AKR1D1

Protein identityUniProt · HPA

UniProt accession

P51857

Gene

AKR1D1

Ensembl

ENSG00000122787

Chromosome

7

Canonical length

326 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Cytosol

OverviewNCBI Gene

The enzyme encoded by this gene is responsible for the catalysis of the 5-beta-reduction of bile acid intermediates and steroid hormones carrying a delta(4)-3-one structure. Deficiency of this enzyme may contribute to hepatic dysfunction. Three transcript variants encoding different isoforms have been found for this gene. Other variants may be present, but their full-length natures have not been determined yet. [provided by RefSeq, Jul 2010]

Canonical amino-acid sequenceUniProt

326 residues, UniProt reviewed canonical sequence.

>P51857|AKR1D1
     1  MDLSAASHRI PLSDGNSIPI IGLGTYSEPK STPKGACATS VKVAIDTGYR HIDGAYIYQN
    61  EHEVGEAIRE KIAEGKVRRE DIFYCGKLWA TNHVPEMVRP TLERTLRVLQ LDYVDLYIIE
   121  VPMAFKPGDE IYPRDENGKW LYHKSNLCAT WEAMEACKDA GLVKSLGVSN FNRRQLELIL
   181  NKPGLKHKPV SNQVECHPYF TQPKLLKFCQ QHDIVITAYS PLGTSRNPIW VNVSSPPLLK
   241  DALLNSLGKR YNKTAAQIVL RFNIQRGVVV IPKSFNLERI KENFQIFDFS LTEEEMKDIE
   301  ALNKNVRFVE LLMWRDHPEY PFHDEY

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AKR1D1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.22

Highest tissue expression

399 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AKR1D1.

Disease | AllUniProt

Conditions AKR1D1 is implicated in, by any mechanism.

• Congenital bile acid synthesis defect 2 (CBAS2) MIM:235555

Disease | GeneticClinVar

25 pathogenic / likely-pathogenic of 238 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Congenital bile acid synthesis defect 2
• AKR1D1-related disorder
• Congenital bile acid synthesis defect

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.13

gnomAD pLI

0

gnomAD missense Z

0.17

DepMap mean gene effect

-0.16

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• androgen metabolic process
• bile acid biosynthetic process
• bile acid catabolic process
• C21-steroid hormone metabolic process
• cholesterol catabolic process
• digestion

Molecular functions

• alcohol dehydrogenase (NADP+) activity
• aldose reductase (NADPH) activity
• Delta4-3-oxosteroid 5beta-reductase activity
• ketosteroid monooxygenase activity
• steroid binding
• steroid dehydrogenase activity

Cellular components

• cytosol

Protein domainsUniProt · Pfam · InterPro

• Aldo/keto reductase, conserved site
• Aldo-keto reductase
• NADP-dependent oxidoreductase domain
• NAD(P)-dependent oxidoreductase domain superfamily
• Aldo/keto reductase family
• Aldo-keto reductase family 1 member D1

KeywordsUniProt

• Bile acid catabolism
• Cytoplasm
• Intrahepatic cholestasis
• Lipid degradation
• Lipid metabolism
• NADP
• Oxidoreductase
• Steroid metabolism