Turner syndrome

Summary

Turner syndrome (MONDO:0019499) is a disease with 6 cohort genes and 94 clinical trials. Top therapeutic interventions include somatropin, estradiol, and lonapegsomatropin.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 6
• ClinVar variants: 7
• Phenotypes (HPO): 115
• Clinical trials: 94

Clinical features

Epidemiology

Prevalence records

23 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	5.5	Europe	Validated
Prevalence at birth	1-9 / 100 000	7.5	Austria	Validated
Prevalence at birth	1-9 / 100 000	7.9	Belgium	Validated
Prevalence at birth	1-5 / 10 000	10.5	Bulgaria	Validated
Prevalence at birth	1-9 / 100 000	3.6	Croatia	Validated
Prevalence at birth	1-5 / 10 000	10.4	Denmark	Validated
Prevalence at birth	1-9 / 100 000	7.1	France	Validated
Prevalence at birth	1-9 / 100 000	8	Germany	Validated
Prevalence at birth	1-9 / 100 000	3.2	Hungary	Validated
Prevalence at birth	1-9 / 100 000	7.1	Ireland	Validated
Prevalence at birth	1-9 / 100 000	3.4	Italy	Validated
Prevalence at birth	1-9 / 100 000	1.1	Malta	Validated
Prevalence at birth	1-5 / 10 000	14	Netherlands	Validated
Prevalence at birth	1-9 / 100 000	4.2	Norway	Validated
Prevalence at birth	1-9 / 100 000	3.6	Poland	Validated
Prevalence at birth	1-9 / 100 000	2.8	Portugal	Validated
Prevalence at birth	1-9 / 100 000	2.8	Spain	Validated
Prevalence at birth	1-5 / 10 000	22.4	Switzerland	Validated
Prevalence at birth	1-5 / 10 000	10.1	United Kingdom	Validated
Prevalence at birth	1-9 / 100 000	2.3	Ukraine	Validated

Signs & symptoms

Clinical features (HPO)

115 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000133	Gonadal dysgenesis	Very frequent (80-99%)
HP:0000137	Abnormality of the ovary	Very frequent (80-99%)
HP:0000470	Short neck	Very frequent (80-99%)
HP:0000823	Delayed puberty	Very frequent (80-99%)
HP:0000837	Increased circulating gonadotropin level	Very frequent (80-99%)
HP:0000879	Short sternum	Very frequent (80-99%)
HP:0000938	Osteopenia	Very frequent (80-99%)
HP:0000939	Osteoporosis	Very frequent (80-99%)
HP:0001510	Growth delay	Very frequent (80-99%)
HP:0001511	Intrauterine growth retardation	Very frequent (80-99%)
HP:0002750	Delayed skeletal maturation	Very frequent (80-99%)
HP:0002967	Cubitus valgus	Very frequent (80-99%)
HP:0003492	High urinary gonadotropins (primary hypogonadism)	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0006610	Wide intermamillary distance	Very frequent (80-99%)
HP:0006709	Aplasia/Hypoplasia of the nipples	Very frequent (80-99%)
HP:0008209	Premature ovarian insufficiency	Very frequent (80-99%)
HP:0008222	Female infertility	Very frequent (80-99%)
HP:0008897	Postnatal growth retardation	Very frequent (80-99%)
HP:0012774	Increased upper to lower segment ratio	Very frequent (80-99%)
HP:0040072	Abnormal forearm bone morphology	Very frequent (80-99%)
HP:0100625	Enlarged thorax	Very frequent (80-99%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Frequent (30-79%)
HP:0005113	Dilatation of the aortic arch	Frequent (30-79%)
HP:0005689	Dermatoglyphic ridges abnormal	Frequent (30-79%)
HP:0006438	Enlargement of the distal femoral epiphysis	Frequent (30-79%)
HP:0006456	Irregular proximal tibial epiphyses	Frequent (30-79%)
HP:0007477	Abnormal dermatoglyphics	Frequent (30-79%)
HP:0009759	Neck pterygia	Frequent (30-79%)
HP:0010044	Short 4th metacarpal	Frequent (30-79%)
HP:0010047	Short 5th metacarpal	Frequent (30-79%)
HP:0010510	Hypermobility of toe joints	Frequent (30-79%)
HP:0002705	High, narrow palate	Frequent (30-79%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000278	Retrognathia	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000403	Recurrent otitis media	Frequent (30-79%)
HP:0000465	Webbed neck	Frequent (30-79%)
HP:0000474	Thickened nuchal skin fold	Frequent (30-79%)
HP:0000475	Broad neck	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000739	Anxiety	Frequent (30-79%)
HP:0000758	Impaired use of nonverbal behaviors	Frequent (30-79%)
HP:0000786	Primary amenorrhea	Frequent (30-79%)
HP:0000822	Hypertension	Frequent (30-79%)
HP:0000869	Secondary amenorrhea	Frequent (30-79%)
HP:0000872	Hashimoto thyroiditis	Frequent (30-79%)
HP:0000914	Shield chest	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Turner syndrome
Mondo ID	MONDO:0019499
MeSH	D014424
Orphanet	881
DOID	DOID:3491
ICD-10-CM	Q96.0
ICD-11	1987089698
NCIT	C26900
SNOMED CT	38804009
UMLS	C0041408
MedGen	21734
GARD	0007831
MedDRA	10045181
NORD	1806
Is cancer (heuristic)	no

Also known as: 45, X syndrome · 45,X gonadal dysgenesis · 45,X syndrome · 45,X/46,XX syndrome · 45,X0 syndrome · 45X syndrome · chromosome X monosomy X · genital dwarfism · genital dwarfism, Turner type · gonadal dysgenesis · gonadal dysgenesis (45,X) · gonadal dysgenesis Turner type · karyotype 45, X · monosomy X · Schereshevkii Turner syndrome · Turner Varny syndrome · Ullrich-Turner syndrome

Data availability: 7 ClinVar variants · 269 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › gonadal disorder › hypogonadism › gonadal dysgenesis › Turner syndrome

Related subtypes (4): testicular dysgenesis syndrome, 46 XX gonadal dysgenesis, 46,XY complete gonadal dysgenesis, 45,X/46,XY mixed gonadal dysgenesis

Subtypes (3): mixed gonadal dysgenesis, monosomy X, Turner syndrome due to structural X chromosome anomalies

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

7 retrieved; paginated sample, class counts are floors:

6 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
973581	NC_000023.11:g.155985220_155986351delinsT		Pathogenic	criteria provided, single submitter
1703581	GRCh37/hg19 Xp22.33-11.22(chrX:168546-52573789)	ACE2	Pathogenic	no assertion criteria provided
1703584	GRCh37/hg19 Xq11.1-28(chrX:62685885-155233731)	AMMECR1	Pathogenic	no assertion criteria provided
1703582	Single allele	HSD17B10	Pathogenic	no assertion criteria provided
1703580	GRCh37/hg19 Xp22.33-q28(chrX:1-155270560)	RBMX2	Pathogenic	no assertion criteria provided
1703583	GRCh37/hg19 Xp22.33-11.21(chrX:168546-57841304)	TMEM47	Pathogenic	no assertion criteria provided
2503342	NM_000264.5(PTCH1):c.3945del (p.Tyr1316fs)	PTCH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 14 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AMMECR1	Orphanet:688581	Midface hypoplasia-hearing impairment-elliptocytosis-nephrocalcinosis syndrome
AMMECR1	Orphanet:86818	Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome
HSD17B10	Orphanet:391428	HSD10 disease, infantile type
HSD17B10	Orphanet:391457	HSD10 disease, neonatal type
HSD17B10	Orphanet:85295	HSD10 disease, atypical type
PTCH1	Orphanet:220386	Semilobar holoprosencephaly
PTCH1	Orphanet:2353	Schilbach-Rott syndrome
PTCH1	Orphanet:280195	Septopreoptic holoprosencephaly
PTCH1	Orphanet:280200	Microform holoprosencephaly
PTCH1	Orphanet:377	Gorlin syndrome
PTCH1	Orphanet:77301	Monosomy 9q22.3 syndrome
PTCH1	Orphanet:93924	Lobar holoprosencephaly
PTCH1	Orphanet:93925	Alobar holoprosencephaly
PTCH1	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ACE2	HGNC:13557	ENSG00000130234	Q9BYF1	Angiotensin-converting enzyme 2	clinvar
TMEM47	HGNC:18515	ENSG00000147027	Q9BQJ4	Transmembrane protein 47	clinvar
RBMX2	HGNC:24282	ENSG00000134597	Q9Y388	RNA-binding motif protein, X-linked 2	clinvar
AMMECR1	HGNC:467	ENSG00000101935	Q9Y4X0	Nuclear protein AMMECR1	clinvar
HSD17B10	HGNC:4800	ENSG00000072506	Q99714	3-hydroxyacyl-CoA dehydrogenase type-2	clinvar
PTCH1	HGNC:9585	ENSG00000185920	Q13635	Protein patched homolog 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACE2	Angiotensin-converting enzyme 2	Essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis.
TMEM47	Transmembrane protein 47	Regulates cell junction organization in epithelial cells.
RBMX2	RNA-binding motif protein, X-linked 2	Involved in pre-mRNA splicing as component of the activated spliceosome.
HSD17B10	3-hydroxyacyl-CoA dehydrogenase type-2	Mitochondrial dehydrogenase involved in pathways of fatty acid, branched-chain amino acid and steroid metabolism.
PTCH1	Protein patched homolog 1	Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH).

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.33

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
Protease	1	6.1×	0.612
Enzyme (other)	1	2.0×	0.719
Transcription factor	1	1.4×	0.719
Other/Unknown	3	0.9×	0.758

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ACE2	Protease	yes	3.4.15.1	Peptidase_M2, Collectrin_dom
TMEM47	Transcription factor	no		PMP22/EMP/MP20/Claudin, P53_induced
RBMX2	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf
AMMECR1	Other/Unknown	no		AMMECR1_domain, AMMECR1, AMMECR1_N
HSD17B10	Enzyme (other)	yes	1.1.1.135	SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf
PTCH1	Other/Unknown	no		SSD, TM_rcpt_patched, HMGCR/SNAP/NPC1-like_SSD

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gall bladder	1
ileal mucosa	1
ileum	1
choroid plexus epithelium	1
saphenous vein	1
urethra	1
calcaneal tendon	1
oocyte	1
secondary oocyte	1
buccal mucosa cell	1
esophagus squamous epithelium	1
trabecular bone tissue	1
liver	1
right adrenal gland	1
right lobe of liver	1
dorsal root ganglion	1
tibia	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACE2	152	tissue_specific	marker	ileal mucosa, ileum, gall bladder
TMEM47	288	ubiquitous	marker	choroid plexus epithelium, saphenous vein, urethra
RBMX2	270	ubiquitous	marker	secondary oocyte, oocyte, calcaneal tendon
AMMECR1	262	ubiquitous	marker	esophagus squamous epithelium, buccal mucosa cell, trabecular bone tissue
HSD17B10	155	ubiquitous	marker	right lobe of liver, liver, right adrenal gland
PTCH1	275	ubiquitous	marker	tibia, dorsal root ganglion, trigeminal ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ACE2	5,940
PTCH1	3,368
HSD17B10	2,961
RBMX2	1,875
TMEM47	1,010
AMMECR1	899

Structural data

PDB: 4 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACE2	Q9BYF1	345
PTCH1	Q13635	16
HSD17B10	Q99714	15
RBMX2	Q9Y388	10

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TMEM47	Q9BQJ4	86.19
AMMECR1	Q9Y4X0	75.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 27. Enrichment computed across 6 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Attachment and Entry	1	713.8×	0.015	ACE2
tRNA processing in the mitochondrion	1	571.0×	0.015	HSD17B10
GLI proteins bind promoters of Hh responsive genes to promote transcription	1	407.9×	0.015	PTCH1
Ligand-receptor interactions	1	356.9×	0.015	PTCH1
rRNA processing in the mitochondrion	1	317.2×	0.015	HSD17B10
tRNA modification in the mitochondrion	1	259.6×	0.015	HSD17B10
Early SARS-CoV-2 Infection Events	1	259.6×	0.015	ACE2
Induction of Cell-Cell Fusion	1	219.6×	0.015	ACE2
Metabolism of Angiotensinogen to Angiotensins	1	158.6×	0.016	ACE2
Activation of SMO	1	158.6×	0.016	PTCH1
Attachment and Entry	1	150.3×	0.016	ACE2
Branched-chain amino acid catabolism	1	119.0×	0.019	HSD17B10
Late SARS-CoV-2 Infection Events	1	73.2×	0.028	ACE2
Peptide hormone metabolism	1	68.0×	0.028	ACE2
Class B/2 (Secretin family receptors)	1	47.6×	0.038	PTCH1
Hedgehog ‘off’ state	1	44.6×	0.038	PTCH1
Hedgehog ‘on’ state	1	39.6×	0.040	PTCH1
SARS-CoV-1 Infection	1	35.7×	0.042	ACE2
Potential therapeutics for SARS	1	28.6×	0.047	ACE2
Mitochondrial protein degradation	1	28.6×	0.047	HSD17B10
SARS-CoV-2 Infection	1	20.1×	0.063	ACE2
SARS-CoV Infections	1	13.9×	0.084	ACE2
mRNA Splicing - Major Pathway	1	13.7×	0.084	RBMX2
Viral Infection Pathways	1	7.7×	0.139	ACE2
Infectious disease	1	6.2×	0.164	ACE2
Disease	1	3.3×	0.283	ACE2
Metabolism of proteins	1	3.1×	0.286	ACE2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
brexanolone metabolic process	1	3370.4×	0.008	HSD17B10
response to chlorate	1	1685.2×	0.008	PTCH1
neural plate axis specification	1	1685.2×	0.008	PTCH1
positive regulation of amino acid transport	1	1685.2×	0.008	ACE2
cell proliferation involved in metanephros development	1	1685.2×	0.008	PTCH1
entry receptor-mediated virion attachment to host cell	1	1685.2×	0.008	ACE2
positive regulation of L-proline import across plasma membrane	1	1685.2×	0.008	ACE2
angiotensin-mediated drinking behavior	1	1123.5×	0.008	ACE2
cell differentiation involved in kidney development	1	1123.5×	0.008	PTCH1
mitochondrial tRNA methylation	1	1123.5×	0.008	HSD17B10
mitochondrial tRNA 5’-end processing	1	1123.5×	0.008	HSD17B10
viral life cycle	1	842.6×	0.008	ACE2
mitochondrial tRNA 3’-end processing	1	842.6×	0.008	HSD17B10
regulation of systemic arterial blood pressure by renin-angiotensin	1	674.1×	0.008	ACE2
C21-steroid hormone metabolic process	1	674.1×	0.008	HSD17B10
epidermal cell fate specification	1	674.1×	0.008	PTCH1
L-isoleucine catabolic process	1	561.7×	0.008	HSD17B10
neural tube patterning	1	561.7×	0.008	PTCH1
hindlimb morphogenesis	1	561.7×	0.008	PTCH1
receptor-mediated virion attachment to host cell	1	561.7×	0.008	ACE2
tryptophan transport	1	481.5×	0.008	ACE2
negative regulation of cell division	1	481.5×	0.008	PTCH1
mammary gland duct morphogenesis	1	481.5×	0.008	PTCH1
positive regulation of gap junction assembly	1	481.5×	0.008	ACE2
positive regulation of epidermal cell differentiation	1	421.3×	0.009	PTCH1
positive regulation of cardiac muscle contraction	1	421.3×	0.009	ACE2
metanephric collecting duct development	1	337.0×	0.011	PTCH1
receptor-mediated endocytosis of virus by host cell	1	306.4×	0.011	ACE2
response to alkaloid	1	306.4×	0.011	PTCH1
prostate gland development	1	280.9×	0.011	PTCH1

Therapeutics

Drugs indicated or in trials for this disease

1 approved drug — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Somatropin	Approved (phase 4)

6 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Estradiol	Phase 3
Estrogens, Conjugated	Phase 3
Ethinyl Estradiol	Phase 3
Medroxyprogesterone Acetate	Phase 3
Oxandrolone	Phase 3
Lonapegsomatropin	Phase 2

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 4

Druggability breadth: 4 of 6 evidence-associated genes (67%) 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
ACE2	CAPTOPRIL
HSD17B10	LEVODOPA

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HSD17B10	249	4
ACE2	8	4
TMEM47	0	0
RBMX2	0	0
AMMECR1	0	0
PTCH1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CAPTOPRIL	4	ACE2, HSD17B10
FLUORESCEIN	4	ACE2
CINACALCET	4	ACE2
HYDROXYCHLOROQUINE	4	ACE2
CHLOROQUINE	4	ACE2
LEVODOPA	4	HSD17B10
PHENYLBUTAZONE	4	HSD17B10
CANDESARTAN CILEXETIL	4	HSD17B10
TELMISARTAN	4	HSD17B10
DIENESTROL	4	HSD17B10
CHOLECALCIFEROL	4	HSD17B10
BUMETANIDE	4	HSD17B10
SALMETEROL XINAFOATE	4	HSD17B10
SULFAPHENAZOLE	4	HSD17B10
RALOXIFENE HYDROCHLORIDE	4	HSD17B10
DICYCLOMINE	4	HSD17B10
CISPLATIN	4	HSD17B10
TETRABENAZINE	4	HSD17B10
DECAMETHONIUM	4	HSD17B10
LABETALOL HYDROCHLORIDE	4	HSD17B10
DIMENHYDRINATE	4	HSD17B10
HYDROXYZINE PAMOATE	4	HSD17B10
MALATHION	4	HSD17B10
PYRITHIONE ZINC	4	HSD17B10
AVOBENZONE	4	HSD17B10
CEFOXITIN SODIUM	4	HSD17B10
OXYMETHOLONE	4	HSD17B10
FEXOFENADINE HYDROCHLORIDE	4	HSD17B10
GEMIFLOXACIN MESYLATE	4	HSD17B10
AMPICILLIN SODIUM	4	HSD17B10

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
ACE2	107	Binding:98, Functional:6, ADMET:3
HSD17B10	41	Binding:39, Functional:2
AMMECR1	6	Binding:6
PTCH1	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ACE2	3.4.15.1, 3.4.17.23	peptidyl-dipeptidase A, angiotensin-converting enzyme 2
HSD17B10	1.1.1.135, 1.1.1.178, 1.1.1.35, 1.1.1.62	GDP-6-deoxy-D-talose 4-dehydrogenase, 3-hydroxy-2-methylbutyryl-CoA dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase, 17beta-estradiol 17-dehydrogenase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ACE2	107

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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)
CAPTOPRIL	4	ACE2, HSD17B10
FLUORESCEIN	4	ACE2
CINACALCET	4	ACE2
HYDROXYCHLOROQUINE	4	ACE2
CHLOROQUINE	4	ACE2
LEVODOPA	4	HSD17B10
PHENYLBUTAZONE	4	HSD17B10
CANDESARTAN CILEXETIL	4	HSD17B10
TELMISARTAN	4	HSD17B10
DIENESTROL	4	HSD17B10
CHOLECALCIFEROL	4	HSD17B10
BUMETANIDE	4	HSD17B10
SALMETEROL XINAFOATE	4	HSD17B10
SULFAPHENAZOLE	4	HSD17B10
RALOXIFENE HYDROCHLORIDE	4	HSD17B10
DICYCLOMINE	4	HSD17B10
CISPLATIN	4	HSD17B10
TETRABENAZINE	4	HSD17B10
DECAMETHONIUM	4	HSD17B10
LABETALOL HYDROCHLORIDE	4	HSD17B10
DIMENHYDRINATE	4	HSD17B10
HYDROXYZINE PAMOATE	4	HSD17B10
MALATHION	4	HSD17B10
PYRITHIONE ZINC	4	HSD17B10
AVOBENZONE	4	HSD17B10
CEFOXITIN SODIUM	4	HSD17B10
OXYMETHOLONE	4	HSD17B10
FEXOFENADINE HYDROCHLORIDE	4	HSD17B10
GEMIFLOXACIN MESYLATE	4	HSD17B10
AMPICILLIN SODIUM	4	HSD17B10

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	ACE2, HSD17B10
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	4	TMEM47, RBMX2, AMMECR1, PTCH1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TMEM47	0	—
RBMX2	0	—
AMMECR1	6	—
PTCH1	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 94.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	64
PHASE4	12
PHASE3	11
PHASE2	7

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06544473	PHASE4	RECRUITING	Determining Dose Equivalence Between Oral and Transdermal Estrogen Treatment in Women With Turner Syndrome
NCT06570460	PHASE4	RECRUITING	Long Term Effects of Oral Versus Transdermal Estrogen Replacement Therapy in Turner Syndrome
NCT06834594	PHASE4	RECRUITING	Bleeding Patterns in Sequential and Continuous Progesterone Supplementation in Adolescents With Turner Syndrome
NCT00134745	PHASE4	COMPLETED	Defining the Optimal Hormonal Replacement Therapy in Turner Syndrome
NCT00256126	PHASE4	COMPLETED	Predictive Markers in Growth Hormone Deficiency (GHD) and Turner Syndrome (TS) Children Treated With SAIZEN®
NCT00266656	PHASE4	COMPLETED	Long-Term Growth and Skeletal Effects of Early Growth Hormone Treatment in Turner Syndrome
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01245374	PHASE4	COMPLETED	Norditropin NordiFlex® Device Compared to the Device Previously Used by Patients or Parents
NCT01419249	PHASE4	COMPLETED	First Year Growth Response Associated Genetic Markers Validation Phase IV Open-label Study in Growth Hormone Deficient and Turner Syndrome Pre-pubertal Children: the PREDICT Pharmacogenetics Validation Study
NCT01518062	PHASE4	COMPLETED	Safety of Somatropin and Induction of Puberty With 17-beta-oestradiol in Girls With Turner Syndrome
NCT01734486	PHASE4	COMPLETED	Growth Response in Girls With Turner Syndrome
NCT03015909	PHASE4	COMPLETED	Evaluation of the Ease of Use, Preference, and Safety of EutropinPen Inj.
NCT05723835	PHASE3	ACTIVE_NOT_RECRUITING	A Research Study Looking at How Safe Somapacitan is and How Well it Works in Children Who Need Help to Grow - REAL 9
NCT07221851	PHASE3	RECRUITING	Trial Investigating the Efficacy and Safety of Weekly Lonapegsomatropin Compared to Daily Somatropin in Children and Adolescents With Short Stature or Growth Failure Due to Growth Hormone Sufficient Disorders
NCT07614152	PHASE3	NOT_YET_RECRUITING	The Efficacy and Safety of Inpegsomatropin Injection in Children With Turner Syndrome(TS) and Short Stature
NCT00029159	PHASE3	COMPLETED	The Effect of Androgen and Growth Hormone on Height and Learning in Girls With Turner Syndrome
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00191113	PHASE3	COMPLETED	Somatropin Treatment to Final Height in Turner Syndrome
NCT00234533	PHASE3	COMPLETED	Study to Define Optimal IGF-1 Monitoring in Children Treated With NutropinAq
NCT00406926	PHASE3	COMPLETED	The Effect of Growth Hormone in Very Young Girls With Turner Syndrome
NCT01518036	PHASE3	COMPLETED	Use of Somatropin in Turner Syndrome
NCT01563926	PHASE3	COMPLETED	Evaluating Acceptance of New Liquid Somatropin Formulation in Children With Growth Hormone Deficiency
NCT01710696	PHASE3	COMPLETED	Induction of Puberty With 17-beta Estradiol in Girls With Turner Syndrome
NCT05690386	PHASE2	ACTIVE_NOT_RECRUITING	A Trial to Investigate Different Doses of Lonapegsomatropin Compared to Somatropin in Individuals With Turner Syndrome
NCT05849389	PHASE2	RECRUITING	Vosoritide for Short Stature in Turner Syndrome
NCT07041814	PHASE2	NOT_YET_RECRUITING	A Study Comparing Different Treatment Approaches for the Initiation of Puberty in Girls With Turner Syndrome Using a TRIFECTA-DARED Approach for Rare Diseases
NCT00001221	PHASE2	COMPLETED	Effect of Biosynthetic Growth Hormone and/or Ethinyl Estradiol on Adult Height in Patients With Turner Syndrome
NCT00001253	PHASE2	COMPLETED	The Effects of Estrogen on Cognition in Girls With Turner Syndrome
NCT03189160	PHASE2	UNKNOWN	A Study of PEG-somatropin Injection to Treat Children of Turner Syndrome
NCT05838885	PHASE2	COMPLETED	A Trial of YPEG-rhGH in Children With Short Stature
NCT01410045	Not specified	ACTIVE_NOT_RECRUITING	Cryopreservation of Ovarian Cortex in Girls With Turner Syndrome
NCT01604395	Not specified	RECRUITING	Long-term Safety and Effectiveness of Growth Hormone With GHD, TS, CRF, SGA , ISS and PWS in Children
NCT02417740	Not specified	RECRUITING	Natural History of Noncirrhotic Portal Hypertension
NCT03185702	Not specified	RECRUITING	UTHealth Turner Syndrome Research Registry
NCT03381300	Not specified	ACTIVE_NOT_RECRUITING	Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome
NCT03440697	Not specified	ACTIVE_NOT_RECRUITING	Pathogenetic Basis of Aortopathy and Aortic Valve Disease
NCT03812913	Not specified	RECRUITING	Neuropsychological Assessment of Children and Adolescents With Turner Syndrome
NCT03836300	Not specified	ENROLLING_BY_INVITATION	Parent and Infant Inter(X)Action Intervention (PIXI)
NCT04252001	Not specified	NOT_YET_RECRUITING	Growing up With the Young Endocrine Support System (YESS!)
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SOMATROPIN	4	10
ESTRADIOL	4	6
LONAPEGSOMATROPIN	4	2
ESTRADIOL VALERATE	4	1
ETHINYL ESTRADIOL	4	1
MEDROXYPROGESTERONE ACETATE	4	1
SOMAPACITAN	4	1
VOSORITIDE	4	1
ESTROGEN	3	1
CHEMBL287148	0	1
CHEMBL4216935	0	1