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BMC Genomics. 2016 Aug 11;17(1):609. doi: 10.1186/s12864-016-2937-2.

Functional relevance of naturally occurring mutations in adhesion G protein-coupled receptor ADGRD1 (GPR133).

Author information

1
From the Section of Molecular Biochemistry, Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103, Leipzig, Germany.
2
From the Section of Molecular Biochemistry, Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103, Leipzig, Germany. schoberg@medizin.uni-leipzig.de.
3
From the Section of Molecular Biochemistry, Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103, Leipzig, Germany. liebscher@medizin.uni-leipzig.de.

Abstract

BACKGROUND:

A large number of human inherited and acquired diseases and phenotypes are caused by mutations in G protein-coupled receptors (GPCR). Genome-wide association studies (GWAS) have shown that variations in the ADGRD1 (GPR133) locus are linked with differences in metabolism, human height and heart frequency. ADGRD1 is a Gs protein-coupled receptor belonging to the class of adhesion GPCRs.

RESULTS:

Analysis of more than 1000 sequenced human genomes revealed approximately 9000 single nucleotide polymorphisms (SNPs) in the human ADGRD1 as listed in public data bases. Approximately 2.4 % of these SNPs are located in exons resulting in 129 non-synonymous SNPs (nsSNPs) at 119 positions of ADGRD1. However, the functional relevance of those variants is unknown. In-depth characterization of these amino acid changes revealed several nsSNPs (A448D, Q600stop, C632fs [frame shift], A761E, N795K) causing full or partial loss of receptor function, while one nsSNP (F383S) significantly increased basal activity of ADGRD1.

CONCLUSION:

Our results show that a broad spectrum of functionally relevant ADGRD1 variants is present in the human population which may cause clinically relevant phenotypes, while being compatible with life when heterozygous.

KEYWORDS:

ADGRD1; Adhesion GPCR; Database; GPR133; Mutations; SNP

PMID:
27516204
PMCID:
PMC4982218
DOI:
10.1186/s12864-016-2937-2
[Indexed for MEDLINE]
Free PMC Article

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