Gene Symbol: AKR1D1
Description: aldo-keto reductase family 1 member D1
Alias: 3o5bred, CBAS2, SRD5B1, 3-oxo-5-beta-steroid 4-dehydrogenase, delta(4)-3-ketosteroid 5-beta-reductase, delta(4)-3-oxosteroid 5-beta-reductase, steroid-5-beta-reductase, beta polypeptide 1 (3-oxo-5 beta-steroid delta 4-dehydrogenase beta 1)
Species: human
Products:     AKR1D1

Top Publications

  1. Chen H, Li H, Wu J, Wu S, Chen H, Yang Y, et al. Panel-Based Next-Generation Sequencing for the Diagnosis of Cholestatic Genetic Liver Diseases: Clinical Utility and Challenges. J Pediatr. 2019;205:153-159.e6 pubmed publisher
    ..5%. Disease-causing mutations, including ATP8B1, ABCB11, ABCB4, ABCC2, TJP2, NR1H4 (FXR), JAG1, AKR1D1, CYP7B1, PKHD1, ATP7B, and SLC25A13, were identified...
  2. Liu J, Zhou S, Zhou J, Gou J, Cheng Y, Cai H, et al. [A case of congenital bile acid synthesis disorder type 2 and literature review]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2018;35:691-693 pubmed publisher
    ..Liver biopsy showed intrahepatic cholestasis. Gene testing has identified a homozygous mutation in AKR1D1 gene...
  3. Wang H, Wen F, Dai D, Wang J, Zhao J, Setchell K, et al. Infant cholestasis patient with a novel missense mutation in the AKR1D1 gene successfully treated by early adequate supplementation with chenodeoxycholic acid: A case report and review of the literature. World J Gastroenterol. 2018;24:4086-4092 pubmed publisher
    Steroid 5β-reductase [aldo-keto reductase family 1 member D1 (AKR1D1)] is essential for bile acid biosynthesis...
  4. Yang F, He Y, Liu H, Tsuei J, Jiang X, Yang L, et al. All-trans retinoic acid regulates hepatic bile acid homeostasis. Biochem Pharmacol. 2014;91:483-9 pubmed publisher
    ..All-trans RA treatment reduced the gene expression levels of Cyp7a1, Cyp8b1, and Akr1d1, which are involved in bile acid synthesis...
  5. Penning T. The aldo-keto reductases (AKRs): Overview. Chem Biol Interact. 2015;234:236-46 pubmed publisher
    ..There are 15 human AKRs of these AKR1B1, AKR1C1-1C3, AKR1D1, and AKR1B10 have been implicated in diabetic complications, steroid hormone dependent malignancies, bile acid ..
  6. Gerritsen L, Milaneschi Y, Vinkers C, van Hemert A, van Velzen L, Schmaal L, et al. HPA Axis Genes, and Their Interaction with Childhood Maltreatment, are Related to Cortisol Levels and Stress-Related Phenotypes. Neuropsychopharmacology. 2017;42:2446-2455 pubmed publisher
    ..Gene-wide significant results were found for dexamethasone suppression (CYP11A1, CYP17A1, POU1F1, AKR1D1), hippocampal volume (CYP17A1, CYP11A1, HSD3B2, PROP1, AVPRA1, SRD5A1), amygdala volume (POMC, CRH, HSD3B2), and ..
  7. Williams S, Hsu F, Keene K, Chen W, Nelson S, Southerland A, et al. Shared genetic susceptibility of vascular-related biomarkers with ischemic and recurrent stroke. Neurology. 2016;86:351-9 pubmed publisher
    ..14 × 10(-9)) in 2,100 VISP participants. We discovered a novel association for CRP level in the AKR1D1 locus (rs2589998, p = 7...
  8. Penning T. Single-molecule enzymology of steroid transforming enzymes: Transient kinetic studies and what they tell us. J Steroid Biochem Mol Biol. 2016;161:5-12 pubmed publisher
    ..We use examples from the hydroxysteroid dehydrogenases (AKR1Cs) and human steroid 5β-reductase (AKR1D1) to illustrate the utility of the approach, which are members of the aldo-keto reductase (AKR) superfamily.
  9. Tanner J, Prasad B, Claw K, Stapleton P, Chaudhry A, Schuetz E, et al. Predictors of Variation in CYP2A6 mRNA, Protein, and Enzyme Activity in a Human Liver Bank: Influence of Genetic and Nongenetic Factors. J Pharmacol Exp Ther. 2017;360:129-139 pubmed
    ..factors, we quantified levels of CYP2A6, cytochrome P450 oxidoreductase (POR), and aldo-keto reductase 1D1 (AKR1D1) mRNA, and CYP2A6 and POR proteins...

More Information


  1. Haznedaroglu I, Malkan U. Local bone marrow renin-angiotensin system in the genesis of leukemia and other malignancies. Eur Rev Med Pharmacol Sci. 2016;20:4089-4111 pubmed
    ..Most of the RAS molecules including ACE, ACE2, AGT, AGTR1, AGTR2, AKR1C4, AKR1D1, ANPEP, ATP6AP2, CMA1, CPA3, CTSA, CTSD, CTSG, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, DPP3, EGFR, ENPEP, ..
  2. Di Costanzo L, Drury J, Christianson D, Penning T. Structure and catalytic mechanism of human steroid 5beta-reductase (AKR1D1). Mol Cell Endocrinol. 2009;301:191-8 pubmed publisher
    ..We have reported the structures of an AKR1D1-NADP(+) binary complex, and AKR1D1-NADP(+)-cortisone, AKR1D1-NADP(+)-progesterone and AKR1D1-NADP(+)-testosterone ..
  3. Mindnich R, Drury J, Penning T. The effect of disease associated point mutations on 5?-reductase (AKR1D1) enzyme function. Chem Biol Interact. 2011;191:250-4 pubmed publisher
    ..The human enzyme, AKR1D1, plays an essential role in bile-acid biosynthesis since the 5?-configuration is required for the emulsifying ..
  4. Chen M, Jin Y, Penning T. In-Depth Dissection of the P133R Mutation in Steroid 5β-Reductase (AKR1D1): A Molecular Basis of Bile Acid Deficiency. Biochemistry. 2015;54:6343-51 pubmed publisher
    Human steroid-5β-reductase (aldo-keto reductase 1D1, AKR1D1) stereospecifically reduces Δ(4)-3-ketosteroids to 5β-dihydrosteroids and is essential for steroid hormone metabolism and bile acid biosynthesis...
  5. Chen M, Drury J, Christianson D, Penning T. Conversion of human steroid 5β-reductase (AKR1D1) into 3β-hydroxysteroid dehydrogenase by single point mutation E120H: example of perfect enzyme engineering. J Biol Chem. 2012;287:16609-22 pubmed publisher
    Human aldo-keto reductase 1D1 (AKR1D1) and AKR1C enzymes are essential for bile acid biosynthesis and steroid hormone metabolism...
  6. Rizner T, Penning T. Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism. Steroids. 2014;79:49-63 pubmed publisher
    Human aldo-keto reductases AKR1C1-AKR1C4 and AKR1D1 play essential roles in the metabolism of all steroid hormones, the biosynthesis of neurosteroids and bile acids, the metabolism of conjugated steroids, and synthetic therapeutic ..
  7. Chen M, Penning T. 5?-Reduced steroids and human ?(4)-3-ketosteroid 5?-reductase (AKR1D1). Steroids. 2014;83:17-26 pubmed publisher
    ..In humans there is only a single 5?-reductase gene AKR1D1, which encodes ?(4)-3-ketosteroid-5?-reductase (AKR1D1)...
  8. Steen N, Tesli M, Kähler A, Methlie P, Hope S, Barrett E, et al. SRD5A2 is associated with increased cortisol metabolism in schizophrenia spectrum disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:1500-6 pubmed publisher
    ..A total of 102 single nucleotide polymorphisms (SNPs) in the SRD5A1, SRD5A2, AKR1D1, HSD11B1 and HSD11B2 genes were genotyped, and significant SNPs analyzed in the sub-sample...
  9. Charbonneau A, Luu The V. Assignment of steroid 5beta-reductase (SRD5B1) and its pseudogene (SRD5BP1) to human chromosome bands 7q32-->q33 and 1q23-->q25, respectively, by in situ hybridization. Cytogenet Cell Genet. 1999;84:105-6 pubmed
  10. Chaudhry A, Thirumaran R, Yasuda K, Yang X, Fan Y, Strom S, et al. Genetic variation in aldo-keto reductase 1D1 (AKR1D1) affects the expression and activity of multiple cytochrome P450s. Drug Metab Dispos. 2013;41:1538-47 pubmed publisher
    ..analysis was previously used to identify a cytochrome P450 (P450) gene subnetwork with Aldo-keto reductase 1D1 (AKR1D1) as a key regulatory driver of this subnetwork...
  11. Valanejad L, Ghareeb M, Shiffka S, Nadolny C, Chen Y, Guo L, et al. Dysregulation of ?4-3-oxosteroid 5?-reductase in diabetic patients: Implications and mechanisms. Mol Cell Endocrinol. 2018;470:127-141 pubmed publisher
    Aldo-keto reductase family 1 member D1 (AKR1D1) is a ?4-3-oxosteroid 5?-reductase required for bile acid synthesis and steroid hormone metabolism...
  12. Jin Y, Chen M, Penning T. Rate of steroid double-bond reduction catalysed by the human steroid 5?-reductase (AKR1D1) is sensitive to steroid structure: implications for steroid metabolism and bile acid synthesis. Biochem J. 2014;462:163-71 pubmed publisher
    Human AKR1D1 (steroid 5?-reductase/aldo-keto reductase 1D1) catalyses the stereospecific reduction of double bonds in ?4-3-oxosteroids, a unique reaction that introduces a 90° bend at the A/B ring fusion to yield 5?-dihydrosteroids...
  13. Morgan N, Hartley J, Setchell K, Simpson M, Brown R, Tee L, et al. A combination of mutations in AKR1D1 and SKIV2L in a family with severe infantile liver disease. Orphanet J Rare Dis. 2013;8:74 pubmed publisher
    ..A novel homozygous frameshift germline mutation (c.587delG) in the AKR1D1 gene; which encodes the enzyme Δ 4-3-oxosteroid 5β-reductase that is required for synthesis of primary bile ..
  14. Drury J, Mindnich R, Penning T. Characterization of disease-related 5beta-reductase (AKR1D1) mutations reveals their potential to cause bile acid deficiency. J Biol Chem. 2010;285:24529-37 pubmed publisher
    ..b>AKR1D1 (aldo-keto reductase 1D1) is the only known human enzyme that stereo-specifically reduces the Delta(4) double bond ..
  15. Faucher F, Cantin L, Luu The V, Labrie F, Breton R. Crystal structures of human Delta4-3-ketosteroid 5beta-reductase (AKR1D1) reveal the presence of an alternative binding site responsible for substrate inhibition. Biochemistry. 2008;47:13537-46 pubmed publisher
    The 5beta-reductases (AKR1D1-3) are unique enzymes able to catalyze efficiently and in a stereospecific manner the 5beta-reduction of the C4-C5 double bond found in Delta4-3-ketosteroids, including steroid hormones and bile acids ..
  16. Chen M, Jin Y, Penning T. The rate-determining steps of aldo-keto reductases (AKRs), a study on human steroid 5β-reductase (AKR1D1). Chem Biol Interact. 2015;234:360-5 pubmed publisher
    ..Using human steroid 5β-reductase (AKR1D1) as a representative enzyme, the influence of substrate structure on the rate-limiting steps of AKR catalysis has ..
  17. Di Costanzo L, Drury J, Penning T, Christianson D. Crystal structure of human liver Delta4-3-ketosteroid 5beta-reductase (AKR1D1) and implications for substrate binding and catalysis. J Biol Chem. 2008;283:16830-9 pubmed publisher
    b>AKR1D1 (steroid 5beta-reductase) reduces all Delta(4)-3-ketosteroids to form 5beta-dihydrosteroids, a first step in the clearance of steroid hormones and an essential step in the synthesis of all bile acids...
  18. Charbonneau A, The V. Genomic organization of a human 5beta-reductase and its pseudogene and substrate selectivity of the expressed enzyme. Biochim Biophys Acta. 2001;1517:228-35 pubmed
    ..Our results thus open an opportunity for studying the new role of 5beta-reductase in the formation of a new type of active steroids. ..
  19. Sumazaki R, Nakamura N, Shoda J, Kurosawa T, Tohma M. Gene analysis in delta 4-3-oxosteroid 5 beta-reductase deficiency. Lancet. 1997;349:329 pubmed
  20. Kondo K, Kai M, Setoguchi Y, Eggertsen G, Sjoblom P, Setoguchi T, et al. Cloning and expression of cDNA of human delta 4-3-oxosteroid 5 beta-reductase and substrate specificity of the expressed enzyme. Eur J Biochem. 1994;219:357-63 pubmed
    ..The substrate specificity of the human enzyme is considerably narrower than that of the rat enzyme, and the enzyme seems to be more important for bile acid biosynthesis than for metabolism of steroid hormones. ..
  21. Goes F, Hamshere M, Seifuddin F, Pirooznia M, Belmonte Mahon P, Breuer R, et al. Genome-wide association of mood-incongruent psychotic bipolar disorder. Transl Psychiatry. 2012;2:e180 pubmed publisher
    ..The results of our polygenic analysis provides support for a modest degree of genetic overlap between BP with MICP and SZ, highlighting that phenotypic correlations across syndromes may be due to the influence of polygenic risk factors. ..
  22. Chen M, Drury J, Penning T. Substrate specificity and inhibitor analyses of human steroid 5?-reductase (AKR1D1). Steroids. 2011;76:484-90 pubmed publisher
    ..In the present study, we systematically determined the substrate specificity of homogeneous human recombinant AKR1D1 using C18, C19, C21, and C27 ?(4)-ketosteroids and assessed the pH-rate dependence of the enzyme...
  23. Panagopoulos I, Mertens F. Characterization of the human CREB3L2 gene promoter. Oncol Rep. 2009;21:615-24 pubmed
    ..its promoter region, showing that it is asymmetrically bidirectional, also driving the expression of a variant of AKR1D1. It has a CRE binding site which is conserved among mammalians; removal or alteration of it resulted in reduced ..
  24. Lee W, Lukacik P, Guo K, Ugochukwu E, Kavanagh K, Marsden B, et al. Structure-activity relationships of human AKR-type oxidoreductases involved in bile acid synthesis: AKR1D1 and AKR1C4. Mol Cell Endocrinol. 2009;301:199-204 pubmed publisher
    ..of bile acids by catalyzing the NADP(H) dependent reduction of 3-keto groups (AKR1C4) and Delta4 double bonds (AKR1D1) of oxysterol precursors...
  25. Xu C, Zhang D, Wu Y, Tian X, Pang Z, Li S, et al. A genome-wide association study of cognitive function in Chinese adult twins. Biogerontology. 2017;18:811-819 pubmed publisher
    ..00 × 10-6), FGFR1OP2 (P = 6.00 × 10-6), and AKR1D1 (P = 2.30 × 10-5)...
  26. Sheehan P, Rice G, Moses E, Brennecke S. 5 Beta-dihydroprogesterone and steroid 5 beta-reductase decrease in association with human parturition at term. Mol Hum Reprod. 2005;11:495-501 pubmed
    ..These data are consistent with a possible role for 5betaDHP in the onset of spontaneous human labour. Further studies exploring this hitherto unrecognized endocrinological pathway are indicated. ..
  27. Ueki I, Kimura A, Chen H, Yorifuji T, Mori J, Itoh S, et al. SRD5B1 gene analysis needed for the accurate diagnosis of primary 3-oxo-Delta4-steroid 5beta-reductase deficiency. J Gastroenterol Hepatol. 2009;24:776-85 pubmed publisher
    ..To determine whether 3-oxo-Delta(4)-steroid 5beta-reductase (SRD5B1) gene analysis is required for the accurate diagnosis of 3-oxo-Delta(4)-steroid 5beta-reductase deficiency, we ..
  28. Cheng Y, Guo L, Deng M, Song Y. [Clinical feature and genetic analysis of a family affected by congenital bile acid synthesis defect type 2: identification of 2 novel mutations in AKR1D1 gene]. Zhongguo Dang Dai Er Ke Za Zhi. 2017;19:734-740 pubmed
    ..bile acid synthesis defect type 2 (CBAS2) is an autosomal recessive disorder caused by biallelic mutations of AKR1D1 gene, which encodes the ?4-3-oxo-steroid 5?-reductase...