AKR1C3

Gene Information
 
Gene Symbol
AKR1C3
 
Aliases
DD3, DDX, HA1753, HAKRB, HAKRe, HSD17B5, PGFS, hluPGFS
 
Entrez Gene ID
 
Gene Name
Aldo-keto reductase family 1, member C3
 
Chromosomal Location
10p15-p14
 
HGNC ID
386
 
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 reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ), and the oxidation of 9alpha,11beta-PGF2 to PGD2. It may play an important role in the pathogenesis of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. Three transcript variants encoding different isoforms have been found for this gene. (provided by RefSeq, Dec 2011)
 
GeneCards ID
 
UniGene
 
RefSeq DNA
 
RefSeq mRNA
  e!Ensembl
Gene
Transcript  
Protein

Gene Ontology (GO)

GO ID Ontology Definition Evidence Reference
GO:0006693 Biological process Prostaglandin metabolic process TAS 9792917
GO:0007186 Biological process G-protein coupled receptor signaling pathway IDA 18508192
GO:0007584 Biological process Response to nutrient IEP 19007764
GO:0008584 Biological process Male gonad development IEP 19942269
GO:0009267 Biological process Cellular response to starvation IEP 18641923
Protein Information
 
Protein Name
3-alpha hydroxysteroid dehydrogenase, type II, 3-alpha-HSD type II, brain, aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II), chlordecone reductase homolog HAKRb, dihydrodiol dehydrogenase 3, dihydrodiol dehydrogenase X, indanol dehydrogenase, prostaglandin F synthase, testosterone 17-beta-dehydrogenase 5, trans-1,2-dihydrobenzene-1,2-diol dehydrogenase, type IIb 3-alpha hydroxysteroid dehydrogenase
 
Function
Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone
 
Refseq Proteins
 
UniProt
 
InterPro
 
KEGG
 
OMIM

Associated Diseases

Diseases References
Hyperandrogenism 18692800, 17583494
Polycystic ovary syndrome (PCOS) 10923281, 17603492, 10207720, 9222646, 15855352, 17235527, 15331560, 15657373, 18812636, 22314079, 23685425, 22621829, 20504873, 21270326, 19240152, 17445806, 24040456, 22564702, 22575725, 23748472, 21853931, 22527903, 21827375, 20840271, 20130411, 20045799, 19549442, 18680073, 17141766, 16785159, 16600233, 16316841, 15853827, 15472214, 14671186, 12615821, 11836319, 19681917, 15717879, 15660727, 17420421, 7652727, 15208835, 16980199, 16334591, 18974244, 14764276, 17023708, 15159251, 9590566, 20001427, 19114407, 14976002, 9861517, 8462390, 1736105, 18309108, 17954428, 16506274, 14968294, 12627878, 18779682, 16581078, 9240771, 19138313, 16259222, 12957327, 16054467, 9100707, 17368007, 1457758, 7981184, 10707556, 9270410, 8856394, 12150695, 12692007, 19015938, 18775353, 18640389, 17873318, 17320517, 17183416, 17218834, 15998260, 15579783, 16820727, 16392771, 16319655, 14647894, 14553866, 11997182, 14739074, 12647277, 12408408, 12365467, 10821297, 10440591, 10374288, 8299479, 19149565, 7828781, 2065046, 19572942, 19421860, 19564534, 18927552, 18296327, 17826042, 17760500, 17259501, 16522281, 15075712, 12877091, 12702035, 12675638, 8949974, 19731182, 19164269, 17952838, 16839860, 15590982, 14626524, 12610050, 12540621, 12148078, 10024191, 8964200, 7782801, 20513276, 19369429, 19214921, 18772854, 16697386, 17181562, 15258201, 15047659, 8736268, 19218574, 17083810, 12042261, 9439531, 19947235, 11820995, 15073570, 18486583, 17119001, 17054989, 17341558, 19501863, 16034410, 17656599, 17726085, 18081728, 18381580, 18487287, 17416795, 19537932, 19190263, 17595259, 19003725, 17550959, 18641048, 19501859, 17003346, 18783798, 17875187, 18493106, 18397979, 17721906, 17492427, 20037278, 18052678, 18426837, 18584408, 17970534, 18796616, 18334592, 17890490, 17640906, 19369430, 19264371, 17618858, 17065684, 19215278, 18710473, 17456573, 20222849, 18426814, 17411394, 19088257, 17337499, 18199128, 22397743, 15886251, 20889251, 22068557, 8671472, 11600878, 10418705, 2350207, 11460890, 15638873, 15820714, 20011249, 20406953, 23678035, 24743397, 22238371, 23979790, 16551740, 24969481, 1387563, 1742627, 1327496, 17204352, 11173902, 18050673, 9187410, 10695479, 16039281, 10648020, 16126968, 15311550, 18600083, 20205861, 11567663, 14995993, 11567664, 14678868, 8060375, 11278457, 12728597, 16477805, 15919609, 15380459, 14963283, 14553864, 10208482, 10064006, 9843166, 19918669, 17850750, 12871373, 15080492, 11733024, 11179976, 11129405, 10520809, 10364094, 10980830, 9498632, 14605330, 12911596, 12719278, 12734779, 12195702, 11816701, 11522017, 11373350, 10798278, 9041098, 9005966, 16789641, 15988701, 11092431, 11057874, 10831181, 9734732, 9423801, 9198234, 18501910, 15820196, 14746139, 12891381, 11372681, 10452346, 9622268, 18624608, 17161063, 16128865, 12911589, 11588944, 11525072, 10417403, 9805421, 9161416, 9258409, 19889809, 18559377, 18593221, 16427606, 15630497, 14993864, 9048903, 9031456, 8831916, 18191049, 17014002, 15901895, 15379715, 12921488, 7698502, 7813812, 8241103, 19888787, 19132219, 16939632, 16091487, 15575342, 12723974, 12540956, 11197396, 15516780, 9496335, 15588467, 15333250, 20201644, 15705377, 15598692, 12923954, 16421614, 16087989, 11753584, 16613757, 16757549, 18274928, 17076827, 15080783, 10657556, 16123358, 17892761, 11739453, 18571785, 17322479, 18437347, 12706940, 18220627, 17903275, 14680981, 19652658, 16839844, 16235156, 14698276, 17171553, 16029943, 15893251, 10416955, 19378424, 11445664, 11287357, 19543691, 19774846, 19375766, 15728208, 18319319, 9506738, 12029003, 12205025, 12660878, 12823641, 16550566, 16891032, 20216410, 20228013, 20148136, 19923378, 19875356, 19768241, 18946782, 16835332, 16773588, 18202591, 18253163, 17357288, 17167506, 17172321, 17027526, 16472051, 16567539, 16030153, 18339973, 18093792, 18239554, 18195475, 17267401, 17229078, 16464856, 15999465, 15978151, 15381186, 15181027, 12917504, 12778364, 12690081, 10422520, 20371668, 20131064, 20464701, 16891995, 15633587, 15561970, 20432261, 19875708, 20075410, 19436757, 19455721, 18953360, 18397542, 18923185, 15645209, 15294059, 14555603, 12898289, 12970313, 12734774, 11854119, 11225716, 19747414, 24628003, 2080142, 15024892, 18377903, 16409817, 12450312, 9286726, 16849416, 8871183, 8728917, 10764686, 16293162, 18175742, 15928193, 11681808, 9186610, 19672469, 15968580, 15780823, 15772559, 15297806, 10665338, 8673927, 11465242, 8355419, 15978107, 10102708, 20088250, 12884639, 1736034, 17046548, 10663216, 8589788, 11209987, 10845889, 19861967, 17896948, 15853833, 15356668, 12601637, 11719834, 10225688, 18083357, 18278185, 8633110, 11358950, 16735799, 9707262, 10546030, 10867719, 18154661, 18675814, 11383921, 10780314, 10631643, 10554079, 9361687, 8403825, 20118711, 17045221, 16990563, 15841306, 15634264, 9472456, 2070877, 17113660, 1772997, 20508843, 19700047, 19408737, 17991133, 17208662, 9308762, 1719559, 18037477, 18239151, 17704301, 17896947, 17912155, 15186635, 12536349, 9859722, 9133556, 16507937, 15869613, 15554360, 10527036, 10487691, 9539185, 9102176, 8843179, 16483878, 14694215, 18457598, 9869004, 16353333, 19106381, 19728971, 15168018, 11788625, 16710733, 20004425, 9275503, 15642079, 12212367, 16261187, 16956689, 9457008, 1541675, 7714116, 8299435, 17044662, 10450832, 9539195, 19828932, 19373236, 17652221, 11229419, 10513036, 8432411, 20150900, 11213538, 9717889, 1986032, 2229287, 18769626, 17087855, 1425092, 20034369, 16821208, 14627747, 17212015, 18394132, 9486987, 11145111, 11250769, 17430682, 16498800, 16444171, 15788447, 12739017, 9578244, 8910101, 8117866, 1999488, 18839419, 18413211, 12377756, 11344187, 11288039, 9550536, 7674911, 7738205, 20046661, 18172342, 18082417, 17300718, 1579553, 19837931, 19043735, 19361458, 17972239, 17589594, 18059082, 17613807, 17264235, 17264953, 16277579, 16225463, 15599552, 15579189, 15072732, 10337870, 7980344, 20156355, 18794246, 17986714, 17636091, 17613800, 17020651, 17166107, 15671910, 17075121, 15258344, 14678864, 16222595, 10900666, 20021721, 10895282, 10722859, 16782141, 15793852, 17147067, 17485319, 12519870, 15202616, 17005171, 12027912, 17878255, 11931523, 16129731, 16986526, 10612449, 16135472, 15070944, 10678256, 8621024, 18651469, 17721641, 12580939, 18805913, 17872473, 9618121, 20029268, 19112726, 20113633, 10228114, 8621025, 10102052, 10215564, 11812752, 10193869, 15533361, 11527094, 10395194, 9763877, 9357929, 9144295, 19851106, 17212381, 16344847, 15220914, 14735482, 12805397, 9342538, 9380811, 20058257, 16491055, 16419701, 15909762, 12582470, 11068094, 10333369, 20011966, 17026484, 15790575, 11824502, 9750463, 14655844, 17979776, 16441233, 11673768, 11271782, 11024570, 10997652, 10703535, 15481773, 19182739, 16105937, 14726256, 11795261, 10523013, 10603674, 15759020, 12605342, 9768648, 9747103, 19915520, 19949425, 16786731, 16522234, 15976687, 12420652, 11259650, 11172704, 11022201, 9924798, 9287057, 9202122, 9100610, 8892415, 14715846, 15910756, 23350621, 16452543, 11218147, 9711997, 9385530, 8923878, 21039282, 18692800, 17940109, 17583494, 16263811
   
References
 
Primary:

Association of the 17-hydroxysteroid dehydrogenase type 5 gene polymorphism (-71A/G HSD17B5 SNP) with hyperandrogenemia in polycystic ovary syndrome (PCOS).

Marioli Dimitra J, Saltamavros Alexandros D, Vervita Vasiliki, Koika Vasiliki, Adonakis George, Decavalas George, Markou Kostas B, Georgopoulos Neoklis A
Division of Reproductive Endocrinology, University of Patras Medical School, University Hospital, Patras, Greece.
Fertil Steril. 2009 Aug;92(2):648-52. doi: 10.1016/j.fertnstert.2008.06.016. Epub
 
Supporting Literature:
PubMed ID Associated gene/s Associated condition Genetic Mutation Diagnostic Criteria Association with PCOS Ethnicity Conclusion
Testosterone 
PCOS 
(SNP)-71G 
Rotterdam criteria 
Related 
Caucasian, African-American, Hispanic, Asian (121 PCOS patients and 128 population controls ) 
SNP-71G in HSD17B5 is a functional polymorphism that may contribute to testosterone excess in a subset of PCOS patients. 
Testosterone, Follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH, and estradiol (E(2)) 
PCOS 
rs898611 
 
Related 
222 PCOS patients, 283 controls 
Our data suggest that there is no association of HSD17B6 and HSD17B5 variants with the occurrence of PCOS in the Chinese population, but the polymorphism of SNP rs898611 is associated with BMI in PCOS patients. 
Testosterone, Androstenedione 
PCOS, hyperandrogenemia 
71A/G HSD17B5 SNP, -71G HSD17B5 
Rotterdam criteria, NIH/NIHCD criteria 
Related 
150 caucasian Greek PCOS women with biochemical hyperandrogenism and chronic anovulation, 51 healthy control subjects 
The -71G HSD17B5 variant is not a major component of the molecular pathogenetic mechanisms of PCOS, although it might contribute to the severity of hyperandrogenemia in women with PCOS and biochemical hyperandrogenism 
Testosterone 
PCOS, hyperandrogenemia 
rs3763676, rs12529, rs7741, rs12387 
 
Related 
Barcelona, Spain (190 girls with precocious pubarche (PP), 71 healthy controls) 
HSD17B5 SNPs predicted to have functional effects do not appear to be a risk factor for PP in girls from Barcelona, despite these girls being at high risk of developing androgen excess in adulthood. 
HSD17B6 
PCOS 
rs1937845 
 
Direct 
Chinese (335 patients with PCOS and 354 controls). 
In conclusion, our findings showed a significant statistical association between HSD17B5 rs1937845 and PCOS risk in Chinese women. 

Unreviewed Literature:

Show/Hide all(2)
PubMed / PMC ID
Title Type of study
26312838
Effect of insulin on AKR1C3 expression in female adipose tissue: in-vivo and in-vitro study of adipose androgen generation in polycystic ovary syndrome. 
In vitro, animal studies 
22329763
17-Hydroxysteroid dehydrogenase type 5 gene polymorphism (-71A/G HSD17B5 SNP) and treatment with oral contraceptive pills in PCOS women without metabolic comorbidities. 
Effect of treatment 

 

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