Table 1.

α₂δ subunit isoforms and mouse and human disease phenotypes

	Mouse		Human
Isoform	Mouse models	Phenotype	Potential cause	Disease
α2δ-1	knock-in1 (GBP insensitive)	no known CNS phenotype1	aberrations of CACNA2D15	epilepsy and intellectual disability5
	knockout2	reduced pain sensitivity3, no known CNS phenotype1
	α2δ-1 over-expressing4	hyperalgesia, tactile allodynia4
α2δ-2	spontaneous loss-of-function mutations6,7,8,9 (ducky, ducky2j, entla), knockout10	ataxia, epilepsy and paroxysmal dyskinesia6,7,8,9,10	homozygous mutations (point11 and frameshift12)	epileptic encephalopathy11,12
			genomic deletion of CACNA2D213,14	potential tumor suppressor gene13,14
			single-nucleotide polymorphisms (SNPs)15	candidate gene in childhood absence epilepsy15
α2δ-3	knockout16	deficits in pain16 and auditory/acoustic startle processing17	SNPs16	reduced sensitivity to acute noxious heat and chronic back pain16
			splice site mutation in CACNA2D318	autism spectrum disorders18
α2δ-4	spontaneous mutation (premature stop)19	structural and functional abnormalities in ribbon synapses, loss of rods19	mutation (premature stop) of CACNA2D420	slowly progressive cone dystrophy and night blindness20
			partial deletion of CACNA2D421	psychiatric disorders21

¹Field et al. 2006,

²Fuller-Bicer et al. 2009,

³Patel et al. 2013,

⁴Li et al. 2006,

⁵Vergult et al. 2014,

⁶Barclay et al. 2001,

⁷Brodbeck et al. 2002,

⁸Brill et al. 2004,

⁹Donato et al. 2006,

¹⁰Ivanov et al. 2004,

¹¹Edvardson et al. 2013,

¹²Pippucci et al. 2013,

¹³Carboni et al. 2003,

¹⁴Hesson et al. 2007,

¹⁵Chioza et al. 2009,

¹⁶Neely et al. 2010,

¹⁷Pirone et al. 2014,

¹⁸Iossifov et al. 2012,

¹⁹Wycisk et al. 2006a,

²⁰Wycisk et al. 2006b,

²¹Van Den Bossche et al. 2012