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GeneE
25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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HSD11B1
hydroxysteroid 11-beta dehydrogenase 1
Chromosome 1 · 1q32.2
NCBI Gene: 3290Ensembl: ENSG00000117594.11HGNC: HGNC:5208UniProt: P28845
273PubMed Papers
21Diseases
6Drugs
2Pathogenic Variants
RESEARCH IMPACT
Trending
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
endoplasmic reticulum membraneprotein homodimerization activitymembraneNADP bindingHyperandrogenism due to cortisone reductase deficiencygastroesophageal reflux diseasePeptic ulcerKnee pain
✦AI Summary

HSD11B1 encodes 11β-hydroxysteroid dehydrogenase type 1, an enzyme that primarily functions as a reductase in vivo to convert inactive glucocorticoids (cortisone) to active forms (cortisol), thereby controlling local tissue glucocorticoid availability 12. The enzyme exhibits broad substrate specificity, metabolizing not only glucocorticoids but also neurosteroids, oxysterols, and bile acids, linking glucocorticoid activation to multiple metabolic pathways. HSD11B1 plays crucial roles in metabolic homeostasis, with elevated expression contributing to obesity, bone loss, and glucose handling impairment in high-fat diet conditions 2. The enzyme is upregulated synergistically by inflammatory cytokines IFNγ and TNFα, mediating anti-inflammatory responses through TSG-6 expression in mesenchymal stem cells 1. Genetic polymorphisms in HSD11B1 are associated with increased susceptibility to type 2 diabetes, metabolic syndrome, and diabetic kidney disease 34. In synovial tissue, adipocyte-expressed HSD11B1 maintains healthy fibroblast phenotypes that are lost in inflammatory arthritis 5. Recent studies suggest HSD11B1 may also influence endometrial cancer risk and depression susceptibility through interactions with environmental factors 67, highlighting its broad physiological significance beyond glucocorticoid metabolism.

Sources cited
1
HSD11B1 converts inactive cortisone to active cortisol and is upregulated by inflammatory cytokines IFNγ and TNFα
PMID: 32328292
2
HSD11B1 contributes to obesity, bone loss, and glucose handling impairment in high-fat diet conditions
PMID: 39362888
3
HSD11B1 polymorphisms are associated with increased risk of type 2 diabetes and metabolic syndrome
PMID: 28750217
4
HSD11B1 variants modulate susceptibility to diabetic kidney disease and insulin resistance in type 1 diabetes
PMID: 32453474
5
Adipocyte-expressed HSD11B1 maintains healthy fibroblast phenotypes that are lost in inflammatory arthritis
PMID: 39543086
6
HSD11B1 may influence endometrial cancer risk
PMID: 39278107
7
HSD11B1 may influence depression susceptibility through interactions with environmental factors
PMID: 40108257
Disease Associationsⓘ21
Hyperandrogenism due to cortisone reductase deficiencyOpen Targets
0.56Moderate
gastroesophageal reflux diseaseOpen Targets
0.50Moderate
Peptic ulcerOpen Targets
0.50Moderate
Knee painOpen Targets
0.28Weak
type 2 diabetes mellitusOpen Targets
0.13Weak
exstrophy-epispadias complexOpen Targets
0.12Weak
neoplasmOpen Targets
0.10Suggestive
obesityOpen Targets
0.10Suggestive
Alzheimer diseaseOpen Targets
0.09Suggestive
hypertensionOpen Targets
0.09Suggestive
ocular hypertensionOpen Targets
0.09Suggestive
melanomaOpen Targets
0.09Suggestive
metabolic syndromeOpen Targets
0.09Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.08Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.08Suggestive
gastrointestinal stromal tumorOpen Targets
0.07Suggestive
cardiovascular diseaseOpen Targets
0.07Suggestive
Disorder of lipid metabolismOpen Targets
0.07Suggestive
leiomyomaOpen Targets
0.07Suggestive
pseudotumor cerebriOpen Targets
0.07Suggestive
Cortisone reductase deficiency 2UniProt
Pathogenic Variants2
NM_005525.4(HSD11B1):c.409C>T (p.Arg137Cys)Pathogenic
Cortisone reductase deficiency 2
☆☆☆☆2011→ Residue 137
NM_005525.4(HSD11B1):c.561G>T (p.Lys187Asn)Pathogenic
Cortisone reductase deficiency 2
☆☆☆☆2011→ Residue 187
View on ClinVar ↗
Drug Targets6
ABT-384Phase II
11-beta-hydroxysteroid dehydrogenase 1 inhibitor
Alzheimer disease
AZD-4017Phase II
11-beta-hydroxysteroid dehydrogenase 1 inhibitor
ocular hypertension
BI-187004Phase II
11-beta-hydroxysteroid dehydrogenase 1 inhibitor
type 2 diabetes mellitus
BMS-823778Phase II
11-beta-hydroxysteroid dehydrogenase 1 inhibitor
CARBENOXOLONEApproved
11-beta-hydroxysteroid dehydrogenase inhibitor
gastroesophageal reflux disease
MK-0736Phase II
11-beta-hydroxysteroid dehydrogenase 1 inhibitor
hypertension
Related Genes
SRD5A1Protein interaction99%AKR1C4Protein interaction98%CYP11B1Protein interaction98%CYP11B2Protein interaction98%CYP17A1Protein interaction98%CYP21A2Protein interaction98%
Tissue Expression6 tissues
Liver
100%
Ovary
10%
Lung
6%
Brain
2%
Heart
1%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
HSD11B1SRD5A1AKR1C4CYP11B1CYP11B2CYP17A1CYP21A2
PROTEIN STRUCTURE
Preparing viewer…
PDB1XU9 · 1.55 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.97LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.61 [0.40–0.97]
RankingsWhere HSD11B1 stands among ~20K protein-coding genes
  • #1,342of 20,598
    Most Researched273 · top 10%
  • #807of 1,025
    FDA-Approved Drug Targets1
  • #4,220of 5,498
    Most Pathogenic Variants2
  • #9,274of 17,882
    Most Constrained (LOEUF)0.97
Genes detectedHSD11B1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Adipocyte associated glucocorticoid signaling regulates normal fibroblast function which is lost in inflammatory arthritis.
PMID: 39543086
Nat Commun · 2024
1.00
2
Targeting osteoblastic 11β-HSD1 to combat high-fat diet-induced bone loss and obesity.
PMID: 39362888
Nat Commun · 2024
0.90
3
Association of HSD11B1 gene polymorphisms with type 2 diabetes and metabolic syndrome in South Indian population.
PMID: 28750217
Diabetes Res Clin Pract · 2017
0.80
4
Large-scale plasma proteomics uncovers novel targets linking ambient air pollution and depression.
PMID: 40108257
Mol Psychiatry · 2025
0.70
5
G6PC1 and G6PC2 influence G6P flux but not HSD11B1 activity.
PMID: 37855366
J Mol Endocrinol · 2023
0.64