AKR1C4

Aldo-keto reductase family 1 member C4, also known as 3α-Hydroxysteroid dehydrogenase type 1 (3α-HSD1),^[5][6][7] is an enzyme that in humans is encoded by the AKR1C4 gene.^[8][9][10] It is known to be necessary for the synthesis of the endogenous neurosteroids allopregnanolone, tetrahydrodeoxycorticosterone, and 3α-androstanediol. It is also known to catalyze the reversible conversion of 3α-androstanediol (5α-androstane-3α,17β-diol) to dihydrotestosterone (DHT, 5α-androstan-17β-ol-3-one) and vice versa.^[11]

AKR1C4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2FVL
Identifiers
Aliases	AKR1C4, 3-alpha-HSD, C11, CDR, CHDR, DD-4, DD4, HAKRA, aldo-keto reductase family 1, member C4, aldo-keto reductase family 1 member C4
External IDs	OMIM: 600451; MGI: 1933427; HomoloGene: 84695; GeneCards: AKR1C4; OMA:AKR1C4 - orthologs
EC number	1.1.1.225
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10p15.1 Start 5,195,462 bp[1] End 5,218,949 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13 A1|13 2.48 cM Start 4,484,305 bp[2] End 4,507,876 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver gallbladder testicle islet of Langerhans duodenum jejunal mucosa gonad granulocyte Achilles tendon muscle of thigh Top expressed in left lobe of liver gallbladder bronchus urethra lobar bronchus Lumen of fundus of stomach abdominal aorta vasculature of trunk proximal convoluted tubule sexually immature organism More reference expression data BioGPS More reference expression data
Gene ontology Molecular function retinal dehydrogenase activity aldo-keto reductase (NADP) activity bile acid transmembrane transporter activity oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor chlordecone reductase activity electron transfer activity oxidoreductase activity androsterone dehydrogenase activity alditol:NADP+ 1-oxidoreductase activity alcohol dehydrogenase (NADP+) activity steroid dehydrogenase activity ketosteroid monooxygenase activity Cellular component cytoplasm cytosol extracellular exosome Biological process cellular response to jasmonic acid stimulus steroid metabolic process daunorubicin metabolic process doxorubicin metabolic process androgen metabolic process retinoid metabolic process bile acid and bile salt transport bile acid biosynthetic process electron transport chain prostaglandin metabolic process progesterone metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1109 83702 Ensembl ENSG00000198610 ENSMUSG00000021210 UniProt P17516 P70694 RefSeq (mRNA) NM_001818 NM_030611 RefSeq (protein) NP_001809 NP_085114 Location (UCSC) Chr 10: 5.2 – 5.22 Mb Chr 13: 4.48 – 4.51 Mb PubMed search [3] [4]
Wikidata
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Function

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 10p15-p14 on chromosome 10.^[10]

Clinical significance

Various antidepressants, including the SSRIs fluoxetine, fluvoxamine, sertraline, and paroxetine, the SNRI venlafaxine, and mirtazapine, have been found to activate certain isoforms of the 3α-hydroxysteroid dehydrogenase, resulting in a selective facilitation of 5α-dihydroprogesterone conversion into allopregnanolone. This action has been implicated in their effectiveness in affective disorders, and has resulted in them being described as selective brain steroidogenic stimulants (SBSSs).^[12][13][14]

Isozymes

HGNC Gene Symbol	Enzyme Name Aliases[15]
AKR1C1	aldo-keto reductase family 1 member C1; 20α-hydroxysteroid dehydrogenase
AKR1C2	aldo-keto reductase family 1 member C2; 3α-hydroxysteroid dehydrogenase type 3
AKR1C3	aldo-keto reductase family 1 member C3; 3α-hydroxysteroid dehydrogenase type 2; 17β-hydroxysteroid dehydrogenase type 5; HSD17B5
AKR1C4	aldo-keto reductase family 1 member C4; 3α-hydroxysteroid dehydrogenase type 1

See also

• Steroidogenic enzyme
• 3α-Hydroxysteroid dehydrogenase
• 3β-hydroxysteroid dehydrogenase