AKR1C1
protein-codingaldo-keto reductase family 1 member C1, the group of Aldo-keto reductases
Gene 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 reaction of progesterone to the inactive form 20-alpha-hydroxy-progesterone. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. [provided by RefSeq, Jul 2008]
- DDH1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to AKR1C1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001353.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 1 | 4 | ||
| missense | 49 | 1 | 1 | 51 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 53 | 3 | 2 | 58 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001344.2 | 9 | MANE Select | |
| Ensembl | ENSP00000370254.4 | 9 | MANE Select | |
| Ensembl | ENSP00000370240.1 | 6 | Standard | |
| Ensembl | ENSP00000416415.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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
Biological Process
- retinoid metabolic process
- xenobiotic metabolic process
- digestion
- steroid metabolic process
- bile acid metabolic process
Molecular Function
- alditol:NADP+ 1-oxidoreductase activity
- aldo-keto reductase (NADP) activity
- protein binding
- alcohol dehydrogenase (NADP+) activity
- steroid dehydrogenase activity
Cellular Component
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000380872
- Coding exons
- 9
- Length
- 90680
- Individuals with no LoFs
- 125578
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 170
- Defined
- 125748
- p
- 0.000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.42 | 211 | 161 | 1.31 | 0.00000840 | 2083 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0014 | 0.0014 | notable |
| Latino/Admixed American | 0.00067 | 0.00067 | rare |
| Ashkenazi Jewish | 0.00040 | 0.00040 | rare |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00054 | 0.00054 | rare |
| South Asian | 0.0017 | 0.0017 | notable |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Intolerance Scores
- LoFtool
- 0.911
- RVIS EVS
- -0.09
- RVIS percentile EVS
- 46.92
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.684
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |