Summary of RGS distribution, function, disease links, and predicted loss of function effects on human physiology
In this table, we summarize the broad tissue distribution and characterized function on physiology for each RGS family member. Note that this is not an all-encompassing list, but rather where each RGS is best defined. Disease links are sourced from human studies when available and animal studies otherwise, usually correlative data between disease phenotype and protein or transcript expression, and are described in the text.
| Overview of RGS Protein Distribution and Function | ||||||
|---|---|---|---|---|---|---|
| RGS Family | RGS | Major Tissue Distribution | Function | Knockout Phenotype | Proposed Disease Links | References |
| R4 subfamily | RGS1 | Immune system (B and T lymphocytes, monocytes, natural killer cells, etc.) | Suppress chemotaxis | Abnormal B cell migration, exaggerated germinal center formation, and atypical spleens | Diseases of the immune system (inflammatory diseases, B cell lymphomas, etc.) | Moratz et al., 2004; Hunt et al., 2008; Smyth et al., 2008; Johnson et al., 2010; Patel et al., 2015 |
| RGS2 | Cardiovascular system and brain | Vascular relaxation | Impaired basal neuronal activity and hypertension | Anxiety, post-traumatic stress disorder, suicide, hypertension | Oliveira-Dos-Santos et al., 2000; Heximer et al., 2003; Yang et al., 2005; Leygraf et al., 2006; Semplicini et al., 2006; Amstadter et al., 2009a,b; Koenen et al., 2009; Lifschytz et al., 2012; Okimoto et al., 2012; Hohoff et al., 2015 | |
| RGS3 | Heart | Still under investigation | Overexpression protects against cardiac hypertrophy | Possible link to cancers | Ooe et al., 2007; Liu et al., 2014; Chen et al., 2016; Wang et al., 2017a | |
| RGS4 | Heart and brain | Respond to cardiovascular stress and modulate neuronal signaling | Susceptible to atrial fibrillation | Schizophrenia, alcoholism | Owen et al., 2001; Chowdari et al., 2002, 2008; Mittmann et al., 2002; Chen et al., 2004; Williams et al., 2004; Prasad et al., 2005; Emilsson et al., 2006; Guo et al., 2006; Campbell et al., 2008a; So et al., 2008; Ding and Hegde, 2009; Ho et al., 2010; Felkin et al., 2011; Lee et al., 2012; Jaba et al., 2013; Opel et al., 2015 | |
| RGS5 | Vasculature | Control vascular remodeling | Reduced blood pressure, improved immune-mediated destruction of solid tumors and survival | Hypertension, atherosclerosis, cancer angiogenesis | Chang et al., 2007; Cho et al., 2008; Hamzah et al., 2008; Nisancioglu et al., 2008; Holobotovskyy et al., 2013; Cheng et al., 2015; Daniel et al., 2016 | |
| RGS8 | Brain (cerebellum) | Still under investigation | None noted | Possible link to seizures | Gold et al., 2002 | |
| RGS13 | Immune system (B and T lymphocytes, mast cells, etc.) | Suppress immune response | Enhanced B cell responses and anaphylaxis | Leukemia/Lymphoma, asthma | Bansal et al., 2008a,b; Pise-Masison et al., 2009; Hwang et al., 2013; Sethakorn and Dulin, 2013; Raedler et al., 2015 | |
| RGS16 | Retina, heart, brain, liver, immune system | Regulate inflammatory response and circadian rhythms | Enhanced inflammatory response in the lung and dysregulated circadian signaling | Circadian clocks/morning wakefulness | Doi et al., 2011; Hayasaka et al., 2011; Shankar et al., 2012; Hu et al., 2016; Jones et al., 2016 | |
| RGS18 | Platelets | Regulation of hemostasis | Reduced bleeding and hyper-responsive platelet activation | Aspirin resistance, amyotrophic lateral sclerosis, suicide | Schosser et al., 2011; Haggmark et al., 2014; Mao et al., 2014; Alshbool et al., 2015 | |
| RGS21 | Bitter and sweet taste cells | Gustatory sensation | Unknown | Still under investigation | Sharma et al., 2016 | |
| R7 subfamily | RGS6 | Brain and heart | Regulate drug reward, anxiety, and depression | Protection from alcohol-seeking behaviors, anxiety and depression-like behavior; enhanced dopamine neurodegeneration | Alcoholism, anxiety and depression, Parkinson’s disease, Alzheimer’s disease, and schizophrenia | Bifsha et al., 2014; Schizophrenia Working Group of the Psychiatric Genomics, 2014; Stewart et al., 2014; Moon et al., 2015; Stewart et al., 2015; Ahlers et al., 2016 |
| RGS7 | Brain | Regulates anxiety and drug reward | Enhanced reward, withdrawal and analgesia, and delayed tolerance to morphine | Panic disorder and multiple sclerosis | Crowe et al., 2001; Gelernter et al., 2001; Hohoff et al., 2009; McCauley et al., 2009 | |
| RGS9 | Retina; brain striatum | Regulation of photoreceptor and striatal signaling | Disrupted striatal dopamine signaling related to stimulants and motor deficits | Retinal dysfunction | Nishiguchi et al., 2004; Cheng et al., 2007; Hartong et al., 2007; Stockman et al., 2008; Michaelides et al., 2010 | |
| RGS11 | Retina | Regulation of photoreceptor signaling | Unknown | Retinal dysfunction | Rao et al., 2007; Cao et al., 2012; Shim et al., 2012 | |
| R12 subfamily | RGS10 | Brain and immune system | Suppression of neuroinflammation | Enhanced neuroinflammation and neurodegeneration | Parkinson’s disease, possible link to schizophrenia and chemoresistant ovarian cancer | Hishimoto et al., 2004; Lee et al., 2008, 2011; Hooks et al., 2010; Tansey and Goldberg, 2010; Ali et al., 2013; Cacan et al., 2014; Hooks and Murph, 2015 |
| RGS12 | Brain, lung, testis, heart, bone, and spleen | Regulates osteoclast differentiation | Growth retardation and increased bone mass | Potential role for osteoporosis | Yang et al., 2013; Yuan et al., 2015b | |
| RGS14 | Brain, spleen, and heart | Regulation of blood calcium homeostasis, long-term potentiation regulation | Improved spatial learning | Kidney disease, possible link to social memory | Lee et al., 2010; Urabe et al., 2012; Yasui et al., 2013; Mahajan et al., 2016 | |
| RZ subfamily | RGS17 | Brain | Regulation of drug dependence | Decreased tumor growth and proliferation | Smoking and substance dependence | James et al., 2009; Yoon et al., 2012; Zhang et al., 2012; Hayes and Roman, 2016 |
| RGS19 | Heart, lung, brain, and liver | Potential links to cardiac development and regulation of cell proliferation | Enhanced analgesia and heart defects | Multiple sclerosis, ovarian cancers | Tso et al., 2011; Vural et al., 2013; Igci et al., 2016 | |
| RGS20 | Brain and eye | Still under investigation | Enhanced analgesia and tolerance to morphine | Hypertension and breast cancer | Garzon et al., 2004; Kohara et al., 2008; Yang et al., 2016a | |