UniProtKB/Swiss-Prot P08686: Variant p.Val282Leu

Steroid 21-hydroxylase
Gene: CYP21A2
Feedback?

Variant information Variant position:

282 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 Valine (V) to Leucine (L) at position 282 (V282L, p.Val282Leu). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

1 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; non-classic form; 50% activity; most common variant; normal KM but 20% reduced Vmax. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs6471 [ dbSNP | Ensembl ]

Sequence information Variant position:

282 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

495 The length of the canonical sequence.
Location on the sequence:

LQGVAQPSMEEGSGQLLEGH V HMAAVDLLIGGTETTANTLS 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                         LQGVAQPSMEEGSGQLLEGHVHMAAVDLLIGGTETTANTLS

                              LQRVGRLRAEEGCGQLLEGHVHMSVVDLFIGGTETTATTLS

Mouse                         LQGVEKQRDGKDEERLHEGHVHMSVVDLFIGGTETTATTLS

Rat                           LQGVEKQRDARDPGQLHERHVHMSVVDLFVGGTETTAATLS

Pig                           LQEAGRQRVEEGQGQLLEGHVHMSVVDLFIGGTETTANTLS

Bovine                        LQGVGRQRVEEGPGQLLEGHVHMSVVDLFIGGTETTASTLS

Cat                           LQGMGKPKVEKGHGRLLEGHVHMSVVDLFIGGTETTATTLS

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 – 495	Steroid 21-hydroxylase
Mutagenesis	269 – 269	S -> CMT. No effect on progesterone 21-hydroxylase activity.
Mutagenesis	282 – 282	V -> I. Decreased 21-hydroxylase activity. Normal KM but 50% reduced Vmax.
Mutagenesis	282 – 282	V -> T. Decreased 21-hydroxylase activity. Normal KM but 10% reduced Vmax.
Helix	279 – 310

Literature citations
Nonsense mutation causing steroid 21-hydroxylase deficiency.
Globerman H.; Amor M.; Parker K.L.; New M.I.; White P.C.;
J. Clin. Invest. 82:139-144(1988)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT AH3 LEU-282; P450XXI (steroid 21-hydroxylase) gene deletions are not found in family studies of congenital adrenal hyperplasia.
Matteson K.J.; Phillips J.A. III; Miller W.L.; Chung B.C.; Orlando P.J.; Frisch H.; Ferrandez A.; Burr I.M.;
Proc. Natl. Acad. Sci. U.S.A. 84:5858-5862(1987)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 266-495 (ISOFORM 1); VARIANT AH3 LEU-282; VARIANT ASN-494; Mutations of P450c21 (steroid 21-hydroxylase) at Cys428, Val281, and Ser268 result in complete, partial, or no loss of enzymatic activity, respectively.
Wu D.-A.; Chung B.-C.;
J. Clin. Invest. 88:519-523(1991)
Cited for: CHARACTERIZATION OF VARIANT AH3 LEU-282; MUTAGENESIS OF SER-269; VAL-282 AND CYS-429; Molecular genetic analysis of nonclassic steroid 21-hydroxylase deficiency associated with HLA-B14,DR1.
Speiser P.W.; New M.I.; White P.C.;
N. Engl. J. Med. 319:19-23(1988)
Cited for: VARIANTS AH3 LEU-212 AND LEU-282; Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
Speiser P.W.; Dupont J.; Zhu D.; Serrat J.; Buegeleisen M.; Tusie-Luna M.-T.; Lesser M.; New M.I.; White P.C.;
J. Clin. Invest. 90:584-595(1992)
Cited for: VARIANTS AH3 LEU-31; ASN-173; ASN-237; GLU-238; LYS-240; LEU-282 AND TRP-357; Screening of CYP21 gene mutations in 129 French patients affected by steroid 21-hydroxylase deficiency.
Barbat B.; Bogyo A.; Raux-Demay M.-C.; Kuttenn F.; Boue J.; Simon-Bouy B.; Serre J.-L.; Boue A.; Mornet E.;
Hum. Mutat. 5:126-130(1995)
Cited for: VARIANTS AH3 ASN-173; ASN-237; LEU-282 AND PRO-484; Mutation analysis in patients with congenital adrenal hyperplasia in the Spanish population: identification of putative novel steroid 21-hydroxylase deficiency alleles associated with the classic form of the disease.
Lobato M.N.; Ordonez-Sanchez M.L.; Tusie-Luna M.T.; Meseguer A.;
Hum. Hered. 49:169-175(1999)
Cited for: VARIANTS AH3 LEU-31; VAL-91; ASN-173; ALA-179; LEU-282; CYS-292; HIS-355; TRP-357 AND SER-454; Identification of CYP21 mutations, one novel, by single strand conformational polymorphism (SSCP) analysis.
Witchel S.F.; Smith R.; Suda-Hartman M.;
Hum. Mutat. 13:172-172(1999)
Cited for: VARIANTS AH3 TYR-170; LEU-282 AND GLN-357; 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-31; GLU-65; ASN-173; ASN-237; LEU-282; SER-292; TRP-357 AND VAL-363; A rapid screening for steroid 21-hydroxylase mutations in patients with congenital adrenal hyperplasia.
Kapelari K.; Ghanaati Z.; Wollmann H.; Ventz M.; Ranke M.B.; Kofler R.; Peters H.;
Hum. Mutat. 13:505-505(1999)
Cited for: VARIANTS AH3 LEU-31; ASN-173; ASN-237; GLU-238; LYS-240; LEU-282 AND TRP-357; A novel missense mutation, GLY424SER, in Brazilian patients with 21-hydroxylase deficiency.
Billerbeck A.E.C.; Bachega T.A.S.S.; Frazatto E.T.; Nishi M.Y.; Goldberg A.C.; Marin M.L.C.; Madureira G.; Monte O.; Arnhold I.J.P.; Mendonca B.B.;
J. Clin. Endocrinol. Metab. 84:2870-2872(1999)
Cited for: VARIANTS AH3 LEU-282; TRP-357 AND SER-425; Molecular analysis of Japanese patients with steroid 21-hydroxylase deficiency.
Asanuma A.; Ohura T.; Ogawa E.; Sato S.; Igarashi Y.; Matsubara Y.; Iinuma K.;
J. Hum. Genet. 44:312-317(1999)
Cited for: VARIANTS AH3 LEU-31; ASN-173; LEU-282 AND TRP-357; VARIANT THR-269; Characterization of single-nucleotide polymorphisms in coding regions of human genes.
Cargill M.; Altshuler D.; Ireland J.; Sklar P.; Ardlie K.; Patil N.; Shaw N.; Lane C.R.; Lim E.P.; Kalyanaraman N.; Nemesh J.; Ziaugra L.; Friedland L.; Rolfe A.; Warrington J.; Lipshutz R.; Daley G.Q.; Lander E.S.;
Nat. Genet. 22:231-238(1999)
Cited for: VARIANTS AH3 LEU-282 AND SER-454; VARIANT THR-269; Predicting phenotype in steroid 21-hydroxylase deficiency? Comprehensive genotyping in 155 unrelated, well defined patients from southern Germany.
Krone N.; Braun A.; Roscher A.A.; Knorr D.; Schwarz H.P.;
J. Clin. Endocrinol. Metab. 85:1059-1065(2000)
Cited for: VARIANTS AH3 LEU-31; ASN-173; LEU-282; GLY-282; PHE-301; CYS-355; TRP-357 AND SER-454; Phenotype-genotype correlation in 56 women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
Deneux C.; Tardy V.; Dib A.; Mornet E.; Billaud L.; Charron D.; Morel Y.; Kuttenn F.;
J. Clin. Endocrinol. Metab. 86:207-213(2001)
Cited for: VARIANTS AH3 LEU-31; ASN-173; LEU-282; MET-318; TRP-357; CYS-436 AND SER-454; 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-31; ASN-173; LEU-282; SER-292; TRP-357; SER-425; HIS-427; SER-454 AND PRO-484; CHARACTERIZATION OF VARIANT AH3 HIS-427; Non-classical 21-hydroxylase deficiency in children: association of adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone with the risk of compound heterozygosity with severe mutations.
Ezquieta B.; Cueva E.; Varela J.; Oliver A.; Fernandez J.; Jariego C.;
Acta Paediatr. 91:892-898(2002)
Cited for: VARIANTS AH3 LEU-31; ASN-173; LEU-282; LEU-284; TRP-357 AND SER-454; Mutational spectrum of congenital adrenal hyperplasia in Slovenian patients: a novel Ala15Thr mutation and Pro30Leu within a larger gene conversion associated with a severe form of the disease.
Dolzan V.; Stopar-Obreza M.; Zerjav-Tansek M.; Breskvar K.; Krzisnik C.; Battelino T.;
Eur. J. Endocrinol. 149:137-144(2003)
Cited for: VARIANTS AH3 THR-16; LEU-31; ASN-173; LEU-282 AND SER-454; Follow-up of 68 children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: relevance of genotype for management.
Pinto G.; Tardy V.; Trivin C.; Thalassinos C.; Lortat-Jacob S.; Nihoul-Fekete C.; Morel Y.; Brauner R.;
J. Clin. Endocrinol. Metab. 88:2624-2633(2003)
Cited for: VARIANTS AH3 LEU-31; LEU-63; ASN-173; LEU-282; PRO-342; TRP-357; SER-454 AND PRO-484; CYP21 gene mutation analysis in 198 patients with 21-hydroxylase deficiency in The Netherlands: six novel mutations and a specific cluster of four mutations.
Stikkelbroeck N.M.; Hoefsloot L.H.; de Wijs I.J.; Otten B.J.; Hermus A.R.; Sistermans E.A.;
J. Clin. Endocrinol. Metab. 88:3852-3859(2003)
Cited for: VARIANTS AH3 ASN-173; LEU-282; ARG-292; TYR-302; TRP-357 AND GLN-484; Functional analysis of two recurrent amino acid substitutions in the CYP21 gene from Italian patients with congenital adrenal hyperplasia.
Barbaro M.; Lajic S.; Baldazzi L.; Balsamo A.; Pirazzoli P.; Cicognani A.; Wedell A.; Cacciari E.;
J. Clin. Endocrinol. Metab. 89:2402-2407(2004)
Cited for: VARIANTS AH3 THR-16; LEU-31; LEU-282 AND SER-483; CHARACTERIZATION OF VARIANTS AH3 THR-16 AND SER-483; 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-31; ASN-173; ASN-237; GLU-238; LYS-240; LEU-282; SER-292; GLN-357; TRP-357; TYR-366; SER-454; LEU-480 AND PRO-484; 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-78; PRO-168; ASN-173; THR-231; LYS-234; LEU-282; SER-292; ASP-293; LYS-321; PRO-342; HIS-355; TRP-357; TRP-370; CYS-409; SER-425; HIS-427 AND SER-454; CHARACTERIZATION OF VARIANTS AH3 PRO-168; ASN-173; LEU-282; ASP-293; LYS-321; TRP-370 AND SER-425;

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.