AKR1C3

aldo-keto reductase family 1 member C3, the group of Aldo-keto reductases

Basic information

Region (hg38): 10:5035354-5107686

Previous symbols: [ "HSD17B5" ]

Links

ENSG00000196139 ∙ NCBI:8644 ∙ OMIM:603966 ∙ HGNC:386 ∙ Uniprot:P42330 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AKR1C3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AKR1C3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			20	2	3	25
nonsense				1		1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	20	3	4

Variants in AKR1C3

This is a list of pathogenic ClinVar variants found in the AKR1C3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-5094471-G-T		Malignant tumor of prostate	Uncertain significance (-)
10-5094492-G-A		not specified	Likely benign (Dec 19, 2022)
10-5096426-C-T		not specified	Uncertain significance (Mar 20, 2024)
10-5096464-C-T		not specified	Uncertain significance (Dec 13, 2022)
10-5096519-T-G		not specified	Uncertain significance (Jan 09, 2024)
10-5096522-G-A			Benign (Nov 15, 2018)
10-5096546-T-C		not specified	Uncertain significance (Oct 27, 2022)
10-5097450-A-G		not specified	Uncertain significance (Mar 11, 2022)
10-5097502-A-T		not specified	Uncertain significance (Oct 26, 2022)
10-5097531-A-G		not specified	Uncertain significance (Jun 17, 2024)
10-5098857-T-G		not specified	Uncertain significance (May 09, 2022)
10-5098866-G-A			Benign (Dec 31, 2019)
10-5099328-C-T		not specified	Uncertain significance (Sep 22, 2023)
10-5099338-G-A			Benign (Dec 31, 2019)
10-5099380-C-G		not specified	Uncertain significance (Dec 08, 2022)
10-5099447-C-T			Likely benign (Dec 31, 2019)
10-5102114-C-T			Likely benign (Jul 21, 2018)
10-5102126-G-A			Benign (Dec 31, 2019)
10-5102131-A-G		not specified	Uncertain significance (Aug 08, 2023)
10-5102162-T-G		not specified	Uncertain significance (May 31, 2023)
10-5102173-G-A		Hypotension	not provided (-)
10-5102485-G-T		not specified	Uncertain significance (Feb 07, 2023)
10-5102535-T-G		not specified	Uncertain significance (Nov 27, 2023)
10-5102552-C-G		not specified	Uncertain significance (Dec 13, 2023)
10-5102562-C-T		not specified	Uncertain significance (Mar 18, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AKR1C3	protein_coding	protein_coding	ENST00000380554	9	72333

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.58e-24	0.0000163	125194	3	551	125748	0.00221

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.81	237	171	1.39	0.00000872	2105
Missense in Polyphen		82	52.055	1.5753		692
Synonymous	-1.82	80	61.8	1.29	0.00000302	600
Loss of Function	-1.83	30	21.0	1.43	0.00000139	223

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0156	0.0155
Ashkenazi Jewish	0.00	0.00
East Asian	0.00459	0.00458
Finnish	0.000462	0.000462
European (Non-Finnish)	0.00109	0.00108
Middle Eastern	0.00459	0.00458
South Asian	0.00174	0.00167
Other	0.00196	0.00196

dbNSFP

Source: dbNSFP

• Function: 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.
• Pathway: Folate biosynthesis - Homo sapiens (human);Steroid hormone biosynthesis - Homo sapiens (human);Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics;Arachidonic acid metabolism - Homo sapiens (human);Doxorubicin Pathway, Pharmacokinetics;Ovarian steroidogenesis - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;Etodolac Action Pathway;Ketoprofen Action Pathway;Ibuprofen Action Pathway;Rofecoxib Action Pathway;Acetylsalicylic Acid Action Pathway;Diflunisal Action Pathway;Doxorubicin Metabolism Pathway;Leukotriene C4 Synthesis Deficiency;Acetaminophen Action Pathway;Celecoxib Action Pathway;Sulindac Action Pathway;Diclofenac Action Pathway;Ketorolac Action Pathway;Naproxen Action Pathway;Etoricoxib Action Pathway;Carprofen Action Pathway;Flurbiprofen Action Pathway;Fenoprofen Action Pathway;Antrafenine Action Pathway;Antipyrine Action Pathway;Lumiracoxib Action Pathway;Magnesium salicylate Action Pathway;Trisalicylate-choline Action Pathway;Nepafenac Action Pathway;Phenylbutazone Action Pathway;Lornoxicam Action Pathway;Salsalate Action Pathway;Tenoxicam Action Pathway;Tiaprofenic Acid Action Pathway;Tolmetin Action Pathway;Salicylic Acid Action Pathway;Salicylate-sodium Action Pathway;Oxaprozin Action Pathway;Valdecoxib Action Pathway;Nabumetone Action Pathway;Indomethacin Action Pathway;Meloxicam Action Pathway;Suprofen Action Pathway;Bromfenac Action Pathway;Mefenamic Acid Action Pathway;Arachidonic Acid Metabolism;Piroxicam Action Pathway;Benzo(a)pyrene metabolism;Metapathway biotransformation Phase I and II;Prostaglandin Synthesis and Regulation;Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;RA biosynthesis pathway;Metabolism of lipids;Synthesis of Prostaglandins (PG) and Thromboxanes (TX);Prostaglandin Leukotriene metabolism;Arachidonic acid metabolism;Metabolism;Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol;allopregnanolone biosynthesis;Synthesis of bile acids and bile salts via 24-hydroxycholesterol;Synthesis of bile acids and bile salts via 27-hydroxycholesterol;Synthesis of bile acids and bile salts;Bile acid and bile salt metabolism;Fatty acid metabolism;Metabolism of steroids;Metabolism of vitamins and cofactors;Signaling by Retinoic Acid;Signaling by Nuclear Receptors;Retinoid metabolism and transport;androgen biosynthesis;G alpha (i) signalling events;Visual phototransduction;GPCR downstream signalling;superpathway of steroid hormone biosynthesis (Consensus)

Recessive Scores

• pRec: 0.307

Intolerance Scores

• loftool: 0.973
• rvis_EVS: 0.78
• rvis_percentile_EVS: 87.14

Haploinsufficiency Scores

• pHI: 0.158
• hipred: N
• hipred_score: 0.112
• ghis: 0.396

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Akr1c18
• Phenotype: reproductive system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: obsolete protein import into nucleus, translocation;retinoid metabolic process;prostaglandin metabolic process;G protein-coupled receptor signaling pathway;response to nutrient;steroid metabolic process;positive regulation of cell population proliferation;male gonad development;cellular response to starvation;positive regulation of cell death;farnesol catabolic process;cyclooxygenase pathway;keratinocyte differentiation;cellular response to reactive oxygen species;progesterone metabolic process;retinol metabolic process;retinal metabolic process;macromolecule metabolic process;daunorubicin metabolic process;doxorubicin metabolic process;regulation of retinoic acid receptor signaling pathway;positive regulation of protein kinase B signaling;oxidation-reduction process;testosterone biosynthetic process;renal absorption;cellular response to cadmium ion;cellular response to calcium ion;cellular response to prostaglandin stimulus;cellular response to corticosteroid stimulus;cellular response to jasmonic acid stimulus;cellular response to prostaglandin D stimulus;negative regulation of retinoic acid biosynthetic process;regulation of testosterone biosynthetic process;positive regulation of endothelial cell apoptotic process;positive regulation of reactive oxygen species metabolic process
• Cellular component: nucleus;cytoplasm;cytosol;extracellular exosome
• Molecular function: retinal dehydrogenase activity;alditol:NADP+ 1-oxidoreductase activity;aldo-keto reductase (NADP) activity;retinol dehydrogenase activity;alcohol dehydrogenase (NADP+) activity;steroid dehydrogenase activity;oxidoreductase activity;oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor;phenanthrene 9,10-monooxygenase activity;dihydrotestosterone 17-beta-dehydrogenase activity;prostaglandin H2 endoperoxidase reductase activity;prostaglandin D2 11-ketoreductase activity;geranylgeranyl reductase activity;ketoreductase activity;prostaglandin-F synthase activity;15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity;androsterone dehydrogenase activity;testosterone dehydrogenase (NAD+) activity;testosterone 17-beta-dehydrogenase (NADP+) activity;ketosteroid monooxygenase activity;trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity;indanol dehydrogenase activity;delta4-3-oxosteroid 5beta-reductase activity;NADP-retinol dehydrogenase activity