Variant "SCL30A8:p.Tyr284*"
Search result: 1 record
Variant information
Gene:
SCL30A8 
Variant:
SCL30A8:p.Tyr284* 
dbSNP ID:
no data 
GWAS trait:
no data 
Modifier statisitcs
Record:
1 
Disorder:
1 
Reference:
1 
Effect type:
Penetrance(1)  
Modifier effect:
Altered incidence(1)  
Detail：
  • Target disease:
    Type 2 Diabetes Mellitus (DOID_9352)
    Effect type:
    Penetrance 
    Modifier effect:
    Altered incidence 
    Evidence:
    Combined OR=0.34, 95% CI: (0.21–0.53), P=1.7×10(-6) 
    Effect:
    SLC30A8 haploinsufficiency protects against T2D
    Reference:
    PMID24584071
    Title:
    Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.
    Species studied:
    Human
    Abstract:
    Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.