Home  |  Contact

UniProtKB/Swiss-Prot P08686: Variant p.Arg408Cys

Steroid 21-hydroxylase
Gene: CYP21A2
Variant information

Variant position:  408
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Arginine (R) to Cysteine (C) at position 408 (R408C, p.Arg408Cys).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from large size and basic (R) to medium size and polar (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description:  In AH3; very low residual activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  408
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  494
The length of the canonical sequence.

Location on the sequence:   LQGAHLDETVWERPHEFWPD  R FLEPGKNSRALAFGCGARVC
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         LQGAHLDETVWERPHEFWPDRFLEPGKNSRALAFGCGARVC

                              LQGAHLDETVWERPQEFRPDRFLVPGASPRVLAFGCGARVC

Mouse                         IQGANLDEMVWELPSKFWPDRFLEPGKNPRTPSFGCGARVC

Rat                           IQGANLDEMVWELPSKFWPDRFLESGKSPRIPTFGCGARVC

Pig                           LQGAHLDETVWEQPHEFRPDRFLAPGANPSALAFGCGARVC

Bovine                        LQGAHLDETVWEQPHEFRPDRFLEPGANPSALAFGCGARVC

Cat                           LQGAHLDDTVWEQPHEFRPDRFLVPGASPRVLAFGCGARVC

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 1 – 494 Steroid 21-hydroxylase
Metal binding 428 – 428 Iron (heme axial ligand)
Mutagenesis 428 – 428 C -> MST. Loss of activity and loss of P450 absorption.
Helix 406 – 409


Literature citations

Three novel mutations in CYP21 gene in Brazilian patients with the classical form of 21-hydroxylase deficiency due to a founder effect.
Billerbeck A.E.C.; Mendonca B.B.; Pinto E.M.; Madureira G.; Arnhold I.J.P.; Bachega T.A.S.S.;
J. Clin. Endocrinol. Metab. 87:4314-4317(2002)
Cited for: VARIANTS AH3 CYS-408 AND SER-424;

Inhibition of CYP21A2 enzyme activity caused by novel missense mutations identified in Brazilian and Scandinavian patients.
Soardi F.C.; Barbaro M.; Lau I.F.; Lemos-Marini S.H.; Baptista M.T.; Guerra-Junior G.; Wedell A.; Lajic S.; de Mello M.P.;
J. Clin. Endocrinol. Metab. 93:2416-2420(2008)
Cited for: VARIANTS AH3 ARG-56; LEU-62; ARG-107; PRO-142; ASN-172; TRP-356; CYS-408 AND SER-453; CHARACTERIZATION OF VARIANTS AH3 ARG-56; LEU-62; ARG-107; PRO-142; CYS-408 AND SER-453;

Phenotype-genotype correlations of 13 rare CYP21A2 mutations detected in 46 patients affected with 21-hydroxylase deficiency and in one carrier.
Tardy V.; Menassa R.; Sulmont V.; Lienhardt-Roussie A.; Lecointre C.; Brauner R.; David M.; Morel Y.;
J. Clin. Endocrinol. Metab. 95:1288-1300(2010)
Cited for: VARIANTS AH3 THR-77; PRO-167; ASN-172; THR-230; LYS-233; LEU-281; SER-291; ASP-292; LYS-320; PRO-341; HIS-354; TRP-356; TRP-369; CYS-408; SER-424; HIS-426 AND SER-453; CHARACTERIZATION OF VARIANTS AH3 PRO-167; ASN-172; LEU-281; ASP-292; LYS-320; TRP-369 AND SER-424;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.