Table 1.

List of ATP6V0A1, ATP6V0A2, ATP6V0A3, and ATP6V0A4 variants.

Gene	Nucleotide change	Amino acid change	Mutation type	Zygosity	Impact on V-ATPase	Associated disease	Variant identifier	Reference
ATP6V0A1	c.T1429C	p.S477P	Missense	Heterozygous	Alters conformation of luminal channel, hindering proton translocation	DEE	VAR_087489	Bott et al. (2021)
ATP6V0A1	c.C1483T	p.R495W	Missense	Compound heterozygous with frameshift mutation: c.445delG, p.E149Kfs18	Loss of positively charged residue near the luminal channel exit hinders proton translocation	PME and ataxia	rs781278654	Bott et al. (2021)
ATP6V0A1	c.C1513G	p.A505P	Missense	Compound heterozygous with deletion: c.del(17)(q21.2)	Undetermined	DEE	VAR_087491	Aoto et al. (2021)
ATP6V0A1	c.A1579G	p.N527D	Missense	Compound heterozygous with splice site mutation: c.196+1G>A	Undetermined	DEE	rs766856192	Aoto et al. (2021)
ATP6V0A1	c.G1652A	p.G551E	Missense	Heterozygous	Deforms environment mediating proton exchange	DEE	VAR_087493	Bott et al. (2021)
ATP6V0A1	c.G2219A	p.R740Q	Missense	Heterozygous	Impedes glutamate protonation thereby disrupting proton translocation	DEE, PME, autism, microcephaly	rs1567871600	Aoto et al. (2021); Bott et al. (2021)
ATP6V0A1	c.G2411A	p.R804H	Missense	Heterozygous	Impedes glutamate protonation thereby disrupting proton translocation	DEE	VAR_087495	Bott et al. (2021)
ATP6V0A2	c.187T	p.R63X	Nonsense	Homozygous	Truncated protein, non-functional subunit a2	ARCL II	rs80356750	Kornak et al. (2008)
ATP6V0A2	c.C1214T	p.P405L	Missense	Homozygous	Compromises subunit a2 stability, complex assembly and Golgi trafficking	ARCL II	rs750788949	Hucthagowder et al. (2009); Esmail et al. (2018a)
ATP6V0A2	c.C2293T	p.Q765X	Nonsense	Homozygous	Truncated protein, non-functional subunit a2	ARCL II	rs80356758	Kornak et al. (2008)
ATP6V0A2	c.C2432C	p.L811P	Missense	Compound heterozygous with splicing mutation: c.2055+2dupT	Changes last α-helix conformation, hindering subunit interactions and proton translocation	ARCL II	rs778642108	Fischer et al. (2012)
ATP6V0A3	c.IVS2+4A→T	p.V26-D39del	Deletion	Homozygous	Unable to assemble with V1 subunit	MIOP	N/A	Kornak et al. (2000)
ATP6V0A3	c.G1024T	p.E342X	Stop	Heterozygous	Truncated protein, non-functional subunit a3	MIOP	N/A	Sobacchi et al. (2001); Susani et al. (2004)
ATP6V0A3	c.G1213A	p.G405R	Missense	Homozygous or compound heterozygous with R444L	Steric hindrance of 1st cytoplasmic loop	MIOP	VAR_019569	Sobacchi et al. (2001); Susani et al. (2004)
ATP6V0A3	c.G1331T	p.R444L	Missense	Homozygous or compound heterozygous with G405R	Protein instability due to hydrophobic Arginine (R)	MIOP	rs137853151	Sobacchi et al. (2001); Susani et al. (2004)
ATP6V0A3	c.G2412A	p.W805X (updated NM_006019.4)	Stop	Heterozygous	Truncated protein, non-functional subunit a3	MIOP	rs1555000308	Kornak et al. (2000)
1. ATP6V0A4 2. ATP6V1B1	1.c.C419T 2.c.A437G	1. p.T140M 2. p.D146G	Missense	Digenic heterozygous	1. Slight conformational change hindering subunit trafficking and assembly 2. Alteration of subunit surface charge leading to the disruption of ATP binding sites	dRTA	1. rs144802156 2. rs782681801	Nagara et al. (2018)
ATP6V0A4	c.C1631T	p.S544L	Missense	Heterozygous	Unable to bind to B1 subunit, assembly issues, weakened ATPase activity	Complete and incomplete dRTA	rs1026435	Imai et al. (2016); Chen et al. (2020)
ATP6V0A4	c.G2420A	p.R807Q	Missense	Homozygous	Reduction of subunit a4 production leading to V-ATPase assembly and activity deficits	dRTA, Sensorineural hearing loss	rs28939081	Stover et al. (2002)
ATP6V0A4	c.G2458C	p.G820R	Missense	Homozygous	Loss of a4 binding to phosphofructokinase-1, formation of salt bridge disrupting proton translocation	dRTA	rs267606671	Esmail et al. (2018a)

ARCL II, autosomal recessive cutis laxa type II; DEE, developmental and epileptic encephalopathies; dRTA, distal renal tubular acidosis; MIOP, malignant infantile osteopetrosis; PME, progressive myoclonus epilepsy.