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CYP21A2 cytochrome P450 family 21 subfamily A member 2 [ Homo sapiens (human) ]

Gene ID: 1589, updated on 7-Apr-2024

Summary

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Official Symbol
CYP21A2provided by HGNC
Official Full Name
cytochrome P450 family 21 subfamily A member 2provided by HGNC
Primary source
HGNC:HGNC:2600
See related
Ensembl:ENSG00000231852 MIM:613815; AllianceGenome:HGNC:2600
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CAH1; CPS1; CA21H; CYP21; CYP21B; P450c21B
Summary
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and hydroxylates steroids at the 21 position. Its activity is required for the synthesis of steroid hormones including cortisol and aldosterone. Mutations in this gene cause congenital adrenal hyperplasia. A related pseudogene is located near this gene; gene conversion events involving the functional gene and the pseudogene are thought to account for many cases of steroid 21-hydroxylase deficiency. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression
Restricted expression toward adrenal (RPKM 498.8) See more
Orthologs
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Genomic context

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See CYP21A2 in Genome Data Viewer
Location:
6p21.33
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (32038415..32041644)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (31891622..31894848)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (32006192..32009421)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene serine/threonine kinase 19B (pseudogene) Neighboring gene complement C4B (Chido/Rodgers blood group) Neighboring gene CYP21A2 5' regulatory region Neighboring gene CYP21A2 recombination region Neighboring gene tenascin XB recombination region Neighboring gene ReSE screen-validated silencer GRCh37_chr6:32013699-32013950 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr6:32014364-32015563 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:32015753-32016386 Neighboring gene tenascin XB Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:32038327-32039327 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:32040222-32041078 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:32041114-32041614 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:32049385-32049900 Neighboring gene RNA, 5S ribosomal pseudogene 206 Neighboring gene Sharpr-MPRA regulatory region 2290 Neighboring gene activating transcription factor 6 beta

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The pathogenic p.Gln319Ter variant is not causing congenital adrenal hyperplasia when inherited in one of the duplicated CYP21A2 genes. Fanis P, et al. Front Endocrinol (Lausanne), 2023. PMID 37324257, Free PMC Article
  2. Genetic analysis and novel variation identification in Chinese patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Xia Y, et al. J Steroid Biochem Mol Biol, 2022 Sep. PMID 35882282
  3. Differences in hormonal levels between heterozygous CYP21A2 pathogenic variant carriers, non-carriers, and females with non-classic congenital hyperplasia. Silva RS, et al. Arch Endocrinol Metab, 2022 Apr 28. PMID 35289513, Free PMC Article
  4. Characteristics of In2G Variant in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency. Kocova M, et al. Front Endocrinol (Lausanne), 2021. PMID 35140681, Free PMC Article
  5. Characterization of Mutations Causing CYP21A2 Deficiency in Brazilian and Portuguese Populations. Prado MJ, et al. Int J Mol Sci, 2021 Dec 28. PMID 35008721, Free PMC Article

See all (380) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Targeted long-read sequencing for comprehensive detection of CYP21A2 mutations in patients with 21-hydroxylase deficiency.
    Title: Targeted long-read sequencing for comprehensive detection of CYP21A2 mutations in patients with 21-hydroxylase deficiency.
  2. Characterization of the CYP21A2 Gene Mutations in Children with Classic Congenital Adrenal Hyperplasia.
    Title: Characterization of the CYP21A2 Gene Mutations in Children with Classic Congenital Adrenal Hyperplasia.
  3. Relation between HLA and copy number variation of steroid 21-hydroxylase in a Swedish cohort of patients with autoimmune Addison's disease.
    Title: Relation between HLA and copy number variation of steroid 21-hydroxylase in a Swedish cohort of patients with autoimmune Addison's disease.
  4. The pathogenic p.Gln319Ter variant is not causing congenital adrenal hyperplasia when inherited in one of the duplicated CYP21A2 genes.
    Title: The pathogenic p.Gln319Ter variant is not causing congenital adrenal hyperplasia when inherited in one of the duplicated CYP21A2 genes.
  5. Congenital adrenal hyperplasia with a CYP21A2 deletion overlapping the tenascin-X gene: an atypical presentation.
    Title: Congenital adrenal hyperplasia with a CYP21A2 deletion overlapping the tenascin-X gene: an atypical presentation.
  6. Genetic analysis and novel variation identification in Chinese patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
    Title: Genetic analysis and novel variation identification in Chinese patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
  7. Pathogenic variants in the CYP21A2 gene cause isolated autosomal dominant congenital posterior polar cataracts.
    Title: Pathogenic variants in the CYP21A2 gene cause isolated autosomal dominant congenital posterior polar cataracts.
  8. Differences in hormonal levels between heterozygous CYP21A2 pathogenic variant carriers, non-carriers, and females with non-classic congenital hyperplasia.
    Title: Differences in hormonal levels between heterozygous CYP21A2 pathogenic variant carriers, non-carriers, and females with non-classic congenital hyperplasia.
  9. Characteristics of In2G Variant in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.
    Title: Characteristics of In2G Variant in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.
  10. Genotypic spectrum of 21-hydroxylase deficiency in an endogamous population.
    Title: Genotypic spectrum of 21-hydroxylase deficiency in an endogamous population.
Submit: New GeneRIF Correction See all GeneRIFs (254)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension.
EBI GWAS Catalog
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC150536, MGC150537

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 17-hydroxyprogesterone 21-hydroxylase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables heme binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables heme binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables iron ion binding IEA
Inferred from Electronic Annotation
more info
  
enables progesterone 21-hydroxylase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables steroid 21-monooxygenase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables steroid 21-monooxygenase activity TAS
Traceable Author Statement
more info
  
enables steroid binding IEA
Inferred from Electronic Annotation
more info
  
enables steroid hydroxylase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in glucocorticoid biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in glucocorticoid biosynthetic process TAS
Traceable Author Statement
more info
  
involved_in mineralocorticoid biosynthetic process TAS
Traceable Author Statement
more info
  
involved_in steroid biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in steroid metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in sterol metabolic process TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
located_in endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
steroid 21-hydroxylase
Names
21-OHase
cytochrome P450 XXI
cytochrome P450, family 21, subfamily A, polypeptide 2
cytochrome P450, subfamily XXIA (steroid 21-hydroxylase, congenital adrenal hyperplasia), polypeptide 2
cytochrome P450-C21B
steroid 21 hydroxylase
steroid 21-monooxygenase
NP_000491.4
NP_001122062.3
NP_001355072.1
NP_001355073.1
XP_024308323.1
XP_047298978.1
XP_047298979.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_007941.3 RefSeqGene

    Range
    5111..8340
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_829

mRNA and Protein(s)

  1. NM_000500.9 → NP_000491.4  steroid 21-hydroxylase isoform a

    See identical proteins and their annotated locations for NP_000491.4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (a).
    Source sequence(s)
    AI479704, AL645922, AV708092, BC125181, DA008890, M17252
    Consensus CDS
    CCDS4735.1
    UniProtKB/Swiss-Prot
    A2BHY6, P04033, P08686, Q01204, Q08AG8, Q16749, Q16806, Q16874, Q5ST44, Q96NU8
    UniProtKB/TrEMBL
    C7DTU9, C7DTW4, C7DTX7, C7DTX9, C7DTZ2, C7DTZ9, K9LHU7, K9LII5, K9LIR4, Q08AG9, Q16742
    Related
    ENSP00000496625.1, ENST00000644719.2
    Conserved Domains (1) summary
    pfam00067
    Location:29 → 479
    p450; Cytochrome P450

  2. NM_001128590.4 → NP_001122062.3  steroid 21-hydroxylase isoform b

    See identical proteins and their annotated locations for NP_001122062.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.
    Source sequence(s)
    AK054616, AV708092, BC125181, CD013985, DA008890, M17252
    Consensus CDS
    CCDS47406.1
    UniProtKB/TrEMBL
    A0A0G2JJF2
    Related
    ENSP00000415043.2, ENST00000435122.3
    Conserved Domains (1) summary
    pfam00067
    Location:29 → 449
    p450; Cytochrome P450

  3. NM_001368143.2 → NP_001355072.1  steroid 21-hydroxylase isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3), as well as variant 4, encodes isoform c.
    Source sequence(s)
    AL645922
    UniProtKB/TrEMBL
    Q9UP07

  4. NM_001368144.2 → NP_001355073.1  steroid 21-hydroxylase isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4), as well as variant 3, encodes isoform c.
    Source sequence(s)
    AL645922
    UniProtKB/TrEMBL
    Q9UP07

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

    Range
    32038415..32041644
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 ALT_REF_LOCI_2

Genomic

  1. NT_113891.3 Reference GRCh38.p14 ALT_REF_LOCI_2

    Range
    3476737..3479966
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 ALT_REF_LOCI_3

Genomic

  1. NT_167245.2 Reference GRCh38.p14 ALT_REF_LOCI_3

    Range
    3279823..3283052
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 ALT_REF_LOCI_5

Genomic

  1. NT_167247.2 Reference GRCh38.p14 ALT_REF_LOCI_5

    Range
    3380452..3383677
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 ALT_REF_LOCI_6

Genomic

  1. NT_167248.2 Reference GRCh38.p14 ALT_REF_LOCI_6

    Range
    3261650..3264877
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024452555.2 → XP_024308323.1  steroid 21-hydroxylase isoform X1

    UniProtKB/Swiss-Prot
    A2BHY6, P04033, P08686, Q01204, Q08AG8, Q16749, Q16806, Q16874, Q5ST44, Q96NU8
    UniProtKB/TrEMBL
    C7DTU9, C7DTW4, C7DTX7, C7DTX9, C7DTZ2, C7DTZ9, K9LHU7, K9LII5, K9LIR4, Q08AG9, Q16742

  2. XM_047443022.1 → XP_047298978.1  steroid 21-hydroxylase isoform X2

  3. XM_047443023.1 → XP_047298979.1  steroid 21-hydroxylase isoform X3

Reference GRCh38.p14 ALT_REF_LOCI_7

Genomic

  1. NT_167249.2 Reference GRCh38.p14 ALT_REF_LOCI_7

    Range
    3339605..3342831
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060930.1 Alternate T2T-CHM13v2.0

    Range
    31891622..31894848
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P08686.2 GenPept UniProtKB/Swiss-Prot:P08686

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