenotype | Rare loss-of-function variants in SLC30A8 have been associated with a monogenic form of diabetes with reduced insulin secretion. | Case reports and ClinVar entries (e.g., Flannick et al., 2014). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | High (nTPM ~ 100) | Predominantly in islets of Langerhans, especially beta cells. |
| Thyroid | Low (nTPM ~ 1) | Minimal expression. |
| Other tissues | Very low or not detected | Expression is largely restricted to endocrine pancreas. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| INS-1 (rat insulinoma) | High | Rodent beta-cell model; used for functional studies. |
| MIN6 (mouse insulinoma) | High | Mouse beta-cell line; expresses ZnT8. |
| EndoC-βH1 (human beta cell) | High | Human beta-cell line; relevant for human studies. |
| HeLa | Low | Non-pancreatic control; minimal expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs13266634 (Arg325Trp) | SNP (missense) | Risk allele frequency ~30-50% in populations | Reduces zinc transport activity; associated with increased T2D risk. |
| rs11558471 (Arg325Gln) | SNP (missense) | Less common | Also affects transport; protective in some populations. |
| Loss-of-function variants (e.g., frameshift, nonsense) | Rare | Very rare (<0.1%) | Homozygous loss-of-function may cause monogenic diabetes; heterozygous carriers have reduced T2D risk (protective). |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function variants (e.g., p.Arg325Trp) impair zinc transport into secretory granules, leading to reduced insulin crystallization and secretion. However, complete loss-of-function (e.g., truncating variants) may paradoxically reduce T2D risk, possibly due to compensatory mechanisms or altered granule morphology.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; overexpression studies suggest increased zinc transport may enhance insulin processing but not necessarily improve secretion.
Dominant Negative (DN)
No dominant-negative effects have been documented; most variants act in a haploinsufficient or recessive manner.
View complete mutation data：
Gene Ontology (GO)
| • Zinc ion transmembrane transporter activity (GO:0005385) | • Zinc ion transport (GO:0006829) |
| • Integral component of membrane (GO:0016021) | • Secretory granule membrane (GO:0030667) |
| • Cellular response to glucose stimulus (GO:0071333) |
Pathways
• Insulin secretion pathway (Reactome: R-HSA-422085)
• Zinc homeostasis (Reactome: R-HSA-435354)
• Regulation of insulin secretion (KEGG: hsa04911)
Protein Summary
ZnT8 is a 369-amino acid protein with six transmembrane domains and a histidine-rich loop. It forms homodimers and functions as a zinc/proton antiporter, exporting zinc from the cytosol into insulin granules. The protein is essential for normal insulin maturation and glucose-stimulated insulin secretion. Its expression is regulated by glucose and transcription factors such as PDX1 and NeuroD1. ZnT8 is also a target of autoantibodies in type 1 diabetes, making it a diagnostic biomarker.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC30A8 Knockout HEK293 Cell Line | EDJ-KQ11217 | Human | 169026 | Details Get a Quote |
| SLC30A8 Knockout HeLa Cell Line | EDJ-KQ58920 | Human | 169026 | Details Get a Quote |
| SLC30A8 Knockout A-549 Cell Line | EDJ-KQ67408 | Human | 169026 | Details Get a Quote |
| SLC30A8 Knockout HCT 116 Cell Line | EDJ-KQ75802 | Human | 169026 | Details Get a Quote |
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