SLC30A8
protein-codingsolute carrier family 30 member 8, the group of Solute carrier family 30
Gene summary
The protein encoded by this gene is a zinc efflux transporter involved in the accumulation of zinc in intracellular vesicles. This gene is expressed at a high level only in the pancreas, particularly in islets of Langerhans. The encoded protein colocalizes with insulin in the secretory pathway granules of the insulin-secreting INS-1 cells. Allelic variants of this gene exist that confer susceptibility to diabetes mellitus, noninsulin-dependent (NIDDM). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~226.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005148
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC30A8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_173851.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 1 | 5 | |||
| missense | 52 | 4 | 2 | 58 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 56 | 8 | 3 | 67 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_776250.2 | 8 | MANE Select | |
| Ensembl | ENSP00000415011.2 | 8 | MANE Select | |
| RefSeq | NP_001166282.1 | 7 | Standard | |
| RefSeq | NP_001166284.1 | 7 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| slc30a8 | Danio rerio | Structure: pancreatic B cell Quality: decreased area abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Zinc homeostasis
- Peptide hormone metabolism
- Metabolism of proteins
- Transport of bile salts and organic acids, metal ions and amine compounds
- SLC-mediated transmembrane transport
Biological Process
- zinc ion transport
- cellular zinc ion homeostasis
- response to glucose
- response to zinc ion
- insulin secretion
Molecular Function
- zinc ion transmembrane transporter activity
- protein binding
- zinc ion binding
- protein homodimerization activity
Cellular Component
- Golgi apparatus
- plasma membrane
- integral component of membrane
- secretory granule
- transport vesicle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000456015
- Coding exons
- 8
- Length
- 226442
- Individuals with no LoFs
- 125557
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 191
- Defined
- 125748
- p
- 0.000760
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.109 | 200 | 204 | 0.979 | 0.0000105 | 2414 |
| Missense (PolyPhen) | 64 | 66.457 | 0.96303 | 835 | ||
| Synonymous | 0.907 | 72 | 82.5 | 0.873 | 0.00000474 | 727 |
| Loss of Function | -0.0479 | 17 | 16.8 | 1.01 | 7.89e-7 | 202 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0014 | 0.0014 | notable |
| Latino/Admixed American | 0.00044 | 0.00043 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.00028 | 0.00028 | rare |
| European (Non-Finnish) | 0.00047 | 0.00047 | rare |
| South Asian | 0.0028 | 0.0028 | notable |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Facilitates the accumulation of zinc from the cytoplasm into intracellular vesicles, being a zinc-efflux transporter. May be a major component for providing zinc to insulin maturation and/or storage processes in insulin-secreting pancreatic beta- cells. {ECO:0000269|PubMed:16984975}.;
Recessive Scores
- pRec
- 0.190
Intolerance Scores
- LoFtool
- 0.998
- RVIS EVS
- 0.09
- RVIS percentile EVS
- 60.47
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.119
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |