Cortisone reductase deficiency 1

Summary

Cortisone reductase deficiency 1 (MONDO:0011503) is a disease caused by H6PD (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: H6PD (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cortisone reductase deficiency 1
Mondo ID	MONDO:0011503
OMIM	604931
DOID	DOID:0090141
NCIT	C131849
UMLS	C3551716
MedGen	764630
GARD	0015375
Is cancer (heuristic)	no

Also known as: apparent cortisone reductase deficiency · cortisone reductase deficiency 1 · cortisone reductase deficiency caused by mutation in H6PD · cortisone reductase deficiency type 1 · CORTRD1 · H6PD cortisone reductase deficiency · hexose-6-phosphate dehydrogenase deficiency

Data availability: 21 ClinVar variants · 3 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 1

Related subtypes (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

ClinVar germline variants

21 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 6 benign, 5 pathogenic, 3 benign/likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
16130	NM_004285.4(H6PD):c.1860_1861insACAGGTGGTTGACCTGTGGCCGGGTCTGA (p.Glu621delinsThrGlyGlyTer)	H6PD	Pathogenic	no assertion criteria provided
31584	NM_004285.4(H6PD):c.960G>A (p.Val320=)	H6PD	Pathogenic	no assertion criteria provided
31585	NM_004285.4(H6PD):c.1076G>A (p.Gly359Asp)	H6PD	Pathogenic	no assertion criteria provided
31586	NM_004285.4(H6PD):c.948C>G (p.Tyr316Ter)	H6PD	Pathogenic	criteria provided, multiple submitters, no conflicts
31587	NM_004285.4(H6PD):c.325del (p.Arg109fs)	H6PD	Pathogenic	no assertion criteria provided
4849419	NM_004285.4(H6PD):c.1113_1116del (p.Leu372fs)	H6PD	Likely pathogenic	criteria provided, single submitter
1030761	NM_004285.4(H6PD):c.1109G>A (p.Arg370Gln)	H6PD	Uncertain significance	criteria provided, multiple submitters, no conflicts
1443977	NM_004285.4(H6PD):c.422A>G (p.Tyr141Cys)	H6PD	Uncertain significance	criteria provided, multiple submitters, no conflicts
2544647	NM_004285.4(H6PD):c.1012G>A (p.Ala338Thr)	H6PD	Uncertain significance	criteria provided, multiple submitters, no conflicts
2562406	NM_004285.4(H6PD):c.896C>T (p.Ala299Val)	H6PD	Uncertain significance	criteria provided, multiple submitters, no conflicts
2689194	NM_004285.4(H6PD):c.1514C>G (p.Ala505Gly)	H6PD	Uncertain significance	criteria provided, single submitter
3588018	NM_004285.4(H6PD):c.857C>T (p.Ala286Val)	H6PD	Uncertain significance	criteria provided, multiple submitters, no conflicts
1264396	NM_004285.4(H6PD):c.2118A>G (p.Ser706=)	H6PD	Benign	criteria provided, multiple submitters, no conflicts
1269315	NM_004285.4(H6PD):c.636G>A (p.Ala212=)	H6PD	Benign	criteria provided, multiple submitters, no conflicts
1288974	NM_004285.4(H6PD):c.741T>C (p.Ala247=)	H6PD	Benign	criteria provided, multiple submitters, no conflicts
1540015	NM_004285.4(H6PD):c.2019T>C (p.Tyr673=)	H6PD	Benign	criteria provided, multiple submitters, no conflicts
1584487	NM_004285.4(H6PD):c.1342G>A (p.Ala448Thr)	H6PD	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
16131	NM_004285.4(H6PD):c.1358G>A (p.Arg453Gln)	H6PD	Benign	criteria provided, multiple submitters, no conflicts
191261	NM_004285.4(H6PD):c.745+88T>A	H6PD	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
402919	NM_004285.4(H6PD):c.-7_1del	H6PD	Benign	criteria provided, multiple submitters, no conflicts
791775	NM_004285.4(H6PD):c.1053C>T (p.Gly351=)	H6PD	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
H6PD	Strong	Autosomal recessive	cortisone reductase deficiency 1	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
H6PD	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
H6PD	HGNC:4795	ENSG00000049239	O95479	GDH/6PGL endoplasmic bifunctional protein	gencc,clinvar

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…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
H6PD	Other/Unknown	no		G6P_DH, 6-phosphogluconolactonase_DevB, Glc/Gal-6P_isomerase

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
germinal epithelium of ovary	1
parotid gland	1
right lobe of 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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
H6PD	5,473

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
H6PD	O95479	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
regulation of cortisol biosynthetic process	1	8426.0×	6e-04	H6PD
pentose-phosphate shunt, oxidative branch	1	4213.0×	6e-04	H6PD
response to alcohol	1	1532.0×	0.001	H6PD
response to nutrient levels	1	366.4×	0.003	H6PD
glucose metabolic process	1	255.3×	0.004	H6PD

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
H6PD	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.