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

Gene ID: 1109, updated on 11-Apr-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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Location:
10p15.1
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (5196837..5218949)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (5198604..5220700)
105.20220307 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 ADP ribosylation factor 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
  • 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. AKR1C4 gene variant associated with low euthymic serum progesterone and a history of mood irritability in males with bipolar disorder. Johansson AG, et al. J Affect Disord, 2011 Sep. PMID 21570127
  2. An estrogen metabolism-related polymorphism of the 17-alpha HSD gene is associated with perimenopausal body mass index. Tempfer CB, et al. Fertil Steril, 2007 Jun. PMID 17207797
  3. Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3alpha-hydroxysteroid dehydrogenase activity. SchĂĽle C, et al. Mol Psychiatry, 2006 Mar. PMID 16344854
  4. Co-operative regulation of the transcription of human dihydrodiol dehydrogenase (DD)4/aldo-keto reductase (AKR)1C4 gene by hepatocyte nuclear factor (HNF)-4alpha/gamma and HNF-1alpha. Ozeki T, et al. Biochem J, 2001 Apr 15. PMID 11284743, Free PMC Article
  5. Human types 1 and 3 3 alpha-hydroxysteroid dehydrogenases: differential lability and tissue distribution. Dufort I, et al. J Clin Endocrinol Metab, 2001 Feb. PMID 11158055

See all (45) citations in PubMed

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

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
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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 dihydrotestosterone 17-beta-dehydrogenase activity IEA
Inferred from Electronic Annotation
more info
  
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 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
  
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_2023_10

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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