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    AKR1C4 aldo-keto reductase family 1 member C4 [ Homo sapiens (human) ]

    Gene ID: 1109, updated on 3-Nov-2024

    Summary

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    Official Symbol
    AKR1C4provided by HGNC
    Official Full Name
    aldo-keto reductase family 1 member C4provided by HGNC
    Primary source
    HGNC:HGNC:387
    See related
    Ensembl:ENSG00000198610 MIM:600451; AllianceGenome:HGNC:387
    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
    C11; CDR; DD4; CHDR; DD-4; HAKRA; 3-alpha-HSD
    Summary
    This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the bioreduction of chlordecone, a toxic organochlorine pesticide, to chlordecone alcohol in liver. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. [provided by RefSeq, Jul 2008]
    Expression
    Restricted expression toward liver (RPKM 165.8) See more
    Orthologs
    all
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    Genomic context

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    See AKR1C4 in Genome Data Viewer
    Location:
    10p15.1
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (5196837..5218949)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (5198604..5220700)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (5238800..5260912)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene aldo-keto reductase family 1 member C3 Neighboring gene U8 small nucleolar RNA Neighboring gene Sharpr-MPRA regulatory region 1972 Neighboring gene aldo-keto reductase family 1 member C8 Neighboring gene MPRA-validated peak852 silencer Neighboring gene MPRA-validated peak853 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr10:5241916-5242139 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_13158 Neighboring gene ARF like GTPase 4A pseudogene 3 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_13180 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr10:5313502-5314701 Neighboring gene long intergenic non-protein coding RNA 2561 Neighboring gene Sharpr-MPRA regulatory region 4527 Neighboring gene aldo-keto reductase family 1 member C7, pseudogene

    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 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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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. the present study suggests that AKR1C1, AKR1C2, AKR1C3, and AKR1C4 are closely associated with drug resistance to both CDDP and 5FU, and that mefenamic acid, an inhibitor of AKR1C, restores sensitivity through inhibition of drug-resistance in human cancer cells.
      Title: Mefenamic acid enhances anticancer drug sensitivity via inhibition of aldo-keto reductase 1C enzyme activity.
    2. Studies indicate that mutations in aldo-keto reductase family 1 (AKR1) enzymes AKR1C1 and AKR1C4 are responsible for sexual development dysgenesis and mutations in AKR1D1 are causative in bile-acid deficiency.
      Title: Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism.
    3. In women only, SNPs in AKR1C4 reduced the likelihood of having exhibited paranoid ideation by circa 60%.
      Title: Polymorphisms in AKR1C4 and HSD3B2 and differences in serum DHEAS and progesterone are associated with paranoid ideation during mania or hypomania in bipolar disorder.
    4. Low progesterone levels and a cystine to serine change at position 145 in AKR1C4 gene are associated with manic/hypomanic irritability in males
      Title: AKR1C4 gene variant associated with low euthymic serum progesterone and a history of mood irritability in males with bipolar disorder.
    5. role of AKR1C4 in the metabolism of testosterone and progesterone via the 5beta-reductase pathway.
      Title: Stereospecific reduction of 5β-reduced steroids by human ketosteroid reductases of the AKR (aldo-keto reductase) superfamily: role of AKR1C1-AKR1C4 in the metabolism of testosterone and progesterone via the 5β-reductase pathway.
    6. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
      Title: Human variation in alcohol response is influenced by variation in neuronal signaling genes.
    7. Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Polymorphisms in innate immunity genes and lung cancer risk in Xuanwei, China.
    8. Structure determination of human AKR1C4 and homology modelling of AKR1D1 followed by docking experiments were used to explore active site geometries.
      Title: Structure-activity relationships of human AKR-type oxidoreductases involved in bile acid synthesis: AKR1D1 and AKR1C4.
    9. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variation in the estrogen metabolic pathway and mammographic density as an intermediate phenotype of breast cancer.
    10. Clinical trial of gene-disease association. (HuGE Navigator)
      Title: Polymorphisms in genes involved in estrogen and progesterone metabolism and mammographic density changes in women randomized to postmenopausal hormone therapy: results from a pilot study.
    Submit: New GeneRIF Correction See all GeneRIFs (13)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    46,XY disorder of sex development due to testicular 17,20-desmolase deficiency
    MedGen: C1839840 OMIM: 614279 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    An atlas of genetic influences on human blood metabolites.
    EBI GWAS Catalog
    Discovery and refinement of loci associated with lipid levels.
    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

    • MGC22581

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 5alpha-androstane-3beta,17beta-diol dehydrogenase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables aldo-keto reductase (NADPH) activity TAS
    Traceable Author Statement
    more info
    		  
    enables aldose reductase (NADPH) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables androstan-3-alpha,17-beta-diol dehydrogenase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables androsterone dehydrogenase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables androsterone dehydrogenase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables bile acid binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables bile acid transmembrane transporter activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables chlordecone reductase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables electron transfer activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables estradiol 17-beta-dehydrogenase [NAD(P)+] activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ketosteroid monooxygenase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables retinal dehydrogenase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables testosterone 17-beta-dehydrogenase (NADP+) activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables testosterone dehydrogenase (NAD+) activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables testosterone dehydrogenase [NAD(P)+] activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in androgen metabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in bile acid and bile salt transport TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in bile acid biosynthetic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in cellular response to jasmonic acid stimulus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in daunorubicin metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in daunorubicin metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in doxorubicin metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in doxorubicin metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in progesterone metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in prostaglandin metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in retinoid metabolic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in steroid metabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm TAS
    Traceable Author Statement
    more info
    		 PubMed 
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 

    General protein information

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    Preferred Names
    aldo-keto reductase family 1 member C4
    Names
    3-alpha-HSD1
    3alpha-hydroxysteroid 3-dehydrogenase
    chlordecone reductase; 3-alpha hydroxysteroid dehydrogenase, type I; dihydrodiol dehydrogenase 4
    dihydrodiol dehydrogenase isozyme DD4
    type I 3-alpha-hydroxysteroid dehydrogenase
    NP_001809.4

    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_031872.2 RefSeqGene

      Range
      5002..27114
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001818.5 → NP_001809.4  aldo-keto reductase family 1 member C4

      Status: REVIEWED

      Source sequence(s)
      AL355303
      Consensus CDS
      CCDS7064.1
      UniProtKB/Swiss-Prot
      P17516, Q5T6A3, Q8WW84, Q9NS54
      Related
      ENSP00000263126.1, ENST00000263126.3
      Conserved Domains (1) summary
      cd19108
      Location:6 → 306
      AKR_AKR1C1-35; AKR1C family of aldo-keto reductase (AKR)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      5196837..5218949
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      5198604..5220700
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P17516.3 GenPept UniProtKB/Swiss-Prot:P17516

    Gene LinkOut

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