UniProtKB/SwissProt variant VAR

Variant information

Variant position:

426

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 Histidine (H) at position 426 (R426H, p.Arg426His).

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 (H)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

0

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; loss of enzymatic activity toward 17-hydroxyprogesterone.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs151344504 [ dbSNP | Ensembl ]

Sequence information

Variant position:

426

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:

PDRFLEPGKNSRALAFGCGA R VCLGEPLARLELFVVLTRLL

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                         PDRFLEPGKNSRALAFGCGARVCLGEPLARLELFVVLTRLL

Mouse                         PDRFLEPGKNPRTPSFGCGARVCLGEPLARLELFVVLARLL

Rat                           PDRFLESGKSPRIPTFGCGARVCLGEPLARLEFFVVLARLL

Pig                           PDRFLAPGANPSALAFGCGARVCLGEPLARLELFVVLVQLL

Bovine                        PDRFLEPGANPSALAFGCGARVCLGESLARLELFVVLLRLL

Cat                           PDRFLVPGASPRVLAFGCGARVCLGEPLARLELFVVLARLL

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.

Type	Positions	Description
Chain	1 – 494	Steroid 21-hydroxylase
Binding site	426 – 426
Binding site	428 – 428	axial binding residue
Mutagenesis	428 – 428	C -> MST. Loss of activity and loss of P450 absorption.

Literature citations

Mutational spectrum of the steroid 21-hydroxylase gene in Austria: identification of a novel missense mutation.
Baumgartner-Parzer S.M.; Schulze E.; Waldhaeusl W.; Pauschenwein S.; Rondot S.; Nowotny P.; Meyer K.; Frisch H.; Waldhauser F.; Vierhapper H.;
J. Clin. Endocrinol. Metab. 86:4771-4775(2001)
Cited for: VARIANTS AH3 LEU-30; ASN-172; LEU-281; SER-291; TRP-356; SER-424; HIS-426; SER-453 AND PRO-483; CHARACTERIZATION OF VARIANT AH3 HIS-426;

Four novel missense mutations in the CYP21A2 gene detected in Russian patients suffering from the classical form of congenital adrenal hyperplasia: identification, functional characterization, and structural analysis.
Grischuk Y.; Rubtsov P.; Riepe F.G.; Groetzinger J.; Beljelarskaia S.; Prassolov V.; Kalintchenko N.; Semitcheva T.; Peterkova V.; Tiulpakov A.; Sippell W.G.; Krone N.;
J. Clin. Endocrinol. Metab. 91:4976-4980(2006)
Cited for: VARIANTS AH3 ARG-169; ARG-178; ARG-302 AND CYS-426; CHARACTERIZATION OF VARIANTS AH3 ARG-169; ARG-178; ARG-302; CYS-426 AND HIS-426; FUNCTION; CATALYTIC ACTIVITY;

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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P08686: Variant p.Arg426His