AKR1C2 (aldo-keto reductase family 1 member C2)

Gene

• Entrez ID: 1646
• Gene name: Aldo-keto reductase family 1 member C2
• Gene symbol: AKR1C2
• Synonyms (NCBI Gene): AKR1C-pseudo, BABP, DD, DD-2, DD/BABP, DD2, DDH2, HAKRD, HBAB, MCDR2, SRXY8, TDD
• Chromosome: 10
• Chromosome location: 10p15.1
• 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 using NADH and/or NADPH as cofacto

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs387906750	T>C	Pathogenic	Coding sequence variant, missense variant
rs387906751	T>G	Pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant
rs797044460	A>C	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006986	hsa-miR-193b-3p	Luciferase reporter assay	21512034
MIRT006986	hsa-miR-193b-3p	Reporter assay;Proteomics	21512034
MIRT776283	hsa-miR-1825	CLIP-seq
MIRT776284	hsa-miR-199a-5p	CLIP-seq
MIRT776285	hsa-miR-199b-5p	CLIP-seq
MIRT776286	hsa-miR-3925-3p	CLIP-seq
MIRT776287	hsa-miR-4302	CLIP-seq
MIRT776288	hsa-miR-4311	CLIP-seq
MIRT776289	hsa-miR-548aa	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
TWIST1	Activation	19051271
TWIST2	Activation	19051271

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004032	Function	Aldose reductase (NADPH) activity	IBA
GO:0004032	Function	Aldose reductase (NADPH) activity	IDA	21232532
GO:0004303	Function	Estradiol 17-beta-dehydrogenase [NAD(P)+] activity	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IEA
GO:0006066	Process	Alcohol metabolic process	IEA
GO:0006629	Process	Lipid metabolic process	IEA
GO:0006693	Process	Prostaglandin metabolic process	IBA
GO:0006693	Process	Prostaglandin metabolic process	IDA	8573067
GO:0007186	Process	G protein-coupled receptor signaling pathway	IDA	18508192
GO:0007586	Process	Digestion	IDA	8573067
GO:0008202	Process	Steroid metabolic process	IDA	8573067
GO:0008202	Process	Steroid metabolic process	IEA
GO:0008284	Process	Positive regulation of cell population proliferation	IDA	18508192
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016655	Function	Oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	IDA	20837989
GO:0030855	Process	Epithelial cell differentiation	IEP	21492153
GO:0031406	Function	Carboxylic acid binding	IDA	8573067
GO:0032052	Function	Bile acid binding	IBA
GO:0032052	Function	Bile acid binding	IDA	8573067
GO:0032787	Process	Monocarboxylic acid metabolic process	IEA
GO:0042445	Process	Hormone metabolic process	IEA
GO:0042448	Process	Progesterone metabolic process	IBA
GO:0042448	Process	Progesterone metabolic process	IDA	21232532
GO:0044597	Process	Daunorubicin metabolic process	IBA
GO:0044597	Process	Daunorubicin metabolic process	IMP	20837989
GO:0044598	Process	Doxorubicin metabolic process	IBA
GO:0044598	Process	Doxorubicin metabolic process	IMP	20837989
GO:0047023	Function	Androsterone dehydrogenase [NAD(P)+] activity	IBA
GO:0047023	Function	Androsterone dehydrogenase [NAD(P)+] activity	IEA
GO:0047044	Function	Androstan-3-alpha,17-beta-diol dehydrogenase (NAD+) activity	IEA
GO:0047086	Function	Ketosteroid monooxygenase activity	IBA
GO:0047086	Function	Ketosteroid monooxygenase activity	IDA	21232532
GO:0047115	Function	Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity	IDA	8573067
GO:0047115	Function	Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity	IEA
GO:0047718	Function	Indanol dehydrogenase activity	IEA
GO:0051897	Process	Positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA	18508192
GO:0071395	Process	Cellular response to jasmonic acid stimulus	IDA	19487289
GO:0071799	Process	Cellular response to prostaglandin D stimulus	IDA	18508192

Other IDs

• MIM: 600450
• HGNC: 385
• e!Ensembl: ENSG00000151632

Protein

• UniProt ID: P52895
• Protein name: Aldo-keto reductase family 1 member C2 (EC 1.-.-.-) (EC 1.1.1.112) (EC 1.1.1.209) (EC 1.1.1.53) (EC 1.1.1.62) (EC 1.3.1.20) (3-alpha-HSD3) (Chlordecone reductase homolog HAKRD) (Dihydrodiol dehydrogenase 2) (DD-2) (DD2) (Dihydrodiol dehydrogenase/bile aci
• Protein function: Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids (PubMed:19218247). Most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by phys
• PDB: 1IHI, 1J96, 1XJB, 2HDJ, 2IPJ, 4JQ1, 4JQ2, 4JQ3, 4JQ4, 4JQA, 4JTQ, 4JTR, 4L1W, 4L1X, 4XO6, 4XO7
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00248	Aldo_ket_red	18 → 301	Aldo/keto reductase family	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in fetal testes. Expressed in fetal and adult adrenal glands. {ECO:0000269|PubMed:21802064}.
• Sequence:

  MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEAVKLAIEAGFHHIDSAHVYNNEEQ
  VGLAIRSKIADGSVKREDIFYTSKLWSNSHRPELVRPALERSLKNLQLDYVDLYLIHFPV
  SVKPGEEVIPKDENGKILFDTVDLCATWEAMEKCKDAGLAKSIGVSNFNHRLLEMILNKP
  GLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPV
  LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTSEEMKAIDGLN
  RNVRYLTLDIFAGPPNYPFSDEY

• Sequence length: 323

Pathways

KEGG:

Steroid hormone biosynthesis
Metabolic pathways
Chemical carcinogenesis - DNA adducts
Chemical carcinogenesis - reactive oxygen species

Reactome:

Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
Synthesis of bile acids and bile salts via 24-hydroxycholesterol
Synthesis of bile acids and bile salts via 27-hydroxycholesterol

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
46,XY disorder of sex development due to testicular 17,20-desmolase deficiency	Pathogenic	rs387906750, rs797044460, rs387906751, rs13222	RCV000022967 RCV000022968 RCV000022969 RCV000022970

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
AKR1C2-related disorder	Benign; Uncertain significance; Likely benign	rs13945, rs565642871, rs1554772823, rs781828411, rs556680647, rs146403999, rs138499660, rs563009289, rs782195517, rs3207909, rs13222	RCV003966160 RCV003392909 RCV003896891 RCV003973861 RCV003911421 RCV003914148 RCV003934532 RCV003941481 RCV003924499 RCV003983098 RCV003973007
CIC-rearranged sarcoma	Benign; Likely benign	rs13222	RCV000993817
Ovarian serous cystadenocarcinoma	Benign	rs3207909	RCV005899826
See cases	Uncertain significance	rs377674622	RCV001844434

Associations from Text Mining
Disease Name	Relationship Type	References
Adenocarcinoma	Inhibit	21829465
Breast Neoplasms	Associate	15212687, 19846565, 21512034, 25526449, 34886806
Carcinogenesis	Associate	36701414
Carcinoma Non Small Cell Lung	Associate	36596057
Carcinoma Renal Cell	Associate	40664780
Carcinoma Squamous Cell	Associate	15188492
Dent Disease	Associate	34680992
Depressive Disorder	Associate	28666923
Ehlers Danlos syndrome type 3	Associate	27518164
Esophageal Neoplasms	Associate	15188492
Esophageal Squamous Cell Carcinoma	Associate	26934124
Fatigue Syndrome Chronic	Associate	37978513
Fatty Liver Alcoholic	Stimulate	21931690
Hypospadias	Associate	24986825
Hypoxia	Associate	36316355
Leukemia Myeloid Acute	Associate	34789073
Lipedema	Associate	32872468
Neoplasm Metastasis	Associate	24244276, 37653798
Neoplasms	Associate	15188492, 25526449, 36701414
Oculocerebrorenal Syndrome	Associate	34680992
Parkinson Disease	Associate	40664780
Prostatic Neoplasms	Associate	33934205
Sarcoma Ewing	Associate	34680992
Squamous Cell Carcinoma of Head and Neck	Associate	36835286
Stomach Neoplasms	Inhibit	36701414
Stomach Neoplasms	Associate	37653798
Tuberculosis Extrapulmonary	Associate	34680992