. 2018 Jun 22;8(8):e00978. doi: 10.1002/brb3.978

Table 3.

Ion channel genes implicated in autism spectrum disorder (ASD) and related pathologies

Genes	Name	Cytogenetic location	Description	Associated phenotypes	References
CACNA1A	Alpha‐1A subunit of P/Q‐type Ca²⁺ channel	19p13.13	Modulates the biophysical properties of P/Q‐type Ca²⁺ channel in neurons	Autism, Asperger or PDD‐NOS, Ataxia, Migraine	Breitenkamp et al. (2015) and Skafidas et al. (2014)
CACNA1B	Alpha‐1B subunit of N‐type Ca²⁺ channel	9q34.3	Modulates the biophysical properties of N‐type Ca²⁺ channelwhich controls neurotransmitter release from neurons	Neurodevelopmental impairments, ASD, speech delay	Breitenkamp et al. (2015) and Yatsenko et al. (2012)
CACNA1C	Alpha‐1C subunit of L‐type Ca²⁺ channel	12p13.33	Plays an important role in the development of the central nervous system and it functions, especially NMDA receptor function in the hippocampus. The mutation is also implicated in defective synaptic plasticity	Timothy syndrome, psychiatric diseases (bipolar disorder, schizophrenia), Brugada syndrome, ASD	Cross‐Disorder Group of the Psychiatric Genomics Consortium (2013) and Li et al. (2015)
CACNA1D	Alpha‐1D subunit of voltage‐gated Ca²⁺ channel	3p21.1	Contributes to different brain functions, such as emotions, memory, and drug dependence. Controls gating and current properties and is involved in pacemaker current	Sinoatrial node dysfunction and deafness, psychiatric diseases, ASD	Pinggera et al. (2015)
CACNA1E	Alpha‐1E subunit of R‐type Ca²⁺ channel	1q25.3	Modulates the biophysical properties of R‐type Ca²⁺ channel	ASD, psychiatric diseases	Lu et al. (2012)
CACNA1F	Alpha‐1F subunit of L‐type Ca²⁺ channel	Xp11.23	Modulates the biophysical properties of L‐type Ca²⁺ channel	Congenital night blindness and autism	Breitenkamp et al. (2015) and Hemara‐Wahanui et al. (2005)
CACNA1G	Alpha‐1G subunit of T‐type Ca²⁺ channel	17q21.33	Modulates the Ca²⁺ influx of T‐type channel in neurons and muscle	ASD, intellectual disability, Juvenile myoclonic epilepsy	Girirajan et al. (2013)
CACNA1H	Alpha‐1H subunit of T‐type Ca²⁺ channel	16p13.3	Abundantly expressed in cerebellum and cerebral cortex, activates small depolarization and contributes to the oscillatory behavior in neurons	ASD, childhood absence epilepsy, idiopathic generalized epilepsy	Splawski et al. (2006)
CACNA1I	Alpha‐1I subunit of T‐type Ca²⁺ channel	22q13.1	Modulates the Ca²⁺ influx of T‐type channel in neurons and generates pacemaker activity		Breitenkamp et al. (2015) and Hussman et al. (2011)
CACNA2D4	Alpha‐2/delta‐4 subunit of voltage‐gated Ca²⁺ channel	12p13.33	Modulates Ca²⁺ influx and voltage‐gated channel properties	Retinal cone dystrophy 4, ASD (when gene deletion occurs along with CACNA1C)	Smith et al. (2012)
CACNA2D3	Alpha‐2/delta‐3 subunit of voltage‐gated Ca²⁺ channel	3p21.1–p14.3	Modulates Ca²⁺ influx and voltage‐gated channel properties	ASD	Breitenkamp et al. (2015) and Skafidas et al. (2014)
CACNB2	Beta‐2 subunit of voltage‐gated Ca²⁺ channel	10p12.33–p12.31	Modulates the kinetics of L‐type calcium channel by increasing its activity	ASD, psychiatric diseases, Brugada syndrome	Breitenkamp et al. (2014)
SCN1A	Voltage‐regulated sodium channel type 1	2q24.3	Expressed in neurons and central and peripheral nervous system. Highly conserved through evolution. Controls channel gating and current	Inherited seizure disorder, Generalized Epilepsy with Febrile Seizures Plus (GEFS+), Juvenile myoclonic epilepsy, mental retardation, ASD	Craig et al. (2012), O'Roak et al. (2011), and Weiss et al. (2003)
SCN2A	Voltage‐regulated sodium channel type 2	2q24.3	Expressed in neurons and central and peripheral nervous system. Controls channel gating and current	Early infantile epileptic, encephalopathy, benign familial infantile seizures, ASD	Celle et al. (2013) and Weiss et al. (2003)
SCN3A	Voltage‐regulated sodium channel type 3	2q24.3	Expressed in neurons and central and peripheral nervous system. Controls biophysical properties of the channel	Epilepsy, ASD	Celle et al. (2013) and Weiss et al. (2003)
SCN7A	Voltage‐regulated sodium channel type 7	2q24.3	Na⁺‐specific channel in excitable cells	ASD (homozygous deletion in autism)	Morrow et al. (2008)
SCN8A	Voltage‐regulated sodium channel type 8	12q13.13	Alters the repetitive firing pattern of cerebellar Purkinje neurons	Cerebellar ataxia, epileptic encephalopathy early infantile, ASD	Weiss et al. (2003)
KCNMA1	Calcium‐activated large conductance potassium channel subfamily A	10q22.3	Synaptic protein regulator of neuronal excitability	Generalized epilepsy and paroxysmal dyskinesia (GEPD), ASD	Laumonnier et al. (2006)
KCNMB4	BK channel beta subunit 4	12q15	Regulatory subunit of BK channel	ASD	Skafidas et al. (2014)
KCNQ3	Potassium voltage‐gated channel (M‐channel)	8q24.22	Modulates the kinetics of the channel	Rolandic epilepsy and idiopathic generalized epilepsy (IGE) including benign neonatal convulsions, ASD	Gilling et al. (2013)
KCNQ5	Potassium voltage‐gated channel (M‐channel)	6q13	Expressed in brain and muscle and implicated in slow activation of the channel. Interacts with KCNQ3	ASD	Gilling et al. (2013)
GRIK2	Glutamate receptor ionotropic kainate 2	6q16.3	Glutamate receptors are the predominant excitatory neurotransmitter receptors in the central nervous system. Converts chemical signal to electrical impulse	Mental retardation, ASD	Ben‐Ari et al. (2012), Kang and Barnes (2013), and Laumonnier et al. (2006)
GRIK3	Glutamate receptor ionotropic kainate 3	1p34.3	Paralog of GRIK2	Schizophrenia, ASD	Ben‐Ari et al. (2012), Kang and Barnes, 2013, and Laumonnier et al. (2006)
CHRNA7	Acetylcholine receptor, neuronal nicotinic, alpha‐7 subunit	15q13.3	Postsynaptic GABAergic interneuron activity. Mediates fast signal transmission at synapses	Schizophrenia, ASD	Ben‐Ari et al. (2012), Kang and Barnes (2013), and Laumonnier et al. (2006)
GABRG3	GABA‐A gamma subunit of GABA receptor family	15q12	Conducts chloride ions upon activation leading to hyperpolarization. Causes inhibitory effect on neurotransmission	Schizophrenia, ASD	Ben‐Ari et al. (2012), Kang and Barnes, 2013, and Laumonnier et al. (2006)