TMEM173 variants and potential importance to human biology and disease

TMEM173 gene encodes the protein STING (stimulator of interferon genes), a key player in host defense against pathogens. Mutations in the human TMEM173 gene cause a life-threatening auto-inflammatory disease called SAVI (STING-associated vasculopathy with onset in infancy). Human STING is also a pro...

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Bibliographic Details
Published in:Genes and immunity 2019-01, Vol.20 (1), p.82-89
Main Authors: Patel, Seema, Jin, Lei
Format: Article
Language:English
Subjects:
45/43
631/208/727/2000
631/250/249/2510/2511
Alleles
Autoimmune Diseases - genetics
Biomedical and Life Sciences
Biomedicine
Cancer
Cancer immunotherapy
Cancer Research
Gene Expression
Genetic Predisposition to Disease
Genotypes
Human Genetics
Humans
Immunology
Infectious diseases
Inflammatory diseases
Interferon
Membrane Proteins - genetics
Mutation
Neoplasms - genetics
Polymorphism, Single Nucleotide
Population genetics
Review
Review Article
Therapeutic applications
Vascular diseases
Vascular Diseases - genetics
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Summary:TMEM173 gene encodes the protein STING (stimulator of interferon genes), a key player in host defense against pathogens. Mutations in the human TMEM173 gene cause a life-threatening auto-inflammatory disease called SAVI (STING-associated vasculopathy with onset in infancy). Human STING is also a promising therapeutic target for cancers and infectious diseases. Recently, Aduro Biotech and Novartis announced a $250M-plus initiative to develop STING-targeting cancer immunotherapies. Thus, understanding the genetics of the human TMEM173 gene is important for both basic and translational research. The human TMEM173 gene has great heterogeneity and population stratification. R232 of STING is the most common human TMEM173 allele. However, >50% of Americans are not R232/R232 . HAQ (R71H-G230A-R293Q) is the second most common human TMEM173 allele. While R232/R232 is the dominant TMEM173 genotype in Europeans, R232/HAQ is the most common TMEM173 genotype in East Asians. Importantly, recent studies suggested that HAQ and H232 are likely loss-of-function TMEM173 alleles. In all, ~30% of East Asians and ~10% of Europeans are HAQ/HAQ , HAQ/H232 , or H232/H232 . Here, we reviewed human TMEM173 alleles, mutations and their potential impact on human health and medicine.
ISSN:1466-4879
1476-5470
DOI:10.1038/s41435-018-0029-9