{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:43:08Z","timestamp":1787928188977,"version":"build-2784847793"},"reference-count":110,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>KIF1A-associated neurological diseases (KANDs) are a group of inherited conditions caused by changes in the microtubule (MT) motor protein KIF1A as a result of KIF1A gene mutations. Anterograde transport of membrane organelles is facilitated by the kinesin family protein encoded by the MT-based motor gene KIF1A. Variations in the KIF1A gene, which primarily affect the motor domain, disrupt its ability to transport synaptic vesicles containing synaptophysin and synaptotagmin leading to various neurological pathologies such as hereditary sensory neuropathy, autosomal dominant and recessive forms of spastic paraplegia, and different neurological conditions. These mutations are frequently misdiagnosed because they result from spontaneous, non-inherited genomic alterations. Whole-exome sequencing (WES), a cutting-edge method, assists neurologists in diagnosing the illness and in planning and choosing the best course of action. These conditions are simple to be identified in pediatric and have a life expectancy of 5\u20137 years. There is presently no permanent treatment for these illnesses, and researchers have not yet discovered a medicine to treat them. Scientists have more hope in gene therapy since it can be used to cure diseases brought on by mutations. In this review article, we discussed some of the experimental gene therapy methods, including gene replacement, gene knockdown, symptomatic gene therapy, and cell suicide gene therapy. It also covered its clinical symptoms, pathogenesis, current diagnostics, therapy, and research advances currently occurring in the field of KAND-related disorders. This review also explained the impact that gene therapy can be designed in this direction and afford the remarkable benefits to the patients and society.<\/jats:p>","DOI":"10.3390\/ph16020147","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T05:50:20Z","timestamp":1674107420000},"page":"147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["KIF1A-Associated Neurological Disorder: An Overview of a Rare Mutational Disease"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0255-0965","authenticated-orcid":false,"given":"Ayushi","family":"Nair","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Amrita Health Science Campus, Kochi 682041, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2673-8022","authenticated-orcid":false,"given":"Alosh","family":"Greeny","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Amrita Health Science Campus, Kochi 682041, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajalakshmi","family":"Rajendran","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Amrita Health Science Campus, Kochi 682041, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9035-5638","authenticated-orcid":false,"given":"Mohamed A.","family":"Abdelgawad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Al Jouf 72341, Saudi Arabia"},{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9179-4373","authenticated-orcid":false,"given":"Mohammed M.","family":"Ghoneim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshni Pushpa","family":"Raghavan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Amrita Health Science Campus, Kochi 682041, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachithra Thazhathuveedu","family":"Sudevan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijo","family":"Mathew","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7203-3712","authenticated-orcid":false,"given":"Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1002\/acn3.452","article-title":"Multigeneration family with dominant SPG30 hereditary spastic paraplegia","volume":"4","author":"Roda","year":"2017","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/jns.12368","article-title":"KIF1A -related disorders in children: A wide spectrum of central and peripheral nervous system involvement","volume":"25","author":"Nemani","year":"2020","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100026","DOI":"10.1016\/j.xhgg.2021.100026","article-title":"Genotype and defects in microtubule-based motility correlate with clinical severity in KIF1A-associated neurological disorder","volume":"2","author":"Boyle","year":"2021","journal-title":"Hum. Genet. Genom. Adv."},{"key":"ref_4","first-page":"140","article-title":"Cerebellar Atrophy in Congenital Fibrosis of the Extraocular Muscles Type 1","volume":"12","author":"Comanducci","year":"2012","journal-title":"Cerebellum"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Baptista, F., Pinto, M.J., Elvas, F., Almeida, R., and Ambr\u00f3sio, A.F. (2013). Diabetes Alters KIF1A and KIF5B Motor Proteins in the Hippocampus. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065515"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1002\/acn3.198","article-title":"De novo mutations in KIF1A cause progressive encephalopathy and brain atrophy","volume":"2","author":"Nieh","year":"2015","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1002\/humu.24118","article-title":"Phenotypic expansion in KIF1A-related dominant disorders: A description of novel variants and review of published cases","volume":"41","author":"Hansen","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"618098","DOI":"10.3389\/fnins.2021.618098","article-title":"The Novel KIF1A Missense Variant (R169T) Strongly Reduces Microtubule Stimulated ATPase Activity and Is Associated with NESCAV Syndrome","volume":"15","author":"Aguilera","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1016\/j.celrep.2017.10.084","article-title":"Capture of Dense Core Vesicles at Synapses by JNK-Dependent Phosphorylation of Synaptotagmin-4","volume":"21","author":"Bharat","year":"2017","journal-title":"Cell Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/0092-8674(95)90538-3","article-title":"The neuron-specific kinesin superfamily protein KIF1A is a uniqye monomeric motor for anterograde axonal transport of synaptic vesicle precursors","volume":"81","author":"Okada","year":"1995","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hammond, J., Cai, D., Blasius, T.L., Li, Z., Jiang, Y., Jih, G.T., Meyhofer, E., and Verhey, K.J. (2009). Mammalian Kinesin-3 Motors Are Dimeric In Vivo and Move by Processive Motility upon Release of Autoinhibition. PLOS Biol., 7.","DOI":"10.1371\/journal.pbio.1000072"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S0092-8674(02)00708-0","article-title":"Role of Phosphatidylinositol(4,5)bisphosphate Organization in Membrane Transport by the Unc104 Kinesin Motor","volume":"109","author":"Klopfenstein","year":"2002","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/j.str.2012.07.002","article-title":"The CC1-FHA Tandem as a Central Hub for Controlling the Dimerization and Activation of Kinesin-3 KIF1A","volume":"20","author":"Huo","year":"2012","journal-title":"Structure"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.1074\/jbc.M211152200","article-title":"Characterization of the Movement of the Kinesin Motor KIF1A in Living Cultured Neurons","volume":"278","author":"Lee","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3389\/fncel.2019.00419","article-title":"Going Too Far Is the Same as Falling Short\u2020: Kinesin-3 Family Members in Hereditary Spastic Paraplegia","volume":"13","author":"Gabrych","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1007\/s00415-015-7899-9","article-title":"Variants in KIF1A gene in dominant and sporadic forms of hereditary spastic paraparesis","volume":"262","author":"Citterio","year":"2015","journal-title":"J. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.ajhg.2011.02.001","article-title":"Excess of De Novo Deleterious Mutations in Genes Associated with Glutamatergic Systems in Nonsyndromic Intellectual Disability","volume":"88","author":"Hamdan","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1038\/ejhg.2014.297","article-title":"Dominant transmission of de novo KIF1A motor domain variant underlying pure spastic paraplegia","volume":"23","author":"Ylikallio","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/humu.22709","article-title":"De Novo Mutations in the Motor Domain of KIF1A Cause Cognitive Impairment, Spastic Paraparesis, Axonal Neuropathy, and Cerebellar Atrophy","volume":"36","author":"Lee","year":"2015","journal-title":"Hum. Mutat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1016\/j.celrep.2016.07.043","article-title":"Autoinhibition of a Neuronal Kinesin UNC-104\/KIF1A Regulates the Size and Density of Synapses","volume":"16","author":"Niwa","year":"2016","journal-title":"Cell Rep."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Iqbal, Z., Rydning, S.L., Wedding, I.M., Koht, J., Pihlstr\u00f8m, L., Rengmark, A.H., Henriksen, S.P., Tallaksen, C.M.E., and Toft, M. (2017). Targeted high throughput sequencing in hereditary ataxia and spastic paraplegia. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186571"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.ajhg.2011.06.013","article-title":"KIF1A, an Axonal Transporter of Synaptic Vesicles, Is Mutated in Hereditary Sensory and Autonomic Neuropathy Type 2","volume":"89","author":"Ramalingam","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"18429","DOI":"10.1073\/pnas.1905690116","article-title":"Disease-associated mutations hyperactivate KIF1A motility and anterograde axonal transport of synaptic vesicle precursors","volume":"116","author":"Chiba","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","first-page":"e2216903120","article-title":"KIF1A is kinetically tuned to be a super-engaging motor under hindering loads","volume":"120","author":"Pyrpassopoulos","year":"2023","journal-title":"Biophys. Comput. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nrm2774","article-title":"Kinesin superfamily motor proteins and intracellular transport","volume":"10","author":"Hirokawa","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e202004227","DOI":"10.1083\/jcb.202004227","article-title":"Pathogenic mutations in the kinesin-3 motor KIF1A diminish force generation and movement through allosteric mechanisms","volume":"220","author":"Budaitis","year":"2021","journal-title":"J. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1126\/science.283.5405.1152","article-title":"A Processive Single-Headed Motor: Kinesin Superfamily Protein KIF1A","volume":"283","author":"Okada","year":"1999","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1091\/mbc.e14-01-0696","article-title":"The family-specific K-loop influences the microtubule on-rate but not the superprocessivity of kinesin-3 motors","volume":"25","author":"Soppina","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1073\/pnas.97.2.640","article-title":"Mechanism of the single-headed processivity: Diffusional anchoring between the K-loop of kinesin and the C terminus of tubulin","volume":"97","author":"Okada","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5562","DOI":"10.1073\/pnas.1400759111","article-title":"Dimerization of mammalian kinesin-3 motors results in superprocessive motion","volume":"111","author":"Soppina","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.cell.2014.03.053","article-title":"High-Resolution Microtubule Structures Reveal the Structural Transitions in \u03b1\u03b2-Tubulin upon GTP Hydrolysis","volume":"157","author":"Alushin","year":"2014","journal-title":"Cell"},{"key":"ref_32","first-page":"E6191","article-title":"Separating the effects of nucleotide and EB binding on microtubule structure","volume":"115","author":"Zhang","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.cell.2015.07.012","article-title":"Mechanistic Origin of Microtubule Dynamic Instability and Its Modulation by EB Proteins","volume":"162","author":"Zhang","year":"2015","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Montemurro, N., Ricciardi, L., Scerrati, A., Ippolito, G., Lofrese, G., Trungu, S., and Stoccoro, A. (2022). The Potential Role of Dysregulated miRNAs in Adolescent Idiopathic Scoliosis and 22q11.2 Deletion Syndrome. J. Pers. Med., 12.","DOI":"10.3390\/jpm12111925"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e2113795119","DOI":"10.1073\/pnas.2113795119","article-title":"De novo mutations in KIF1A-associated neuronal disorder (KAND) dominant-negatively inhibit motor activity and axonal transport of synaptic vesicle precursors","volume":"119","author":"Anazawa","year":"2022","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_36","unstructured":"Lumpkins, C. (2022, July 21). KIF1A-Related Disorder. NORD (National Organization for Rare Disorders). Available online: https:\/\/rarediseases.org\/rare-diseases\/kif1a-related-disorder\/."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41431-019-0497-z","article-title":"KIF1A variants are a frequent cause of autosomal dominant hereditary spastic paraplegia","volume":"28","author":"Pennings","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/ejhg.2011.261","article-title":"KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: Distinct phenotypes according to the nature of the mutations","volume":"20","author":"Klebe","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/ana.20375","article-title":"Confirmation of a hereditary motor and sensory neuropathy IIC locus at chromosome 12q23-q24","volume":"57","author":"McEntagart","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_40","unstructured":"Adam, M., Everman, D., Mirzaa, G., Pagon, R., Wallace, S., Bean, L.J., Gripp, K., and Amemiya, A. (2022, July 20). Hereditary Spastic Paraplegia Overview, GeneReviews\u00ae, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1509\/."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s10038-018-0523-y","article-title":"Locus and allelic heterogeneity in five families with hereditary spastic paraplegia","volume":"64","author":"Hebbar","year":"2018","journal-title":"J. Hum. Genet."},{"key":"ref_42","unstructured":"Rosenberg, R.N., and Pascual, J.M. (2015). Chapter 77\u2014Hereditary Spastic Paraplegia. Rosenberg\u2019s Molecular and Genetic Basis of Neurological and Psychiatric Disease, Academic Press. [5th ed.]."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1002\/ajmg.a.31416","article-title":"Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation","volume":"140A","author":"Rauch","year":"2006","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.ajhg.2010.04.006","article-title":"Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies","volume":"86","author":"Miller","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.neuroscience.2019.08.016","article-title":"Clinical Application of Targeted Next-Generation Sequencing Panels and Whole Exome Sequencing in Childhood Epilepsy","volume":"418","author":"Costain","year":"2019","journal-title":"Neuroscience"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"434","DOI":"10.3389\/fneur.2019.00434","article-title":"Diagnostic Yield and Treatment Impact of Targeted Exome Sequencing in Early-Onset Epilepsy","volume":"10","author":"Demos","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_47","first-page":"188","article-title":"New diagnostic pathways for mitochondrial disease","volume":"4","author":"Watson","year":"2020","journal-title":"J. Transl. Genet. Genom."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1111\/dmcn.14722","article-title":"Diagnostic yield and treatment impact of whole-genome sequencing in paediatric neurological disorders","volume":"63","author":"Lee","year":"2020","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_49","unstructured":"(2022, July 22). KIF1A. Wikipedia. Available online: https:\/\/en.wikipedia.org\/w\/index.php?title=KIF1A&oldid=1077108149."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1038\/s41598-020-59026-y","article-title":"Systematic dissection of biases in whole-exome and whole-genome sequencing reveals major determinants of coding sequence coverage","volume":"10","author":"Barbitoff","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41525-018-0053-8","article-title":"Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases","volume":"3","author":"Clark","year":"2018","journal-title":"npj Genom. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1080\/1061186X.2019.1630415","article-title":"Gene therapy for neurological disorders: Challenges and recent advancements","volume":"28","author":"Pena","year":"2019","journal-title":"J. Drug Target."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nrneurol.2013.56","article-title":"Progress in gene therapy for neurological disorders","volume":"9","author":"Simonato","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2174\/1566523220999200917114101","article-title":"Exploring the Role of Gene Therapy for Neurological Disorders","volume":"21","author":"Puranik","year":"2021","journal-title":"Curr. Gene Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1517\/14712598.2016.1114096","article-title":"Gene therapy for neurological disorders","volume":"16","author":"Choong","year":"2015","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_56","first-page":"204","article-title":"Development of gene therapy for neurological disorders","volume":"9","author":"Manfredsson","year":"2010","journal-title":"Discov. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1023\/B:JOBB.0000041773.20072.9e","article-title":"Development of Mitochondrial Gene Replacement Therapy","volume":"36","author":"Khan","year":"2004","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/j.biocel.2009.04.023","article-title":"RNA interference as a gene knockdown technique","volume":"42","author":"Shan","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/sj.mt.6300190","article-title":"The Suicide Gene Therapy Challenge: How to Improve a Successful Gene Therapy Approach","volume":"15","author":"Bonini","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/jhg.2015.108","article-title":"De novo KIF1A mutations cause intellectual deficit, cerebellar atrophy, lower limb spasticity and visual disturbance","volume":"60","author":"Ohba","year":"2015","journal-title":"J. Hum. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1093\/nar\/gkg509","article-title":"SIFT: Predicting amino acid changes that affect protein function","volume":"31","author":"Ng","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/hmg\/10.6.591","article-title":"Prediction of deleterious human alleles","volume":"10","author":"Sunyaev","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"W645","DOI":"10.1093\/nar\/gkl229","article-title":"Applications for protein sequence-function evolution data: mRNA\/protein expression analysis and coding SNP scoring tools","volume":"34","author":"Thomas","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.expneurol.2014.06.011","article-title":"Hereditary spastic paraplegia: Clinical-genetic characteristics and evolving molecular mechanisms","volume":"261","author":"Giudice","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1093\/brain\/awl012","article-title":"Autosomal recessive spastic paraplegia (SPG30) with mild ataxia and sensory neuropathy maps to chromosome 2q37.3","volume":"129","author":"Klebe","year":"2006","journal-title":"Brain"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1055\/s-0034-1386767","article-title":"Hereditary Spastic Paraplegia: Clinical Principles and Genetic Advances","volume":"34","author":"Fink","year":"2014","journal-title":"Semin. Neurol."},{"key":"ref_67","unstructured":"Adam, M., Everman, D., Mirzaa, G., Pagon, R., Wallace, S., Bean, L.J., Gripp, K., and Amemiya, A. (1993). 2q37 Microdeletion Syndrome\u2014Retired Chapter, For Historical Reference Only. GeneReviews\u00ae, University of Washington."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"12527","DOI":"10.1038\/s41598-017-12999-9","article-title":"Autosomal dominant transmission of complicated hereditary spastic paraplegia due to a dominant negative mutation of KIF1A, SPG30 gene","volume":"7","author":"Cheon","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1126\/science.1096621","article-title":"KIF1A Alternately Uses Two Loops to Bind Microtubules","volume":"305","author":"Nitta","year":"2004","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1101\/gr.117143.110","article-title":"Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis","volume":"21","author":"Erlich","year":"2011","journal-title":"Genome Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1136\/jnnp.2007.137596","article-title":"SPG10 is a rare cause of spastic paraplegia in European families","volume":"79","author":"Schule","year":"2008","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1083\/jcb.141.2.431","article-title":"Defect in Synaptic Vesicle Precursor Transport and Neuronal Cell Death in KIF1A Motor Protein\u2013deficient Mice","volume":"141","author":"Yonekawa","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/35078000","article-title":"Switch-based mechanism of kinesin motors","volume":"411","author":"Kikkawa","year":"2001","journal-title":"Nature"},{"key":"ref_76","unstructured":"(2022, August 06). Nescav Syndrome Disease: Malacards\u2014Research Articles, Drugs, Genes, Clinical Trials. Available online: https:\/\/www.malacards.org\/card\/nescav_syndrome."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/jhg.2014.80","article-title":"KIF1A mutation in a patient with progressive neurodegeneration","volume":"59","author":"Okamoto","year":"2014","journal-title":"J. Hum. Genet."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/00019605-199604000-00006","article-title":"PEHO or PEHO-like syndrome?","volume":"5","author":"Chitty","year":"1996","journal-title":"Clin. Dysmorphol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1136\/jmg.30.11.932","article-title":"Diagnostic criteria and genetics of the PEHO syndrome","volume":"30","author":"Somer","year":"1993","journal-title":"J. Med. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"165","DOI":"10.4103\/1817-1745.92866","article-title":"Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy and PEHO-like syndrome: Report of two cases","volume":"6","author":"Anal","year":"2011","journal-title":"J. Pediatr. Neurosci."},{"key":"ref_81","first-page":"405","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Anesthesia Analg."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/S0140-6736(09)61376-3","article-title":"Autism","volume":"374","author":"Levy","year":"2009","journal-title":"Lancet"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1111\/jns.12235","article-title":"A de novo dominant mutation in KIF1A associated with axonal neuropathy, spasticity and autism spectrum disorder","volume":"22","author":"Tomaselli","year":"2017","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"839","DOI":"10.2169\/internalmedicine.3661-19","article-title":"A Novel de novo KIF1A Mutation in a Patient with Autism, Hyperactivity, Epilepsy, Sensory Disturbance, and Spastic Paraplegia","volume":"59","author":"Kurihara","year":"2020","journal-title":"Intern. Med."},{"key":"ref_85","first-page":"620","article-title":"A study on KIF1A gene missense variant analysis and its protein expression and structure profiles of an autism spectrum disorder family trio","volume":"38","author":"Huang","year":"2021","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2886","DOI":"10.1007\/s10803-018-3552-7","article-title":"Additive Effect of Variably Penetrant 22q11.2 Duplication and Pathogenic Mutations in Autism Spectrum Disorder: To Which Extent Does the Tree Hide the Forest?","volume":"48","author":"Demily","year":"2018","journal-title":"J. Autism Dev. Disord."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6152","DOI":"10.1073\/pnas.1817924116","article-title":"Intracellular cargo transport by single-headed kinesin motors","volume":"116","author":"Schimert","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1126\/science.1226734","article-title":"Tug-of-War in Motor Protein Ensembles Revealed with a Programmable DNA Origami Scaffold","volume":"338","author":"Derr","year":"2012","journal-title":"Science"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e05472","DOI":"10.7554\/eLife.05472","article-title":"Tuning myosin-driven sorting on cellular actin networks","volume":"4","author":"Hariadi","year":"2015","journal-title":"Elife"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nsmb.3391","article-title":"Intraflagellar transport dynein is autoinhibited by trapping of its mechanical and track-binding elements","volume":"24","author":"Toropova","year":"2017","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/cm.21339","article-title":"Cargo rigidity affects the sensitivity of dynein ensembles to individual motor pausing","volume":"73","author":"Chau","year":"2016","journal-title":"Cytoskeleton"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1073\/pnas.1201390110","article-title":"Measuring collective transport by defined numbers of processive and nonprocessive kinesin motors","volume":"110","author":"Furuta","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Cong, D., Ren, J., Zhou, Y., Wang, S., Liang, J., Ding, M., and Feng, W. (2021). Motor domain-mediated autoinhibition dictates axonal transport by the kinesin UNC-104\/KIF1A. PLOS Genet., 17.","DOI":"10.1371\/journal.pgen.1009940"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"E11209","DOI":"10.1073\/pnas.1811209115","article-title":"Coiled-coil 1-mediated fastening of the neck and motor domains for kinesin-3 autoinhibition","volume":"115","author":"Ren","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1083\/jcb.201309066","article-title":"KIF13B enhances the endocytosis of LRP1 by recruiting LRP1 to caveolae","volume":"204","author":"Kanai","year":"2014","journal-title":"J. Cell Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"28774","DOI":"10.1074\/jbc.M000715200","article-title":"GAKIN, a Novel Kinesin-like Protein Associates with the Human Homologue of the Drosophila Discs Large Tumor Suppressor in T Lymphocytes","volume":"275","author":"Hanada","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"7004","DOI":"10.1073\/pnas.111145398","article-title":"All kinesin superfamily protein, KIF, genes in mouse and human","volume":"98","author":"Miki","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_98","unstructured":"(2023, January 08). Frontiers|Breaking Boundaries in the Brain\u2014Advances in Editing Tools for Neurogenetic Disorders. Available online: https:\/\/www.frontiersin.org\/articles\/10.3389\/fgeed.2021.623519\/full."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1089\/hum.2019.264","article-title":"High-Throughput In Vitro, Ex Vivo, and In Vivo Screen of Adeno-Associated Virus Vectors Based on Physical and Functional Transduction","volume":"31","author":"Westhaus","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1073\/pnas.91.3.883","article-title":"Chimeric restriction endonuclease","volume":"91","author":"Kim","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"17382","DOI":"10.1073\/pnas.1211446109","article-title":"Efficient TALEN-mediated gene knockout in livestock","volume":"109","author":"Carlson","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.dnarep.2013.04.015","article-title":"DNA repair mechanisms in dividing and non-dividing cells","volume":"12","author":"Iyama","year":"2013","journal-title":"DNA Repair"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/nature20565","article-title":"In vivo genome editing via CRISPR\/Cas9 mediated homology-independent targeted integration","volume":"540","author":"Suzuki","year":"2016","journal-title":"Nature"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/s41422-019-0213-0","article-title":"Precise in vivo genome editing via single homology arm donor mediated intron-targeting gene integration for genetic disease correction","volume":"29","author":"Suzuki","year":"2019","journal-title":"Cell Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/s41586-019-1711-4","article-title":"Search-and-replace genome editing without double-strand breaks or donor DNA","volume":"576","author":"Anzalone","year":"2019","journal-title":"Nature"},{"key":"ref_106","unstructured":"(2023, January 10). Homology-Mediated End Joining-Based Targeted Integration Using CRISPR\/Cas9|Cell Research. Available online: https:\/\/www.nature.com\/articles\/cr201776."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.neuron.2017.10.004","article-title":"Virus-Mediated Genome Editing via Homology-Directed Repair in Mitotic and Postmitotic Cells in Mammalian Brain","volume":"96","author":"Nishiyama","year":"2017","journal-title":"Neuron"},{"key":"ref_108","unstructured":"(2023, January 10). Microhomology-Mediated End-Joining-Dependent Integration of Donor DNA in Cells and Animals Using TALENs and CRISPR\/Cas9|Nature Communications. Available online: https:\/\/www.nature.com\/articles\/ncomms6560."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"P\u0142oski, R. (2016). Next Generation Sequencing\u2014General Information about the Technology, Possibilities, and Limitations. Clinical Applications for Next-Generation Sequencing, Academic Press.","DOI":"10.1016\/B978-0-12-801739-5.00001-5"},{"key":"ref_110","unstructured":"Gleason, C.A., and Juul, S.E. (2018). 18\u2014Prenatal Diagnosis. Avery\u2019s Diseases of the Newborn, Elsevier. [10th ed.]."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/2\/147\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:10:30Z","timestamp":1760119830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/2\/147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,19]]},"references-count":110,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ph16020147"],"URL":"https:\/\/doi.org\/10.3390\/ph16020147","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,19]]}}}