Kennedy disease

Summary

Kennedy disease (MONDO:0010735) is a disease caused by AR (GenCC Definitive), with 2 cohort genes and 11 clinical trials. Top therapeutic interventions include dutasteride and goserelin.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: AR (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 667
• Phenotypes (HPO): 13
• Clinical trials: 11

Clinical features

Epidemiology

Prevalence records

5 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	3.8	Europe	Validated
Annual incidence	<1 / 1 000 000	0.09	Italy	Validated
Point prevalence	1-9 / 100 000		Italy	Validated
Point prevalence	1-9 / 100 000	7.6	Finland	Validated
Prevalence at birth	1-9 / 100 000	1.6	Italy	Validated

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0000144	Decreased fertility	Very frequent (80-99%)
HP:0000771	Gynecomastia	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001260	Dysarthria	Very frequent (80-99%)
HP:0001265	Hyporeflexia	Very frequent (80-99%)
HP:0001288	Gait disturbance	Very frequent (80-99%)
HP:0001618	Dysphonia	Very frequent (80-99%)
HP:0003202	Skeletal muscle atrophy	Very frequent (80-99%)
HP:0100022	Abnormality of movement	Very frequent (80-99%)
HP:0100639	Erectile dysfunction	Very frequent (80-99%)
HP:0000029	Testicular atrophy	Occasional (5-29%)
HP:0003119	Abnormal circulating lipid concentration	Occasional (5-29%)
HP:0005978	Type II diabetes mellitus	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Kennedy disease
Mondo ID	MONDO:0010735
MeSH	D055534
OMIM	313200
Orphanet	481
DOID	DOID:0060161
NCIT	C85233
UMLS	C1839259
MedGen	333282
GARD	0006818
MedDRA	10068600
Is cancer (heuristic)	no

Also known as: Kennedy disease · Kennedy’s disease · SBMA · SMAX1 · spinal and bulbar muscular atrophy of Kennedy, X-linked recessive · spinal and bulbar muscular atrophy, X-linked 1 · spinal and bulbar muscular atrophy, X-linked type 1 · X-linked BSMA · X-linked bulbospinal amyotrophy · X-linked bulbospinal muscular atrophy · X-linked spinal and bulbar muscular atrophy

Data availability: 667 ClinVar variants · 5 GenCC gene-disease records · 27 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › inherited neurodegenerative disorder › Kennedy disease

Related subtypes (81): Huntington disease and related disorders, agenesis of the corpus callosum with peripheral neuropathy, striatonigral degeneration, angioid streaks of choroid, amyotrophic lateral sclerosis-parkinsonism-dementia complex, inherited Creutzfeldt-Jakob disease, mitochondrial DNA depletion syndrome 4a, cerebellar ataxia-hypogonadism syndrome, myoclonic cerebellar dyssynergia, cerebral sclerosis similar to Pelizaeus-Merzbacher disease, Chediak-Higashi syndrome, encephalopathy due to beta-mercaptolactate-cysteine disulfiduria, PEHO syndrome, deafness dystonia syndrome, fatal familial insomnia, Huntington disease-like 1, neuronal intranuclear inclusion disease, ataxia-telangiectasia-like disorder, radiation sensitivity/chromosome instability syndrome, autosomal dominant, Huntington disease-like 2, microphthalmia-brain atrophy syndrome, neurodegenerative syndrome due to cerebral folate transport deficiency, hereditary sensory neuropathy-deafness-dementia syndrome, infantile cerebellar-retinal degeneration, Alzheimer disease 17, hypotonia, infantile, with psychomotor retardation and characteristic facies, Alzheimer disease 18, diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome, severe neurodegenerative syndrome with lipodystrophy, developmental and epileptic encephalopathy, 35, combined oxidative phosphorylation deficiency 29, neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, neuronal ceroid lipofuscinosis, frontotemporal dementia with motor neuron disease, frontotemporal dementia, GM2 gangliosidosis, attenuated Chédiak-Higashi syndrome, autosomal recessive cerebral atrophy, neurodegeneration with brain iron accumulation, fatal post-viral neurodegenerative disorder, ferro-cerebro-cutaneous syndrome, PRKAR1B-related neurodegenerative dementia with intermediate filaments, ITM2B amyloidosis, corticobasal syndrome, infantile-onset axonal motor and sensory neuropathy-optic atrophy-neurodegenerative syndrome, recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome, posterior cortical atrophy, progressive supranuclear palsy, leukodystrophy, hereditary spastic paraplegia, facial onset sensory and motor neuronopathy, X-linked neurodegenerative syndrome, Bertini type, X-linked neurodegenerative syndrome, Hamel type, boylan dew greco syndrome, hereditary motor neuron disease, neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline, frontotemporal dementia and/or amyotrophic lateral sclerosis, neurodegeneration, childhood-onset, with hypotonia, respiratory insufficiency, and brain imaging abnormalities, neurodegeneration with ataxia and late-onset optic atrophy, neurodegeneration, childhood-onset, with cerebellar atrophy, neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia, neurodegeneration, infantile-onset, biotin-responsive, hereditary optic atrophy, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome, familial Alzheimer disease, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, hereditary cerebellar ataxia, DCTN1-related neurodegeneration, early-childhood-onset neurodegeneration with retinitis pigmentosa, sensorineural hearing loss, and demyelinating peripheral neuropathy, TUBB4A-related neurologic disorder, neurodegeneration, childhood-onset, with progressive microcephaly, neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, neurodegeneration and seizures due to copper transport defect, neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, neurodegenerative disorder, X-linked, female-restricted, with parkinsonism and cognitive impairment, neurodegenerative disorder with cerebellar and caudate atrophy, APP-related brain and vascular amyloidosis

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

600 retrieved; paginated sample, class counts are floors:

254 likely benign, 105 pathogenic, 84 benign, 73 uncertain significance, 28 benign/likely benign, 24 conflicting classifications of pathogenicity, 21 likely pathogenic, 10 pathogenic/likely pathogenic, 1 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065434	NM_000044.6(AR):c.2237T>C (p.Met746Thr)	AR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068775	NM_000044.6(AR):c.2225G>T (p.Trp742Leu)	AR	Pathogenic	criteria provided, single submitter
1071361	NC_000023.10:g.(?66905832)(66905988_?)del	AR	Pathogenic	criteria provided, single submitter
1071362	NC_000023.10:g.(?66863078)(66943703_?)del	AR	Pathogenic	criteria provided, single submitter
1072748	NM_000044.6(AR):c.1737del (p.Cys580fs)	AR	Pathogenic	criteria provided, single submitter
1076800	NM_000044.6(AR):c.1063G>T (p.Glu355Ter)	AR	Pathogenic	criteria provided, multiple submitters, no conflicts
1298359	NM_000044.6(AR):c.2255G>A (p.Trp752Ter)	AR	Pathogenic	criteria provided, multiple submitters, no conflicts
1338469	NM_000044.6(AR):c.2197G>A (p.Asp733Asn)	AR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1342730	NM_000044.6(AR):c.2494C>T (p.Arg832Ter)	AR	Pathogenic	criteria provided, multiple submitters, no conflicts
1344505	NM_000044.6(AR):c.2407dup (p.Gln803fs)	AR	Pathogenic	criteria provided, multiple submitters, no conflicts
1368614	NM_000044.6(AR):c.1443C>A (p.Tyr481Ter)	AR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1394063	NM_000044.6(AR):c.2319_2321dup (p.Tyr774Ter)	AR	Pathogenic	criteria provided, single submitter
1410848	NM_000044.6(AR):c.1477C>T (p.Gln493Ter)	AR	Pathogenic	criteria provided, single submitter
1421027	NM_000044.6(AR):c.358C>T (p.Gln120Ter)	AR	Pathogenic	criteria provided, single submitter
1437090	NM_000044.6(AR):c.1885+2T>G	AR	Pathogenic	criteria provided, single submitter
1454388	NC_000023.10:g.(?66941655)(66943683_?)del	AR	Pathogenic	criteria provided, single submitter
1454419	NM_000044.6(AR):c.1707del (p.Cys570fs)	AR	Pathogenic	criteria provided, single submitter
1454671	NM_000044.6(AR):c.829_833dup (p.Val279fs)	AR	Pathogenic	criteria provided, single submitter
1455502	NM_000044.6(AR):c.2512G>T (p.Glu838Ter)	AR	Pathogenic	criteria provided, single submitter
1460010	NC_000023.10:g.(?66931224)(66931551_?)del	AR	Pathogenic	criteria provided, single submitter
1460367	NM_000044.6(AR):c.2515C>A (p.Leu839Ile)	AR	Pathogenic	criteria provided, single submitter
1470535	NM_000044.6(AR):c.1A>T (p.Met1Leu)	AR	Pathogenic	criteria provided, multiple submitters, no conflicts
1518028	NM_000044.6(AR):c.2750del (p.Phe917fs)	AR	Pathogenic	criteria provided, single submitter
1803254	NM_000044.6(AR):c.1605del (p.Pro534_Tyr535insTer)	AR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1999095	NM_000044.6(AR):c.1224T>A (p.Tyr408Ter)	AR	Pathogenic	criteria provided, single submitter
2001392	NM_000044.6(AR):c.304A>T (p.Arg102Ter)	AR	Pathogenic	criteria provided, single submitter
2016344	NM_000044.6(AR):c.2191_2199del (p.Val731_Asp733del)	AR	Pathogenic	criteria provided, single submitter
2017437	NM_000044.6(AR):c.733del (p.Val245fs)	AR	Pathogenic	criteria provided, single submitter
2067703	NM_000044.6(AR):c.2162dup (p.Ala722fs)	AR	Pathogenic	criteria provided, single submitter
2077770	NM_000044.6(AR):c.1756A>T (p.Arg586Ter)	AR	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 26 · Orphanet: 4 · 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
AR	Definitive	X-linked	Kennedy disease	13
AREG	Definitive	X-linked	Kennedy disease	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AR	Orphanet:481	Kennedy disease
AR	Orphanet:90797	Partial androgen insensitivity syndrome
AR	Orphanet:95706	Non-syndromic posterior hypospadias
AR	Orphanet:99429	Complete androgen insensitivity syndrome

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
AR	HGNC:644	ENSG00000169083	P10275	Androgen receptor	gencc,clinvar
AREG	HGNC:651	ENSG00000109321	P15514	Amphiregulin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AR	Androgen receptor	Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.
AREG	Amphiregulin	Ligand of the EGF receptor/EGFR.

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
Nuclear receptor	1	192.9×	0.010
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AR	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Andrgn_rcpt, Znf_hrmn_rcpt
AREG	Other/Unknown	no		EGF

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
nipple	1
seminal vesicle	1
urethra	1
endometrium epithelium	1
mucosa of urinary bladder	1
right lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AR	250	ubiquitous	marker	seminal vesicle, urethra, nipple
AREG	216	ubiquitous	marker	mucosa of urinary bladder, endometrium epithelium, right lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AR	7,400
AREG	2,745

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AR	P10275	95
AREG	P15514	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 63. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by Overexpressed Wild-Type EGFR in Cancer	1	1427.5×	0.016	AREG
Inhibition of Signaling by Overexpressed EGFR	1	634.4×	0.016	AREG
Signaling by EGFR in Cancer	1	571.0×	0.016	AREG
EGFR interacts with phospholipase C-gamma	1	571.0×	0.016	AREG
NFE2L2 regulating tumorigenic genes	1	475.8×	0.016	AREG
RUNX2 regulates bone development	1	407.9×	0.016	AR
GRB2 events in EGFR signaling	1	380.7×	0.016	AREG
SHC1 events in EGFR signaling	1	356.9×	0.016	AREG
Cellular responses to stress	2	36.8×	0.016	AR, AREG
Cellular responses to stimuli	2	31.5×	0.016	AR, AREG
Post-translational protein modification	2	19.2×	0.016	AR, AREG
GAB1 signalosome	1	317.2×	0.017	AREG
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	271.9×	0.017	AREG
RUNX2 regulates osteoblast differentiation	1	228.4×	0.017	AR
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	228.4×	0.017	AREG
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	1	219.6×	0.017	AREG
PI3K/AKT Signaling in Cancer	1	184.2×	0.017	AREG
EGFR downregulation	1	173.0×	0.017	AREG
SUMOylation of intracellular receptors	1	167.9×	0.017	AR
Cargo concentration in the ER	1	167.9×	0.017	AREG
Nuclear events mediated by NFE2L2	1	167.9×	0.017	AREG
Signaling by EGFR	1	163.1×	0.017	AREG
RHO GTPases activate PKNs	1	158.6×	0.017	AR
Metabolism of proteins	2	12.4×	0.017	AR, AREG
Negative regulation of the PI3K/AKT network	1	139.3×	0.018	AREG
Transcriptional regulation by RUNX2	1	126.9×	0.019	AR
Nuclear Receptor transcription pathway	1	100.2×	0.022	AR
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	96.8×	0.022	AR
Signal Transduction	2	10.2×	0.022	AR, AREG
SUMO E3 ligases SUMOylate target proteins	1	89.2×	0.023	AR

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
mammary gland alveolus development	2	991.3×	6e-05	AR, AREG
male somatic sex determination	1	8426.0×	0.002	AR
prostate induction	1	8426.0×	0.002	AR
regulation of developmental growth	1	4213.0×	0.002	AR
lateral sprouting involved in mammary gland duct morphogenesis	1	4213.0×	0.002	AR
positive regulation of integrin biosynthetic process	1	2808.7×	0.002	AR
dichotomous subdivision of terminal units involved in mammary gland duct morphogenesis	1	2808.7×	0.002	AREG
tertiary branching involved in mammary gland duct morphogenesis	1	2808.7×	0.002	AR
positive regulation of epithelial cell proliferation involved in prostate gland development	1	2808.7×	0.002	AR
cell-cell signaling	2	69.6×	0.002	AR, AREG
morphogenesis of an epithelial fold	1	2106.5×	0.003	AR
animal organ formation	1	1685.2×	0.003	AR
male genitalia morphogenesis	1	1685.2×	0.003	AR
epithelial cell differentiation involved in prostate gland development	1	1685.2×	0.003	AR
mammary gland branching involved in thelarche	1	1404.3×	0.003	AREG
epithelial cell proliferation involved in mammary gland duct elongation	1	1404.3×	0.003	AREG
cellular response to testosterone stimulus	1	1203.7×	0.003	AR
positive regulation of cell population proliferation	2	33.6×	0.003	AR, AREG
prostate gland growth	1	1053.2×	0.003	AR
prostate gland epithelium morphogenesis	1	936.2×	0.004	AR
ERBB2-EGFR signaling pathway	1	842.6×	0.004	AREG
positive regulation of intracellular estrogen receptor signaling pathway	1	601.9×	0.004	AR
Leydig cell differentiation	1	601.9×	0.004	AR
positive regulation of insulin-like growth factor receptor signaling pathway	1	601.9×	0.004	AR
membraneless organelle assembly	1	561.7×	0.004	AR
regulation of systemic arterial blood pressure	1	526.6×	0.004	AR
cellular response to steroid hormone stimulus	1	526.6×	0.004	AR
positive regulation of keratinocyte proliferation	1	495.6×	0.004	AREG
intracellular receptor signaling pathway	1	495.6×	0.004	AR
epithelial cell morphogenesis	1	468.1×	0.004	AR

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Dutasteride.

Drug target analysis

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

Druggability breadth: 2 of 2 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
AR	PROGESTERONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AR	116	4
AREG	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PROGESTERONE	4	AR
ENZALUTAMIDE	4	AR
HYDROCORTISONE ACETATE	4	AR
EPLERENONE	4	AR
CHLORMADINONE ACETATE	4	AR
ARIPIPRAZOLE	4	AR
MOMETASONE FUROATE	4	AR
TESTOSTERONE PROPIONATE	4	AR
ESTRADIOL ACETATE	4	AR
OXANDROLONE	4	AR
BECLOMETHASONE DIPROPIONATE	4	AR
DIFLORASONE DIACETATE	4	AR
ETHYNODIOL DIACETATE	4	AR
HALCINONIDE	4	AR
DYDROGESTERONE	4	AR
FLUMETHASONE PIVALATE	4	AR
HALOBETASOL PROPIONATE	4	AR
ESTRADIOL CYPIONATE	4	AR
CLOCORTOLONE PIVALATE	4	AR
FLURANDRENOLIDE	4	AR
MEGESTROL ACETATE	4	AR
NORETHINDRONE ACETATE	4	AR
SERTACONAZOLE	4	AR
PYRVINIUM	4	AR
PRASUGREL	4	AR
OXICONAZOLE	4	AR
NILUTAMIDE	4	AR
MIFEPRISTONE	4	AR
PREDNISOLONE	4	AR
ESTRADIOL	4	AR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
AR	2,100	Binding:1727, Functional:339, ADMET:33, Unclassified:1
AREG	1	Functional:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
AR	2,100

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

30 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)
PROGESTERONE	4	AR
ENZALUTAMIDE	4	AR
HYDROCORTISONE ACETATE	4	AR
EPLERENONE	4	AR
CHLORMADINONE ACETATE	4	AR
ARIPIPRAZOLE	4	AR
MOMETASONE FUROATE	4	AR
TESTOSTERONE PROPIONATE	4	AR
ESTRADIOL ACETATE	4	AR
OXANDROLONE	4	AR
BECLOMETHASONE DIPROPIONATE	4	AR
DIFLORASONE DIACETATE	4	AR
ETHYNODIOL DIACETATE	4	AR
HALCINONIDE	4	AR
DYDROGESTERONE	4	AR
FLUMETHASONE PIVALATE	4	AR
HALOBETASOL PROPIONATE	4	AR
ESTRADIOL CYPIONATE	4	AR
CLOCORTOLONE PIVALATE	4	AR
FLURANDRENOLIDE	4	AR
MEGESTROL ACETATE	4	AR
NORETHINDRONE ACETATE	4	AR
SERTACONAZOLE	4	AR
PYRVINIUM	4	AR
PRASUGREL	4	AR
OXICONAZOLE	4	AR
NILUTAMIDE	4	AR
MIFEPRISTONE	4	AR
PREDNISOLONE	4	AR
ESTRADIOL	4	AR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	AR
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	AREG

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)
AREG	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 11.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	7
PHASE2	2
PHASE4	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00851461	PHASE4	COMPLETED	Effect of Goserelin (Zoladex®) in Spinal and Bulbar Muscular Atrophy
NCT00303446	PHASE2	COMPLETED	Dutasteride to Treat Spinal and Bulbar Muscular Atrophy (SBMA)
NCT05517603	PHASE1/PHASE2	COMPLETED	A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Of AJ201 In Patients
NCT06411912	PHASE2	COMPLETED	A Study of NIDO-361 in Patients With SBMA
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT05966038	Not specified	RECRUITING	ALS/MND Natural History Study Data Repository
NCT07443449	Not specified	ACTIVE_NOT_RECRUITING	International SBMA Project (KDA)
NCT01984957	Not specified	COMPLETED	Differential Study of Muscle Transcriptome
NCT02501395	Not specified	COMPLETED	MRI in Patients With Kennedy Disease
NCT03560661	Not specified	COMPLETED	Acoustic and Perceptual Markers of Dysarthria in Amyotrophic Lateral Sclerosis (ALS)
NCT05107349	Not specified	UNKNOWN	Cell Signaling, Reinnervation and Metabolism in Kennedy Disease and Amyotrophic Lateral Sclerosis (ALS)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DUTASTERIDE	4	1
GOSERELIN	4	1