Congenital adrenal hyperplasia
diseaseOn this page
Also known as adrenal hyperplasiaadrenal hyperplasia, congenitaladrenogenital disorderadrenogenital syndromeCAHcongenital adrenal gland hyperplasia
Summary
Congenital adrenal hyperplasia (MONDO:0018479) is a disease (an umbrella term covering 8 Mondo subtypes) with 7 cohort genes and 83 clinical trials. The dominant Reactome pathway is Glucocorticoid biosynthesis (4 cohort genes). Top therapeutic interventions include crinecerfont, cortisone acetate, and fludrocortisone acetate.
At a glance
- Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
- Umbrella term: 8 Mondo subtypes
- Cohort genes: 7
- ClinVar variants: 131
- Clinical trials: 83
Clinical features
Epidemiology
Prevalence records
19 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Annual incidence | 1-5 / 10 000 | 13.35 | Europe | Validated |
| Point prevalence | 1-9 / 100 000 | 10 | Europe | Validated |
| Point prevalence | 1-9 / 100 000 | 1.36 | China | Validated |
| Prevalence at birth | 1-9 / 100 000 | 8.6 | France | Validated |
| Prevalence at birth | 1-5 / 10 000 | 12.8 | Germany | Validated |
| Prevalence at birth | 1-5 / 10 000 | 10.2 | Sweden | Validated |
| Prevalence at birth | 1-9 / 100 000 | 4 | Belgium | Validated |
| Prevalence at birth | 1-9 / 100 000 | 9.3 | Switzerland | Validated |
| Prevalence at birth | 1-9 / 100 000 | 6.9 | New Zealand | Validated |
| Prevalence at birth | 1-9 / 100 000 | 6.3 | Cuba | Validated |
| Prevalence at birth | 1-9 / 100 000 | 6.7 | Taiwan, Province of China | Validated |
| Prevalence at birth | 1-5 / 10 000 | 38.8 | India | Validated |
| Prevalence at birth | 1-9 / 100 000 | 7.98 | Czech Republic | Validated |
| Prevalence at birth | 1-9 / 100 000 | 6.7 | Europe | Not yet validated |
| Prevalence at birth | 1-9 / 100 000 | 6.65 | Italy | Not yet validated |
| Prevalence at birth | 1-9 / 100 000 | 5.6 | United Kingdom | Not yet validated |
| Prevalence at birth | 1-9 / 100 000 | 7.65 | Netherlands | Not yet validated |
| Prevalence at birth | 1-9 / 100 000 | 5.35 | Japan | Not yet validated |
| Prevalence at birth | 1-9 / 100 000 | 4.8 | United States | Not yet validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | congenital adrenal hyperplasia |
| Mondo ID | MONDO:0018479 |
| MeSH | D000312 |
| Orphanet | 418 |
| DOID | DOID:0050811 |
| ICD-11 | 172733763 |
| NCIT | C34360 |
| SNOMED CT | 237751000 |
| UMLS | C0001627 |
| MedGen | 7900 |
| GARD | 0001467 |
| MedDRA | 10010323 |
| NORD | 992 |
| Is cancer (heuristic) | no |
Also known as: adrenal hyperplasia · adrenal hyperplasia, congenital · adrenogenital disorder · adrenogenital syndrome · CAH · congenital adrenal gland hyperplasia
Data availability: 131 ClinVar variants.
Disease family
An umbrella term covering 8 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 › steroid inherited metabolic disorder › congenital adrenal hyperplasia
Related subtypes (2): apparent mineralocorticoid excess, congenital bile acid synthesis defect
Subtypes (8): congenital lipoid adrenal hyperplasia due to STAR deficency, congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency, classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency, congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency, congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency, non-classic congenital adrenal hyperplasia, classic congenital adrenal hyperplasia
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
131 retrieved; paginated sample, class counts are floors:
37 pathogenic, 34 pathogenic/likely pathogenic, 34 likely pathogenic, 22 conflicting classifications of pathogenicity, 3 uncertain significance, 1 benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1723345 | NM_000500.9(CYP21A2):c.[710T>A;713T>A] | Pathogenic | criteria provided, single submitter | |
| 31662 | NM_000500.7(CYP21A2):c.[710T>A;713T>A;719T>A] | Pathogenic | criteria provided, multiple submitters, no conflicts | |
| 1073771 | NM_000497.4(CYP11B1):c.421C>T (p.Arg141Ter) | CYP11B1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1179 | NM_000497.4(CYP11B1):c.124C>T (p.Pro42Ser) | CYP11B1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1186 | NM_000497.4(CYP11B1):c.281C>T (p.Pro94Leu) | CYP11B1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1458049 | NM_000497.4(CYP11B1):c.348G>C (p.Trp116Cys) | CYP11B1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 2581368 | NM_000497.4(CYP11B1):c.199del (p.Glu67fs) | CYP11B1 | Pathogenic | criteria provided, single submitter |
| 550599 | NM_000497.4(CYP11B1):c.235T>A (p.Phe79Ile) | CYP11B1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 556405 | NM_000497.4(CYP11B1):c.1361G>A (p.Arg454His) | CYP11B1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 56830 | NM_000497.4(CYP11B1):c.1066C>T (p.Gln356Ter) | CYP11B1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 56831 | NM_000497.4(CYP11B1):c.427C>T (p.Arg143Trp) | CYP11B1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 56833 | NM_000497.4(CYP11B1):c.917C>T (p.Ala306Val) | CYP11B1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 857403 | NM_000497.4(CYP11B1):c.1358G>A (p.Arg453Gln) | CYP11B1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1065950 | NM_000102.4(CYP17A1):c.1117C>T (p.His373Tyr) | CYP17A1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1065951 | NM_000102.4(CYP17A1):c.1117C>G (p.His373Asp) | CYP17A1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1066592 | NM_000102.4(CYP17A1):c.1226C>T (p.Pro409Leu) | CYP17A1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1338524 | NM_000102.4(CYP17A1):c.1319G>A (p.Arg440His) | CYP17A1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1777 | NM_000102.4(CYP17A1):c.1435_1438dup (p.Pro480fs) | CYP17A1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1785 | NM_000102.4(CYP17A1):c.286C>T (p.Arg96Trp) | CYP17A1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1788 | NM_000102.4(CYP17A1):c.1073G>A (p.Arg358Gln) | CYP17A1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1794 | NM_000102.4(CYP17A1):c.1039C>T (p.Arg347Cys) | CYP17A1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1796 | NM_000102.4(CYP17A1):c.1084C>T (p.Arg362Cys) | CYP17A1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1802 | NM_000102.4(CYP17A1):c.287G>A (p.Arg96Gln) | CYP17A1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 2681093 | NM_000102.4(CYP17A1):c.1263G>A (p.Ala421=) | CYP17A1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2681098 | NM_000102.4(CYP17A1):c.995T>C (p.Ile332Thr) | CYP17A1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2681112 | NM_000102.4(CYP17A1):c.973AAG[2] (p.Lys327del) | CYP17A1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2681119 | NM_000102.4(CYP17A1):c.1318C>T (p.Arg440Cys) | CYP17A1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3235268 | NM_000102.4(CYP17A1):c.1169C>G (p.Thr390Arg) | CYP17A1 | Pathogenic | criteria provided, single submitter |
| 12150 | NM_000500.9(CYP21A2):c.518T>A (p.Ile173Asn) | CYP21A2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 12151 | NM_000500.9(CYP21A2):c.844G>T (p.Val282Leu) | CYP21A2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| PORCN | Orphanet:2092 | Focal dermal hypoplasia |
| PORCN | Orphanet:98938 | Colobomatous microphthalmia |
| CYP11A1 | Orphanet:168558 | 46,XY difference of sex development-adrenal insufficiency due to CYP11A1 deficiency |
| CYP11A1 | Orphanet:289548 | Inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency |
| CYP11B1 | Orphanet:403 | Familial hyperaldosteronism type I |
| CYP11B1 | Orphanet:90795 | Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency |
| CYP17A1 | Orphanet:90793 | Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency |
| CYP17A1 | Orphanet:90796 | 46,XY difference of sex development due to isolated 17,20-lyase deficiency |
| CYP21A2 | Orphanet:315306 | Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, salt wasting form |
| CYP21A2 | Orphanet:315311 | Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, simple virilizing form |
| HSD3B2 | Orphanet:90791 | Congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency |
| POR | Orphanet:63269 | Antley-Bixler syndrome with genital anomaly and disorder of steroidogenesis |
| POR | Orphanet:95699 | Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency |
Cohort genes → proteins
7 cohort genes, 7 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 7 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| PORCN | HGNC:17652 | ENSG00000102312 | Q9H237 | Protein-serine O-palmitoleoyltransferase porcupine | clinvar |
| CYP11A1 | HGNC:2590 | ENSG00000140459 | P05108 | Cholesterol side-chain cleavage enzyme, mitochondrial | clinvar |
| CYP11B1 | HGNC:2591 | ENSG00000160882 | P15538 | Cytochrome P450 11B1, mitochondrial | clinvar |
| CYP17A1 | HGNC:2593 | ENSG00000148795 | P05093 | Steroid 17-alpha-hydroxylase/17,20 lyase | clinvar |
| CYP21A2 | HGNC:2600 | ENSG00000231852 | P08686 | Steroid 21-hydroxylase | clinvar |
| HSD3B2 | HGNC:5218 | ENSG00000203859 | P26439 | 3 beta-hydroxysteroid dehydrogenase/Delta 5–>4-isomerase type 2 | clinvar |
| POR | HGNC:9208 | ENSG00000127948 | P16435 | NADPH–cytochrome P450 reductase | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| PORCN | Protein-serine O-palmitoleoyltransferase porcupine | Protein-serine O-palmitoleoyltransferase that acts as a key regulator of the Wnt signaling pathway by mediating the attachment of palmitoleate, a 16-carbon monounsaturated fatty acid (C16:1(9Z)), to Wnt proteins. |
| CYP11A1 | Cholesterol side-chain cleavage enzyme, mitochondrial | A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones. |
| CYP11B1 | Cytochrome P450 11B1, mitochondrial | A cytochrome P450 monooxygenase involved in the biosynthesis of adrenal corticoids. |
| CYP17A1 | Steroid 17-alpha-hydroxylase/17,20 lyase | A cytochrome P450 monooxygenase involved in corticoid and androgen biosynthesis. |
| CYP21A2 | Steroid 21-hydroxylase | A cytochrome P450 monooxygenase that plays a major role in adrenal steroidogenesis. |
| HSD3B2 | 3 beta-hydroxysteroid dehydrogenase/Delta 5–>4-isomerase type 2 | 3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. |
| POR | NADPH–cytochrome P450 reductase | This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. |
Protein-family classification
Druggable: 7 · 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) | 7 | 12.0× | 3e-08 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| PORCN | Enzyme (other) | yes | 2.3.1.250 | MBOAT_fam, LPLAT_7/PORCN-like |
| CYP11A1 | Enzyme (other) | yes | 1.14.15.6 | Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS |
| CYP11B1 | Enzyme (other) | yes | 1.14.15.4 | Cyt_P450, Cyt_P450_mitochondrial, Cyt_P450_CS |
| CYP17A1 | Enzyme (other) | yes | 1.14.14.19 | Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS |
| CYP21A2 | Enzyme (other) | yes | 1.14.14.16 | Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS |
| HSD3B2 | Enzyme (other) | yes | 1.1.1.145 | 3Beta_OHSteriod_DH/Estase, NAD(P)-bd_dom_sf, Lipid_A_modif_metabolic_enz |
| POR | Enzyme (other) | yes | 1.6.2.4 | Flavdoxin-like, OxRdtase_FAD/NAD-bd, Flavoprot_Pyr_Nucl_cyt_Rdtase |
Expression context
Cohort genes with no expression data: 0.
4 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) | 7 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| right adrenal gland | 7 |
| right adrenal gland cortex | 6 |
| left adrenal gland | 3 |
| adrenal tissue | 2 |
| lower esophagus mucosa | 1 |
| adrenal cortex | 1 |
| right lobe of liver | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| PORCN | 184 | ubiquitous | marker | lower esophagus mucosa, right adrenal gland cortex, right adrenal gland |
| CYP11A1 | 136 | broad | marker | adrenal tissue, right adrenal gland, right adrenal gland cortex |
| CYP11B1 | 137 | yes | right adrenal gland cortex, right adrenal gland, left adrenal gland | |
| CYP17A1 | 165 | tissue_specific | yes | right adrenal gland, right adrenal gland cortex, left adrenal gland |
| CYP21A2 | 130 | tissue_specific | marker | right adrenal gland, left adrenal gland, right adrenal gland cortex |
| HSD3B2 | 157 | tissue_specific | yes | right adrenal gland, right adrenal gland cortex, adrenal cortex |
| POR | 266 | ubiquitous | marker | adrenal tissue, right lobe of liver, right adrenal gland |
Protein interactions among cohort
Intra-cohort edges: 4.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| HSD3B2 | 2,968 |
| CYP17A1 | 2,720 |
| POR | 2,263 |
| CYP11A1 | 2,123 |
| CYP11B1 | 1,596 |
| PORCN | 802 |
| CYP21A2 | 28 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| CYP11A1 | HSD3B2 | string_interaction |
| CYP11B1 | HSD3B2 | string_interaction |
| CYP17A1 | HSD3B2 | string_interaction |
| CYP17A1 | POR | string_interaction |
Structural data
PDB: 6 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| CYP17A1 | P05093 | 17 |
| POR | P16435 | 9 |
| PORCN | Q9H237 | 7 |
| CYP11A1 | P05108 | 4 |
| CYP11B1 | P15538 | 2 |
| CYP21A2 | P08686 | 2 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| HSD3B2 | P26439 | 94.30 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 21. Enrichment computed across 7 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Glucocorticoid biosynthesis | 4 | 502.0× | 7e-10 | CYP11B1, CYP17A1, CYP21A2, HSD3B2 |
| Endogenous sterols | 3 | 168.8× | 5e-06 | CYP11A1, CYP11B1, CYP21A2 |
| Mineralocorticoid biosynthesis | 2 | 407.9× | 6e-05 | CYP21A2, HSD3B2 |
| Androgen biosynthesis | 2 | 296.6× | 9e-05 | CYP17A1, HSD3B2 |
| Cytochrome P450 - arranged by substrate type | 2 | 203.9× | 2e-04 | CYP11B1, POR |
| Metabolism of steroid hormones | 2 | 148.3× | 3e-04 | CYP11B1, HSD3B2 |
| Phase I - Functionalization of compounds | 2 | 62.8× | 0.001 | CYP11B1, POR |
| Defective CYP17A1 causes AH5 | 1 | 1631.4× | 0.002 | CYP17A1 |
| LGK974 inhibits PORCN | 1 | 815.7× | 0.002 | PORCN |
| Defective CYP11B1 causes AH4 | 1 | 815.7× | 0.002 | CYP11B1 |
| Defective CYP21A2 causes AH3 | 1 | 815.7× | 0.002 | CYP21A2 |
| Metabolism of steroids | 2 | 39.3× | 0.002 | CYP11B1, HSD3B2 |
| Biological oxidations | 2 | 37.1× | 0.002 | CYP11B1, POR |
| Defective CYP11A1 causes AICSR | 1 | 326.3× | 0.005 | CYP11A1 |
| Metabolic disorders of biological oxidation enzymes | 1 | 125.5× | 0.011 | CYP11B1 |
| Pregnenolone biosynthesis | 1 | 116.5× | 0.011 | CYP11A1 |
| WNT ligand biogenesis and trafficking | 1 | 60.4× | 0.020 | PORCN |
| Metabolism | 3 | 5.0× | 0.020 | CYP11B1, HSD3B2, POR |
| Metabolism of lipids | 2 | 9.0× | 0.021 | CYP11B1, HSD3B2 |
| Diseases of metabolism | 1 | 11.5× | 0.088 | CYP11B1 |
| Disease | 1 | 1.9× | 0.427 | CYP11B1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| glucocorticoid biosynthetic process | 4 | 875.4× | 2e-10 | CYP11A1, CYP11B1, CYP17A1, CYP21A2 |
| cortisol biosynthetic process | 3 | 902.8× | 6e-08 | CYP11B1, CYP17A1, CYP21A2 |
| sterol metabolic process | 3 | 361.1× | 6e-07 | CYP11A1, CYP11B1, CYP21A2 |
| cellular response to peptide hormone stimulus | 3 | 361.1× | 6e-07 | CYP11A1, CYP11B1, POR |
| steroid biosynthetic process | 3 | 257.9× | 1e-06 | CYP17A1, CYP21A2, HSD3B2 |
| cortisol metabolic process | 2 | 802.5× | 2e-05 | CYP11A1, CYP11B1 |
| C21-steroid hormone biosynthetic process | 2 | 535.0× | 3e-05 | CYP11A1, CYP11B1 |
| androgen biosynthetic process | 2 | 535.0× | 3e-05 | CYP17A1, HSD3B2 |
| steroid metabolic process | 2 | 96.3× | 1e-03 | CYP17A1, CYP21A2 |
| nitrate catabolic process | 1 | 2407.4× | 0.002 | POR |
| positive regulation of growth plate cartilage chondrocyte proliferation | 1 | 2407.4× | 0.002 | POR |
| positive regulation of steroid hormone biosynthetic process | 1 | 2407.4× | 0.002 | POR |
| steroid hormone biosynthetic process | 1 | 2407.4× | 0.002 | CYP11A1 |
| cholesterol metabolic process | 2 | 56.0× | 0.002 | CYP11A1, CYP11B1 |
| protein palmitoleylation | 1 | 1203.7× | 0.002 | PORCN |
| nitric oxide catabolic process | 1 | 1203.7× | 0.002 | POR |
| organofluorine metabolic process | 1 | 1203.7× | 0.002 | POR |
| Wnt protein secretion | 1 | 802.5× | 0.003 | PORCN |
| P450-containing electron transport chain | 1 | 802.5× | 0.003 | POR |
| mineralocorticoid biosynthetic process | 1 | 601.9× | 0.004 | CYP21A2 |
| demethylation | 1 | 601.9× | 0.004 | POR |
| protein lipidation | 1 | 481.5× | 0.004 | PORCN |
| C21-steroid hormone metabolic process | 1 | 481.5× | 0.004 | HSD3B2 |
| aldosterone biosynthetic process | 1 | 481.5× | 0.004 | CYP11B1 |
| carnitine metabolic process | 1 | 343.9× | 0.006 | POR |
| flavonoid metabolic process | 1 | 300.9× | 0.006 | POR |
| lipid modification | 1 | 267.5× | 0.007 | PORCN |
| progesterone metabolic process | 1 | 240.7× | 0.007 | CYP17A1 |
| electron transport chain | 1 | 218.9× | 0.008 | POR |
| vitamin D metabolic process | 1 | 218.9× | 0.008 | CYP11A1 |
Therapeutics
Drugs indicated for this disease
6 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.
| Drug | Development status |
|---|---|
| Cortisone Acetate | Approved (phase 4) |
| Crinecerfont | Approved (phase 4) |
| Dexamethasone | Approved (phase 4) |
| Hydrocortisone | Approved (phase 4) |
| Prednisolone | Approved (phase 4) |
| Prednisone | Approved (phase 4) |
Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Abiraterone Acetate, Fludrocortisone Acetate.
Drug target analysis
Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 6 · Undrugged: 1
Druggability breadth: 7 of 7 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 |
|---|---|
| CYP11A1 | AMINOGLUTETHIMIDE |
| CYP11B1 | FLUCONAZOLE |
| CYP17A1 | CLOTRIMAZOLE |
| CYP21A2 | KETOCONAZOLE |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| CYP17A1 | 16 | 4 |
| CYP11B1 | 13 | 4 |
| CYP21A2 | 4 | 4 |
| PORCN | 2 | 2 |
| CYP11A1 | 1 | 4 |
| POR | 1 | 2 |
| HSD3B2 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| AMINOGLUTETHIMIDE | 4 | CYP11A1, CYP17A1 |
| FLUCONAZOLE | 4 | CYP11B1 |
| POSACONAZOLE | 4 | CYP11B1, CYP17A1 |
| LETROZOLE | 4 | CYP11B1 |
| KETOCONAZOLE | 4 | CYP11B1, CYP17A1, CYP21A2 |
| ABIRATERONE | 4 | CYP11B1, CYP17A1, CYP21A2 |
| OSILODROSTAT | 4 | CYP11B1, CYP17A1 |
| ETOMIDATE | 4 | CYP11B1 |
| METYRAPONE | 4 | CYP11B1 |
| CLOTRIMAZOLE | 4 | CYP17A1 |
| TESTOSTERONE PROPIONATE | 4 | CYP17A1 |
| TIOCONAZOLE | 4 | CYP17A1 |
| ISOCONAZOLE | 4 | CYP17A1 |
| ABIRATERONE ACETATE | 4 | CYP17A1 |
| BIFONAZOLE | 4 | CYP17A1 |
| ECONAZOLE | 4 | CYP17A1 |
| MICONAZOLE | 4 | CYP17A1 |
| BAXDROSTAT | 3 | CYP11B1 |
| ORTERONEL | 3 | CYP17A1, CYP21A2 |
| GALETERONE | 3 | CYP17A1, CYP21A2 |
| WNT-974 | 2 | PORCN |
| VOROZOLE | 2 | CYP11B1 |
| DEXFADROSTAT | 2 | CYP11B1 |
| AZALANSTAT | 2 | CYP11B1, CYP17A1 |
| FADROZOLE | 2 | CYP11B1 |
| LAPACHONE | 2 | POR |
| ETC-159 | 1 | PORCN |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 7.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| CYP17A1 | 239 | Binding:198, ADMET:37, Functional:4 |
| CYP11B1 | 113 | Binding:95, ADMET:16, Functional:2 |
| PORCN | 31 | Binding:31 |
| POR | 21 | ADMET:14, Binding:7 |
| CYP21A2 | 15 | Binding:10, ADMET:5 |
| HSD3B2 | 3 | Binding:3 |
| CYP11A1 | 1 | Functional:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| PORCN | 2.3.1.250 | [Wnt protein] O-palmitoleoyl transferase |
| CYP11A1 | 1.14.15.6 | cholesterol monooxygenase (side-chain-cleaving) |
| CYP11B1 | 1.14.15.4 | steroid 11beta-monooxygenase |
| CYP17A1 | 1.14.14.19, 1.14.14.32 | steroid 17alpha-monooxygenase, 17alpha-hydroxyprogesterone deacetylase |
| CYP21A2 | 1.14.14.16 | steroid 21-monooxygenase |
| HSD3B2 | 1.1.1.145, 5.3.3.1 | 3beta-hydroxy-DELTA5-steroid dehydrogenase, steroid DELTA-isomerase |
| POR | 1.6.2.4 | NADPH-hemoprotein reductase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| CYP11B1 | 113 |
| CYP17A1 | 239 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
26 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) |
|---|---|---|
| AMINOGLUTETHIMIDE | 4 | CYP11A1, CYP17A1 |
| FLUCONAZOLE | 4 | CYP11B1 |
| POSACONAZOLE | 4 | CYP11B1, CYP17A1 |
| KETOCONAZOLE | 4 | CYP11B1, CYP17A1, CYP21A2 |
| ABIRATERONE | 4 | CYP11B1, CYP17A1, CYP21A2 |
| OSILODROSTAT | 4 | CYP11B1, CYP17A1 |
| ETOMIDATE | 4 | CYP11B1 |
| METYRAPONE | 4 | CYP11B1 |
| CLOTRIMAZOLE | 4 | CYP17A1 |
| TESTOSTERONE PROPIONATE | 4 | CYP17A1 |
| TIOCONAZOLE | 4 | CYP17A1 |
| ISOCONAZOLE | 4 | CYP17A1 |
| ABIRATERONE ACETATE | 4 | CYP17A1 |
| BIFONAZOLE | 4 | CYP17A1 |
| ECONAZOLE | 4 | CYP17A1 |
| MICONAZOLE | 4 | CYP17A1 |
| BAXDROSTAT | 3 | CYP11B1 |
| ORTERONEL | 3 | CYP17A1, CYP21A2 |
| GALETERONE | 3 | CYP17A1, CYP21A2 |
| WNT-974 | 2 | PORCN |
| VOROZOLE | 2 | CYP11B1 |
| DEXFADROSTAT | 2 | CYP11B1 |
| AZALANSTAT | 2 | CYP11B1, CYP17A1 |
| FADROZOLE | 2 | CYP11B1 |
| LAPACHONE | 2 | POR |
| ETC-159 | 1 | PORCN |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 4 | CYP11A1, CYP11B1, CYP17A1, CYP21A2 |
| B | Phased (≥1) drug, not yet approved | 2 | PORCN, POR |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 1 | HSD3B2 |
| E | Difficult family or no structure, no drug | 0 |
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) |
|---|---|---|
| HSD3B2 | 3 | CYP17A1, CYP11A1, CYP11B1 |
Clinical trials & evidence
Clinical trials
Clinical trials: 83.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 45 |
| PHASE2 | 16 |
| PHASE3 | 9 |
| PHASE1 | 5 |
| PHASE1/PHASE2 | 4 |
| PHASE4 | 2 |
| PHASE2/PHASE3 | 2 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT03760835 | PHASE4 | RECRUITING | Congenital Adrenal Hyperplasia Once Daily Hydrocortisone Treatment |
| NCT04536662 | PHASE4 | UNKNOWN | Comparisons of Different Forms of Glucocorticoid on the Recovery of Reproductive Function in Patients With 21α-hydroxylase Deficiency |
| NCT04490915 | PHASE3 | ACTIVE_NOT_RECRUITING | Global Safety and Efficacy Registration Study of Crinecerfont for Congenital Adrenal Hyperplasia |
| NCT04806451 | PHASE3 | ACTIVE_NOT_RECRUITING | Global Safety and Efficacy Registration Study of Crinecerfont in Pediatric Participants With Classic Congenital Adrenal Hyperplasia (CAHtalyst Pediatric Study) |
| NCT07144163 | PHASE3 | RECRUITING | A Study to Evaluate Atumelnant in Adults With Congenital Adrenal Hyperplasia |
| NCT07159841 | PHASE2/PHASE3 | RECRUITING | A Study in Pediatric Participants With Congenital Adrenal Hyperplasia (Balance-CAH) |
| NCT00001521 | PHASE3 | COMPLETED | Three Drug Combination Therapy Versus Conventional Treatment of Children With Congenital Adrenal Hyperplasia |
| NCT02552251 | PHASE2/PHASE3 | UNKNOWN | COrticosteroid in Congenital Adrenal Hyperplasia |
| NCT02716818 | PHASE3 | COMPLETED | Comparison of Chronocort® With Standard Glucocorticoid Therapy in Patients With Congenital Adrenal Hyperplasia |
| NCT03062280 | PHASE3 | COMPLETED | A Study of the Efficacy, Safety and Tolerability of Chronocort in Treating CAH |
| NCT03532022 | PHASE3 | WITHDRAWN | Open-label Comparison of Chronocort® Versus Standard Glucocorticoid Replacement Therapy |
| NCT05063994 | PHASE3 | COMPLETED | Comparison of Chronocort Versus Standard Hydrocortisone Replacement Therapy in Participants Aged 16 Years and Over With Congenital Adrenal Hyperplasia |
| NCT05299554 | PHASE3 | COMPLETED | Long-term Safety Study of Chronocort in the Treatment of Participants With Congenital Adrenal Hyperplasia |
| NCT04783181 | PHASE1/PHASE2 | ACTIVE_NOT_RECRUITING | A Study of Gene Therapy for Classic Congenital Adrenal Hyperplasia (CAH) |
| NCT05669950 | PHASE1/PHASE2 | RECRUITING | A Trial of Lu AG13909 in Participants With Congenital Adrenal Hyperplasia |
| NCT06712823 | PHASE2 | RECRUITING | An Extension Study to Evaluate Safety and Efficacy in Participants Treated With CRN04894 |
| NCT07187375 | PHASE2 | RECRUITING | Pharmacokinetics, Safety and Tolerability of Crinecerfont in Participants With Congenital Adrenal Hyperplasia Who Are Less Than 2 Years Old |
| NCT07536269 | PHASE2 | NOT_YET_RECRUITING | Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Crinecerfont in Participants With Classic Congenital Adrenal Hyperplasia (CAH) Who Are Less Than 4 Years Old |
| NCT00000102 | PHASE1/PHASE2 | COMPLETED | Congenital Adrenal Hyperplasia: Calcium Channels as Therapeutic Targets |
| NCT00519818 | PHASE1/PHASE2 | COMPLETED | Comparison of Two Forms of Hydrocortisone in Patients With Congenital Adrenal Hyperplasia |
| NCT00621985 | PHASE2 | COMPLETED | Dexamethasone Treatment of Congenital Adrenal Hyperplasia |
| NCT01735617 | PHASE2 | COMPLETED | Pilot Study to Characterize and Examine the Pharmacokinetics and Efficacy of Chronocort® in Adults With CAH |
| NCT01771328 | PHASE2 | UNKNOWN | Continuous Subcutaneous Hydrocortisone Infusion in Congenital Adrenal Hyperplasia |
| NCT01859312 | PHASE2 | COMPLETED | Comparison of Cortisol Pump With Standard Treatment for Congenital Adrenal Hyperplasia |
| NCT02804178 | PHASE2 | COMPLETED | A Study of ATR-101 for the Treatment of Congenital Adrenal Hyperplasia |
| NCT03257462 | PHASE2 | COMPLETED | Study of SPR001 in Adults With Classic Congenital Adrenal Hyperplasia |
| NCT03548246 | PHASE2 | WITHDRAWN | Androgen Reduction in Congenital Adrenal Hyperplasia |
| NCT03669549 | PHASE2 | TERMINATED | Nevanimibe HCl for the Treatment of Classic CAH |
| NCT03687242 | PHASE2 | COMPLETED | Study to Evaluate the Safety and Efficacy of SPR001 in Subjects With Classic Congenital Adrenal Hyperplasia |
| NCT04457336 | PHASE2 | TERMINATED | A Ph2b to Evaluate Clinical Efficacy and Safety of Tildacerfont in Adult CAH |
| NCT04544410 | PHASE2 | TERMINATED | A Ph2b to Evaluate Tildacerfont in the Reduction of Glucocorticoid Steroid Doses in Adult CAH |
| NCT05128942 | PHASE2 | TERMINATED | A Phase 2 Study to Evaluate the Safety, Efficacy and PK of Tildacerfont in Children Aged 2-17 Years With CAH |
| NCT05907291 | PHASE2 | COMPLETED | Evaluate the Safety, Efficacy, and Pharmacokinetics of CRN04894 in Participants With Congenital Adrenal Hyperplasia (TouCAHn) |
| NCT02349503 | PHASE1 | WITHDRAWN | Safety, Pharmacokinetics and Pharmacodynamics of NBI-77860 in Adolescent Females With Congenital Adrenal Hyperplasia |
| NCT02574910 | PHASE1 | TERMINATED | Androgen Reduction in Congenital Adrenal Hyperplasia, Phase 1 |
| NCT03019614 | PHASE1 | COMPLETED | An Open Label Study in Healthy Volunteers to Compare Chronocort® to Hydrocortisone |
| NCT03051893 | PHASE1 | COMPLETED | A Two-part, Study to Compare the Pharmacokinetics and Dose Proportionality of up to 6 Chronocort Formulations |
| NCT03718234 | PHASE1 | COMPLETED | Subcutaneous Hydrocortisone Children With Congenital Adrenal Hyperplasia |
| NCT00250159 | Not specified | RECRUITING | Natural History Study of Patients With Excess Androgen |
| NCT04252001 | Not specified | NOT_YET_RECRUITING | Growing up With the Young Endocrine Support System (YESS!) |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| CRINECERFONT | 4 | 4 |
| CORTISONE ACETATE | 4 | 2 |
| FLUDROCORTISONE ACETATE | 4 | 2 |
| HYDROCORTISONE | 4 | 2 |
| HYDROCORTISONE CYPIONATE | 4 | 2 |
| FLUTAMIDE | 4 | 1 |
| LETROZOLE | 4 | 1 |
| NIFEDIPINE | 4 | 1 |
| PREDNISOLONE | 4 | 1 |
| PREDNISONE | 4 | 1 |
| TESTOLACTONE | 4 | 1 |
| TILDACERFONT | 2 | 5 |
| ATUMELNANT | 2 | 4 |
| NEVANIMIBE | 2 | 3 |
| FLUDROCORTISONE | 2 | 2 |
| VERUCERFONT | 2 | 1 |
| CHEMBL4740452 | 0 | 2 |
| CHEMBL15720 | 0 | 1 |
| CHEMBL166839 | 0 | 1 |
| CHEMBL4759307 | 0 | 1 |
Related Atlas pages
- Cohort genes: PORCN, CYP11A1, CYP11B1, CYP17A1, CYP21A2, HSD3B2, POR
- Drugs: Crinecerfont, Cortisone Acetate, Fludrocortisone Acetate, Hydrocortisone, Hydrocortisone Cypionate, Flutamide, Letrozole, Nifedipine, Prednisolone, Prednisone, Testolactone