Functional and Structural Consequences of Nine CYP21A2 Mutations Ranging from Very Mild to Severe Effects

Table 3

Enzyme activities, in silico prediction of the effect on protein structure, and final prediction of the phenotype for the novel mutations and for the common mutations used as a reference (in bold).

Mutation (cDNA)	Protein change	Location in the protein	In silico prediction	Enzyme activity		Phenotype prediction (hemizygous/homozygous state)
				17OHP	Prog
c.43G>A	p.Ala15Thr	First hydrophobic domain	ND	100 (0)	96 (6)	Normal variant (NV)
c.34C>A	p.Leu12Met	First hydrophobic domain	ND	99 (1)	100 (1)	NV
c.800C>T	p.Pro267Leu	Loop between α-helix H and α-helix I	No effect	97 (1)	87 (7)	NV/very mild NC
c.46C>T	p.Arg16Cys	First hydrophobic domain	ND	95 (3)	81 (3)	NV/very mild NC
c.301_302TC>AA	p.Ser101Asn	Loop between α-helix B′ and α-helix C	Minor effect	94 (3)	74 (2)	NV/very mild NC
c.1444C>T	p.Pro482Ser		ND	91 (6)	61 (6)	Very mild NC
c.604A>G	p.Ser202Gly	Loop between α-helix F and α-helix F′	Minor effect	85 (2)	81 (3)	Very mild NC
c.1349C>T	p.Thr450Met	β-sheet β8	Minor effect	78 (6)	43 (5)	Mild NC
c.1357C>T	p.Pro453Ser		ND	73 (8)	34 (10)	NC
c.841G>T	p.Val281Leu	I	ND	57 (8)	29 (5)	NC
c.338C>T	p.Ser113Phe	Loop between α-helix B′ and α-helix C	Severe effect; interferes with active site helices	4 (1)	4 (2)	CL
c.1348A>C	p.Thr450Pro	β-sheet β8	Very severe effect	<1	<1	CL
c.515T>A	p.Ile172Asn	E	ND	<1	<1	CL
c.1165_1173delCAAGGCGCC	p.Gln389_Ala391del	α-helix L	Deleterious	0	<1	CL

Enzyme activity is expressed in % of wild-type activity, with values presented as mean (1SD) of at least four independent experiments. ND: not determined. Mutations are ordered according to the residual enzyme activity with the reference mutations in bold.