AKR1C1

aldo-keto reductase family 1 member C1, the group of Aldo-keto reductases

Basic information

Region (hg38): 10:4963252-4983283

Previous symbols: [ "DDH1" ]

Links

ENSG00000187134 ∙ NCBI:1645 ∙ OMIM:600449 ∙ HGNC:384 ∙ Uniprot:Q04828 ∙ 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 AKR1C1 gene.

• Inborn genetic diseases (18 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AKR1C1 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				2	1	3
missense			17	1	1	19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	17	3	2

Variants in AKR1C1

This is a list of pathogenic ClinVar variants found in the AKR1C1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-4963452-C-T		not specified	Uncertain significance (May 17, 2023)
10-4963518-C-T		not specified	Uncertain significance (Feb 22, 2023)
10-4963520-C-T		not specified	Uncertain significance (Jul 09, 2021)
10-4965939-C-G		not specified	Uncertain significance (Feb 05, 2024)
10-4965948-T-G		not specified	Likely benign (Apr 21, 2022)
10-4965957-A-T		not specified	Uncertain significance (Jun 27, 2022)
10-4965991-A-T		not specified	Uncertain significance (Jun 24, 2022)
10-4966946-G-C		not specified	Uncertain significance (Feb 06, 2023)
10-4966949-C-G		not specified	Uncertain significance (Jun 02, 2023)
10-4966996-T-C			Benign (Jun 26, 2018)
10-4967024-A-C		not specified	Uncertain significance (Nov 03, 2023)
10-4968380-A-G			Likely benign (Dec 31, 2019)
10-4968880-A-G		not specified	Uncertain significance (Apr 07, 2023)
10-4968882-C-T		not specified	Uncertain significance (Mar 01, 2023)
10-4972216-T-C		not specified	Uncertain significance (Jan 03, 2022)
10-4972223-A-G		not specified	Uncertain significance (Oct 03, 2022)
10-4972246-T-G		not specified	Uncertain significance (Oct 14, 2023)
10-4972309-T-C		not specified	Uncertain significance (May 24, 2023)
10-4972600-C-T		not specified	Uncertain significance (May 16, 2022)
10-4972621-G-T		not specified	Uncertain significance (Aug 28, 2023)
10-4972630-G-T		not specified	Uncertain significance (Jan 07, 2022)
10-4972652-G-A		not specified	Uncertain significance (Oct 05, 2021)
10-4972653-A-C			Likely benign (Jun 25, 2018)
10-4972663-C-G		not specified	Uncertain significance (Apr 27, 2023)
10-4972728-G-T		not specified	Uncertain significance (Feb 27, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AKR1C1	protein_coding	protein_coding	ENST00000380872	9	90680

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.52e-15	0.00572	125578	0	170	125748	0.000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.42	211	161	1.31	0.00000840	2083
Missense in Polyphen		75	54.9	1.3661		715
Synonymous	-1.85	78	59.8	1.31	0.00000289	607
Loss of Function	-0.431	21	19.0	1.11	0.00000121	221

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00209	0.00209
Ashkenazi Jewish	0.000397	0.000397
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000538	0.000536
Middle Eastern	0.000272	0.000272
South Asian	0.00173	0.00173
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Converts progesterone to its inactive form, 20-alpha- dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the intrahepatic bile acid concentration. Has a low bile-binding ability. May play a role in myelin formation. {ECO:0000269|PubMed:11013348, ECO:0000269|PubMed:8573067}.
• Pathway: Steroid hormone biosynthesis - Homo sapiens (human);Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human);Benzo(a)pyrene metabolism;Metapathway biotransformation Phase I and II;Prostaglandin Synthesis and Regulation;Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;Metabolism of lipids;Androgen and estrogen biosynthesis and 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;Metabolism of steroids;Metabolism of vitamins and cofactors;C21-steroid hormone biosynthesis and metabolism;Xenobiotics metabolism;Retinoid metabolism and transport;G alpha (i) signalling events;Visual phototransduction;GPCR downstream signalling (Consensus)

Intolerance Scores

• loftool: 0.911
• rvis_EVS: -0.09
• rvis_percentile_EVS: 46.92

Haploinsufficiency Scores

• pHI: 0.0295
• hipred: N
• hipred_score: 0.183
• ghis: 0.417

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.684

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: retinoid metabolic process;xenobiotic metabolic process;digestion;steroid metabolic process;bile acid metabolic process;bile acid and bile salt transport;intestinal cholesterol absorption;epithelial cell differentiation;progesterone metabolic process;retinal metabolic process;cholesterol homeostasis;daunorubicin metabolic process;doxorubicin metabolic process;response to organophosphorus;protein homooligomerization;oxidation-reduction process;cellular response to jasmonic acid stimulus
• Cellular component: cytosol;extracellular exosome
• Molecular function: alditol:NADP+ 1-oxidoreductase activity;aldo-keto reductase (NADP) activity;protein binding;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;17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase activity;androsterone dehydrogenase (B-specific) activity;ketosteroid monooxygenase activity;trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity;indanol dehydrogenase activity