Reviewed, UniProtKB/Swiss-Prot P08686 (CP21A_HUMAN)

Names and origin

Protein names

Recommended name:
    Steroid 21-hydroxylase
    EC=1.14.99.10
Alternative name(s):
    Cytochrome P450 21
    Cytochrome P450 XXI
    21-OHase
    P450-C21
    P-450c21
    P450-C21B

Gene names

Name:	CYP21A2
Synonyms:	CYP21, CYP21B

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	494 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Specifically catalyzes the 21-hydroxylation of steroids. Required for the adrenal synthesis of mineralocorticoids and glucocorticoids.
Catalytic activity	A steroid + AH2 + O2 = a 21-hydroxysteroid + A + H2O.
Cofactor	Heme group.
Subcellular location	Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
Domain	The leucine-rich hydrophobic amino acid N-terminal region probably helps to anchor the protein to the microsomal membrane.
Involvement in disease	Defects in CYP21A2 are the cause of adrenal hyperplasia type 3 (AH3) [MIM:201910]. AH3 is a form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late onset (NC or LOAH), and 'cryptic' (asymptomatic). Ref.3 Ref.5 Ref.10 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.45 Ref.46 Ref.47 Ref.48 Ref.49 Ref.50 Ref.51 Ref.52
Miscellaneous	The human genome contains 2 genes, C4A and C4B, for C4 complement component separated by approximately 10 kb. 3'to each of the C4 genes there is a steroid 21-hydroxylase gene. The gene 3'to C4A is a pseudogene.
Sequence similarities	Belongs to the cytochrome P450 family.

Ontologies

Keywords
Biological process	Steroidogenesis
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Disease	Congenital adrenal hyperplasia Disease mutation
Ligand	Heme Iron Lipid-binding Metal-binding Steroid-binding
Molecular function	Monooxygenase Oxidoreductase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	C21-steroid hormone biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell microsome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro steroid 21-monooxygenase activity Inferred from electronic annotation. Source: EC steroid binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 494	494	Steroid 21-hydroxylase		PRO_0000051976
Regions
	Region	342 – 358	17	Steroid-binding By similarity
Sites
	Metal binding	428	1	Iron (heme axial ligand)
Natural variations
	Natural variant	9	1	L → LL in allele CYP21A2*2. Ref.5 Ref.15 Ref.4		VAR_018363
	Natural variant	15	1	A → T in AH3; salt wasting form; no significant difference in activity compared with the wild-type. Ref.46 Ref.51		VAR_026059
	Natural variant	30	1	P → L in AH3; non-classic form; 50% activity; 10% of non-classic AH3 Texan patients. Ref.17 Ref.18 Ref.26 Ref.29 Ref.31 Ref.32 Ref.34 Ref.38 Ref.39 Ref.40 Ref.41 Ref.43 Ref.46 Ref.47 Ref.51 Ref.52		VAR_001281
	Natural variant	30	1	P → Q in AH3; does not affect membrane binding; enzyme function abolished. Ref.17 Ref.18 Ref.26 Ref.29 Ref.31 Ref.32 Ref.34 Ref.38 Ref.39 Ref.40 Ref.41 Ref.43 Ref.46 Ref.47 Ref.51 Ref.52		VAR_026060
	Natural variant	62	1	H → L in AH3. Ref.47		VAR_018364
	Natural variant	64	1	G → E in AH3; no activity. Ref.31		VAR_007923
	Natural variant	90	1	G → V in AH3. Ref.26		VAR_026061
	Natural variant	98	1	K → R		VAR_001282
	Natural variant	102	1	K → R in allele CYP21A2*3. Ref.5 Ref.52		VAR_001283
	Natural variant	105	1	P → L in AH3. Ref.20 Ref.25		VAR_001284
	Natural variant	124	1	R → H in AH3. Ref.50		VAR_026062
	Natural variant	169	1	C → Y in AH3. Ref.30		VAR_001285
	Natural variant	172	1	I → N in AH3; simple virilizing form; 1-2% activity. Ref.14 Ref.15 Ref.16 Ref.18 Ref.22 Ref.26 Ref.31 Ref.32 Ref.34 Ref.35 Ref.38 Ref.39 Ref.40 Ref.41 Ref.43 Ref.46 Ref.47 Ref.48 Ref.49 Ref.52		VAR_001286
	Natural variant	178	1	G → A in AH3. Ref.26		VAR_026063
	Natural variant	183	1	D → E in allele CYP21A2*4.		VAR_001287
	Natural variant	196	1	Missing in AH3; moderate. Ref.28		VAR_008688
	Natural variant	211	1	V → L in AH3; non-classic form; pathogenicity uncertain. Ref.13		VAR_026064
	Natural variant	236	1	I → N in AH3; salt wasting form. Ref.18 Ref.22 Ref.31 Ref.32 Ref.52		VAR_001288
	Natural variant	237	1	V → E in AH3; salt wasting form. Ref.18 Ref.32 Ref.52		VAR_001289
	Natural variant	239	1	M → K in AH3; salt wasting form. Ref.18 Ref.32 Ref.52		VAR_001290
	Natural variant	261	1	L → P in AH3. Ref.39		VAR_026065
	Natural variant	268	1	S → T in allele CYP21A2*5. dbSNP rs6472. Ref.3 Ref.17 Ref.34 Ref.36		VAR_001291
	Natural variant	281	1	V → G in AH3; salt wasting form. Ref.10 Ref.13 Ref.18 Ref.22 Ref.26 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.36 Ref.38 Ref.40 Ref.41 Ref.43 Ref.46 Ref.47 Ref.48 Ref.51 Ref.52		VAR_026066
	Natural variant	281	1	V → L in AH3; non-classic form; 50% activity; most common variant; 59% of non-classic AH3 Texan patients; normal KM but 20% reduced Vmax. dbSNP rs6471. Ref.10 Ref.13 Ref.18 Ref.22 Ref.26 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.36 Ref.38 Ref.40 Ref.41 Ref.43 Ref.46 Ref.47 Ref.48 Ref.51 Ref.52		VAR_001292
	Natural variant	283	1	M → L in AH3. Ref.43		VAR_026067
	Natural variant	291	1	G → C in AH3. Ref.20 Ref.26 Ref.28 Ref.31 Ref.41 Ref.48 Ref.52		VAR_026068
	Natural variant	291	1	G → R in AH3. Ref.20 Ref.26 Ref.28 Ref.31 Ref.41 Ref.48 Ref.52		VAR_018365
	Natural variant	291	1	G → S in AH3; salt wasting form; less then 1% activity. Ref.20 Ref.26 Ref.28 Ref.31 Ref.41 Ref.48 Ref.52		VAR_001293
	Natural variant	300	1	L → F in AH3; salt wasting form. Ref.38		VAR_026069
	Natural variant	301	1	S → Y in AH3. Ref.48		VAR_018366
	Natural variant	304	1	V → M in hyperandrogenism; due to 21-hydroxylase deficiency; non-classic type; residual activity of 46% for conversion of 17-hydroxyprogesterone and 26% for conversion of progesterone compared with the normal enzyme. Ref.44		VAR_026070
	Natural variant	317	1	L → M in AH3. Ref.40		VAR_026071
	Natural variant	339	1	R → H in AH3; non-classic form; 50% activity. Ref.5		VAR_001294
	Natural variant	341	1	R → P in AH3. Ref.47 Ref.48		VAR_018367
	Natural variant	341	1	R → W in AH3; non-classic form; mild. Ref.47 Ref.48		VAR_001295
	Natural variant	354	1	R → C in AH3; salt wasting form. Ref.26 Ref.38		VAR_026072
	Natural variant	354	1	R → H in AH3. Ref.26 Ref.38		VAR_026073
	Natural variant	356	1	R → P in AH3; salt wasting form; 0.15% activity. Ref.15 Ref.18 Ref.24 Ref.26 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.38 Ref.39 Ref.40 Ref.41 Ref.43 Ref.47 Ref.48 Ref.49 Ref.52		VAR_001296
	Natural variant	356	1	R → Q in AH3; simple virilizing form; mild; 0.65% activity. Ref.15 Ref.18 Ref.24 Ref.26 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.38 Ref.39 Ref.40 Ref.41 Ref.43 Ref.47 Ref.48 Ref.49 Ref.52		VAR_001297
	Natural variant	356	1	R → W in AH3; salt wasting form. Ref.15 Ref.18 Ref.24 Ref.26 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.38 Ref.39 Ref.40 Ref.41 Ref.43 Ref.47 Ref.48 Ref.49 Ref.52		VAR_001298
	Natural variant	362	1	A → V in AH3; no activity. Ref.31		VAR_007924
	Natural variant	363	1	L → W in AH3. Ref.42		VAR_026074
	Natural variant	365	1	H → Y in AH3. Ref.52		VAR_026075
	Natural variant	375	1	G → S in hyperandrogenism; due to 21-hydroxylase deficiency; almost completely abolished enzyme activity. Ref.44		VAR_026076
	Natural variant	380	1	E → D in AH3; salt wasting form. Ref.23		VAR_001299
	Natural variant	408	1	R → C in AH3; should lead to complete impairment of enzymatic activity. Ref.45		VAR_026077
	Natural variant	424	1	G → S in AH3. Ref.33 Ref.41 Ref.45		VAR_026078
	Natural variant	426	1	R → H in AH3; exhibit only low enzyme activity toward 17-hydroxyprogesterone. Ref.41		VAR_026079
	Natural variant	435	1	R → C in AH3. Ref.40		VAR_026080
	Natural variant	453	1	P → S in AH3; non-classic form; 50% activity; 23% of non-classic AH3 Texan patients; almost completely abolished enzyme activity when associated with S-375. dbSNP rs6445. Ref.5 Ref.19 Ref.20 Ref.25 Ref.26 Ref.36 Ref.38 Ref.40 Ref.41 Ref.43 Ref.46 Ref.47 Ref.52		VAR_001300
	Natural variant	479	1	R → L in AH3. Ref.52		VAR_026081
	Natural variant	482	1	P → S in AH3; rediced enzyme activity to 70% of normal. Ref.51		VAR_026082
	Natural variant	483	1	R → P in AH3; moderate; 1-2% of activity. Ref.21 Ref.22 Ref.28 Ref.39 Ref.41 Ref.47 Ref.48 Ref.49 Ref.52		VAR_001301
	Natural variant	483	1	R → Q in AH3. Ref.21 Ref.22 Ref.28 Ref.39 Ref.41 Ref.47 Ref.48 Ref.49 Ref.52		VAR_018368
	Natural variant	483	1	R → W in AH3; salt wasting form. Ref.21 Ref.22 Ref.28 Ref.39 Ref.41 Ref.47 Ref.48 Ref.49 Ref.52		VAR_026083
	Natural variant	493	1	N → S in AH3; could be a polymorphism; allele CYP21A2*6. dbSNP rs6473. Ref.34		VAR_001302
Experimental info
	Mutagenesis	268	1	S → C, M or T: No loss of function. Ref.10
	Mutagenesis	281	1	V → I: Normal KM but 50% reduced Vmax.
	Mutagenesis	281	1	V → T: Normal KM but 10% reduced Vmax.
	Mutagenesis	428	1	C → M, S or T: Loss of activity and loss of P450 absorption. Ref.10
	Sequence conflict	311	1	P → L Ref.9
	Sequence conflict	346	1	N → I Ref.9
	Sequence conflict	426	1	R → P in AAB59440. Ref.2
	Sequence conflict	437	1	E → D in AAB59440. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P08686-1 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: 7E1FF83B59FBA136	FASTA	494	55,887
	10 20 30 40 50 60 MLLLGLLLLP LLAGARLLWN WWKLRSLHLP PLAPGFLHLL QPDLPIYLLG LTQKFGPIYR 70 80 90 100 110 120 LHLGLQDVVV LNSKRTIEEA MVKKWADFAG RPEPLTYKLV SKNYPDLSLG DYSLLWKAHK 130 140 150 160 170 180 KLTRSALLLG IRDSMEPVVE QLTQEFCERM RAQPGTPVAI EEEFSLLTCS IICYLTFGDK 190 200 210 220 230 240 IKDDNLMPAY YKCIQEVLKT WSHWSIQIVD VIPFLRFFPN PGLRRLKQAI EKRDHIVEMQ 250 260 270 280 290 300 LRQHKESLVA GQWRDMMDYM LQGVAQPSME EGSGQLLEGH VHMAAVDLLI GGTETTANTL 310 320 330 340 350 360 SWAVVFLLHH PEIQQRLQEE LDHELGPGAS SSRVPYKDRA RLPLLNATIA EVLRLRPVVP 370 380 390 400 410 420 LALPHRTTRP SSISGYDIPE GTVIIPNLQG AHLDETVWER PHEFWPDRFL EPGKNSRALA 430 440 450 460 470 480 FGCGARVCLG EPLARLELFV VLTRLLQAFT LLPSGDALPS LQPLPHCSVI LKMQPFQVRL 490 QPRGMGAHSP GQNQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure of human steroid 21-hydroxylase genes." White P.C., New M.I., Dupont B. Proc. Natl. Acad. Sci. U.S.A. 83:5111-5115(1986) [PubMed: 3487786] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly arranged in human chromosome: a pseudogene and a genuine gene." Higashi Y., Yoshioka H., Yamane M., Gotoh O., Fujii-Kuriyama Y. Proc. Natl. Acad. Sci. U.S.A. 83:2841-2845(1986) [PubMed: 3486422] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Molecular characterization of the HLA-linked steroid 21-hydroxylase B gene from an individual with congenital adrenal hyperplasia." Rodrigues N.R., Dunham I., Yu C.Y., Carroll M.C., Porter R.R., Campbell R.D. EMBO J. 6:1653-1661(1987) [PubMed: 3038528] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT AH3 THR-268, VARIANT SER-493.
[4]	"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) [PubMed: 3267225] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-281, VARIANT LEU-9 INS.
[5]	"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) [PubMed: 1406709] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-9 INS ARG-102 AND SER-493, VARIANTS AH3 HIS-339 AND SER-453. Tissue: Peripheral blood.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-493.
[7]	"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) [PubMed: 8485582] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 109-185, VARIANT ASN-172.
[8]	"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) [PubMed: 3871526] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 149-182.
[9]	"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) [PubMed: 3497399] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 265-494, VARIANT LEU-281.
[10]	"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) [PubMed: 1864962] [Abstract] Cited for: CHARACTERIZATION OF VARIANT AH3 LEU-281, MUTAGENESIS OF SER-268 AND CYS-428.
[11]	"Molecular genetics of 21-hydroxylase deficient late-onset adrenal hyperplasia." Gunn S.K., Sherman L.D., Therrell B.L., Owerbach D.I. Semin. Reprod. Endocrinol. 11:347-352(1993) Cited for: REVIEW ON AH3 VARIANTS.
[12]	"Mutations in steroid 21-hydroxylase (CYP21)." White P.C., Tusie-Luna M.-T., New M.I., Speiser P.W. Hum. Mutat. 3:373-378(1994) [PubMed: 8081391] [Abstract] Cited for: REVIEW ON AH3 VARIANTS.
[13]	"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) [PubMed: 3260007] [Abstract] Cited for: VARIANTS AH3 LEU-211 AND LEU-281.
[14]	"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) [PubMed: 3257825] [Abstract] Cited for: VARIANT AH3 ASN-172.
[15]	"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) [PubMed: 2303461] [Abstract] Cited for: VARIANTS AH3 ASN-172 AND TRP-356, VARIANT LEU-9 INS.
[16]	"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) [PubMed: 1937474] [Abstract] Cited for: VARIANT AH3 ASN-172.
[17]	"A mutation (Pro-30 to Leu) in CYP21 represents a potential nonclassic steroid 21-hydroxylase deficiency allele." Tusie-Luna M.T., Speiser P.W., Dumic M., New M.I., White P.C. Mol. Endocrinol. 5:685-692(1991) [PubMed: 2072928] [Abstract] Cited for: VARIANT AH3 LEU-30, VARIANT THR-268.
[18]	"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) [PubMed: 1644925] [Abstract] Cited for: VARIANTS AH3 LEU-30; ASN-172; ASN-236; GLU-237; LYS-239; LEU-281 AND TRP-356.
[19]	"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) [PubMed: 1406699] [Abstract] Cited for: VARIANT AH3 SER-453.
[20]	"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) [PubMed: 1496017] [Abstract] Cited for: VARIANTS AH3 LEU-105; SER-291 AND SER-453.
[21]	"Steroid 21-hydroxylase (P450c21): a new allele and spread of mutations through the pseudogene." Wedell A., Luthman H. Hum. Genet. 91:236-240(1993) [PubMed: 8478006] [Abstract] Cited for: VARIANT AH3 PRO-483.
[22]	"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) [PubMed: 7749410] [Abstract] Cited for: VARIANTS AH3 ASN-172; ASN-236; LEU-281 AND PRO-483, VARIANT SER-493.
[23]	"E380D: a novel point mutation of CYP21 in an HLA-homozygous patient with salt-losing congenital adrenal hyperplasia due to 21-hydroxylase deficiency." Kirby-Keyser L., Porter C.C., Donohoue P.A. Hum. Mutat. 9:181-182(1997) [PubMed: 9067760] [Abstract] Cited for: VARIANT AH3 ASP-380.
[24]	"A cluster of missense mutations at Arg356 of human steroid 21-hydroxylase may impair redox partner interaction." Lajic S., Levo A., Nikoshkov A., Lundberg Y., Partanen J., Wedell A. Hum. Genet. 99:704-709(1997) [PubMed: 9187661] [Abstract] Cited for: VARIANTS AH3 PRO-356 AND GLN-356.
[25]	"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) [PubMed: 8989258] [Abstract] Cited for: VARIANTS AH3 LEU-105 AND SER-453.
[26]	"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) [PubMed: 10364682] [Abstract] Cited for: VARIANTS AH3 LEU-30; VAL-90; ASN-172; ALA-178; LEU-281; CYS-291; HIS-354; TRP-356 AND SER-453.
[27]	"Molecular genetic analysis of patients carrying steroid 21-hydroxylase deficiency in the Mexican population: identification of possible new mutations and high prevalence of apparent germ-line mutations." Ordonez-Sanchez M.L., Ramirez-Jimenez S., Lopez-Gutierrez A.U., Riba L., Gamboa-Cardiel S., Cerrillo-Hinojosa M., Altamirano-Bustamante N., Calzada-Leon R., Robles-Valdes C., Mendoza-Morfin F., Tusie-Luna M.T. Hum. Genet. 102:170-177(1998) [PubMed: 9580109] [Abstract] Cited for: VARIANTS AH3, VARIANTS.
[28]	"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) [PubMed: 9497336] [Abstract] Cited for: VARIANTS AH3 GLU-196 DEL; SER-291 AND PRO-483.
[29]	"Effects of missense mutations and deletions on membrane anchoring and enzyme function of human steroid 21-hydroxylase (P450c21)." Lajic S., Nikoshkov A., Holst M., Wedell A. Biochem. Biophys. Res. Commun. 257:384-390(1999) [PubMed: 10198222] [Abstract] Cited for: VARIANT AH3 GLN-30, CHARACTERIZATION OF VARIANT AH3 GLN-30.
[30]	"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) [PubMed: 10094562] [Abstract] Cited for: VARIANTS AH3 TYR-169; LEU-281 AND GLN-356.
[31]	"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) [PubMed: 10408778] [Abstract] Cited for: VARIANTS AH3 LEU-30; GLU-64; ASN-172; ASN-236; LEU-281; SER-291; TRP-356 AND VAL-362.
[32]	"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) [PubMed: 10408786] [Abstract] Cited for: VARIANTS AH3 LEU-30; ASN-172; ASN-236; GLU-237; LYS-239; LEU-281 AND TRP-356.
[33]	"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) [PubMed: 10443693] [Abstract] Cited for: VARIANTS AH3 LEU-281; TRP-356 AND SER-424.
[34]	"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) [PubMed: 10496074] [Abstract] Cited for: VARIANTS AH3 LEU-30; ASN-172; LEU-281; TRP-356 AND SER-493, VARIANT THR-268.
[35]	"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) [PubMed: 10051010] [Abstract] Cited for: VARIANTS AH3 ASN-172 AND TRP-356.
[36]	"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) [PubMed: 10391209] [Abstract] Cited for: VARIANTS AH3 LEU-281 AND SER-453, VARIANTS THR-268 AND SER-493.
[37]	Erratum 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. 23:373-373(1999)
[38]	"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) [PubMed: 10720040] [Abstract] Cited for: VARIANTS AH3 LEU-30; ASN-172; LEU-281; GLY-281; PHE-300; CYS-354; TRP-356 AND SER-453.
[39]	"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) [PubMed: 11598371] [Abstract] Cited for: VARIANTS AH3 LEU-30; ASN-172; PRO-261; TRP-356 AND PRO-483.
[40]	"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) [PubMed: 11232002] [Abstract] Cited for: VARIANTS AH3 LEU-30; ASN-172; LEU-281; MET-317; TRP-356; CYS-435 AND SER-453.
[41]	"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) [PubMed: 11600539] [Abstract] 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.
[42]	"Novel mutations in the human CYP21 gene." Levo A., Partanen J. Prenat. Diagn. 21:885-889(2001) [PubMed: 11746135] [Abstract] Cited for: VARIANT AH3 TRP-363.
[43]	"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) [PubMed: 12222711] [Abstract] Cited for: VARIANTS AH3 LEU-30; ASN-172; LEU-281; LEU-283; TRP-356 AND SER-453.
[44]	"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) [PubMed: 12050257] [Abstract] Cited for: VARIANTS HYPERANDROGENISM MET-304; SER-375 AND SER-453, CHARACTERIZATION OF VARIANTS HYPERANDROGENISM MET-304; SER-375 AND SER-453.
[45]	"Three novel mutations in CYP21 gene in Brazilian patients with the classical form of 21-hydroxylase deficiency due to a founder effect." Billerbeck A.E.C., Mendonca B.B., Pinto E.M., Madureira G., Arnhold I.J.P., Bachega T.A.S.S. J. Clin. Endocrinol. Metab. 87:4314-4317(2002) [PubMed: 12213891] [Abstract] Cited for: VARIANTS AH3 CYS-408 AND SER-424.
[46]	"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) [PubMed: 12887291] [Abstract] Cited for: VARIANTS AH3 THR-15; LEU-30; ASN-172; LEU-281 AND SER-453.
[47]	"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) [PubMed: 12788866] [Abstract] Cited for: VARIANTS AH3 LEU-30; LEU-62; ASN-172; LEU-281; PRO-341; TRP-356; SER-453 AND PRO-483.
[48]	"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) [PubMed: 12915679] [Abstract] Cited for: VARIANTS AH3 ASN-172; LEU-281; ARG-291; TYR-301; PRO-341; TRP-356 AND GLN-483.
[49]	"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) [PubMed: 14715874] [Abstract] Cited for: VARIANTS AH3 ASN-172; TRP-356 AND TRP-483.
[50]	"Three novel mutations in Japanese patients with 21-hydroxylase deficiency." Usui T., Nishisho K., Kaji M., Ikuno N., Yorifuji T., Yasuda T., Kuzuya H., Shimatsu A. Horm. Res. 61:126-132(2004) [PubMed: 14676460] [Abstract] Cited for: VARIANT AH3 HIS-124.
[51]	"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) [PubMed: 15126570] [Abstract] Cited for: VARIANTS AH3 THR-15; LEU-30; LEU-281 AND SER-482, CHARACTERIZATION OF VARIANTS AH3 THR-15 AND SER-482.
[52]	"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) [PubMed: 15110320] [Abstract] 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.
+	Additional computationally mapped references.

Web resources

Cytochrome P450 Allele Nomenclature Committee

CYP21A2 alleles

GeneReviews

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBLGenBankDDBJ

M19711 Genomic DNA. Translation: AAA83248.1.
M13936 Genomic DNA. Translation: AAA59695.1.
K02771 Genomic DNA. Translation: AAA59706.1.
M12792 Genomic DNA. Translation: AAB59440.1.
M26856 Genomic DNA. Translation: AAA52064.1.
X58906 Genomic DNA. Translation: CAA41709.1.
BC125182 mRNA. Translation: AAI25183.1.

IPI

IPI00894349.

PIR

O4HUC2. A25446.

UniGene

Hs.485104
Hs.654479

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2GEG	model	-	C	27-494	[»]

ModBase

Search...

Genome annotation databases

Ensembl

ENSG00000168482. Homo sapiens. [Contig view]
ENSG00000198457. Homo sapiens. [Contig view]
ENSG00000206338. Homo sapiens. [Contig view]

Organism-specific databases

GeneCards

GC06P032114.

HGNC

HGNC:2600. CYP21A2.

MIM

201910. gene+phenotype.

Orphanet

418. Congenital adrenal hyperplasia.

PharmGKB

PA27096.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P08686.

Enzyme and pathway databases

BRENDA

1.14.99.10. 247.

Reactome

REACT_13433. Biological oxidations.
REACT_602. Lipid and lipoprotein metabolism.

Gene expression databases

CleanEx

HS_CYP21A2.

GermOnline

ENSG00000198457. Homo sapiens.

Family and domain databases

InterPro

IPR001128. Cyt_P450.
IPR017973. Cyt_P450_C.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]

Gene3D

G3DSA:1.10.630.10. Cyt_P450. 1 hit.

PANTHER

PTHR19383. Cyt_P450. 1 hit.

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PRINTS

PR00463. EP450I.
PR00385. P450.

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

SOURCE

Search...

Entry information

Entry name

CP21A_HUMAN

Accession

Primary (citable) accession number: P08686
Secondary accession number(s): P04033 , Q01204, Q08AG8, Q16749

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1986
Last sequence update:	January 1, 1988
Last modified:	June 16, 2009
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)