CACNA1H mutations in autism spectrum disorders

Splawski, Igor; Yoo, Dana S.; Stotz, Stephanie C.; Cherry, Allison; Clapham, David E.; Keating, Mark T.

doi:10.1074/jbc.m603316200

Cited by 255Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersIon channel regulation and function

CACNA1H mutations in autism spectrum disorders

Open access

Splawski, Igor, Yoo, Dana S., Stotz, Stephanie C., Cherry, Allison, Clapham, David E., Keating, Mark T.·2006·Journal of Biological Chemistry

DOI 10.1074/jbc.m603316200

Open this paper in CoChat — free account Open PDF

Abstract

Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by impaired social interaction, communication skills, and restricted and repetitive behavior. The genetic causes for autism are largely unknown. Previous studies implicate CACNA1C (L-type Ca(V)1.2) calcium channel mutations in a disorder associated with autism (Timothy syndrome). Here, we identify missense mutations in the calcium channel gene CACNA1H (T-type Ca(V)3.2) in 6 of 461 individuals with ASD. These mutations are located in conserved and functionally relevant domains and are absent in 480 ethnically matched controls (p = 0.014, Fisher's exact test). Non-segregation within the pedigrees between the mutations and the ASD phenotype clearly suggest that the mutations alone are not responsible for the condition. However, functional analysis shows that all these mutations significantly reduce Ca(V)3.2 channel activity and thus could affect neuronal function and potentially brain development. We conclude that the identified mutations could contribute to the development of the ASD phenotype.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1074/jbc.m603316200

Cites

27 of 27 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

ASD children have altered gut microbiota profiles compared with NT children, although some studies report no significant difference.
“In the literature it has been reported that ASD children have altered gut microbiota profiles compared with NT children, although in some studies, no significant difference has been reported [19,20]”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [20]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders
Lord, C., Rutter, M., & Le Couteur, A. (1994) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02172145 · Cited by 9,065 · see citing works
The Autism Diagnostic Observation Schedule—Generic: A Standard Measure of Social and Communication Deficits Associated with the Spectrum of Autism
Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Leventhal, B. L., DiLavore, P. C., Pickles, A., & Rutter, M. (2000) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1005592401947 · Cited by 7,520 · see citing works
Ion Channels/Excitable Membranes
(2011) · Springer eBooks · doi:10.1007/springerreference_33998 · Cited by 4,066 · see citing works
Ion Channels/Excitable Membranes
Terlau, H., & Kirchhoff, F. (2006) · Springer eBooks · doi:10.1007/3-540-29623-9_5640 · Cited by 1,805 · see citing works
Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels
Perez‐Reyes, E. (2003) · Physiological Reviews · doi:10.1152/physrev.00018.2002 · Cited by 1,655 · see citing works
CaV1.2 Calcium Channel Dysfunction Causes a Multisystem Disorder Including Arrhythmia and Autism
Splawski, I., Timothy, K. W., Sharpe, L. M., Decher, N., Kumar, P., Bloise, R., Napolitano, C., Schwartz, P. J., Joseph, R. M., Condouris, K., et al. (2004) · Cell · doi:10.1016/j.cell.2004.09.011 · Cited by 1,586 · see citing works
Epidemiological Surveys of Autism and Other Pervasive Developmental Disorders: An Update
Fombonne, E. (2003) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1025054610557 · Cited by 1,505 · see citing works
Sleep and arousal: thalamocortical mechanisms
McCormick, D. A., & Bal, T. (1997) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.20.1.185 · Cited by 1,267 · see citing works
The genetics of autism
Muhle, R., Trentacoste, S. V., & Rapin, I. (2004) · Pediatrics · doi:10.1542/peds.113.5.e472 · Cited by 1,207 · see citing works
Voltage Sensor of Kv1.2: Structural Basis of Electromechanical Coupling
Long, S. B., Campbell, E. B., & MacKinnon, R. (2005) · Science · doi:10.1126/science.1116270 · Cited by 982 · see citing works
Differential Distribution of Three Members of a Gene Family Encoding Low Voltage-Activated (T-Type) Calcium Channels
Talley, E. M., Cribbs, L. L., Lee, J., Daud, A. N., Perez‐Reyes, E., & Bayliss, D. A. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-06-01895.1999 · Cited by 790 · see citing works
Mutations in the hminK gene cause long QT syndrome and suppress lKs function
Splawski, I., Tristani‐Firouzi, M., Lehmann, M. H., Sanguinetti, M. C., & Keating, M. T. (1997) · Nature Genetics · doi:10.1038/ng1197-338 · Cited by 767 · see citing works
Postnatal neurodevelopmental disorders: meeting at the synapse?
Zoghbi, H. Y. (2003) · Science · doi:10.1126/science.1089071 · Cited by 691 · see citing works
Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations
Splawski, I., Timothy, K. W., Decher, N., Kumar, P., Sachse, F. B., Beggs, A. H., Sanguinetti, M. C., & Keating, M. T. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502506102 · Cited by 624 · see citing works
Brain anatomy and development in autism: review of structural MRI studies
Brambilla, P., Hardan, A., di Nemi, S. U., Perez, J., Soares, J. C., & Barale, F. (2003) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2003.06.001 · Cited by 418 · see citing works
Association between genetic variation of CACNA1H and childhood absence epilepsy
Chen, Y., Lu, J., Pan, H., Zhang, Y., Wu, H., Xu, K., Liu, X., Jiang, Y., Bao, X., Yao, Z., et al. (2003) · Annals of Neurology · doi:10.1002/ana.10607 · Cited by 380 · see citing works
The Autism Genetic Resource Exchange: A Resource for the Study of Autism and Related Neuropsychiatric Conditions
Geschwind, D. H., Sowinski, J., Lord, C., Iversen, P., Shestack, J., Jones, P., Ducat, L., & Spence, S. J. (2001) · The American Journal of Human Genetics · doi:10.1086/321292 · Cited by 302 · see citing works
Sodium channels SCN1A, SCN2A and SCN3A in familial autism
Weiss, L. A., Escayg, A., Kearney, J. A., Trudeau, M., MacDonald, B. T., Mori, M., Reichert, J. G., Buxbaum, J. D., & Meisler, M. H. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001241 · Cited by 294 · see citing works
Autism
Volkmar, F. R., & Pauls, D. L. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14471-6 · Cited by 288 · see citing works
Autism Spectrum Disorders: Early Detection, Intervention, Education, and Psychopharmacological Management
Bryson, S. E., Rogers, S. J., & Fombonne, E. J. (2003) · The Canadian Journal of Psychiatry · doi:10.1177/070674370304800802 · Cited by 275 · see citing works
Gating Effects of Mutations in the Cav3.2 T-type Calcium Channel Associated with Childhood Absence Epilepsy
Khosravani, H., Altier, C., Simms, B., Hamming, K. S. C., Snutch, T. P., Mezeyova, J., McRory, J. E., & Zamponi, G. W. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c400006200 · Cited by 186 · see citing works
Functional Characterization and Neuronal Modeling of the Effects of Childhood Absence Epilepsy Variants ofCACNA1H, a T-Type Calcium Channel
Vitko, I., Chen, Y., Arias, J. M., Shen, Y., Wu, X., & Perez‐Reyes, E. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0847-05.2005 · Cited by 180 · see citing works
Effects of Cav3.2 channel mutations linked to idiopathic generalized epilepsy
Khosravani, H., Bladen, C., Parker, D. B., Snutch, T. P., McRory, J. E., & Zamponi, G. W. (2005) · Annals of Neurology · doi:10.1002/ana.20458 · Cited by 111 · see citing works
Overexpression of T‐type calcium channels in HEK‐293 cells increases intracellular calcium without affecting cellular proliferation
Chemin, J., Monteil, A., Briquaire, C., Richard, S., Perez‐Reyes, E., Nargeot, J., & Lory, P. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01832-9 · Cited by 110 · see citing works
A profile of alternative RNA splicing and transcript variation of CACNA1H, a human T-channel gene candidate for idiopathic generalized epilepsies
Zhong, X., Liu, J. R., Kyle, J. W., Hanck, D. A., & Agnew, W. S. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl068 · Cited by 97 · see citing works
Review of animal models for autism: implication of thyroid hormone
Sadamatsu, M., Kanai, H., Xu, X., Liu, Y., & Kato, N. (2006) · Congenital Anomalies · doi:10.1111/j.1741-4520.2006.00094.x · Cited by 65 · see citing works
Biography of Mark T. Keating
Nuzzo, R. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503300102 · Cited by 8 · see citing works

Flagged first, then by citations

Research works printed but not linked: 2

Joksovic, P., Nelson, M., Jevtovic-Todorovic, V., Patel, M., Perez-Reyes, E., Campbell, K., Chen, C. C., and Todorovic, S. (2006) J. Physiol., in press 10. Khosravani, H., Altier, C., Simms, B., Hamming, K. S., Snutch, T. P., Mezeyova, J., McRory, J. E., and Zamponi, G. W. (2004) J. Biol. Chem. 279, 9681-9684
Splawski, I., Timothy, K. W., Decher, N., Kumar, P., Sachse, F. B., Beggs, A. H., Sanguinetti, M. C., and Keating, M. T. (2005) Proc. Natl. Acad. Sci.

Sorted by citations

A Model for Neural Development and Treatment of Rett Syndrome Using Human Induced Pluripotent Stem Cells
Marchetto, M. C. N., Carromeu, C., Acab, A., Yu, D., Yeo, G. W., Mu, Y., Chen, G., Gage, F. H., & Muotri, A. R. (2010) · Cell · doi:10.1016/j.cell.2010.10.016 · Cited by 1,329 · see citing works
The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential
Zamponi, G., Striessnig, J., Koschak, A., & Dolphin, A. (2015) · Pharmacological Reviews · doi:10.1124/pr.114.009654 · Cited by 1,004 · see citing works
Neuronal Voltage-Gated Calcium Channels: Structure, Function, and Dysfunction
Simms, B., & Zamponi, G. W. (2014) · Neuron · doi:10.1016/j.neuron.2014.03.016 · Cited by 671 · see citing works
Autism spectrum disorders-a genetics review
Miles, J. H. (2011) · Genetics in Medicine · doi:10.1097/gim.0b013e3181ff67ba · Cited by 567 · see citing works
Energetics, epigenetics, mitochondrial genetics
Wallace, D. C., & Fan, W. (2009) · Mitochondrion · doi:10.1016/j.mito.2009.09.006 · Cited by 507 · see citing works
The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation
Tahiliani, M., Mei, P., Fang, R., Leonor, T., Rutenberg, M. S., Shimizu, F., Li, J., Rao, A., & Shi, Y. G. (2007) · Nature · doi:10.1038/nature05823 · Cited by 429 · see citing works
Communication Between the Synapse and the Nucleus in Neuronal Development, Plasticity, and Disease
Cohen, S., & Greenberg, M. E. (2008) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.24.110707.175235 · Cited by 400 · see citing works
KCC2 Expression Promotes the Termination of Cortical Interneuron Migration in a Voltage-Sensitive Calcium-Dependent Manner
Bortone, D., & Polleux, F. (2009) · Neuron · doi:10.1016/j.neuron.2009.01.034 · Cited by 387 · see citing works
Targeting voltage-gated calcium channels in neurological and psychiatric diseases
Zamponi, G. W. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.5 · Cited by 371 · see citing works
Epigenetics of autism spectrum disorders
Schanen, N. C. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl213 · Cited by 341 · see citing works
Key role for gene dosage and synaptic homeostasis in autism spectrum disorders
Toro, R., Konyukh, M., Delorme, R., Leblond, C., Chaste, P., Fauchereau, F., Coleman, M., Leboyer, M., Gillberg, C., & Bourgeron, T. (2010) · Trends in Genetics · doi:10.1016/j.tig.2010.05.007 · Cited by 331 · see citing works
Common DNA methylation alterations in multiple brain regions in autism
Ladd‐Acosta, C., Hansen, K. D., Briem, E., Fallin, M. D., Kaufmann, W. E., & Feinberg, A. P. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.114 · Cited by 328 · see citing works
Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia
Piton, A., Gauthier, J., Hamdan, F. F., Lafrenière, R. G., Yang, Y., Henrion, É., Laurent, S. B., Noreau, A., Thibodeau, P., Karemera, L., et al. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.54 · Cited by 312 · see citing works
The Expanding Spectrum of Primary Aldosteronism: Implications for Diagnosis, Pathogenesis, and Treatment
Vaidya, A., Mulatero, P., Baudrand, R. F., & Adler, G. K. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00139 · Cited by 311 · see citing works
An Overview of the Main Genetic, Epigenetic and Environmental Factors Involved in Autism Spectrum Disorder Focusing on Synaptic Activity
Masini, E., Loi, E., Vega-Benedetti, A. F., Carta, M., Doneddu, G., Fadda, R., & Zavattari, P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218290 · Cited by 293 · see citing works
Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons
Krey, J. F., Pașca, S. P., Shcheglovitov, A., Yazawa, M., Schwemberger, R., Rasmusson, R. L., & Dolmetsch, R. E. (2013) · Nature Neuroscience · doi:10.1038/nn.3307 · Cited by 252 · see citing works
Physiology and Pathology of Calcium Signaling in the Brain
Kawamoto, E. M., Vivar, C., & Camandola, S. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00061 · Cited by 250 · see citing works
Autism genetics
Persico, A. M., & Napolioni, V. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.06.012 · Cited by 242 · see citing works
Genetic disruption of voltage-gated calcium channels in psychiatric and neurological disorders
Heyes, S., Pratt, W. S., Rees, E., Dahimène, S., Ferron, L., Owen, M. J., & DOLPHIN, A. C. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.09.002 · Cited by 234 · see citing works
Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons
Griesi-Oliveira, K., Acab, A., Gupta, A. R., Sunaga, D. Y., Chailangkarn, T., Nicol, X., Nunez, Y., Walker, M. F., Murdoch, J. D., Sanders, S. J., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.141 · Cited by 236 · see citing works
Extended spectrum of idiopathic generalized epilepsies associated with CACNA1H functional variants
Heron, S. E., Khosravani, H., Varela, D., Bladen, C., Williams, T. C., Newman, M. R., Scheffer, I. E., Berkovic, S. F., Mulley, J. C., & Zamponi, G. W. (2007) · Annals of Neurology · doi:10.1002/ana.21169 · Cited by 219 · see citing works
Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions
Ristori, M. V., Quagliariello, A., Reddel, S., Ianiro, G., Vicari, S., Gasbarrini, A., & Putignani, L. (2019) · Nutrients · doi:10.3390/nu11112812 · Cited by 214 · see citing works
The Low-Threshold Calcium Channel Cav3.2 Determines Low-Threshold Mechanoreceptor Function
François, A., Schütter, N., Laffray, S., Sanguesa, J., Pizzoccaro, A., Dubel, S. J., Mantilleri, A., Nargeot, J., Noël, J., Wood, J. N., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2014.12.042 · Cited by 199 · see citing works
Mutations in the calcium-related gene IL1RAPL1 are associated with autism
Piton, A., Michaud, J. L., Peng, H., Aradhya, S., Gauthier, J., Mottron, L., Champagne, N., Lafreniere, R. G., Hamdan, F. F., S2D team, et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn300 · Cited by 195 · see citing works
Autism genetics: searching for specificity and convergence
Berg, J. M., & Geschwind, D. H. (2012) · Genome Biology · doi:10.1186/gb-2012-13-7-247 · Cited by 192 · see citing works
Cryo-EM structures of apo and antagonist-bound human Cav3.1
Zhao, Y., Huang, G., Wu, Q., Wu, K. K., Li, R., Lei, J., Pan, X., & Yan, N. (2019) · Nature · doi:10.1038/s41586-019-1801-3 · Cited by 183 · see citing works
Etiologies underlying sex differences in autism spectrum disorders
Schaafsma, S. M., & Pfaff, D. W. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.03.006 · Cited by 178 · see citing works
Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders
Schaaf, C. P., Sabo, A., Sakai, Y., Crosby, J., Muzny, D., Hawes, A., Lewis, L., Akbar, H., Varghese, R., Boerwinkle, E., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr243 · Cited by 175 · see citing works
Role of voltage-gated calcium channels in epilepsy
Zamponi, G. W., Lory, P., & Perez‐Reyes, E. (2009) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-009-0772-x · Cited by 175 · see citing works
CACNA1H Mutations Are Associated With Different Forms of Primary Aldosteronism
Daniil, G., Fernandes-Rosa, F. L., Chemin, J., Blesneac, I., Beltrand, J., Polak, M., Jeunemaı̂tre, X., Boulkroun, S., Amar, L., Strom, T. M., et al. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.10.002 · Cited by 171 · see citing works
Molecular mechanisms of autism: a possible role for Ca2+ signaling
Krey, J. F., & Dolmetsch, R. E. (2007) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2007.01.010 · Cited by 169 · see citing works
Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops
Mullins, C., Fishell, G., & Tsien, R. W. (2016) · Neuron · doi:10.1016/j.neuron.2016.02.017 · Cited by 167 · see citing works
Genetics of Autism Spectrum Disorder: Current Status and Possible Clinical Applications
Yoo, H. (2015) · Experimental Neurobiology · doi:10.5607/en.2015.24.4.257 · Cited by 157 · see citing works
Pluripotent stem cells in neurodegenerative and neurodevelopmental diseases
Marchetto, M. C. N., Winner, B., & Gage, F. H. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq159 · Cited by 152 · see citing works
Neuropsychopathology of Autism Spectrum Disorder: Complex Interplay of Genetic, Epigenetic, and Environmental Factors
Bhandari, R., Paliwal, J. K., & Kuhad, A. (2020) · Advances in neurobiology · doi:10.1007/978-3-030-30402-7_4 · Cited by 156 · see citing works
A novel mutation in JARID1C/SMCX in a patient with autism spectrum disorder (ASD)
Adegbola, A. A., Gao, H., Sommer, S. S., & Browning, M. F. (2008) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32142 · Cited by 148 · see citing works
L‐type calcium channels and psychiatric disorders: A brief review
Casamassima, F., Hay, A. C., Benedetti, A., Lattanzi, L., Cassano, G. B., & Perlis, R. H. (2010) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31122 · Cited by 136 · see citing works
Genetic Calcium Signaling Abnormalities in the Central Nervous System: Seizures, Migraine, and Autism
Gargus, J. J. (2008) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2008.03572.x · Cited by 131 · see citing works
Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders
Andrade, A., Brennecke, A., Mallat, S., Brown, J., Gomez-Rivadeneira, J., Czepiel, N., & Londrigan, L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20143537 · Cited by 127 · see citing works
Channelopathy pathogenesis in autism spectrum disorders
Schmunk, G., & Gargus, J. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00222 · Cited by 118 · see citing works
The Role of Calcium Channels in EpilepsyPreprint
Rajakulendran, S., & Hanna, M. G. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a022723 · Cited by 120 · see citing works
The I–II Loop Controls Plasma Membrane Expression and Gating of Cav3.2 T-Type Ca2+Channels: A Paradigm for Childhood Absence Epilepsy Mutations
Vitko, I., Bidaud, I., Arias, J. M., Mezghrani, A., Lory, P., & Perez‐Reyes, E. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1817-06.2007 · Cited by 117 · see citing works
The Neurobiology of Lipid Metabolism in Autism Spectrum Disorders
Tamiji, J., & Crawford, D. A. (2010) · Neurosignals · doi:10.1159/000323189 · Cited by 114 · see citing works
T-type calcium channels in neuropathic pain
Bourinet, E., François, A., & Laffray, S. (2015) · Pain · doi:10.1097/j.pain.0000000000000469 · Cited by 112 · see citing works
Autism spectrum disorders: The quest for genetic syndromes
Zafeiriou, D., Ververi, A., Dafoulis, V., Kalyva, E., & Vargiami, E. (2013) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32152 · Cited by 104 · see citing works
T-type calcium channels: From molecule to therapeutic opportunities
Weiss, N., & Zamponi, G. W. (2019) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2019.01.008 · Cited by 107 · see citing works
Excitotoxicity in the Pathogenesis of Autism
Essa, M. M., Braidy, N., Vijayan, K. R., Subash, S., & Guillemin, G. J. (2012) · Neurotoxicity Research · doi:10.1007/s12640-012-9354-3 · Cited by 97 · see citing works
Support for calcium channel gene defects in autism spectrum disorders
Lu, A. T.-H., Dai, X., Martínez-Agosto, J. A., & Cantor, R. M. (2012) · Molecular Autism · doi:10.1186/2040-2392-3-18 · Cited by 94 · see citing works
Genetic T-type calcium channelopathies
Weiss, N., & Zamponi, G. W. (2019) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2019-106163 · Cited by 91 · see citing works
Voltage-gated calcium channels and disease.
Cain, S., & Snutch, T. (2011) · Biofactors · doi:10.1002/biof.158 · Cited by 77 · see citing works
Mechanisms by which a CACNA1H mutation in epilepsy patients increases seizure susceptibility
Eckle, V., Shcheglovitov, A., Vitko, I., Dey, D., Yap, C. C., Winckler, B., & Perez‐Reyes, E. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.264176 · Cited by 86 · see citing works
Epigenome-wide analysis identifies genes and pathways linked to neurobehavioral variation in preterm infants
Everson, T. M., Marsit, C. J., Michael O’Shea, T., Burt, A., Hermetz, K., Carter, B. S., Helderman, J., Hofheimer, J. A., McGowan, E. C., Neal, C. R., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-42654-4 · Cited by 82 · see citing works
Neuronal Cav3 channelopathies: recent progress and perspectives
Lory, P., Nicole, S., & Monteil, A. (2020) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-020-02429-7 · Cited by 80 · see citing works
High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene
Strom, S. P., Stone, J. L., ten Bosch, J. R., Merriman, B., Cantor, R. M., Geschwind, D. H., & Nelson, S. F. (2009) · Molecular Psychiatry · doi:10.1038/mp.2009.41 · Cited by 80 · see citing works
T-type calcium channel Cav3.2 deficient mice show elevated anxiety, impaired memory and reduced sensitivity to psychostimulants
Gangarossa, G., Laffray, S., Bourinet, E., & Valjent, E. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00092 · Cited by 79 · see citing works
Dysregulation of large-conductance Ca2+-activated K+ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation
Higgins, J. J., Hao, J., Kosofsky, B. E., & Rajadhyaksha, A. M. (2008) · Neurogenetics · doi:10.1007/s10048-008-0128-2 · Cited by 77 · see citing works
Voltage-gated calcium channels in genetic diseases
Bidaud, I., Mezghrani, A., Swayne, L. A., Monteil, A., & Lory, P. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.08.049 · Cited by 77 · see citing works
Forced‐exercise delays neuropathic pain in experimental diabetes: effects on voltage‐activated calcium channels
Shankarappa, S. A., Piedras-Renterı́a, E. S., & Stubbs, E. B. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07302.x · Cited by 76 · see citing works
Regulation of T-type calcium channels: Signalling pathways and functional implications
Huc-Brandt, S., Monteil, A., Bidaud, I., Barbara, G. S., Chemin, J., & Lory, P. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2008.11.003 · Cited by 74 · see citing works
Increased activities of Na+/K+-ATPase and Ca2+/Mg2+-ATPase in the frontal cortex and cerebellum of autistic individuals
Ji, L., Chauhan, A., Brown, W. T., & Chauhan, V. (2009) · Life Sciences · doi:10.1016/j.lfs.2009.10.008 · Cited by 72 · see citing works
Functional Characterization of Schizophrenia-Associated Variation in CACNA1C
Eckart, N., Song, Q., Yang, R. J., Wang, R., Zhu, H., McCallion, A. S., & Avramopoulos, D. (2016) · PLoS ONE · doi:10.1371/journal.pone.0157086 · Cited by 74 · see citing works
An Intrinsic Transcriptional Program Underlying Synaptic Scaling during Activity Suppression
Schaukowitch, K., Reese, A. L., Kim, S.-K., Kilaru, G., Joo, J., Kavalali, E. T., & Kim, T.-K. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.01.033 · Cited by 71 · see citing works
Spatial transcriptomics reveals the distinct organization of mouse prefrontal cortex and neuronal subtypes regulating chronic pain
Bhattacherjee, A., Zhang, C., Watson, B. R., Djekidel, M. N., Moffitt, J. R., & Zhang, Y. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01455-9 · Cited by 71 · see citing works
Genetic associations between voltage-gated calcium channels and autism spectrum disorder: a systematic review
Liao, X., & Li, Y. (2020) · Molecular Brain · doi:10.1186/s13041-020-00634-0 · Cited by 70 · see citing works
The Mitochondrial Aspartate/Glutamate Carrier AGC1 and Calcium Homeostasis: Physiological Links and Abnormalities in Autism
Napolioni, V., Persico, A. M., Porcelli, V., & Palmieri, L. (2011) · Molecular Neurobiology · doi:10.1007/s12035-011-8192-2 · Cited by 70 · see citing works
Altered heavy metals and transketolase found in autistic spectrum disorder
Obrenovich, M. E., Shamberger, R. J., & Lonsdale, D. (2011) · Biological Trace Element Research · doi:10.1007/s12011-011-9146-2 · Cited by 67 · see citing works
Retrieval of Context-Associated Memory is Dependent on the Cav3.2 T-Type Calcium Channel
Chen, C., Shen, J.-W., Chung, N.-C., Min, M., Cheng, S.-J., & Liu, I. Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029384 · Cited by 66 · see citing works
The inherited methylome landscape is directly altered with paternal aging and associated with offspring neurodevelopmental disorders
Denomme, M. M., Haywood, M. E., Parks, J. C., Schoolcraft, W. B., & Katz‐Jaffe, M. G. (2020) · Aging Cell · doi:10.1111/acel.13178 · Cited by 63 · see citing works
The impact of C-tactile low-threshold mechanoreceptors on affective touch and social interactions in mice
Huzard, D., Martín, M., Maingret, F., Chemin, J., Jeanneteau, F. D., Méry, P., Fossat, P., Bourinet, E., & François, A. (2022) · Science Advances · doi:10.1126/sciadv.abo7566 · Cited by 61 · see citing works
Calcium Channelopathies: Voltage-Gated Calcium Channels
Adams, P. J., & Snutch, T. P. (2007) · Springer eBooks · doi:10.1007/978-1-4020-6191-2_8 · Cited by 56 · see citing works
Age-related downregulation of the CaV3.1 T-type calcium channel as a mediator of amyloid beta production
Rice, R. A., Berchtold, N. C., Cotman, C. W., & Green, K. N. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.10.090 · Cited by 57 · see citing works
Neural Burst Firing and Its Roles in Mental and Neurological Disorders
Shao, J., Liu, Y., Gao, D., Tu, J., & Yang, F. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.741292 · Cited by 53 · see citing works
Mitochondrial and ion channel gene alterations in autism
Smith, M., Flodman, P. L., Gargus, J. J., Simon, M. T., Verrell, K., Haas, R., Reiner, G., Naviaux, R. K., Osann, K., Spence, M. A., et al. (2012) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.04.004 · Cited by 54 · see citing works
Somatic and inherited mutations in primary aldosteronism
Fernandes-Rosa, F. L., Boulkroun, S., & Zennaro, M. (2017) · Journal of Molecular Endocrinology · doi:10.1530/jme-17-0035 · Cited by 54 · see citing works
Primary Aldosteronism Diagnosis and Management
Hundemer, G. L., & Vaidya, A. (2019) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2019.08.002 · Cited by 53 · see citing works
Dendritic Integration Dysfunction in Neurodevelopmental Disorders
Nelson, A. D., & Bender, K. J. (2021) · Developmental Neuroscience · doi:10.1159/000516657 · Cited by 52 · see citing works
The E646D-ATP13A4 Mutation Associated with Autism Reveals a Defect in Calcium Regulation
Vallipuram, J., Grenville, J., & Crawford, D. A. (2009) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-009-9445-8 · Cited by 50 · see citing works
Mitochondrial Energy-Deficient Endophenotype in Autism
Gargus, J. J., & Imtiaz, F. (2008) · American journal of biochemistry & biotechnology/American journal of biochemistry and biotechnology · doi:10.3844/ajbbsp.2008.198.207 · Cited by 52 · see citing works
Glycan susceptibility factors in autism spectrum disorders
Dwyer, C. A., & Esko, J. D. (2016) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2016.07.001 · Cited by 49 · see citing works
L-Type Calcium Channels Modulation by Estradiol
Vega-Vela, N. E., Osorio, D., Ávila-Rodriguez, M., González, J., García‐Segura, L. M., Echeverrı́a, V., & Barreto, G. E. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0045-6 · Cited by 51 · see citing works
Rare mutations of CACNB2 found in autism spectrum disease-affected families alter calcium channel function
Breitenkamp, A. F. S., Matthes, J., Nass, R. D., Sinzig, J., Lehmkuhl, G., Nürnberg, P., & Herzig, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0095579 · Cited by 49 · see citing works
Epigenetic Mechanisms in Autism Spectrum Disorder
Zhubi, A., Cook, E. H., Guidotti, A., & Grayson, D. R. (2014) · International review of neurobiology · doi:10.1016/b978-0-12-801311-3.00006-8 · Cited by 51 · see citing works
T-type calcium channels in chronic pain: mouse models and specific blockers
François, A., Laffray, S., Pizzoccaro, A., Eschalier, A., & Bourinet, E. (2014) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-014-1484-4 · Cited by 46 · see citing works
Alternative splicing of voltage-gated calcium channels: from molecular biology to disease
Liao, P. H., Zhang, H. Y., & Soong, T. W. (2009) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-009-0635-5 · Cited by 46 · see citing works
RareRELNvariants affect Reelin-DAB1 signal transduction in autism spectrum disorder
Sánchez-Sánchez, S. M., Magdalon, J., Griesi‐Oliveira, K., Yamamoto, G. L., Santacruz-Pérez, C., Fogo, M. S., Passos‐Bueno, M. R., & Sertie, A. L. (2018) · Human Mutation · doi:10.1002/humu.23584 · Cited by 45 · see citing works
New insights into DNA methylation signatures: SMARCA2 variants in Nicolaides-Baraitser syndrome
Chater‐Diehl, E., Ejaz, R., Cytrynbaum, C. S., Siu, M. T., Turinsky, A. L., Choufani, S., Goodman, S. J., Abdul-Rahman, O. A., Bedford, M., Dorrani, N., et al. (2019) · BMC Medical Genomics · doi:10.1186/s12920-019-0555-y · Cited by 45 · see citing works
Neuronal T-type calcium channels: what's new? Iftinca: T-type channel regulation.
Iftinca, M. (2011) · Europe PMC (PubMed Central) · Cited by 44 · see citing works
T-type current modulation by the actin-binding protein Kelch-like 1
Aromolaran, K. A., Benzow, K. A., Cribbs, L. L., Koob, M. D., & Piedras-Renterı́a, E. S. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00235.2009 · Cited by 41 · see citing works
Targeting inhibitory cerebellar circuitry to alleviate behavioral deficits in a mouse model for studying idiopathic autism
Chao, O. Y.-H., de Velasco, E. M. F., Pathak, S. S., Maitra, S., Zhang, H., Duvick, L. A., Wickman, K., Orr, H. T., Hirai, H., & Yang, Y. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0656-5 · Cited by 51 · see citing works
Old and New Concepts in the Molecular Pathogenesis of Primary Aldosteronism
Prada, E. T. A., Burrello, J., Reincke, M., & Williams, T. A. (2017) · Hypertension · doi:10.1161/hypertensionaha.117.10111 · Cited by 39 · see citing works
Spontaneous Vesicle Fusion Is Differentially Regulated at Cholinergic and GABAergic Synapses
Liu, H., Li, L., Wang, W., Gong, J., Yang, X., & Hu, Z. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.023 · Cited by 35 · see citing works
Exome sequencing findings in 27 patients with myoclonic‐atonic epilepsy: Is there a major genetic factor?
Routier, L., Verny, F., Barcia, G., Chémaly, N., Desguerre, I., Colleaux, L., & Nabbout, R. (2019) · Clinical Genetics · doi:10.1111/cge.13581 · Cited by 38 · see citing works
Voltage-gated Calcium Channels and Autism Spectrum Disorders
Breitenkamp, A. F., Matthes, J., & Herzig, S. (2015) · Current Molecular Pharmacology · doi:10.2174/1874467208666150507105235 · Cited by 36 · see citing works
Post-translational histone modifications and their interaction with sex influence normal brain development and elaboration of neuropsychiatric disorders
Singh, G., Singh, V., & Schneider, J. S. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.10.016 · Cited by 35 · see citing works
Signaling Complexes of Voltage-Gated Calcium Channels and G Protein-Coupled Receptors
Altier, C., & Zamponi, G. W. (2008) · Journal of Receptors and Signal Transduction · doi:10.1080/10799890801941947 · Cited by 36 · see citing works
Presynaptic Calcium Channels: Structure, Regulators, and Blockers
Kisilevsky, A. E., & Zamponi, G. W. (2007) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-74805-2_3 · Cited by 35 · see citing works
Calmodulin regulates Cav3 T-type channels at their gating brake
Chemin, J., Taiakina, V., Monteil, A., Piazza, M. J., Guan, W., Stephens, R. F., Kitmitto, A., Pang, Z. P., DOLPHIN, A. C., Perez‐Reyes, E., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.807925 · Cited by 35 · see citing works
Intragenic deletions of IL1RAPL1: Report of two cases and review of the literature
Behnecke, A., Hinderhofer, K., Bartsch, O., Nümann, A., Ipach, M., Damatova, N., Haaf, T., Dufke, A., Rieß, O., & Moog, U. (2010) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33656 · Cited by 34 · see citing works
Alternative splicing modulates diltiazem sensitivity of cardiac and vascular smooth muscle Ca v 1.2 calcium channels
Zhang, H. Y., Liao, P. H., Wang, J. J., Yu, D. J., & Soong, T. W. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00798.x · Cited by 34 · see citing works
Autism throughout genetics: Perusal of the implication of ion channels
Daghsni, M., Rima, M., Fajloun, Z., Ronjat, M., Brusés, J. L., Mrad, R., & WAARD, M. M. D. (2018) · Brain and Behavior · doi:10.1002/brb3.978 · Cited by 33 · see citing works

Rare mutations of CACNB2 found in autism spectrum disease-affected families alter calcium channel function
Breitenkamp, A. F. S., Matthes, J., Nass, R. D., Sinzig, J., Lehmkuhl, G., Nürnberg, P., & Herzig, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0095579 · Cited by 49 · see citing works
Contribution of CACNA1H Variants in Autism Spectrum Disorder Susceptibility
Viggiano, M., D’Andrea, T., Cameli, C., Posar, A., Visconti, P., Scaduto, M. C., Colucci, R., Rochat, M. J., Ceroni, F., Milazzo, G., et al. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.858238 · Cited by 14 · see citing works
RESEARCH ARTICLE Schizophrenia Related Variants in CACNA1C
Autism, A. C. R. O. (2016)
Dissecting the Role of CaV1.2 Dysfunction in the Pathogenesis of Autism Spectrum Disorder
Herold, K., Bamgboye, M. A., DiSilvestre, D. A., Hussey, J. W., Owoyemi, J. O., Meredith, A. L., & Dick, I. E. (2021) · Biophysical Journal · doi:10.1016/j.bpj.2020.11.1121
A New Homozygous CACNB2 Mutation has Functional Relevance and Supports a Role for Calcium Channels in Autism Spectrum Disorder
Graziano, C., Despang, P., Palombo, F., Severi, G., Posar, A., Cassio, A., Pippucci, T., Isidori, F., Matthes, J., & Bonora, E. (2019) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-020-04551-y · Cited by 8 · see citing works

Authors: Splawski, I., Yoo, D. S., Stotz, S. C., Cherry, A., Clapham, D. E., & Keating, M. T.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Stotz, Stephanie C.
ORCID: Stotz, Stephanie C.
Clapham, David E.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2006-08
Volume: 281
Issue: 31
Pages: 22085-22091
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m603316200
OpenAlex: W2003315040
Cited by: 255
References: 27
Citations by year: 2026: 4 · 2025: 10 · 2024: 10 · 2023: 12 · 2022: 16 · 2021: 11 · 2020: 13 · 2019: 15 · 2018: 15 · 2017: 9 · 2016: 9 · 2015: 16 · 2014: 19 · 2013: 19 · 2012: 15
FWCI: 5.73
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 5186 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Charles H. Hood Foundation
Fondation pour la Recherche Médicale
National Institutes of Health
Canadian Institutes of Health Research
National Heart, Lung, and Blood Institute (HL46401, HL-52338, P50HL052338, T32HL007572)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords: autism spectrum disorder, CACNA1H, T-type calcium channels, Cav3.2, missense mutations, Timothy syndrome, L-type calcium channels, calcium channel activity, genetic susceptibility, brain development
MeSH terms: Autistic Disorder, DNA Mutational Analysis, Electrophysiology, Family Health, Humans, Kinetics, Pedigree, Case-Control Studies, Conserved Sequence, Molecular Epidemiology, Mutation, Missense, Calcium Channels, T-Type

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

CACNA1H mutations in autism spectrum disorders

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks