Table 3.

Small GTPases and Related Diseases (Rho, Arf, Rab, and Ran families).

Small GTPase	Related disease	Pathway/mechanism	References
Rac3	A novel neurodevelopmental syndrome	De novo monoallelic missense variants in Rac3, including one recurrent change	Costain et al., 2019
RhoA	Diabetic Parkinson’s disease or dementia	Accelerated neuron loss via the 5-hydroxytryptamine 2 receptor	Zimering, 2018
Cdc42	Epileptic-seizures	Regulating synaptic inhibition	Zhang Y. et al., 2015
Rac1	Fragile X syndrome	Rac1 is necessary for normal spine development and long-term synaptic plasticity	Bongmba et al., 2011
Rac1	Epilepsy	Patients suffering from temporal lobe epilepsy (TLE) and experimental epileptic rats	Li et al., 2016
RhoB	Glioblastoma	Cytokine-induced STAT3 activation, activated p53 and p21	Ma et al., 2015
Rac1 and Cdc42	Developmental delay, secondary macrocephaly, seizures, and ataxic gait	De novo PAK1 mutations c.392A>G (p.Tyr131Cys) and c.1286A>G (p.Tyr429Cys)	Harms et al., 2018
Rac1	Drug withdrawal	Rac1-dependent GABAAR endocytosis, synaptic plasticity as well as learning and memory	Wang et al., 2017
Rac1	Alcohol use disorders	Rac1/Arfaptin/Arf6 pathway	Peru Y Colón de Portugal et al., 2012
RhoA	Cocaine	Phosphorylated ERM levels and synaptic changes in the NAcc	Kim et al., 2009
Rab7	Parkinson’s disease	Clearance of α-synuclein aggregates	Saridaki et al., 2018
Rab11	Parkinson’s disease	Reduces α-synuclein aggregation and toxicity	Chutna et al., 2014
Rab39b	Parkinson’s disease	Reduce steady-state levels of α-synuclein	Wilson et al., 2014
Rab	Infantile encephalopathy	Rab GTPase-Activating Protein dysregulates mTOR signaling	Chong et al., 2016
Rab1A	Alzheimer’s disease	Mediates Golgi dynamics	Mohamed et al., 2017
Rab3A	Alzheimer’s disease	Localizes in presynaptic vesicles and regulates exocytosis	Udayar et al., 2013
Rab4	Alzheimer’s disease	Regulates endosomal recycling	Ginsberg et al., 2011
Rab5	Alzheimer’s disease	Modulates endosomal membrane trafficking, sorting and endosomal fusion	Ginsberg et al., 2010a,b
Rab6	Alzheimer’s disease	Regulates retrograde Golgi-ER trafficking	Scheper et al., 2007
Rab7A	Alzheimer’s disease	Controls transport to late endosomes and lysosomes/regulates tau secretion	Ginsberg et al., 2011; Rodriguez et al., 2017; Zafar et al., 2017
Rab8	Alzheimer’s disease	Modulates polarized trafficking	Shimohama et al., 1999; Kametani et al., 2004; Li et al., 2012
Rab10	Alzheimer’s disease	pRab10-T73, decrease in Aβ42 and Aβ42/Aβ40 ratio	Ridge et al., 2017; Yan et al., 2018
Rab11A/Rab11B	Alzheimer’s disease	Regulates both endocytic and exocytic trafficking pathways	Udayar et al., 2013; Buggia-Prevot et al., 2014; Xu et al., 2015; Zhao et al., 2015
Rab14	Alzheimer’s disease	Endocytic recycling and Golgi-endosome trafficking	Linford et al., 2012; Prekeris, 2012
Rab17	Alzheimer’s disease	Involved in phagocytic removal of apoptotic cells	Udayar et al., 2013
Rab24	Alzheimer’s disease	Involved in autophagy	Ginsberg et al., 2010a
Rab27	Alzheimer’s disease	Regulates exocytosis, endocytosis and phagocytosis	Ginsberg et al., 2011
Rab36	Alzheimer’s disease	Involved in late endosome and lysosome distribution	Udayar et al., 2013
Rab3a	Glioma	Increases cyclin D1 expression	Kim et al., 2014
Rab38	Glioblastomas	Whole genome mRNA expression microarray data on 220 glioma samples from the Chinese glioma genome atlas	Wang and Jiang, 2013
Rab28	Cone-rod dystrophy	Retinal dystrophies	Roosing et al., 2013
Arf1	Creutzfeldt-Jakob disease	Arf/Rho/MLC signaling	Zafar et al., 2015
Arl2 and Arl3	Retina disease	Participate in the trafficking of lipidated membrane-associated proteins and colocalize in the inner segment with UNC119A and PDEδ	Veltel et al., 2008a; Zhang H. et al., 2015; Hanke-Gogokhia et al., 2016a,b; Moshiri et al., 2017
Arf6	Alcohol use disorders	Rac1/Arfaptin/Arf6 pathway	Peru Y Colón de Portugal et al., 2012
Arl6	Diabetic retinopathy	Regulates VEGFR2 trafficking and signal transduction	Zhu et al., 2017
Arl6	ALS	Potential driver pathophysiological events involving endoplasmic reticulum stress and autophagy	Zhai et al., 2015
Arf72A	Retina disease	Rescues the ninaE(D1)-related membrane accumulation and suppresses ninaE(D1)-triggered retinal degeneration	Lee et al., 2011
Arl2	Bardet–Biedl syndrome type 3	Disrupt a threonine residue important for GTP binding and function of several related small GTP-binding proteins	Fan et al., 2004
Ran	Frontotemporal dementia	Regulates nuclear import via TDP-43 pathway	Ward et al., 2014
Ran	Alzheimer’s disease	Transcription regulators in the nucleus	Mastroeni et al., 2013
Ran	Glioblastoma multiforme	The Survivin-Ran complex	Guvenc et al., 2013

ALS, amyotrophic lateral sclerosis.