Table 1.

Channel modifications leading to the loss or gain of P2X7 macropore function.

Designation	Type of modification	Outcome	Reference
Modification leading to Loss of P2X7 Macropore function
V76A	SNP	Partial loss of macropore function	(Stokes et al., 2010; Oyanguren-Desez et al., 2011)
R117W	SNP	Partial loss of channel and macropore function	(Roger et al., 2010; Wiley et al., 2011; Jiang et al., 2013)
G150R	SNP	Loss of macropore function	(Stokes et al., 2010)
E186K	SNP	Loss of channel and macropore function	(Roger et al., 2010; Wiley et al., 2011; Jiang et al., 2013)
N187D	SNP	Possible loss of function	(Chong et al., 2010b)
L191P	SNP	Partial loss of channel and macropore function	(Roger et al., 2010; Wiley et al., 2011; Jiang et al., 2013)
R276H	SNP	Loss of macropore function	(Stokes et al., 2010)
R307Q	SNP	Loss of macropore function	(Gu et al., 2004; Gartland et al., 2012; Jorgensen et al., 2012; Gu et al., 2015)
A348T	SNP	Mild increase of channel function in human P2X7 and mild decrease in channel function in rat P2X7	(Cabrini et al., 2005; Bradley et al., 2011)
T357S	SNP	Partial loss of channel and macropore function	(Cabrini et al., 2005; Shemon et al., 2006)
Q460R	SNP	Partial loss of channel and macropore function	(Cabrini et al., 2005; Stokes et al., 2010)
E496A	SNP	Loss of channel and macropore function	(Gu et al., 2001; Boldt et al., 2003; Cabrini et al., 2005; Roger et al., 2010; Sun et al., 2010; Gidlof et al., 2012; Wesselius et al., 2012; Jiang et al., 2013)
I568N	SNP	Loss of channel and pore function due to impaired P2X7 trafficking to the plasma membrane	(Wiley et al., 2003)
P2X7 variant B	Splice variant	Loss of macropore function (P2X7 variant A and B coexpression leads to gain of macropore function)	(Cheewatrakoolpong et al., 2005; Adinolfi et al., 2010)
P2X7 variant C	Splice variant	Assumed to have lost macropore function	(Cheewatrakoolpong et al., 2005; Benzaquen et al., 2019)
P2X7 variant D	Splice variant	Assumed to have lost macropore function	(Cheewatrakoolpong et al., 2005; Benzaquen et al., 2019)
P2X7 variant E	Splice variant	Assumed to have lost macropore function	(Cheewatrakoolpong et al., 2005; Benzaquen et al., 2019)
P2X7 variant F	Splice variant	Assumed to have lost macropore function	(Cheewatrakoolpong et al., 2005; Benzaquen et al., 2019)
P2X7 variant G	Splice variants	Loss of macropore function	(Cheewatrakoolpong et al., 2005; Benzaquen et al., 2019)
P2X7 variant H	Splice variants	Loss of macropore function	(Cheewatrakoolpong et al., 2005)
P2X7 variant J	Splice variant	Loss of macropore function (P2X7 variant J act as a dominant negative when coexpressed with P2X7 variant A leading to loss macropore function)	(Feng et al., 2006)
N187A	Impaired N-glycosylation	Loss of macropore function	(Lenertz et al., 2010)
R578Q	Impaired N-glycosylation	Loss of macropore function	(Wickert et al., 2013)
R277 or Y298	Proteolytic cleavage	Loss of macropore function following MMP-2 cleavage of P2X7 extracellular domain	(Young et al., 2018)
C-terminal tail	Binding partner	NMMHC-IIA	(Guo et al., 2007; Gu et al., 2009)
TM domains	Cholesterol binding	Loss of macropore function	(Robinson et al., 2014; Karasawa et al., 2017)
C362S and C363S	Prevent cholesterol inhibition rescue	Loss of macropore function	(Karasawa et al., 2017)
Modification leading to Gain of P2X7 Macropore function
H155Y	SNP	Gain of macropore function	(Cabrini et al., 2005; Stokes et al., 2010; Oyanguren-Desez et al., 2011; Jiang et al., 2013)
A166G	SNP	Gain of macropore function	(Jiang et al., 2013)
H270R	SNP	Gain of macropore function	(Stokes et al., 2010)
R125	ADP-ribosylation of mouse P2X7	Gating of mouse P2X7 macropore	(Adriouch et al., 2008)
R206K, R276K, R277K (mouse)	Mutation	Gain of macropore function in mouse P2X7	(Adriouch et al., 2008)
TM domain	phosphatidylglycerol and sphingomyelin binding	Gain of macropore function	(Karasawa et al., 2017)