Gene: AKR1C4

1109
3-alpha-HSD|C11|CDR|CHDR|DD-4|DD4|HAKRA
aldo-keto reductase family 1 member C4
protein-coding
10p15.1
Ensembl:ENSG00000198610 MIM:600451 Vega:OTTHUMG00000017591 UniprotKB:P17516
NG_031872.1
PubMed
ND
1   
NA (AD)  NA (ND)   (Frontal_Cortex)
3.921e-1 (AD)  4.576e-1 (ND)

DNA Methylation

Probe Locus(GRCh37) Gene Region p-val Trait PubMed ID
cg20130789chr10:5260740AKR1C43'UTR6.041e-5Alcohol use disorders26763658

Gene Expression in Different Tissues

Temporal and Spatial Expressions (BrainSpan)

Footnote:
SC: sub-cortical regions; SM: sensory-motor regions; FC: frontal cortex; and TP: temporal-parietal cortex
ST1: fetal (13 - 26 postconception weeks), ST2: early infancy to late childhood (4 months to 11 years), and ST3: adolescence to adulthood (13 - 23 years)
The bar shown representes average value of the expressions.

Top Co-expressed Genes in Brain-Frontal Cortex (BA9) (GTEx v7)

Top 10 positively co-expressed genes

Gene Symbol Pearson Correlation Coefficient
XAGE1A0.457
OPN1LW0.45
LINC004230.434
DPPA50.429
HIST1H2AB0.414
WFDC110.394
BSPH10.387
TRIM550.369
NUP210L0.36
C11orf860.35

Top 10 negatively co-expressed genes

Gene Symbol Pearson Correlation Coefficient
PGA5-0.211
SHBG-0.207
MAMSTR-0.193
DCDC2B-0.193
AP1M2-0.187
SPATC1L-0.185
HES5-0.184
NBPF6-0.181
FJX1-0.181
IHH-0.178

Drugs/Compounds

ID Drug Name Drug Type CAS Num Status Role
DB00157NADHSmall Molecule58-68-4Approved|NutraceuticalTarget
ID Drug Name Action PubMed
C0252051,10-phenanthroline"1,10-phenanthroline results in decreased activity of AKR1C4 protein"12604236
C0552381-chloro-4-(2,2-dichloro-1-(4-chlorophenyl)ethenyl)-3-(methylsulfonyl)benzene"1-chloro-4-(2,2-dichloro-1-(4-chlorophenyl)ethenyl)-3-(methylsulfonyl)benzene results in increased expression of AKR1C4 mRNA"23333615
C0165151-indanolAKR1C4 protein results in increased oxidation of 1-indanol8543560
C0181563',3'',5',5''-tetrabromophenolphthalein"3',3'',5',5''-tetrabromophenolphthalein results in decreased activity of AKR1C4 protein"12604236
C0326424-aminophenylarsenoxide4-aminophenylarsenoxide binds to AKR1C4 protein26598702
C0326424-aminophenylarsenoxidearsenic trioxide inhibits the reaction [4-aminophenylarsenoxide binds to AKR1C4 protein]26598702
C0381934-hydroxybenzoic acid4-hydroxybenzoic acid analog results in decreased activity of AKR1C4 protein27163852
C0165834-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanoneAKR1C4 protein results in increased metabolism of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone11306090
C0165834-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanoneAKR1C4 protein results in increased reduction of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone28257955
C0165834-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanonedrospirenone inhibits the reaction [AKR1C4 protein results in increased reduction of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone]28257955
C0165834-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanoneProgesterone inhibits the reaction [AKR1C4 protein results in increased reduction of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone]28257955
C0165834-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanoneTestosterone inhibits the reaction [AKR1C4 protein results in increased reduction of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone]28257955
C0459935-dihydrocortisoneAKR1C4 protein results in increased reduction of 5-dihydrocortisone8543560
C4546875-dihydrodeoxycorticosteroneAKR1C4 protein affects the reduction of 5-dihydrodeoxycorticosterone12604236
C0053999,10-phenanthrenequinone"AKR1C4 protein results in increased reduction of 9,10-phenanthrenequinone"21851338
C0053999,10-phenanthrenequinone"AKR1C4 protein results in increased reduction of and affects the activity of 9,10-phenanthrenequinone"21910479
C0313909-cis-retinalAKR1C4 protein results in increased reduction of 9-cis-retinal21851338
D000082AcetaminophenAcetaminophen results in decreased expression of AKR1C4 mRNA29067470
D016604Aflatoxin B1Aflatoxin B1 affects the expression of AKR1C4 protein20106945
D016604Aflatoxin B1Aflatoxin B1 results in decreased expression of AKR1C4 mRNA22100608|2715375
D000447AldehydesAldehydes results in decreased expression of AKR1C4 mRNA25014914
D0435825-alpha-DihydroprogesteroneAKR1C4 protein affects the reduction of 5-alpha-Dihydroprogesterone12604236
D00409220-alpha-DihydroprogesteroneAKR1C4 protein results in increased chemical synthesis of 20-alpha-Dihydroprogesterone11158055
D013196DihydrotestosteroneAKR1C4 protein results in increased metabolism of Dihydrotestosterone14672942
D013196DihydrotestosteroneAKR1C4 protein results in increased reduction of Dihydrotestosterone11158055|8543560
D013196DihydrotestosteroneFlufenamic Acid inhibits the reaction [AKR1C4 protein results in increased metabolism of Dihydrotestosterone]14672942
D015113Androstane-3,17-diol"AKR1C4 protein results in increased chemical synthesis of Androstane-3,17-diol"11158055
C006632arsenic trioxidearsenic trioxide inhibits the reaction [4-aminophenylarsenoxide binds to AKR1C4 protein]26598702
D001553BenzbromaroneBenzbromarone results in decreased activity of AKR1C4 protein12604236
C017228benzo(a)pyrene 7,8-dihydrodiol"[AKR1C4 protein co-treated with NADP] results in increased oxidation of and affects the activity of benzo(a)pyrene 7,8-dihydrodiol"21910479
C076588benzo(a)pyrene-7,8-dione"[AKR1C4 protein co-treated with NADP] results in increased reduction of and affects the activity of benzo(a)pyrene-7,8-dione"21910479
C076588benzo(a)pyrene-7,8-dione"AKR1C4 protein results in increased chemical synthesis of benzo(a)pyrene-7,8-dione"22394341
D001564Benzo(a)pyreneAKR1C4 protein results in increased metabolism of Benzo(a)pyrene22394341
D004958EstradiolEstradiol results in decreased expression of AKR1C4 mRNA20106945
C006780bisphenol Abisphenol A results in decreased expression of AKR1C4 mRNA25181051
D019819BudesonideAKR1C4 protein results in increased reduction of Budesonide21276783
D019819BudesonideBudesonide inhibits the reaction [AKR1C4 protein results in increased reduction of tetralol]21276783
C018475butyraldehydebutyraldehyde results in decreased expression of AKR1C4 mRNA26079696
C055494caffeic acid phenethyl estercaffeic acid phenethyl ester results in decreased activity of AKR1C4 protein27163852
D002635Chenodeoxycholic AcidChenodeoxycholic Acid results in decreased expression of AKR1C4 mRNA27174168
D007631ChlordeconeAKR1C4 protein results in increased reduction of Chlordecone11158055|2427522
C100187chloropicrinchloropicrin results in increased expression of AKR1C4 mRNA26352163
D019826Cholic AcidAKR1C4 protein results in increased abundance of Cholic Acid3468121
D002911ChrysenesAKR1C4 protein results in increased reduction of and affects the activity of Chrysenes21910479
C005522cloxazolamcloxazolam results in decreased activity of AKR1C4 protein12604236
D009249NADP"[AKR1C4 protein co-treated with NADP] results in increased oxidation of and affects the activity of benzo(a)pyrene 7,8-dihydrodiol"21910479
D009249NADP"[AKR1C4 protein co-treated with NADP] results in increased reduction of and affects the activity of benzo(a)pyrene-7,8-dione"21910479
D009249NADPNADP inhibits the reaction [AKR1C4 protein results in increased oxidation of Hydroxysteroids]14672942
C065868COSS-86 protocolAKR1C4 results in decreased susceptibility to COSS-86 protocol14767549
C010092cresolphthaleincresolphthalein results in decreased activity of AKR1C4 protein12604236
D016572CyclosporineCyclosporine results in decreased expression of AKR1C4 mRNA20106945
D003975DiazepamDiazepam results in decreased activity of AKR1C4 protein11995921|1260423
D002945Cisplatin[Cisplatin co-treated with jinfukang] results in increased expression of AKR1C4 mRNA27392435
D004101DihydroxydihydrobenzopyrenesAKR1C4 protein results in increased reduction of and affects the activity of Dihydroxydihydrobenzopyrenes21910479
C035144drospirenonedrospirenone inhibits the reaction [AKR1C4 protein results in increased reduction of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone]28257955
D004967EstrogensAKR1C4 gene polymorphism affects the susceptibility to [Estrogens co-treated with Medroxyprogesterone Acetate]15987428
D005439Flufenamic AcidFlufenamic Acid inhibits the reaction [AKR1C4 protein results in increased metabolism of Dihydrotestosterone]14672942
D005439Flufenamic AcidFlufenamic Acid results in decreased activity of AKR1C4 protein12604236
C007734flunisolideAKR1C4 protein results in increased reduction of flunisolide21276783
C007734flunisolideflunisolide inhibits the reaction [AKR1C4 protein results in increased reduction of tetralol]21276783
D005445FlunitrazepamFlunitrazepam results in decreased activity of AKR1C4 protein11995921
D017965gamma-Linolenic Acidgamma-Linolenic Acid results in increased expression of AKR1C4 mRNA20664735
D006034Glycyrrhetinic AcidGlycyrrhetinic Acid results in decreased activity of AKR1C4 protein12604236
D006589HexestrolHexestrol results in decreased activity of AKR1C4 protein12604236
D006830Hydralazine[Hydralazine co-treated with Valproic Acid] results in increased expression of AKR1C4 mRNA17183730
D006854HydrocortisoneAKR1C4 protein results in increased reduction of Hydrocortisone21276783
D006914HydroxysteroidsAKR1C4 protein results in increased abundance of Hydroxysteroids14672942
D006914HydroxysteroidsAKR1C4 protein results in increased oxidation of Hydroxysteroids14672942
D006914HydroxysteroidsNADP inhibits the reaction [AKR1C4 protein results in increased oxidation of Hydroxysteroids]14672942
D007213IndomethacinIndomethacin results in decreased activity of AKR1C4 protein12604236
D007220Industrial WasteIndustrial Waste results in decreased expression of AKR1C4 mRNA26055946
C544151jinfukang[Cisplatin co-treated with jinfukang] results in increased expression of AKR1C4 mRNA27392435
C544151jinfukangjinfukang results in increased expression of AKR1C4 mRNA27392435
D008469Meclofenamic AcidMeclofenamic Acid results in decreased activity of AKR1C4 protein27163852
D008472MedazepamMedazepam results in decreased activity of AKR1C4 protein12604236
D017258Medroxyprogesterone AcetateAKR1C4 gene polymorphism affects the susceptibility to [Estrogens co-treated with Medroxyprogesterone Acetate]15987428
D017258Medroxyprogesterone AcetateMedroxyprogesterone Acetate results in decreased activity of AKR1C4 protein12604236
D009567NitrazepamNitrazepam results in decreased activity of AKR1C4 protein11995921
C570897NSC668394NSC668394 results in increased expression of AKR1C4 mRNA27137931
C016627octyl gallateoctyl gallate results in decreased activity of AKR1C4 protein27163852
C036006oxcarbazepineAKR1C4 protein results in increased reduction of oxcarbazepine25063510
D052638Particulate MatterParticulate Matter results in increased expression of AKR1C4 mRNA24769257
C046012pentanalpentanal results in decreased expression of AKR1C4 mRNA26079696
D020113PhenolphthaleinPhenolphthalein results in decreased activity of AKR1C4 protein12604236|8543560
C042125phenolphthalein diphosphatephenolphthalein diphosphate results in decreased activity of AKR1C4 protein8543560
C048693phenolphthalein monophosphatephenolphthalein monophosphate results in decreased activity of AKR1C4 protein8543560
D011278PregnanesAKR1C4 protein affects the metabolism of Pregnanes metabolite12604236
D011280PregnanoloneAKR1C4 protein affects the metabolism of Pregnanolone12604236
D011374ProgesteroneProgesterone results in increased expression of AKR1C4 mRNA23012394
D011374ProgesteroneAKR1C4 gene polymorphism results in decreased abundance of Progesterone21570127
D011374ProgesteroneAKR1C4 protein affects the abundance of Progesterone21570127
D011374ProgesteroneAKR1C4 protein affects the metabolism of Progesterone15987428
D011374ProgesteroneAKR1C4 protein results in increased reduction of Progesterone11158055
D011374ProgesteroneProgesterone results in increased expression of AKR1C4 mRNA19690047
D011374ProgesteroneProgesterone inhibits the reaction [AKR1C4 protein results in increased reduction of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone]28257955
C005556propionaldehydepropionaldehyde results in decreased expression of AKR1C4 mRNA26079696
D012822Silicon DioxideSilicon Dioxide analog results in decreased expression of AKR1C4 mRNA25895662
D013739TestosteroneTestosterone inhibits the reaction [AKR1C4 protein results in increased reduction of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone]28257955
D013749TetrachlorodibenzodioxinTetrachlorodibenzodioxin results in increased expression of AKR1C4 mRNA20106945
C009413tetrahydrodeoxycorticosteroneAKR1C4 protein affects the oxidation of tetrahydrodeoxycorticosterone12604236
C019106tetralolAKR1C4 protein affects the oxidation of tetralol12604236
C019106tetralolBudesonide inhibits the reaction [AKR1C4 protein results in increased reduction of tetralol]21276783
C019106tetralolflunisolide inhibits the reaction [AKR1C4 protein results in increased reduction of tetralol]21276783
D013944ThymolphthaleinThymolphthalein results in decreased activity of AKR1C4 protein8543560
D014520UrethaneUrethane results in decreased expression of AKR1C4 mRNA28818685
D014635Valproic Acid[Hydralazine co-treated with Valproic Acid] results in increased expression of AKR1C4 mRNA17183730
D014635Valproic AcidValproic Acid results in decreased methylation of AKR1C4 gene29154799

GO/Pathway

GO ID GO Term Qualifier Evidence PubMed
GO:0001758retinal dehydrogenase activity-IDA21851338  
GO:0004032alditol:NADP+ 1-oxidoreductase activity-IBA21873635  
GO:0004033aldo-keto reductase (NADP) activity-TAS-  
GO:0005496steroid binding-IBA21873635  
GO:0008106alcohol dehydrogenase (NADP+) activity-IBA21873635  
GO:0009055electron transfer activity-TAS8172617  
GO:0015125bile acid transmembrane transporter activity-TAS8172617  
GO:0016229steroid dehydrogenase activity-IBA21873635  
GO:0016491oxidoreductase activity-IBA21873635  
GO:0016655oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor-IDA20837989  
GO:0032052bile acid binding-IBA21873635  
GO:0047023androsterone dehydrogenase activity-IBA21873635  
GO:0047023androsterone dehydrogenase activity-IDA21851338  
GO:0047086ketosteroid monooxygenase activity-IBA21873635  
GO:0047743chlordecone reductase activity-IEA-  
GO ID GO Term Qualifier Evidence PubMed
GO:0001523retinoid metabolic process-TAS-  
GO:0006693prostaglandin metabolic process-IBA21873635  
GO:0006699bile acid biosynthetic process-TAS-  
GO:0008202steroid metabolic process-IBA21873635  
GO:0008202steroid metabolic process-TAS8274401  
GO:0008207C21-steroid hormone metabolic process-IBA21873635  
GO:0008209androgen metabolic process-TAS7650035  
GO:0015721bile acid and bile salt transport-TAS8172617  
GO:0022900electron transport chain-IEA-  
GO:0042448progesterone metabolic process-IBA21873635  
GO:0044597daunorubicin metabolic process-IBA21873635  
GO:0044597daunorubicin metabolic process-IMP20837989  
GO:0044598doxorubicin metabolic process-IBA21873635  
GO:0044598doxorubicin metabolic process-IMP20837989  
GO:0071395cellular response to jasmonic acid stimulus-IDA19487289  
GO ID GO Term Qualifier Evidence PubMed
GO:0005737cytoplasm-TAS2187532  
GO:0005829cytosol-IBA21873635  
GO:0005829cytosol-TAS-  
GO:0070062extracellular exosome-HDA23533145  
KEGG ID KEGG Term
hsa00120Primary bile acid biosynthesis
hsa00140Steroid hormone biosynthesis
hsa00980Metabolism of xenobiotics by cytochrome P450
hsa01100Metabolic pathways
Reactome ID Reactome Term Evidence
R-HSA-1430728MetabolismTAS
R-HSA-162582Signal TransductionTAS
R-HSA-192105Synthesis of bile acids and bile saltsTAS
R-HSA-193368Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterolTAS
R-HSA-193775Synthesis of bile acids and bile salts via 24-hydroxycholesterolTAS
R-HSA-193807Synthesis of bile acids and bile salts via 27-hydroxycholesterolTAS
R-HSA-194068Bile acid and bile salt metabolismTAS
R-HSA-196854Metabolism of vitamins and cofactorsTAS
R-HSA-2187338Visual phototransductionTAS
R-HSA-372790Signaling by GPCRTAS
R-HSA-388396GPCR downstream signallingTAS
R-HSA-418594G alpha (i) signalling eventsTAS
R-HSA-556833Metabolism of lipidsTAS
R-HSA-6806667Metabolism of fat-soluble vitaminsTAS
R-HSA-8957322Metabolism of steroidsTAS
R-HSA-975634Retinoid metabolism and transportTAS

Interactions (STRING v10.5, Interaction Score >= 0.400)

Publications (Co-occurrence of gene symbol strings and ANCO-Dependence terms)

PMID Title (Year) Author Journal
28743530Different inhibitory potential of sex hormones on NNK detoxification in vitro: A possible explanation for gender-specific lung cancer risk. (2017 Oct 1)Stapelfeld CCancer Lett