Table 3.

Natural mutations and SNPs of different members of TRPC.

Channel	cDNA and Protein Accession Numbers	Position	Nucleotide Change	Amino Acid Change	Effect	Disease	Reference
TRPC3	NM_019510 NP_062383	Exon	1903A>G	T635A	Increased TRPC3 activity	Hereditary cerebellar ataxias	[155]
TRPC4	NM_016179 NP_057263	Exon	2869A>G (3104A>G *)	I957V	Increased TRPC4 activity	Reduced risk of MI	[156]
TRPC4	NM_016179 NP_057263	Intron	rs9547991: NG_029849.2:g.232148A>G	No change	n.a.	Lung cancer	[157]
TRPC4	NM_016179 NP_057263	Intron	rs978156: NG_029849.2:g.172052G>A	No change	n.a.	Lung cancer	[157]
TRPC6	NM_004621 NP_004612	Exon	202C>T	R68W	Increased plasma membrane trafficking and activity of TRPC6	Proteinuria and FSGS	[139]
TRPC6	NM_004621 NP_004612	Exon	265delA	S89NfsX8	n.a.	FSGS	[158]
TRPC6	NM_004621 NP_004612	Exon	325G>A	G109S	Increased basal and maximum activity of TRPC6	FSGS	[137,159]
TRPC6	NM_004621 NP_004612	Exon	328T>G	N110H	Increased basal and maximum activity of TRPC6	FSGS	[137,160]
TRPC6	NM_004621 NP_004612	Exon	333C>T	I111I	n.a.	Proteinuria and FSGS	[161]
TRPC6	NM_004621 NP_004612	Exon	C335>A	P112Q	Increased plasma membrane trafficking, basal, and maximum activity of TRPC6	FSGS	[127]
TRPC6	NM_004621 NP_004612	Exon	362G>C	C121S	n.a.	Proteinuria and FSGS	[161]
TRPC6	NM_004621 NP_004612	Exon	374A>G	N125S	Increased/decreased TRPC6 activity	FSGS	[137,141,159]
TRPC6	NM_004621 NP_004612	Exon	389A>T	D130V	n.a.	Proteinuria and FSGS	[161]
TRPC6	NM_004621 NP_004612	Exon	395T>C (495T>C *)	M132T	Delayed inactivation, increased basal and maximum activity of TRPC6	FSGS	[137,138,158]
TRPC6	NM_004621 NP_004612	Exon	n.a.	N143S	Increased maximum activity of TRPC6	FSGS	[128,137]
TRPC6	NM_004621 NP_004612	Exon	484G>C	G162R	n.a.	Proteinuria and FSGS	[161]
TRPC6	NM_004621 NP_004612	Exon	524G>A	R175Q	Increased TRPC6 activity	FSGS	[162]
TRPC6	NM_004621 NP_004612	Exon	523C>T	R175W	Increased basal TRPC6 activity	SRNS	[137,163]
TRPC6	NM_004621 NP_004612	Exon	653A>T	H218L	Increased maximum activity and expression of TRPC6	FSGS	[137,141]
TRPC6	NM_004621 NP_004612	Exon	n.a.	S270T	Delayed TRPC6 inactivation	FSGS	[128,164]
TRPC6	NM_004621 NP_004612	Exon	1079G>A	R360H	n.a.	FSGS	[165]
TRPC6	NM_004621 NP_004612	Exon	n.a.	L395A	Decreased TRPC6 activity	SRNS/FSGS	[137,166]
TRPC6	NM_004621 NP_004612	Exon	1211C>T	A404V	Increased maximum activity of TRPC6	IHPS	[137,150]
TRPC6	NM_004621 NP_004612	Exon	2270G>A	G757D	Decreased TRPC6 activity	FSGS	[137,158]
TRPC6	NM_004621 NP_004612	Exon	2339T>C	L780P	Decreased TRPC6 activity	FSGS	[137,159]
TRPC6	NM_004621 NP_004612	Exon	2617_2620 delGATA	D873RfsX5	n.a.	Heterogenous phenotype ranging from asymptomatic minimal change disease to end-stage kidney disease	[25]
TRPC6	NM_004621 NP_004612	Exon	n.a.	K874X	Delayed TRPC6 inactivation	FSGS	[128,138]
TRPC6	NM_004621 NP_004612	Exon	2656G>A	E886K	n.a.	SRNS/FSGS	[167]
TRPC6	NM_004621 NP_004612	Exon	2665C>A	Q889K	Increased basal and maximum activity of TRPC6	FSGS	[137,168]
TRPC6	NM_004621 NP_004612	Exon	n.a.	R895C	Increased TRPC6 expression, increased/decreased TRPC6 activity	FSGS	[128,137]
TRPC6	NM_004621 NP_004612	Exon	2684G>T	R895L	Increased TRPC6 activity	FSGS	[141]
TRPC6	NM_004621 NP_004612	Exon	n.a.	E897K	Increased basal and maximum activity of TRPC6	FSGS	[128,137]
TRPC6	NM_004621 NP_004612	Promoter	rs3922961: NG_011476.2:g.4512A>C	No change	n.a.	IHPS	[150]
TRPC6	NM_004621 NP_004612	Promoter	rs3824934: NG_011476.2:g.5172C>G	No change	Increased TRPC6 expression	IPAH	[151]
TRPC6	NM_004621 NP_004612	Promoter	rs3824934: NG_011476.2:g.5172C>G	No change	Increased TRPC6 expression	SRNS	[142]
TRPC6	NM_004621 NP_004612	Intron	rs7118839: NG_011476.2:g.50182G>A	No change	n.a.	IHPS	[150]
TRPC6	NM_004621 NP_004612	Intron	rs7925662: NG_011476.2:g.51354A>G	No change	n.a.	NPSLE	[152]
TRPC6	NM_004621 NP_004612	Intron	rs11224816: NG_011476.1:g.63374A>G	No change	n.a.	ME/CFS	[153]
TRPC7	NM_020389 NP_065122	Intron	rs11748198: NC_000005.9:g.135575829C>A	No change	n.a.	Lung cancer	[157]

* Denotes the numbering reported in the original paper. (We have standardized the numbering to numbering in coding sequences. Therefore, number ‘1’ represents the nucleotide ‘A’ in the start codon ‘ATG’.) ESKD: end-stage kidney disease. FSGS: focal and segmental glomerulosclerosis. IHPS: infantile hypertrophic pyloric stenosis. IPAH: idiopathic pulmonary arterial hypertension. ME/CFS: myalgic encephalomyelitis/chronic fatigue syndrome. MI: myocardial infarction. NPSLE: neuropsychiatric manifestations. SRNS: steroid resistant nephrotic syndrome.