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Table 1
List of ion channel genes exhibiting alternative splicing in patients with mTLE
Genes by gene class	GenBank accession number (reference transcript*)	GenBank accession number (variant transcript*)	Alternative splicing event: change of mRNA transcript composition in epilepsy^†	Alternatively spliced region	Splice array p value

Calcium channels
CACNA1A	NM_023035	U79668	ES: 26% ↓ variant/reference ratio	EXON 48	0.002
	NM_023035	CQ723237	ASA: 24% ↓ reference/total ratio	EXON 23	0.003
	NM_023035	BE972738	NE: 36% ↓ variant/total ratio	3' downstream	<0.001
CACNA1C	NM_000719	CQ722696	ASD: 94% ↓ variant/reference ratio	EXON 2	<0.001
	NM_000719	CQ722691	ASD: 23% ↓ variant/reference ratio	EXON 24	0.017
CACNA1H	NM_021098	CQ730788	ASA: 25% ↓ variant/reference ratio	EXON 34	<0.001
CACNA1I	NM_001003406	AX068892	NE: 36% ↓ variant/reference ratio	INTRON 1	0.012
	NM_001003406	AX068892	NE: 23% ↓ variant/reference ratio	INTRONS 20/21	0.009
CACNA2D1	NM_000722	BG211441	ES: 28% ↑ reference/total ratio	EXON 8	0.003
CACNB1	NM_000723	NM_199247	NE: 28% ↑ variant/reference ratio	INTRON 6	<0.001
	NM_000723	BP316738	NE: 28% ↑ variant/reference ratio	INTRON 6	0.002
CACNB2	NM_201596	AF465485	ES: 20% ↓ variant/reference ratio	EXON 7	0.020
CACNB3	NM_000725	AK122911	NEs: 28% ↓ variant/total ratio	5' upstream	<0.001
CACNB4	NM_000726	AY054985	NE: 31% ↑ variant/reference ratio	INTRON 2	0.012
CACNG4	NM_014405	AW134993	PIED: 45% ↑ reference/total ratio	EXON 4	0.009
	NM_014405	AI675178	PIED: 41% ↓ variant/reference ratio	EXON 4	0.003

Chloride channels
CLCN2	NM_004366	BC021578	ES: 38% ↓ reference/total ratio	EXON 13	<0.001
CLCN3	NM_001829	CQ732096	ASA: 22% ↓ variant/reference ratio	EXON 2	0.004
	NM_001829	CQ736554	NE: 32% ↑ reference/total ratio	INTRON 12	0.012
CLCN6	NM_001286	BC050457	ASA: 16% ↓ variant/reference ratio	EXON 20	0.016
CLCN7	NM_001287	AK096963	IR: 36% ↓ variant/reference ratio	INTRON 18	<0.001
	NM_001287	BQ920088	ASA: 21% ↓ variant/reference ratio	EXON 12	0.004
CLIC5	NM_016929	BC039380	ASA: 20% ↓ reference/total ratio	EXON 5	0.013

Sodium channels
SCN2A2	NM_021007	BC029489	ES: 23% ↑ reference/total ratio	EXON 1	0.006
SCN9A	NM_002977	BG108767	ASD: 26% ↓ variant/reference ratio	EXON 16	0.003
SCNN1A	NM_001038	BF033087	PIED: 21% ↓ variant/reference ratio	EXON 13	<0.001
SCNN1D	NM_002978	AX230571	NE: 52% ↑ variant/total ratio	INTRON 2	0.012
	NM_002978	AK127357	NE: 77% ↑ variant/total ratio	5' upstream	0.002

Potassium channels
KCNAB2	NM_003636	BG720519	ES: 35% ↑ variant/reference ratio	EXON 1	0.014
	NM_003636	BM823724	NEs: 19% ↓ variant/total ratio	5' upstream	0.015
	NM_003636	CA495339	IR: 24% ↓ reference/total ratio	INTRON 11	0.020
KCNC3	NM_004977	AK127492	ASD: 27% ↓ variant/reference ratio	EXON 5	0.020
KCNH5	NM_172376	NM_139318	NE: 24% ↑ variant/total ratio	3' downstream	<0.001
KCNJ1	NM_153767	NM_000220	NE: 27% ↓ variant/reference ratio	INTRON 3	<0.001
KCNJ6	NM_002240	CQ738104	NEs: 24% ↓ variant/total ratio	INTRON 2	0.017
KCNJ15	NM_170736	NM_002243	NE: 108% ↑ variant/total ratio	5' upstream	<0.001
	NM_170736	NM_170737	NE: 2.5x ↑ reference/total ratio	INTRON 2	<0.001
	NM_170736	CQ732921	NEs: 42% ↓ variant/reference ratio	INTRON 2	0.005
	NM_170736	BM544058	NE: 98% ↑ variant/total ratio	5' upstream	<0.001
	NM_170736	BF105170	NE: 78% ↑ variant/total ratio	5' upstream	0.003
	NM_170736	BI518753	NE: 2.5x ↑ reference/total ratio	INTRON 2	<0.001
KCNK1	NM_002245	AV733795	PIED: 34% ↓ variant/reference ratio	EXON 2	0.010
	NM_002245	BG699040	NE: 45% ↓ variant/total ratio	INTRON 1	0.009
	NM_002245	BF212472	NEs: 23% ↓ variant/total ratio	INTRON 1	0.017
	NM_002245	BU661246	NEs: 48% ↓ variant/total ratio	INTRON 1	<0.001
KCNK2	NM_014217	BU956092	ES: 62% ↑ reference/total ratio	EXON 4	0.008
KCNK4	NM_016611	NM_033310	NE: 102% ↑ variant/total ratio	5' upstream	0.005
KCNK12	NM_022055	AX302031	NEs: 20% ↓ variant/total ratio	INTRON 1	0.014
KCNMA1	NM_002247	CQ870200	NE: 24% ↓ variant/reference ratio	EXON 20	0.006
	NM_002247	CQ870204	PIED: 32% ↓ variant/reference ratio	3' downstream	0.020
	NM_002247	BG185868	NE: 28% ↓ variant/reference ratio	EXON 9	0.014
KCNN2	NM_021614	NM_170775	NE: 26% ↓ variant/total ratio	INTRON 3	0.002
KCNQ2	NM_004518	AY358189	NE: 28% ↓ variant/reference ratio	INTRON 7	0.018
	NM_004518	BG772772	NEs: 23% ↓ variant/reference ratio	INTRON 7	0.018
HCN3	NM_020897	CQ715247	EsS: 15% ↓ variant/reference ratio	EXONS 3-4	0.012
SLICK	NM_198503	CQ728754	EsS: 28% ↓ reference/total ratio	EXONS 22-25	0.019
	NM_198503	CQ728754	ES: 57% ↑ variant/reference ratio	EXON 15	0.003

GABA receptors
GABRA2	NM_000807	CD014113	ES: 26% ↑ reference/total ratio	EXON 8	<0.001
	NM_000807	CD014116	EsS: 29% ↑ reference/total ratio	EXONS 4-9	<0.001
	NM_000807	CD014112	EsS: 35% ↑ reference/total ratio	EXON 4	<0.001
	NM_000807	CD014107	EsS: 31% ↑ reference/total ratio	EXONS 7/8	<0.001
	NM_000807	CD014110	EsS: 36% ↑ reference/total ratio	EXONS 6-8	<0.001
	NM_000807	CD014109	EsS: 40% ↑ reference/total ratio	EXONS 6/7	<0.001
GABRA3	NM_000808	AX897950	ES: 17% ↓ reference/total ratio	EXON 7	0.007
GABRG2	NM_198904	NM_198903	ASA: 22% ↑ reference/total ratio	EXON 4	0.005
GABRR1	NM_002042	CB959800	NEs: 17% ↓ variant/total ratio	5' upstream	0.007

Ionotropic glutamate receptors
GRIA1	NM_000827	A46050	NE: 34% ↓ variant/reference ratio	INTRON 14	0.012
	NM_000827	M64752	NE: 39% ↓ variant/reference ratio	INTRON 14	0.008
GRIA2	NM_000826	BC010574	NE: 44% ↓ variant/reference ratio	INTRON 13	0.007
	NM_000826	AX147452	NE: 61% ↓ variant/reference ratio	INTRON 13/EXON14	0.005
	NM_000826	AV748963	NE: 44% ↓ variant/reference ratio	EXON 14	0.015
GRIA3	NM_007325	NM_181894	NEs: 19% ↑ variant/reference ratio	INTRON 2	0.006
GRIK2	NM_021956	CQ715784	ASD: 65% ↓ reference/total ratio	EXON 10	<0.001
GRIK4	NM_014619	CQ869986	NEs: 29% ↓ variant/total ratio	5' upstream	0.006
	NM_014619	CQ715345	NE: 31% ↓ variant/total ratio	INTRON 4	0.015
	NM_014619	CQ715345	ES: 23% ↑ reference/total	EXON 7	0.005
GRIK5	NM_002088	CQ719647	ASD: 24% ↓ reference/total ratio	EXON 16	0.008
	NM_002088	AX665460	ASD: 23% ↓ variant/reference ratio	EXON 18	0.004
	NM_002088	CN420154	EsS: 27% ↓ variant/reference	EXONS 12-14	0.020

FXYD domain ion transport regulators
FXYD1	NM_021902	BQ181273	IR: 51% ↓ variant/reference ratio	INTRON 7	<0.001
FXYD6	NM_022003	AX430335	NE: 31% ↓ variant/total ratio	5' upstream	<0.001
	NM_022003	AX892598	NE: 35% ↓ variant/total ratio	5' upstream	<0.001
	NM_022003	BC018652	NEs: 38% ↓ variant/reference ratio	EXON 1/INTRON 1	<0.001
	NM_022003	AL832811	NE: 33% ↓ variant/reference ratio	INTRON 1	<0.001
	NM_022003	AW270073	ES: 34% ↓ variant/reference ratio	EXON 9	<0.001
	NM_022003	BI823239	NE: 48% ↓ variant/reference ratio	INTRON 1	<0.001
	NM_022003	BF527041	NE: 36% ↓ variant/reference ratio	INTRON 1	0.002
	NM_022003	BP372334	NE: 45% ↓ variant/reference ratio	INTRON 1	<0.001
	NM_022003	BE263758	NE: 37% ↓ variant/reference ratio	EXON 2	<0.001
	NM_022003	BX488702	ASA: 50% ↓ variant/reference ratio	INTRON 2	<0.001
	NM_022003	BI598749	NE: 40% ↓ variant/reference ratio	INTRON 1	0.006
FXYD7	NM_022006	CQ722304	ES: 21% ↓ variant/reference ratio	EXON 4	0.007

Transient receptor potential cation channels
TRPA1	NM_007332	BF570694	ASD: 37% ↓ reference/total ratio	EXON 25	<0.001
TRPC4	NM_016179	AF421362	ES: 24% ↓ reference/total ratio	EXON 3	0.004
TRPM1	NM_002420	AX480882	ASD:43% ↓ variant/reference ratio	EXON 17	<0.001
TRPM7	NM_017672	CQ728707	EsS: 35% ↑ variant/reference ratio	EXONS 7-11	<0.001
TRPV1	NM_080704	NM_080705	NE: 31% ↑ variant/total ratio	INTRON 1	0.007
	NM_080704	AX686983	ES: 35% ↑ variant/reference ratio	EXON 8	0.005
TRPV2	NM_016113	BQ645005	ASD: 25% ↓ variant/reference ratio	EXON 15	0.005

Glycine receptors
GLRB	NM_000824	CD013911	ES: 31% ↑ variant/reference ratio	EXON 9	0.004

Inositol triphosphate receptors
ITPR1	NM_002223	CQ727353	EsS: 22% ↑ variant/reference ratio	EXONS 52-54	0.020

Purinergic receptors
P2RX1	NM_002558	BM469621	NE: 57% ↑ variant/total ratio	INTRON 3	<0.001
	NM_002558	BP372168	ASD: 17% ↑ reference/total ratio	EXON 1	0.002
P2RXL1	NM_005446	BC064805	ASD: 24% ↑ variant/reference ratio	EXON 1	0.013

Cyclic nucleotide gated channels
CNGA1	NM_000087	CN366905	NEs: 20% ↓ variant/total ratio	5' upstream	0.011
CNGB3	NM_019098	AI150392	ES: 19% ↓ variant/total ratio	EXON 18	0.016

Amiloride-sensitive cation channel
ACCN2	NM_020039	BC028722	NE: 19% ↓ variant/reference	INTRON 3	0.017
	NM_020039	AX683970	NE: 23% ↓ variant/reference	INTRON 3	0.019

Two pore segment channels
TPCN1	NM_017901	CQ729206	ASA: 27% ↑ variant/reference ratio	EXON 10	<0.001
TPCN2	NM_139075	AW178475	NE: 87% ↑ variant/total ratio	INTRON 9	<0.001

Mucolipin
MCOLN1	NM_020533	BQ723075	ASD: 17% ↓ variant/reference ratio	EXON 2	<0.001
	NM_020533	CA489568	ASD: 69% ↑ variant/reference ratio	EXON 7	0.011

Ryanodine receptors
RYR3	NM_001036	CQ730808	ES: 28% ↑ variant/total ratio	EXON 84	0.017

Miscellaneous other ion channels/interacting proteins
C6orf69	NM_173562	BC023525	EsS: 33% ↑ reference/total ratio	EXONS 3-5	0.003
KCNIP2 (potassium channel interacting protein)	NM_014591	NM_173191	ASA: 37% ↑ variant/reference ratio	EXON 3	0.004
	NM_014591	NM_173193	EsS: 19% ↑ variant/reference ratio	EXONS 2-3	0.018
	NM_014591	NM_173197	ES: 9% ↓ reference/total ratio	EXON 7	0.015
MLC1 (megalencephalic leuko-encephalopathy with subcortical cysts)	NM_015166	BX451200	ASD: 31% ↓ variant/reference ratio	EXON 8	0.009
PKD1L2 (polycystic kidney disease 1-like)	NM_052892	CQ741519	ES: 82% ↑ variant/reference ratio	EXON 7	0.006
PKD2L2 (polycystic kidney disease 2like)	NM_014386	AF182034	NEs: 38% ↑ variant/total ratio	INTRON 13/3' downstream	0.005
SH3KBP1 (SH3KBP1 binding protein)	NM_138392	BX366064	ASD: 26% ↓ variant/reference ratio	EXON 10	0.002
	NM_138392	AL523485	ASD: 26% ↑ reference/total ratio	EXON 13	0.005
VGCNL1 (voltage-gated channel)	NM_052867	BM556576	NE: 31% ↓ variant/total ratio	INTRON 7	<0.001
	NM_052867	AK094669	EsS: 28% ↓ reference/total ratio	INTRON 12	0.019

*Reference transcript refers to traditionally spliced gene product, while the variant refers to the alternatively spliced mRNA transcript. ^†Change was quantified using splice array samples (control versus mTLE temporal cortex, n = 10/group). The ratio selected to quantify an event was determined based on best available probe choice (see Materials and methods section). ASA, alternative splice acceptor site; ASD, alternative splice donor site; ES, exon skipped; EsS, exons skipped; IR, intron retention; NE, novel exon; NEs, novel exons; PIED, partial internal exon deletion.
Heinzen et al. Genome Biology 2007 8:R32 doi:10.1186/gb-2007-8-3-r32

Table 1