TABLE 1.

Amino acids substitutions in hyperactive mALAS-2 variants

Targeted positions are indicated in italics. Amino acids observed in other ALASs are indicated with bold type, while those underlined are not observed in nature.

Wild-type ALAS	Y422	V	Q	A	I	N	Y	P	T	V	P	R	G	E	E	L	L	R439
Single variants
A8				T
D8																Q
G7						H
Quadruple variant
F1												K	K	Q		Q
Penta variant
F10							I					Q	N	T		N
Hexa variants
A4		I		P			C				R	K		N
F3				G			H					H	N	K		K
H1							N				N	I	E	K		K
Hepta variant
SS2		L					R				E	I	N	Q		K