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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
    mouse all
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    Genomic context

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    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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    NEW Try the new Transcript table

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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