Table 7.

Classification of CACNA1D missense mutations by characteristic functional changes.

Type	Mutation	Disease phenotype	Characteristic functional changes (channel complexes of mutant α1-subunits with α2δ1 and β3)	References
1	G403D	APAs; hyperaldosteronism or hyperinsulinism with seizures and developmental delay	Inactivation almost abolished (voltage-dependence of inactivation not measurable) Voltage-dependence of activation shifted to hyperpolarized voltages or unchanged	[15]
	G403R	APAs		[15]
	G407R	ASD (and ID)		[10]
2	V259D	APAs	Voltage-dependence of activation strongly shifted to hyperpolarized voltages Inactivation not abolished* with voltage-dependence of inactivation strongly shifted to hyperpolarized voltages or unchanged * may be faster, slower, more or less complete after 5 s depolarizations to Vmax	[11]
	V401L	ASD, ID and seizures		[9]
	F747L	APAs		[11]
	A749G	ASD (and ID)		[9,16]
	I750M	APAs; hyperaldosteronism with seizures and developmental delay		[11,15]
	V1153G	APAs		[12]
3	Q558H	ID, seizures, hearing impairment	Slower and less complete inactivation during 3–5s depolarizations to Vmax and no changes in voltage-dependence of gating	[14]
	P1336R	APAs		[11]
4	R990H	APAs	Mutation-induced (depolarizing) ω-current	[11,21]