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Aldo-keto reductase family 1, member C4 (chlordecone reductase; 3-alpha hydroxysteroid dehydrogenase, type I; dihydrodiol dehydrogenase 4)
PBB Protein AKR1C4 image.jpg
PDB rendering based on 2fvl.
Available structures: 2fvl
Symbol(s) AKR1C4; CDR; 3-alpha-HSD; C11; CHDR; DD4; HAKRA; MGC22581
External IDs OMIM: 600451 MGI2653678 Homologene79480
RNA expression pattern

PBB GE AKR1C4 210558 at tn.png


More reference expression data

Human Mouse
Entrez 1109 432720
Ensembl ENSG00000198610 ENSMUSG00000071551
Uniprot P17516 na
Refseq NM_001818 (mRNA)
NP_001809 (protein)
NM_001013785 (mRNA)
NP_001013807 (protein)
Location Chr 10: 5.23 - 5.25 Mb Chr 13: 4.23 - 4.25 Mb
Pubmed search [1] [2]

Aldo-keto reductase family 1, member C4 (chlordecone reductase; 3-alpha hydroxysteroid dehydrogenase, type I; dihydrodiol dehydrogenase 4), also known as AKR1C4, is a human gene.[1]

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.[1]


Further reading

  • Binstock JM, Iyer RB, Hamby CV; et al. (1992). "Human hepatic 3 alpha-hydroxysteroid dehydrogenase: possible identity with human hepatic chlordecone reductase.". Biochem. Biophys. Res. Commun. 187 (2): 760–6. PMID 1530633. 
  • Winters CJ, Molowa DT, Guzelian PS (1990). "Isolation and characterization of cloned cDNAs encoding human liver chlordecone reductase.". Biochemistry. 29 (4): 1080–7. PMID 2187532. 
  • Khanna M, Qin KN, Cheng KC (1995). "Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular cloning of multiple cDNAs encoding structurally related proteins in humans.". J. Steroid Biochem. Mol. Biol. 53 (1-6): 41–6. PMID 7626489. 
  • Khanna M, Qin KN, Wang RW, Cheng KC (1995). "Substrate specificity, gene structure, and tissue-specific distribution of multiple human 3 alpha-hydroxysteroid dehydrogenases.". J. Biol. Chem. 270 (34): 20162–8. PMID 7650035. 
  • Khanna M, Qin KN, Klisak I; et al. (1995). "Localization of multiple human dihydrodiol dehydrogenase (DDH1 and DDH2) and chlordecone reductase (CHDR) genes in chromosome 10 by the polymerase chain reaction and fluorescence in situ hybridization.". Genomics. 25 (2): 588–90. PMID 7789999. 
  • Deyashiki Y, Ogasawara A, Nakayama T; et al. (1994). "Molecular cloning of two human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzymes that are identical with chlordecone reductase and bile-acid binder.". Biochem. J. 299 ( Pt 2): 545–52. PMID 8172617. 
  • Qin KN, New MI, Cheng KC (1994). "Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase.". J. Steroid Biochem. Mol. Biol. 46 (6): 673–9. PMID 8274401. 
  • Kume T, Iwasa H, Shiraishi H; et al. (2000). "Characterization of a novel variant (S145C/L311V) of 3alpha-hydroxysteroid/dihydrodiol dehydrogenase in human liver.". Pharmacogenetics. 9 (6): 763–71. PMID 10634139. 
  • Nishizawa M, Nakajima T, Yasuda K; et al. (2000). "Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes.". Genes Cells. 5 (2): 111–25. PMID 10672042. 
  • Dufort I, Labrie F, Luu-The V (2001). "Human types 1 and 3 3 alpha-hydroxysteroid dehydrogenases: differential lability and tissue distribution.". J. Clin. Endocrinol. Metab. 86 (2): 841–6. PMID 11158055. 
  • Ozeki T, Takahashi Y, Kume T; et al. (2001). "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.". Biochem. J. 355 (Pt 2): 537–44. PMID 11284743. 
  • Ozeki T, Takahashi Y, Nakayama K, Kamataki T (2002). "Hepatocyte nuclear factor (HNF)-4 alpha/gamma, HNF-1 alpha, and vHNF-1 regulate the cell-specific expression of the human dihydrodiol dehydrogenase (DD)4/AKR1C4 gene.". Arch. Biochem. Biophys. 405 (2): 185–90. PMID 12220531. 
  • Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. PMID 12477932. doi:10.1073/pnas.242603899. 
  • Ozeki T, Takahashi Y, Nakayama K; et al. (2003). "Hepatocyte nuclear factor-4 alpha/gamma and hepatocyte nuclear factor-1 alpha as causal factors of interindividual difference in the expression of human dihydrodiol dehydrogenase 4 mRNA in human livers.". Pharmacogenetics. 13 (1): 49–53. PMID 12544512. 
  • Deloukas P, Earthrowl ME, Grafham DV; et al. (2004). "The DNA sequence and comparative analysis of human chromosome 10.". Nature. 429 (6990): 375–81. PMID 15164054. doi:10.1038/nature02462. 
  • Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. PMID 15489334. doi:10.1101/gr.2596504. 
  • Schüle C, Romeo E, Uzunov DP; et al. (2006). "Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3alpha-hydroxysteroid dehydrogenase activity.". Mol. Psychiatry. 11 (3): 261–72. PMID 16344854. doi:10.1038/sj.mp.4001782.