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 FamilyRGSMajor Tissue DistributionFunctionKnockout PhenotypeProposed Disease LinksReferences
R4 subfamilyRGS1Immune system (B and T lymphocytes, monocytes, natural killer cells, etc.)Suppress chemotaxisAbnormal B cell migration, exaggerated germinal center formation, and atypical spleensDiseases 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
RGS2Cardiovascular system and brainVascular relaxationImpaired basal neuronal activity and hypertensionAnxiety, post-traumatic stress disorder, suicide, hypertensionOliveira-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
RGS3HeartStill under investigationOverexpression protects against cardiac hypertrophyPossible link to cancersOoe et al., 2007; Liu et al., 2014; Chen et al., 2016; Wang et al., 2017a
RGS4Heart and brainRespond to cardiovascular stress and modulate neuronal signalingSusceptible to atrial fibrillationSchizophrenia, alcoholismOwen 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
RGS5VasculatureControl vascular remodelingReduced blood pressure, improved immune-mediated destruction of solid tumors and survivalHypertension, atherosclerosis, cancer angiogenesisChang 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
RGS8Brain (cerebellum)Still under investigationNone notedPossible link to seizuresGold et al., 2002
RGS13Immune system (B and T lymphocytes, mast cells, etc.)Suppress immune responseEnhanced B cell responses and anaphylaxisLeukemia/Lymphoma, asthmaBansal et al., 2008a,b; Pise-Masison et al., 2009; Hwang et al., 2013; Sethakorn and Dulin, 2013; Raedler et al., 2015
RGS16Retina, heart, brain, liver, immune systemRegulate inflammatory response and circadian rhythmsEnhanced inflammatory response in the lung and dysregulated circadian signalingCircadian clocks/morning wakefulnessDoi et al., 2011; Hayasaka et al., 2011; Shankar et al., 2012; Hu et al., 2016; Jones et al., 2016
RGS18PlateletsRegulation of hemostasisReduced bleeding and hyper-responsive platelet activationAspirin resistance, amyotrophic lateral sclerosis, suicideSchosser et al., 2011; Haggmark et al., 2014; Mao et al., 2014; Alshbool et al., 2015
RGS21Bitter and sweet taste cellsGustatory sensationUnknownStill under investigationSharma et al., 2016
R7 subfamilyRGS6Brain and heartRegulate drug reward, anxiety, and depressionProtection from alcohol-seeking behaviors, anxiety and depression-like behavior; enhanced dopamine neurodegenerationAlcoholism, anxiety and depression, Parkinson’s disease, Alzheimer’s disease, and schizophreniaBifsha 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
RGS7BrainRegulates anxiety and drug rewardEnhanced reward, withdrawal and analgesia, and delayed tolerance to morphinePanic disorder and multiple sclerosisCrowe et al., 2001; Gelernter et al., 2001; Hohoff et al., 2009; McCauley et al., 2009
RGS9Retina; brain striatumRegulation of photoreceptor and striatal signalingDisrupted striatal dopamine signaling related to stimulants and motor deficitsRetinal dysfunctionNishiguchi et al., 2004; Cheng et al., 2007; Hartong et al., 2007; Stockman et al., 2008; Michaelides et al., 2010
RGS11RetinaRegulation of photoreceptor signalingUnknownRetinal dysfunctionRao et al., 2007; Cao et al., 2012; Shim et al., 2012
R12 subfamilyRGS10Brain and immune systemSuppression of neuroinflammationEnhanced neuroinflammation and neurodegenerationParkinson’s disease, possible link to schizophrenia and chemoresistant ovarian cancerHishimoto 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
RGS12Brain, lung, testis, heart, bone, and spleenRegulates osteoclast differentiationGrowth retardation and increased bone massPotential role for osteoporosisYang et al., 2013; Yuan et al., 2015b
RGS14Brain, spleen, and heartRegulation of blood calcium homeostasis, long-term potentiation regulationImproved spatial learningKidney disease, possible link to social memoryLee et al., 2010; Urabe et al., 2012; Yasui et al., 2013; Mahajan et al., 2016
RZ subfamilyRGS17BrainRegulation of drug dependenceDecreased tumor growth and proliferationSmoking and substance dependenceJames et al., 2009; Yoon et al., 2012; Zhang et al., 2012; Hayes and Roman, 2016
RGS19Heart, lung, brain, and liverPotential links to cardiac development and regulation of cell proliferationEnhanced analgesia and heart defectsMultiple sclerosis, ovarian cancersTso et al., 2011; Vural et al., 2013; Igci et al., 2016
RGS20Brain and eyeStill under investigationEnhanced analgesia and tolerance to morphineHypertension and breast cancerGarzon et al., 2004; Kohara et al., 2008; Yang et al., 2016a