UniProtKB/SwissProt variant VAR

Variant information

Variant position:

291

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 Glycine (G) to Serine (S) at position 291 (G291S, p.Gly291Ser).

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 glycine (G) to small size and polar (S)

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; salt wasting form; less then 1% activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs201552310 [ dbSNP | Ensembl ]

Sequence information

Variant position:

291

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:

EGSGQLLEGHVHMAAVDLLI G GTETTANTLSWAVVFLLHHP

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                         EGSGQLLEGHVHMAAVDLLIGGTETTANTLSWAVVFLLHHP

Mouse                         KDEERLHEGHVHMSVVDLFIGGTETTATTLSWAVAFLLHHP

Rat                           RDPGQLHERHVHMSVVDLFVGGTETTAATLSWAVAFLLHHP

Pig                           EGQGQLLEGHVHMSVVDLFIGGTETTANTLSWAVVYLLHHP

Bovine                        EGPGQLLEGHVHMSVVDLFIGGTETTASTLSWAVAFLLHHP

Cat                           KGHGRLLEGHVHMSVVDLFIGGTETTATTLSWAVAFLLHHP

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
Mutagenesis	281 – 281	V -> I. Normal KM but 50% reduced Vmax.
Mutagenesis	281 – 281	V -> T. Normal KM but 10% reduced Vmax.
Helix	278 – 309

Literature citations

Steroid 21-hydroxylase deficiency: three additional mutated alleles and establishment of phenotype-genotype relationships of common mutations.
Wedell A.; Ritzen E.M.; Haglund-Stengler B.; Luthman H.;
Proc. Natl. Acad. Sci. U.S.A. 89:7232-7236(1992)
Cited for: VARIANTS AH3 LEU-105; SER-291 AND SER-453;

Naturally occurring mutants of human steroid 21-hydroxylase (P450c21) pinpoint residues important for enzyme activity and stability.
Nikoshkov A.; Lajic S.; Vlamis-Gardikas A.; Tranebjaerg L.; Holst M.; Wedell A.; Luthman H.;
J. Biol. Chem. 273:6163-6165(1998)
Cited for: VARIANTS AH3 GLU-196 DEL; SER-291 AND PRO-483;

Steroid 21-hydroxylase deficiency: mutational spectrum in Denmark, three novel mutations, and in vitro expression analysis.
Ohlsson G.; Mueller J.; Skakkebaek N.E.; Schwartz M.;
Hum. Mutat. 13:482-486(1999)
Cited for: VARIANTS AH3 LEU-30; GLU-64; ASN-172; ASN-236; LEU-281; SER-291; TRP-356 AND VAL-362;

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;

Detection and assignment of CYP21 mutations using peptide mass signature genotyping.
Zeng X.; Witchel S.F.; Dobrowolski S.F.; Moulder P.V.; Jarvik J.W.; Telmer C.A.;
Mol. Genet. Metab. 82:38-47(2004)
Cited for: VARIANTS AH3 LEU-30; ASN-172; ASN-236; GLU-237; LYS-239; LEU-281; SER-291; GLN-356; TRP-356; TYR-365; SER-453; LEU-479 AND PRO-483; VARIANT ARG-102;

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.Gly291Ser