Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

“…Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). …”
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Genome-wide analyses identify KIF5A as a novel ALS gene by Nicolas, A, Kenna, KP, Renton, AE, Ticozzi, N, Faghri, F, Chia, R, Dominov, JA, Kenna, BJ, Nalls, MA, Keagle, P, Rivera, AM, Van Rheenen, W, Murphy, NA, Van Vugt, JJFA, Geiger, JT, Van Der Spek, RA, Pliner, HA, Shankaracharya, Smith, BN, Marangi, G, Topp, SD, Abramzon, Y, Gkazi, AS, Eicher, JD, Kenna, A, Italsgen Consortium, Mora, G, Calvo, A, Mazzini, L, Riva, N, Mandrioli, J, Caponnetto, C, Battistini, S, Volanti, P, La Bella, V, Conforti, FL, Borghero, G, Messina, S, Simone, IL, Trojsi, F, Salvi, F, Logullo, FO, D'Alfonso, S, Corrado, L, Capasso, M, Ferrucci, L, Genomic Translation For ALS Care (GTAC) Consortium, Moreno, CDAM, Kamalakaran, S, Goldstein, DB, ALS Sequencing Consortium, Gitler, AD, Harris, T, Myers, RM, NYGC ALS Consortium, Phatnani, H, Musunuri, RL, Evani, US, Abhyankar, A, Zody, MC, Answer ALS Foundation, Kaye, J, Finkbeiner, S, Wyman, SK, Lenail, A, Lima, L, Fraenkel, E, Svendsen, CN, Thompson, LM, Van Eyk, JE, Berry, JD, Miller, TM, Kolb, SJ, Cudkowicz, M, Baxi, E, Clinical Research In ALS And Related Disorders For Therapeutic Development (CREATE) Consortium, Benatar, M, Taylor, JP, Rampersaud, E, Wu, G, Wuu, J, Slagen Consortium, Lauria, G, Verde, F, Fogh, I, Tiloca, C, Comi, GP, Sorarù, G, Cereda, C, French ALS Consortium, Corcia, P, Laaksovirta, H, Myllykangas, L, Jansson, L, Valori, M, Ealing, J, Hamdalla, H, Rollinson, S, Pickering-Brown, S, Orrell, RW, Sidle, KC, Malaspina, A, Hardy, J, Singleton, AB, Johnson, JO, Arepalli, S, Sapp, PC, McKenna-yasek, D, Polak, M, Asress, S, Al-Sarraj, S, King, A, Troakes, C, Vance, C, De Belleroche, J, Baas, F, Asbroek, ALMA, Muñoz-Blanco, JL, Hernandez, DG, Ding, J, Gibbs, JR, Scholz, SW, Floeter, MK, Campbell, RH, Landi, F, Bowser, R, Pulst, SM, Ravits, JM, Macgowan, DJL, Kirby, J, Pioro, EP, Pamphlett, R, Broach, J, Gerhard, G, Dunckley, TL, Brady, CB, Kowall, NW, Troncoso, JC, Le Ber, I, Mouzat, K, Lumbroso, S, Heiman-Patterson, TD, Kamel, F, Van Den Bosch, L, Baloh, RH, Strom, TM, Meitinger, T, Shatunov, A, Van Eijk, KR, De Carvalho, M, Kooyman, M, Middelkoop, B, Moisse, M, McLaughlin, RL, Van Es, MA, Weber, M, Boylan, KB, Van Blitterswijk, M, Rademakers, R, Morrison, KE, Basak, AN, Mora, JS, Drory, VE, Shaw, PJ, Turner, MR, Talbot, K, Hardiman, O, Williams, KL, Fifita, JA, Nicholson, GA, Blair, IP, Rouleau, GA, Esteban-Pérez, J, García-Redondo, A, Al-Chalabi, A, Project Mine ALS Sequencing Consortium, Rogaeva, E, Zinman, L, Ostrow, LW, Maragakis, NJ, Rothstein, JD, Simmons, Z, Cooper-Knock, J, Brice, A, Goutman, SA, Feldman, EL, Gibson, SB, Taroni, F, Ratti, A, Gellera, C, Van Damme, P, Robberecht, W, Fratta, P, Sabatelli, M, Lunetta, C, Ludolph, AC, Andersen, PM, Weishaupt, JH, Camu, W, Trojanowski, JQ, Van Deerlin, VM, Brown, RH, Van Den Berg, LH, Veldink, JH, Harms, MB, Glass, JD, Stone, DJ, Tienari, P, Silani, V, Chiò, A, Shaw, CE, Traynor, BJ, Landers, JE

“…Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). …”

KIF5A upregulation in hepatocellular carcinoma: A novel prognostic biomarker associated with unique tumor microenvironment status by Qi Liu, Qi Liu, Yu-yang Liu, Xue-min Chen, Xue-min Chen, Bing-yan Tao, Kuang Chen, Wei-min Li, Wei-min Li, Chang-tao Xu, Chang-tao Xu, Ying Shi, Hao Li, Hao-run Liu, Hao-run Liu

Subjects: “…KIF5A…”
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Impaired motor unit recovery and maintenance in a knock-in mouse model of ALS-associated Kif5a variant by Kelly A. Rich, Megan G. Pino, Mehmet E. Yalvac, Ashley Fox, Hallie Harris, Maria H.H. Balch, W. David Arnold, Stephen J. Kolb

Subjects: “…KIF5A…”
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Computational study of the motor neuron protein KIF5A to identify nsSNPs, bioactive compounds, and its key regulators by Rupesh Kumar, Thirumurthy Madhavan, Kalaiarasan Ponnusamy, Honglae Sohn, Shazia Haider

“…Introduction: Kinesin family member 5A (KIF5A) is a motor neuron protein expressed in neurons and involved in anterograde transportation of organelles, proteins, and RNA. …”
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A human proteogenomic-cellular framework identifies KIF5A as a modulator of astrocyte process integrity with relevance to ALS by Kornélia Szebényi, Inigo Barrio-Hernandez, George M. Gibbons, Luca Biasetti, Claire Troakes, Pedro Beltrao, András Lakatos

“…We show that this may underly cytoskeletal and trafficking changes in SOD1 ALS astrocytes characterised by low KIF5A levels, which can be rescued by c-Jun N-terminal Kinase-1 (JNK1), a kinesin transport regulator. …”
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Correction: Spastic Paraplegia Mutation N256S in the Neuronal Microtubule Motor KIF5A Disrupts Axonal Transport in a Drosophila HSP Model

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Generation of an iPSC line from a patient with spastic paraplegia type 10 carrying a novel mutation in KIF5A gene by Serena Santangelo, Patrizia Bossolasco, Stefania Magri, Claudia Colombrita, Sabrina Invernizzi, Cinzia Gellera, Lorenzo Nanetti, Daniela Di Bella, Vincenzo Silani, Franco Taroni, Antonia Ratti

“…We generated an iPSC line from a patient with spastic paraplegia type 10 (SPG10) carrying the novel missense variant c.50G > A (p.R17Q) in the N-terminal motor domain of the kinesin family member 5A (KIF5A) gene.This patient-derived in vitro cell model will help to investigate the role of different KIF5A mutations in inducing neurodegeneration in spastic paraplegia and in other KIF5A-related disorders, including Charcot-Marie-Tooth type 2 (CMT2) and amyotrophic lateral sclerosis (ALS).…”
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KIF5A and KLC1 expression in Alzheimer’s disease: relationship and genetic influences [version 2; peer review: 2 approved, 1 approved with reservations] by Seth Love, Neil Scolding, Alastair Wilkins, Scott Miners, Kelly Hares

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Activation of TLR7-mediated autophagy increases epileptic susceptibility via reduced KIF5A-dependent GABAA receptor transport in a murine model by Jing Liu, Pingyang Ke, Haokun Guo, Juan Gu, Yan Liu, Xin Tian, Xuefeng Wang, Fei Xiao

“…Furthermore, activation of TLR7 induced autophagy and decreased the expression of kinesin family member 5 A (KIF5A), which influenced interactions with γ-aminobutyric acid type A receptor (GABAAR)-associated protein and GABAARβ2/3, thus producing abnormal GABAAR-mediated postsynaptic transmission. …”
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Lab resource: Single cell line generation and characterization of a human-derived induced pluripotent stem cell line (IGIBi005-A) from a patient with spastic paraplegia/ataxia/ALS phenotype due to the mutation of the gene Kinesin Family Member 5A (KIF5A) by Istaq Ahmad, Divya Goel, Anindita Ghosh, Himanshi Kapoor, Deepak Kumar, Achal K. Srivastava, Mohammed Faruq

“…Human Kinesin Family Member 5A (KIF5A) gene mutations have been identified as a putative genetic cause of amyotrophic lateral sclerosis (ALS). …”
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Identifying signatures of positive selection in human populations from North Africa by Rocio Caro-Consuegra, Marcel Lucas-Sánchez, David Comas, Elena Bosch

“…Our results show private candidate genes for selection in NA involved in insulin processing (KIF5A), immune function (KIF5A, IL1RN, TLR3), and haemoglobin phenotypes (BCL11A). …”
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Specific depletion of the motor protein KIF5B leads to deficits in dendritic transport, synaptic plasticity and memory by Junjun Zhao, Albert Hiu Ka Fok, Ruolin Fan, Pui-Yi Kwan, Hei-Lok Chan, Louisa Hoi-Ying Lo, Ying-Shing Chan, Wing-Ho Yung, Jiandong Huang, Cora Sau Wan Lai, Kwok-On Lai

“…Here we show that knockdown of KIF5A or KIF5B differentially affects excitatory synapses and dendritic transport in hippocampal neurons. …”
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The molecular genetics of non-ALS motor neuron diseases. by James, P, Talbot, K

“…Recently, mutations in a number of novel genes have been associated with Lower Motor Neuron (HSPB1, HSPB8, GARS, Dynactin), Upper Motor Neuron (Spastin, Atlastin, Paraplegin, HSP60, KIF5A, NIPA1) or mixed ALS-like phenotypes (Alsin, Senataxin, VAPB, BSCL2). …”

A Novel Four Mitochondrial Respiration-Related Signature for Predicting Biochemical Recurrence of Prostate Cancer by Zhongyou Xia, Haolin Liu, Shicheng Fan, Hongtao Tu, Yongming Jiang, Hai Wang, Peng Gu, Xiaodong Liu

“…We identified 11 DE-MR-BCRGs by overlapping 132 DE-MRGs and 13 BCR-DEGs and constructed a risk model consisting of 4 genes (<i>APOE</i>, <i>DNAH8</i>, <i>EME2</i>, and <i>KIF5A</i>). Furthermore, we established an accurate nomogram, including a risk score and a Gleason score, for the BCR prediction of PCa patients. …”
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Phenotypic and Genetic Heterogeneity of Adult Patients with Hereditary Spastic Paraplegia from Serbia by Stojan Perić, Vladana Marković, Ayşe Candayan, Els De Vriendt, Nikola Momčilović, Andrija Savić, Nataša Dragašević-Mišković, Marina Svetel, Zorica Stević, Ivo Božović, Šarlota Mesaroš, Jelena Drulović, Ivana Basta, Igor Petrović, Olivera Tamaš, Milija Mijajlović, Ivana Novaković, Dragoslav Sokić, Albena Jordanova

“…One patient had a heterozygous de novo variant in the KIF5A gene, and one had a compound heterozygous mutation in the ZYFVE26 gene. …”
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Recent progress of the genetics of amyotrophic lateral sclerosis and challenges of gene therapy by Hui Wang, LiPing Guan, LiPing Guan, Min Deng

“…Recent studies have identified ALS related genes including ANXA11, ARPP21, CAV1, C21ORF2, CCNF, DNAJC7, GLT8D1, KIF5A, NEK1, SPTLC1, TIA1, and WDR7. These genetic discoveries contribute to a better understanding of ALS and show the potential to aid the development of better ALS treatments. …”
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The role of hereditary spastic paraplegia related genes in multiple sclerosis. A study of disease susceptibility and clinical outcome. by DeLuca, G, Ramagopalan, S, Cader, M, Dyment, D, Herrera, B, Orton, S, Degenhardt, A, Pugliatti, M, Sadovnick, A, Sotgiu, S, Ebers, G

“…Genotyping the two sets of MS patients and controls could not provide any evidence to suggest that genes involved in the pathogenesis of HSP (Paraplegin, NIPA1, KIF5A, HSPD1, Atlastin, Spartin, Spastin, PLP1, L1CAM, Maspardin and BSCL2) play a role in susceptibility to, or modifying the course of, MS, although small effects of these genes cannot be ruled out.…”

Clinical relevance of single-subject brain metabolism patterns in amyotrophic lateral sclerosis mutation carriers by Giacomo Tondo, Letizia Mazzini, Silvia Paola Caminiti, Maria Francesca Sarnelli, Lucia Corrado, Roberta Matheoud, Sandra D'Alfonso, Roberto Cantello, Gian Mauro Sacchetti, Daniela Perani, Cristoforo Comi, Fabiola De Marchi

“…Patients were selected based on the presence of ALS gene mutation (C9orf72, SOD1, TBK1, and KIF5A). Following a validated voxel-based Statistical Parametric Mapping (SPM) procedure, we obtained hypometabolism maps at single-subject level. …”
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Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis by Ali Yousefian-Jazi, YunHee Seol, Jieun Kim, Hannah L. Ryu, Junghee Lee, Hoon Ryu

“…Herein, we discuss current literatures on the four newly identified ALS-associated genes (<i>CYLD</i>, <i>S1R</i>, <i>GLT8D1</i>, and <i>KIF5A</i>) and the previously well-known ALS genes including <i>SOD1</i>, <i>TARDBP</i>, <i>FUS</i>, and <i>C9orf72</i>. …”
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