TAS2R38

TAS2R38
Name	TAS2R38
Chromosome	7q34
Location	7q34

TAS2R38 TAS2R38 is a human bitter taste receptor gene expressed in oral and extraoral tissues, discovered through molecular genetics and sensory physiology studies involving researchers at institutions such as National Institutes of Health, Harvard University, University of California, San Diego, University of Chicago, and Max Planck Society. It encodes a G protein–coupled receptor identified during genome-wide surveys and comparative genomics projects associated with groups like Broad Institute and Wellcome Trust. Work linking TAS2R38 to phenotypes has been published in journals including Nature, Science, Proceedings of the National Academy of Sciences, The Lancet, and American Journal of Human Genetics.

Introduction

TAS2R38 was characterized within the TAS2R family during targeted sequencing efforts related to sensory receptor repertoires at organizations such as European Molecular Biology Laboratory, Cold Spring Harbor Laboratory, Sanger Institute, Johns Hopkins University, and University of Pennsylvania. Early functional assays used heterologous expression systems developed by laboratories at Stanford University, Massachusetts Institute of Technology, and University of Cambridge, and behavioral phenotyping drew on methods from Duke University, University of Michigan, Yale University, Columbia University, and University of Oxford.

Gene and Protein Structure

The TAS2R38 gene is located on chromosome 7q34 within a cluster of TAS2R genes mapped by consortia including Human Genome Project, International HapMap Project, and 1000 Genomes Project. The protein is a seven-transmembrane G protein–coupled receptor sharing topology with receptors characterized by teams at Scripps Research Institute, Rockefeller University, University College London, ETH Zurich, and University of Basel. Structural inferences have been informed by comparative modeling using templates from studies at University of California, San Francisco, The Scripps Research Institute, University of Tokyo, Max Planck Institute for Biophysical Chemistry, and cryo-EM advances reported by Howard Hughes Medical Institute collaborators.

Genetic Variation and Haplotypes

Common polymorphisms at TAS2R38 include missense variants historically genotyped in cohorts assembled by Framingham Heart Study, UK Biobank, NHLBI, The Human Genome Diversity Project, and National Health and Nutrition Examination Survey. Principal haplotypes, often referenced in association studies by teams at Cold Spring Harbor Laboratory, University of Cambridge, University of Oxford, Harvard Medical School, and Institut Pasteur, correlate with taste sensitivity phenotypes measured using paradigms from Monell Chemical Senses Center, Florida State University, Penn State University, Rutgers University, and University of Florida.

Gustatory Function and Mechanism

TAS2R38 mediates perception of specific bitter ligands in assays developed in collaboration with researchers at Monell Chemical Senses Center, Max Planck Institute for Chemistry, Duke University Medical Center, University of Geneva, and Karolinska Institutet. Activation couples to G protein subunits and downstream effectors characterized in signaling studies from University of Pennsylvania Perelman School of Medicine, Yale School of Medicine, UCL Institute of Ophthalmology, University of California, Irvine, and University of North Carolina. Ligand specificity experiments that identified compounds such as phenylthiocarbamide involved chemists from Massachusetts Institute of Technology, University of Illinois at Urbana-Champaign, Columbia University, University of Wisconsin–Madison, and University of Colorado.

Physiological and Health Implications

Variants in TAS2R38 have been associated with dietary behavior, oral health, and respiratory outcomes in epidemiological cohorts run by National Institutes of Health, Centers for Disease Control and Prevention, World Health Organization, European Respiratory Society, and American Dental Association. Studies linking receptor function to innate immunity and mucosal defense invoked investigators at Scripps Research Institute, University of California, San Francisco, University of Texas Southwestern Medical Center, Vanderbilt University, and Mayo Clinic. Clinical associations with chronic rhinosinusitis, nutrition, and metabolic traits have been reported in collaborative work involving Johns Hopkins Medicine, Cleveland Clinic, Mount Sinai Health System, Karolinska University Hospital, and Aarhus University Hospital.

Population Genetics and Evolution

Population-level analyses of TAS2R38 polymorphisms were conducted using samples and analytic pipelines from 1000 Genomes Project, Human Genome Diversity Project, HapMap Consortium, International HapMap Project, and Simons Genome Diversity Project. Geographic variation and balancing selection hypotheses were examined by evolutionary geneticists affiliated with Max Planck Institute for Evolutionary Anthropology, University of California, Berkeley, University of Cambridge, University of Oxford, and Stanford University. Comparative studies across primates and mammals referenced data generated by Broad Institute, Ensembl, NCBI, Zoonomia Consortium, and Functional Annotation of the Mammalian Genome (FANTOM) networks.

Research and Clinical Applications

Ongoing translational research leverages TAS2R38 genotyping in personalized nutrition, public health screening, and therapeutic target discovery pursued at NIH Clinical Center, Translational Genomics Research Institute, Broad Institute, Wellcome Sanger Institute, and European Molecular Biology Laboratory. Drug discovery and formulation efforts that consider bitter receptor activation include collaborations with pharmaceutical companies and institutes such as Pfizer, Novartis, Roche, GlaxoSmithKline, and AstraZeneca. Clinical trials and implementation science projects integrating sensory genetics have been coordinated by teams at Massachusetts General Hospital, Brigham and Women's Hospital, UCLA Health, University College London Hospitals, and Karolinska Institutet University Hospital.

Category:Taste receptors