AKR1C2

aldo-keto reductase family 1 member C2, the group of Aldo-keto reductases

Basic information

Region (hg38): 10:4987775-5018031

Previous symbols: [ "DDH2", "TDD" ]

Links

ENSG00000151632 ∙ NCBI:1646 ∙ OMIM:600450 ∙ HGNC:385 ∙ Uniprot:P52895 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 46,XY disorder of sex development due to testicular 17,20-desmolase deficiency (Supportive), mode of inheritance: AR
• 46,XY disorder of sex development due to testicular 17,20-desmolase deficiency (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
46,XY sex reversal 8	AR	Genitourinary; Oncologic	Surveillance and/or awareness of cancer risk, and preventive measures may be beneficial to reduce the risk of gonadal tumors	Endocrine; Genitourinary; Oncologic	4352099; 21802064

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AKR1C2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AKR1C2 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				7	2	9
missense			18	1	2	21
nonsense						0
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region					1	1
non coding				1	45	46
Total	0	0	21	9	49

Variants in AKR1C2

This is a list of pathogenic ClinVar variants found in the AKR1C2 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-4989685-C-T			Benign (Jul 09, 2018)
10-4989699-G-T			Benign (Feb 04, 2019)
10-4989823-C-T			Benign (Jul 09, 2018)
10-4990047-A-AG			Benign (Jul 05, 2018)
10-4990092-C-T			Benign (Jul 09, 2018)
10-4990094-C-G			Benign (Jul 09, 2018)
10-4990242-C-A			Benign (Jul 09, 2018)
10-4991645-C-A			Benign (Jul 09, 2018)
10-4991646-A-G			Benign (Jul 09, 2018)
10-4991824-T-C			Benign (Jul 09, 2018)
10-4991861-T-G		46,XY disorder of sex development due to testicular 17,20-desmolase deficiency	Pathogenic (Aug 12, 2011)
10-4991964-A-G			Benign (Jul 10, 2018)
10-4992025-C-T			Benign (Jul 09, 2018)
10-4992190-T-C			Benign (Feb 04, 2019)
10-4995068-T-C			Benign (Oct 05, 2019)
10-4995242-TC-T			Benign (Jul 09, 2018)
10-4995336-TGC-T		46,XY disorder of sex development due to testicular 17,20-desmolase deficiency	Uncertain significance (May 02, 2023)
10-4995339-G-A		not specified	Uncertain significance (Sep 25, 2023)
10-4995378-G-A		not specified	Uncertain significance (Feb 08, 2023)
10-4995382-C-T		AKR1C2-related disorder	Likely benign (Apr 03, 2019)
10-4995392-C-T		not specified	Uncertain significance (Dec 31, 2023)
10-4995393-G-A		AKR1C2-related disorder	Benign (Nov 25, 2019)
10-4995401-A-C		not specified	Uncertain significance (Dec 28, 2022)
10-4995445-G-T		AKR1C2-related disorder	Likely benign (Aug 24, 2022)
10-4995523-G-C			Benign (Jul 09, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AKR1C2	protein_coding	protein_coding	ENST00000380753	9	30257

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.90e-11	0.0709	125516	0	231	125747	0.000919

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.873	176	146	1.20	0.00000713	2083
Missense in Polyphen		73	63.343	1.1524		904
Synonymous	-1.87	77	58.8	1.31	0.00000306	610
Loss of Function	0.140	16	16.6	0.963	0.00000101	212

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00108	0.00107
Ashkenazi Jewish	0.00605	0.00607
East Asian	0.00252	0.00245
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000318	0.000316
Middle Eastern	0.00252	0.00245
South Asian	0.00180	0.00180
Other	0.000979	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha- DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol). Has a high bile-binding ability. {ECO:0000269|PubMed:15929998, ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338, ECO:0000269|PubMed:8573067}.
• Pathway: Steroid hormone biosynthesis - Homo sapiens (human);Chemical carcinogenesis - Homo sapiens (human);Benzo(a)pyrene metabolism;Metapathway biotransformation Phase I and II;Prostaglandin Synthesis and Regulation;Metabolism of lipids;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;Metabolism of steroids (Consensus)

Intolerance Scores

• loftool: 0.916
• rvis_EVS: -0.09
• rvis_percentile_EVS: 46.74

Haploinsufficiency Scores

• pHI: 0.0666
• hipred: N
• hipred_score: 0.195
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.908

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Akr1c21

Gene ontology

• Biological process: prostaglandin metabolic process;G protein-coupled receptor signaling pathway;digestion;steroid metabolic process;positive regulation of cell population proliferation;epithelial cell differentiation;progesterone metabolic process;daunorubicin metabolic process;doxorubicin metabolic process;positive regulation of protein kinase B signaling;oxidation-reduction process;cellular response to jasmonic acid stimulus;cellular response to prostaglandin D stimulus
• Cellular component: cytoplasm;cytosol
• Molecular function: alditol:NADP+ 1-oxidoreductase 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;carboxylic acid binding;bile acid binding;ketosteroid monooxygenase activity;trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity