Cortisone reductase deficiency 2

Summary

Cortisone reductase deficiency 2 (MONDO:0013842) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cortisone reductase deficiency 2
Mondo ID	MONDO:0013842
OMIM	614662
DOID	DOID:0090140
NCIT	C131084
UMLS	C3553382
MedGen	766296
GARD	0015830
Is cancer (heuristic)	no

Also known as: 11-beta-hydroxysteroid dehydrogenase type 1 deficiency · cortisone reductase deficiency 2 · cortisone reductase deficiency caused by mutation in HSD11B1 · cortisone reductase deficiency type 2 · CORTRD2 · HSD11B1 cortisone reductase deficiency

Data availability: 6 ClinVar variants · 2 GenCC gene-disease records.

Disease family

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 › cortisone reductase deficiency 2

Related subtypes (1): cortisone reductase deficiency 1

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

ClinVar germline variants

6 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 2 pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
31588	NM_005525.4(HSD11B1):c.409C>T (p.Arg137Cys)	HSD11B1	Pathogenic	no assertion criteria provided
31589	NM_005525.4(HSD11B1):c.561G>T (p.Lys187Asn)	HSD11B1	Pathogenic	no assertion criteria provided
8911	NM_181755.2(HSD11B1):c.[331+53_331+54insA;332-29T>G]		Uncertain significance	no assertion criteria provided
3107072	NM_005525.4(HSD11B1):c.845C>T (p.Thr282Met)	HSD11B1	Uncertain significance	criteria provided, multiple submitters, no conflicts
375729	NM_005525.4(HSD11B1):c.332-29T>G	HSD11B1	Benign	criteria provided, multiple submitters, no conflicts
375731	NM_005525.4(HSD11B1):c.331+53dup	HSD11B1	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
HSD11B1	Moderate	Autosomal dominant	cortisone reductase deficiency 2	3

Orphanet rare-disease linkage (cohort genes)

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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HSD11B1	HGNC:5208	ENSG00000117594	P28845	11-beta-hydroxysteroid dehydrogenase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 0 · Druggable fraction: 1.0

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	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
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.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
decidua	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HSD11B1	233	broad	marker	decidua, right lobe of liver, liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HSD11B1	3,931

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HSD11B1	P28845	42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
steroid catabolic process	1	2407.4×	8e-04	HSD11B1
lung development	1	198.3×	0.005	HSD11B1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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

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: 1; 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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.