Cortisone reductase deficiency

Summary

Cortisone reductase deficiency (MONDO:0000193) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• Phenotypes (HPO): 10

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		11	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

10 HPO clinical features (Orphanet curated; top 10 by frequency):

HPO ID	Term	Frequency
HP:0000822	Hypertension	Frequent (30-79%)
HP:0000858	Irregular menstruation	Frequent (30-79%)
HP:0008258	Congenital adrenal hyperplasia	Frequent (30-79%)
HP:0025436	Elevated serum 11-deoxycortisol	Frequent (30-79%)
HP:0030348	Increased circulating androgen concentration	Frequent (30-79%)
HP:0031186	Abnormal circulating deoxycorticosterone level	Frequent (30-79%)
HP:0000826	Precocious puberty	Occasional (5-29%)
HP:0002900	Hypokalemia	Occasional (5-29%)
HP:0003351	Decreased circulating renin concentration	Occasional (5-29%)
HP:0012412	Premature adrenarche	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	cortisone reductase deficiency
Mondo ID	MONDO:0000193
MeSH	C536447
OMIM	604931
Orphanet	168588
DOID	DOID:0090139
SNOMED CT	124138004
UMLS	C1291245
MedGen	266223
GARD	0009882
Is cancer (heuristic)	no

Also known as: 11-alpha beta-hydroxysteroid dehydrogenase type I deficiency of · 11-beta-hydroxysteroid dehydrogenase deficiency type 1 · deficiency of (R)-20-hydroxysteroid dehydrogenase · deficiency of cortisone reductase · HSD 11B1 deficiency · hyperandrogenism due to cortisone reductase deficiency

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inherited lipid metabolism disorder › cortisone reductase deficiency

Related subtypes (28): familial hyperlipidemia, hypolipoproteinemia, steroid inherited metabolic disorder, corticosterone methyloxidase type 1 deficiency, lipoid proteinosis, 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency, vitamin D hydroxylation-deficient rickets, type 1B, mitochondrial trifunctional protein deficiency, pancreatic triacylglycerol lipase deficiency, glucocorticoid resistance, syndromic dyslipidemia, inborn disorder of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation, disorder of plasmalogens biosynthesis, disorder of phospholipids, sphingolipids and fatty acids biosynthesis, inborn disorder of ketolysis, lysosomal lipid storage disorder, sterol metabolism disorder, disorder of sphingolipid biosynthesis, glycosylphosphatidylinositol biosynthesis defect 18, neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, developmental and epileptic encephalopathy, 77, developmental and epileptic encephalopathy, 80, developmental and epileptic encephalopathy, 55, inherited fatty acid metabolism disorder, glycosylphosphatidylinositol biosynthesis defect 16, glycosylphosphatidylinositol biosynthesis defect 15, glycosylphosphatidylinositol biosynthesis defect 17, CYP7B1-related disorder of oxysterol accumulation

Subtypes (2): cortisone reductase deficiency 1, cortisone reductase deficiency 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
H6PD	Strong	Autosomal recessive	cortisone reductase deficiency 1	4
HSD11B1	Moderate	Autosomal dominant	cortisone reductase deficiency 2	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
H6PD	Orphanet:168588	Hyperandrogenism due to cortisone reductase deficiency
HSD11B1	Orphanet:168588	Hyperandrogenism due to cortisone reductase deficiency

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
H6PD	HGNC:4795	ENSG00000049239	O95479	GDH/6PGL endoplasmic bifunctional protein	gencc
HSD11B1	HGNC:5208	ENSG00000117594	P28845	11-beta-hydroxysteroid dehydrogenase 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
H6PD	GDH/6PGL endoplasmic bifunctional protein	Bifunctional enzyme localized in the lumen of the endoplasmic reticulum that catalyzes the first two steps of the oxidative branch of the pentose phosphate pathway/shunt, an alternative to glycolysis and a major source of reducing power an…
HSD11B1	11-beta-hydroxysteroid dehydrogenase 1	Controls the reversible conversion of biologically active glucocorticoids such as cortisone to cortisol, and 11-dehydrocorticosterone to corticosterone in the presence of NADP(H).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
H6PD	Other/Unknown	no		G6P_DH, 6-phosphogluconolactonase_DevB, Glc/Gal-6P_isomerase
HSD11B1	Enzyme (other)	yes	1.1.1.146	SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right lobe of liver	2
germinal epithelium of ovary	1
parotid gland	1
decidua	1
liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
H6PD	274	ubiquitous	marker	parotid gland, germinal epithelium of ovary, right lobe of liver
HSD11B1	233	broad	marker	decidua, right lobe of liver, liver

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
H6PD	5,473
HSD11B1	3,931

Intra-cohort edges

A	B	Sources
H6PD	HSD11B1	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HSD11B1	P28845	42
H6PD	O95479	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Prednisone ADME	1	1268.9×	0.001	HSD11B1
Glucocorticoid biosynthesis	1	878.5×	0.001	HSD11B1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of cortisol biosynthetic process	1	4213.0×	0.002	H6PD
pentose-phosphate shunt, oxidative branch	1	2106.5×	0.002	H6PD
steroid catabolic process	1	1203.7×	0.002	HSD11B1
response to alcohol	1	766.0×	0.002	H6PD
response to nutrient levels	1	183.2×	0.008	H6PD
glucose metabolic process	1	127.7×	0.009	H6PD
lung development	1	99.1×	0.010	HSD11B1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
HSD11B1	FUROSEMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HSD11B1	13	4
H6PD	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FUROSEMIDE	4	HSD11B1
CARBENOXOLONE	4	HSD11B1
CURCUMIN	3	HSD11B1
EPIGALOCATECHIN GALLATE	3	HSD11B1
URSOLIC ACID	2	HSD11B1
MK-0736	2	HSD11B1
AZD-4017	2	HSD11B1
ENOXOLONE	2	HSD11B1
BI-187004	2	HSD11B1
BMS-823778 FREE BASE	2	HSD11B1
GLYCYRRHIZIN	2	HSD11B1
BMS-816336	1	HSD11B1
HSD-016	1	HSD11B1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
HSD11B1	311	Binding:308, Functional:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HSD11B1	1.1.1.146, 1.1.1.B40	11beta-hydroxysteroid dehydrogenase,

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
HSD11B1	311

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

13 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
FUROSEMIDE	4	HSD11B1
CARBENOXOLONE	4	HSD11B1
CURCUMIN	3	HSD11B1
EPIGALOCATECHIN GALLATE	3	HSD11B1
URSOLIC ACID	2	HSD11B1
MK-0736	2	HSD11B1
AZD-4017	2	HSD11B1
ENOXOLONE	2	HSD11B1
BI-187004	2	HSD11B1
BMS-823778 FREE BASE	2	HSD11B1
GLYCYRRHIZIN	2	HSD11B1
BMS-816336	1	HSD11B1
HSD-016	1	HSD11B1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	HSD11B1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	H6PD

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
H6PD	0	HSD11B1

Clinical trials & evidence

Clinical trials

Clinical trials: 0.