Variant position:  453

Type of variant:  LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.]

Residue change:  From Proline (P) to Serine (S) at position 453 (P453S, p.Pro453Ser).

Physico-chemical properties:  Change from medium size and hydrophobic (P) to small size and polar (S)

BLOSUM score:  -1

Variant description:  In AH3; non-classic form; simple virilizing form when associated with L-62; 50% of activity; almost completely abolished enzyme activity when associated with S-375.

Other resources:  

• Variant rs6445 [ dbSNP | Ensembl ]

Variant position:  453

Protein sequence length:  494

Location on the sequence:   LARLELFVVLTRLLQAFTLL  P SGDALPSLQPLPHCSVILKM

Residue conservation: 

Human                         LARLELFVVLTRLLQAFTLLPSG-DALPSLQPLPHCSVILKM

Mouse                         LARLELFVVLARLLQAFTLLPPPDGTLPSLQPQPYAGINLP

Rat                           LARLEFFVVLARLLQTFTLLPPPDGTLPSLQPLPYTGINLL

Pig                           LARLELFVVLVQLLQAFTLLPPE-GALPSLQPHPHSGINLK

Bovine                        LARLELFVVLLRLLQAFTLLPPPVGALPSLQPDPYCGVNLK

Cat                           LARLELFVVLARLLHAFTLLPPT-GPLPSLRPRSHCGINLT

Sequence annotation in neighborhood:  

R339H and P453S: CYP21 mutations associated with nonclassic steroid 21-hydroxylase deficiency that are not apparent gene conversions.
Helmberg A.; Tusie-Luna M.-T.; Tabarelli M.; Kofler R.; White P.C.;
Mol. Endocrinol. 6:1318-1322(1992)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS LEU-9 INS; ARG-102 AND SER-493; VARIANTS AH3 HIS-339 AND SER-453;

Pro-453 to Ser mutation in CYP21 is associated with nonclassic steroid 21-hydroxylase deficiency.
Owerbach D.; Sherman L.; Ballard A.L.; Azziz R.;
Mol. Endocrinol. 6:1211-1215(1992)
Cited for: VARIANT AH3 SER-453;

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;

Synergistic effect of partially inactivating mutations in steroid 21-hydroxylase deficiency.
Nikoshkov A.; Lajic S.; Holst M.; Wedell A.; Luthman H.;
J. Clin. Endocrinol. Metab. 82:194-199(1997)
Cited for: VARIANTS AH3 LEU-105 AND SER-453;

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-30; VAL-90; ASN-172; ALA-178; LEU-281; CYS-291; HIS-354; TRP-356 AND SER-453;

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-281 AND SER-453; VARIANTS THR-268 AND SER-493;

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-30; ASN-172; LEU-281; GLY-281; PHE-300; CYS-354; TRP-356 AND SER-453;

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-30; ASN-172; LEU-281; MET-317; TRP-356; CYS-435 AND SER-453;

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;

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-30; ASN-172; LEU-281; LEU-283; TRP-356 AND SER-453;

Novel mutations in CYP21 detected in individuals with hyperandrogenism.
Lajic S.; Clauin S.; Robins T.; Vexiau P.; Blanche H.; Bellanne-Chantelot C.; Wedell A.;
J. Clin. Endocrinol. Metab. 87:2824-2829(2002)
Cited for: VARIANTS HYPERANDROGENISM MET-304; SER-375 AND SER-453; CHARACTERIZATION OF VARIANTS HYPERANDROGENISM MET-304; SER-375 AND SER-453;

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-15; LEU-30; ASN-172; LEU-281 AND SER-453;

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-30; LEU-62; ASN-172; LEU-281; PRO-341; TRP-356; SER-453 AND PRO-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-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;

p.H62L, a rare mutation of the CYP21 gene identified in two forms of 21-hydroxylase deficiency.
Menassa R.; Tardy V.; Despert F.; Bouvattier-Morel C.; Brossier J.P.; Cartigny M.; Morel Y.;
J. Clin. Endocrinol. Metab. 93:1901-1908(2008)
Cited for: VARIANTS AH3 LEU-30; LEU-62; ASN-172; TRP-356 AND SER-453; CHARACTERIZATION OF VARIANTS AH3 LEU-62 AND SER-453;

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;

Functional and structural consequences of a novel point mutation in the CYP21A2 gene causing congenital adrenal hyperplasia: potential relevance of helix C for P450 oxidoreductase-21-hydroxylase interaction.
Riepe F.G.; Hiort O.; Grotzinger J.; Sippell W.G.; Krone N.; Holterhus P.M.;
J. Clin. Endocrinol. Metab. 93:2891-2895(2008)
Cited for: VARIANTS AH3 GLN-121 AND SER-453; CHARACTERIZATION OF VARIANT AH3 GLN-121;

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;