UniProtKB/Swiss-Prot P08686: Variant p.Ile173Asn

Steroid 21-hydroxylase
Gene: CYP21A2
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Variant information Variant position:

173 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 Isoleucine (I) to Asparagine (N) at position 173 (I173N, p.Ile173Asn). 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 medium size and hydrophobic (I) to medium size and polar (N) 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; simple virilizing form; 1-4% activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs6475 [ dbSNP | Ensembl ]

Sequence information Variant position:

173 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:

AQPGTPVAIEEEFSLLTCSI I CYLTFGDKIKDDNLMPAYYK 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                         AQPGTPVAIEEEFSLLTCSIICYLTFGDKIKDDNLMPAYYK

                              AQAGTPVAIQKEFSLLTCAIICHLTFGDK--EDTLVHTFHD

Mouse                         AQAGTPVAIHKEFSFLTCSIISCLTFGDK--DSTLVQTLHD

Rat                           AQAGASVAIHKEFSLLTCSIISCLTFGDK-QDSTLLNATHS

Pig                           AQAGTPVTIQKEFSVLTCSIICCLTFGDK--EDTLVHALHD

Bovine                        VQAGAPVTIQKEFSLLTCSIICYLTFGNK--EDTLVHAFHD

Cat                           AQAGTPVAIQKEFSFLTCSVICCLTFGDK--EDTLVHAFHD

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
Helix	160 – 177

Literature citations
A de novo pathological point mutation at the 21-hydroxylase locus: implications for gene conversion in the human genome.
Collier S.; Tassabehji M.; Sinnott P.; Strachan T.;
Nat. Genet. 3:260-265(1993)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 110-186; VARIANT AH3 ASN-173; Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 genes in HLA, the major histocompatibility complex in man.
Carroll M.C.; Campbell R.D.; Porter R.R.;
Proc. Natl. Acad. Sci. U.S.A. 82:521-525(1985)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 150-183; VARIANT AH3 ASN-173; Mutation in the CYP21B gene (Ile-172-->Asn) causes steroid 21-hydroxylase deficiency.
Amor M.; Parker K.L.; Globerman H.; New M.I.; White P.C.;
Proc. Natl. Acad. Sci. U.S.A. 85:1600-1604(1988)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 150-183; VARIANT AH3 ASN-173; A missense mutation at Ile172-->Asn or Arg356-->Trp causes steroid 21-hydroxylase deficiency.
Chiou S.-H.; Hu M.-C.; Chung B.-C.;
J. Biol. Chem. 265:3549-3552(1990)
Cited for: VARIANTS AH3 ASN-173 AND TRP-357; Substitution of Ile-172 to Asn in the steroid 21-hydroxylase B (P450c21B) gene in a Finnish patient with the simple virilizing form of congenital adrenal hyperplasia.
Partanen J.; Campbell R.D.;
Hum. Genet. 87:716-720(1991)
Cited for: VARIANT AH3 ASN-173; 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; 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; 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; Mutation screening in British 21-hydroxylase deficiency families and development of novel microsatellite based approaches to prenatal diagnosis.
Lako M.; Ramsden S.; Campbell R.D.; Strachan T.;
J. Med. Genet. 36:119-124(1999)
Cited for: VARIANTS AH3 ASN-173 AND TRP-357; 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; Molecular analysis of CYP-21 mutations for congenital adrenal hyperplasia in Singapore.
Loke K.Y.; Lee Y.S.; Lee W.W.R.; Poh L.K.S.;
Horm. Res. 55:179-184(2001)
Cited for: VARIANTS AH3 LEU-31; ASN-173; PRO-262; TRP-357 AND PRO-484; 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; Molecular genetic analysis of Tunisian patients with a classic form of 21-hydroxylase deficiency: identification of four novel mutations and high prevalence of Q318X mutation.
Kharrat M.; Tardy V.; M'Rad R.; Maazoul F.; Jemaa L.B.; Refai M.; Morel Y.; Chaabouni H.;
J. Clin. Endocrinol. Metab. 89:368-374(2004)
Cited for: VARIANTS AH3 ASN-173; TRP-357 AND TRP-484; 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; 21-Hydroxylase and 11beta-hydroxylase mutations in Romanian patients with classic congenital adrenal hyperplasia.
Grigorescu Sido A.; Weber M.M.; Grigorescu Sido P.; Clausmeyer S.; Heinrich U.; Schulze E.;
J. Clin. Endocrinol. Metab. 90:5769-5773(2005)
Cited for: VARIANTS AH3 LEU-31; ASN-173 AND TRP-357; 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-31; LEU-63; ASN-173; TRP-357 AND SER-454; CHARACTERIZATION OF VARIANTS AH3 LEU-63 AND SER-454; 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-57; LEU-63; ARG-108; PRO-143; ASN-173; TRP-357; CYS-409 AND SER-454; CHARACTERIZATION OF VARIANTS AH3 ARG-57; LEU-63; ARG-108; PRO-143; CYS-409 AND SER-454; 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.