Wilson-Turner syndrome

Summary

Wilson-Turner syndrome (MONDO:0010665) is a disease caused by LAS1L (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: LAS1L (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 143
• Phenotypes (HPO): 28

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		28	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0000028	Cryptorchidism	Very frequent (80-99%)
HP:0000219	Thin upper lip vermilion	Very frequent (80-99%)
HP:0000336	Prominent supraorbital ridges	Very frequent (80-99%)
HP:0000347	Micrognathia	Very frequent (80-99%)
HP:0000455	Broad nasal tip	Very frequent (80-99%)
HP:0000490	Deeply set eye	Very frequent (80-99%)
HP:0000574	Thick eyebrow	Very frequent (80-99%)
HP:0000712	Emotional lability	Very frequent (80-99%)
HP:0000771	Gynecomastia	Very frequent (80-99%)
HP:0001182	Tapered finger	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001761	Pes cavus	Very frequent (80-99%)
HP:0001763	Pes planus	Very frequent (80-99%)
HP:0001773	Short foot	Very frequent (80-99%)
HP:0001956	Truncal obesity	Very frequent (80-99%)
HP:0001999	Abnormal facial shape	Very frequent (80-99%)
HP:0002465	Poor speech	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0008551	Microtia	Very frequent (80-99%)
HP:0010620	Malar prominence	Very frequent (80-99%)
HP:0200055	Small hand	Very frequent (80-99%)
HP:0000044	Hypogonadotropic hypogonadism	Frequent (30-79%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001328	Specific learning disability	Occasional (5-29%)
HP:0000518	Cataract	Excluded (0%)
HP:0000540	Hypermetropia	Excluded (0%)
HP:0009909	Uplifted earlobe	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Wilson-Turner syndrome
Mondo ID	MONDO:0010665
MeSH	C536708
OMIM	309585
Orphanet	3459
DOID	DOID:0060814
ICD-11	2015561482
SNOMED CT	719834005
UMLS	C1839736
MedGen	333393
GARD	0005579
Is cancer (heuristic)	no

Also known as: intellectual disability, X-linked, syndromic 6 · intellectual disability, X-linked, syndromic 6 (formerly) · intellectual disability, X-linked, with gynecomastia and obesity · intellectual disability, X-linked, with gynecomastia and obesity (formerly) · mental retardation, X-linked, syndromic 6 · mental retardation, X-linked, syndromic 6 (formerly) · mental retardation, X-linked, with gynecomastia and obesity · mental retardation, X-linked, with gynecomastia and obesity (formerly) · MRXS6 · Wilson Turner intellectual disability syndrome (formerly) · Wilson Turner mental retardation syndrome (formerly) · Wilson-Turner syndrome, X-linked recessive · Wilson-TURNER X-linked intellectual disability syndrome · Wilson-TURNER X-linked mental retardation syndrome · WTS · X-linked intellectual disability - gynecomastia - obesity · X-linked intellectual disability-gynecomastia-obesity syndrome

Data availability: 143 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › syndromic intellectual disability › X-linked syndromic intellectual disability › Wilson-Turner syndrome

Related subtypes (80): X-linked intellectual disability-psychosis-macroorchidism syndrome, X-linked intellectual disability-plagiocephaly syndrome, intellectual disability, X-linked 49, MEHMO syndrome, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability, Stocco dos Santos type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome, X-linked intellectual disability-cerebellar hypoplasia syndrome, Allan-Herndon-Dudley syndrome, syndromic X-linked intellectual disability Claes-Jensen type, X-linked intellectual disability-retinitis pigmentosa syndrome, syndromic X-linked intellectual disability 14, syndromic X-linked intellectual disability 94, intellectual disability, X-linked syndromic, Turner type, syndromic X-linked intellectual disability Shrimpton type, X-linked intellectual disability-craniofacioskeletal syndrome, syndromic X-linked intellectual disability Raymond type, syndromic X-linked intellectual disability 17, syndromic X-linked intellectual disability Nascimento type, syndromic X-linked intellectual disability Chudley-Schwartz type, X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome, X-linked intellectual disability, Cantagrel type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, intellectual disability, X-linked 99, syndromic, female-restricted, intellectual disability, X-linked, syndromic, Bain type, Borjeson-Forssman-Lehmann syndrome, Coffin-Lowry syndrome, syndromic X-linked intellectual disability 5, X-linked intellectual disability-seizures-psoriasis syndrome, Renpenning syndrome, Partington syndrome, syndromic X-linked intellectual disability 12, severe X-linked intellectual disability, Gustavson type, syndromic X-linked intellectual disability Snyder type, Prieto syndrome, skeletal dysplasia-intellectual disability syndrome, X-linked intellectual disability-spastic quadriparesis syndrome, early-onset parkinsonism-intellectual disability syndrome, X-linked intellectual disability, Schimke type, X-linked intellectual disability, Cilliers type, X-linked intellectual disability, van Esch type, X-linked intellectual disability-epilepsy syndrome, ATR-X-related syndrome, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, X-linked intellectual disability, Schutz type, X-linked intellectual disability-hypotonia-movement disorder syndrome, X-linked intellectual disability with isolated growth hormone deficiency, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-precocious puberty-obesity syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability-macrocephaly-macroorchidism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Seemanova type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, X-linked intellectual disability-acromegaly-hyperactivity syndrome, X-linked intellectual disability-corpus callosum agenesis-spastic quadriparesis syndrome, fried syndrome, X-linked intellectual disability-ataxia-apraxia syndrome, intellectual developmental disorder, X-linked, syndromic, Pilorge type, Paganini-Miozzo syndrome, intellectual developmental disorder, X-linked, syndromic, Hackmann-Di Donato type, intellectual disability, X-linked, syndromic, 35, intellectual disability, X-linked, syndromic, Houge type, MED12-related intellectual disability syndrome, NAA10-related syndrome, ATP6AP2-related disorder, X-linked intellectual disability with hypopituitarism, SOX3-related X-linked pituitary hormone deficiency with or without intellectual developmental disorder, intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies, intellectual developmental disorder, X-linked, syndromic 37, CASK-related intellectual disability

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

143 retrieved; paginated sample, class counts are floors:

60 uncertain significance, 58 likely benign, 10 benign, 6 conflicting classifications of pathogenicity, 5 benign/likely benign, 2 likely pathogenic, 1 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
253106	NM_031206.7(LAS1L):c.806C>G (p.Ala269Gly)	LAS1L	Pathogenic	no assertion criteria provided
374326	NM_031206.7(LAS1L):c.1243C>T (p.Arg415Trp)	LAS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4759342	NM_031206.7(LAS1L):c.2082dup (p.Leu697fs)	LAS1L	Likely pathogenic	criteria provided, single submitter
666263	NM_031206.7(LAS1L):c.1237G>A (p.Gly413Arg)	LAS1L	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1021687	NM_031206.7(LAS1L):c.948C>T (p.Cys316=)	LAS1L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1906687	NM_031206.7(LAS1L):c.947G>A (p.Cys316Tyr)	LAS1L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
464820	NM_031206.7(LAS1L):c.1082C>G (p.Pro361Arg)	LAS1L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
464822	NM_031206.7(LAS1L):c.1735G>A (p.Val579Ile)	LAS1L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
464823	NM_031206.7(LAS1L):c.1892G>C (p.Gly631Ala)	LAS1L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
704102	NM_031206.7(LAS1L):c.5C>T (p.Ser2Leu)	LAS1L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1005027	NM_031206.7(LAS1L):c.2051G>A (p.Arg684Gln)	LAS1L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1022624	NM_031206.7(LAS1L):c.706A>G (p.Thr236Ala)	LAS1L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1045920	NM_031206.7(LAS1L):c.1282G>A (p.Val428Met)	LAS1L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1056523	NM_031206.7(LAS1L):c.1837A>G (p.Thr613Ala)	LAS1L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1193682	NM_031206.7(LAS1L):c.320G>A (p.Gly107Asp)	LAS1L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1206216	NM_031206.7(LAS1L):c.1850C>A (p.Ser617Tyr)	LAS1L	Uncertain significance	criteria provided, single submitter
1334035	NM_031206.7(LAS1L):c.1298C>T (p.Thr433Ile)	LAS1L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1395058	NM_031206.7(LAS1L):c.674A>G (p.Gln225Arg)	LAS1L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1402133	NM_031206.7(LAS1L):c.1270G>A (p.Val424Ile)	LAS1L	Uncertain significance	criteria provided, single submitter
1402244	NM_031206.7(LAS1L):c.1889G>T (p.Arg630Ile)	LAS1L	Uncertain significance	criteria provided, single submitter
1448734	NM_031206.7(LAS1L):c.704G>A (p.Ser235Asn)	LAS1L	Uncertain significance	criteria provided, single submitter
1679798	Single allele	LAS1L	Uncertain significance	criteria provided, single submitter
1690406	NM_031206.7(LAS1L):c.1871G>A (p.Arg624Lys)	LAS1L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1699481	NM_031206.7(LAS1L):c.663C>A (p.Asp221Glu)	LAS1L	Uncertain significance	criteria provided, multiple submitters, no conflicts
1701638	NM_031206.7(LAS1L):c.1764AGAGGAGGA[1] (p.Glu591_Glu593del)	LAS1L	Uncertain significance	criteria provided, single submitter
1701765	NM_031206.7(LAS1L):c.515-6C>G	LAS1L	Uncertain significance	criteria provided, single submitter
1804952	NM_031206.7(LAS1L):c.1613G>A (p.Ser538Asn)	LAS1L	Uncertain significance	criteria provided, single submitter
1805162	NM_031206.7(LAS1L):c.1285G>A (p.Ala429Thr)	LAS1L	Uncertain significance	criteria provided, single submitter
1806335	NM_031206.7(LAS1L):c.1571C>A (p.Pro524His)	LAS1L	Uncertain significance	criteria provided, multiple submitters, no conflicts
2169683	NM_031206.7(LAS1L):c.1822G>T (p.Val608Leu)	LAS1L	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · 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
LAS1L	Strong	X-linked	Wilson-Turner syndrome	6
HDAC8	Supportive	X-linked	Wilson-Turner syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LAS1L	Orphanet:3459	Wilson-Turner syndrome
LAS1L	Orphanet:404521	Spinal muscular atrophy with respiratory distress type 2
HDAC8	Orphanet:199	Cornelia de Lange syndrome
HDAC8	Orphanet:3459	Wilson-Turner 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
LAS1L	HGNC:25726	ENSG00000001497	Q9Y4W2	Ribosomal biogenesis protein LAS1L	gencc,clinvar
HDAC8	HGNC:13315	ENSG00000147099	Q9BY41	Histone deacetylase 8	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LAS1L	Ribosomal biogenesis protein LAS1L	Required for the synthesis of the 60S ribosomal subunit and maturation of the 28S rRNA.
HDAC8	Histone deacetylase 8	Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LAS1L	Other/Unknown	no		Las1
HDAC8	Enzyme (other)	yes	3.5.1.98	HDACs, HDAC_I/II, Ureohydrolase_dom_sf

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
adrenal tissue	1
colonic epithelium	1
left adrenal gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LAS1L	278	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
HDAC8	244	ubiquitous	marker	colonic epithelium, adrenal tissue, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HDAC8	3,087
LAS1L	2,183

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HDAC8	Q9BY41	53
LAS1L	Q9Y4W2	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
Notch-HLH transcription pathway	1	203.9×	0.023	HDAC8
NOTCH1 Intracellular Domain Regulates Transcription	1	119.0×	0.023	HDAC8
Constitutive Signaling by NOTCH1 PEST Domain Mutants	1	98.5×	0.023	HDAC8
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	1	98.5×	0.023	HDAC8
rRNA processing in the nucleus and cytosol	1	80.4×	0.023	LAS1L
rRNA processing	1	73.2×	0.023	LAS1L
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	73.2×	0.023	HDAC8
HDACs deacetylate histones	1	60.1×	0.025	HDAC8
Resolution of Sister Chromatid Cohesion	1	43.3×	0.031	HDAC8
Major pathway of rRNA processing in the nucleolus and cytosol	1	30.9×	0.036	LAS1L
Separation of Sister Chromatids	1	30.4×	0.036	HDAC8
Metabolism of RNA	1	20.8×	0.047	LAS1L

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
maturation of LSU-rRNA	1	766.0×	0.006	LAS1L
mitotic sister chromatid cohesion	1	561.7×	0.006	HDAC8
maturation of 5.8S rRNA	1	526.6×	0.006	LAS1L
regulation of telomere maintenance	1	421.3×	0.006	HDAC8
negative regulation of protein ubiquitination	1	142.8×	0.013	HDAC8
heterochromatin formation	1	127.7×	0.013	HDAC8
rRNA processing	1	70.8×	0.020	LAS1L
regulation of protein stability	1	62.9×	0.020	HDAC8
chromatin organization	1	49.6×	0.022	HDAC8
negative regulation of transcription by RNA polymerase II	1	8.9×	0.110	HDAC8

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 0

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
HDAC8	CELECOXIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HDAC8	37	4
LAS1L	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CELECOXIB	4	HDAC8
PHENYLBUTANOIC ACID	4	HDAC8
SODIUM PHENYLBUTYRATE	4	HDAC8
ROMIDEPSIN	4	HDAC8
BELINOSTAT	4	HDAC8
PANOBINOSTAT	4	HDAC8
VORINOSTAT	4	HDAC8
GIVINOSTAT	4	HDAC8
DAUNORUBICIN	4	HDAC8
BORTEZOMIB	4	HDAC8
BENDAMUSTINE	4	HDAC8
CURCUMIN	3	HDAC8
CAFFEIC ACID	3	HDAC8
PRACINOSTAT	3	HDAC8
TACEDINALINE	3	HDAC8
ENTINOSTAT	3	HDAC8
TUCIDINOSTAT	3	HDAC8
ABEXINOSTAT	3	HDAC8
MOLIBRESIB	2	LAS1L
NANATINOSTAT	2	HDAC8
AR-42	2	HDAC8
CHLOROGENIC ACID	2	HDAC8
DACINOSTAT	2	HDAC8
FIMEPINOSTAT	2	HDAC8
BUTYRIC ACID	2	HDAC8
QUISINOSTAT	2	HDAC8
RICOLINOSTAT	2	HDAC8
MOCETINOSTAT	2	HDAC8
CITARINOSTAT	2	HDAC8
SODIUM BUTYRATE	2	HDAC8

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
HDAC8	2,631	Binding:2599, ADMET:25, Functional:6, Toxicity:1
LAS1L	6	Binding:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HDAC8	3.5.1.98	histone deacetylase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
HDAC8	2,631

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)
CELECOXIB	4	HDAC8
PHENYLBUTANOIC ACID	4	HDAC8
SODIUM PHENYLBUTYRATE	4	HDAC8
ROMIDEPSIN	4	HDAC8
BELINOSTAT	4	HDAC8
PANOBINOSTAT	4	HDAC8
VORINOSTAT	4	HDAC8
GIVINOSTAT	4	HDAC8
DAUNORUBICIN	4	HDAC8
BORTEZOMIB	4	HDAC8
BENDAMUSTINE	4	HDAC8
CURCUMIN	3	HDAC8
CAFFEIC ACID	3	HDAC8
PRACINOSTAT	3	HDAC8
TACEDINALINE	3	HDAC8
ENTINOSTAT	3	HDAC8
TUCIDINOSTAT	3	HDAC8
ABEXINOSTAT	3	HDAC8
MOLIBRESIB	2	LAS1L
NANATINOSTAT	2	HDAC8
AR-42	2	HDAC8
CHLOROGENIC ACID	2	HDAC8
DACINOSTAT	2	HDAC8
FIMEPINOSTAT	2	HDAC8
BUTYRIC ACID	2	HDAC8
QUISINOSTAT	2	HDAC8
RICOLINOSTAT	2	HDAC8
MOCETINOSTAT	2	HDAC8
CITARINOSTAT	2	HDAC8
SODIUM BUTYRATE	2	HDAC8

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	HDAC8
B	Phased (≥1) drug, not yet approved	1	LAS1L
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.