WAGR syndrome

Summary

WAGR syndrome (MONDO:0008681) is a disease with 5 cohort genes and 3 clinical trials. Top therapeutic interventions include lufenuron.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 5
• ClinVar variants: 1,475
• Phenotypes (HPO): 18
• Clinical trials: 3

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000	0.2	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

18 HPO clinical features (Orphanet curated; top 18 by frequency):

HPO ID	Term	Frequency
HP:0008053	Aplasia/Hypoplasia of the iris	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000232	Everted lower lip vermilion	Frequent (30-79%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000364	Hearing abnormality	Frequent (30-79%)
HP:0000505	Visual impairment	Frequent (30-79%)
HP:0000508	Ptosis	Frequent (30-79%)
HP:0000518	Cataract	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0100627	Displacement of the urethral meatus	Frequent (30-79%)
HP:0000062	Ambiguous genitalia	Occasional (5-29%)
HP:0000501	Glaucoma	Occasional (5-29%)
HP:0001513	Obesity	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0007299	Dysfunction of lateral corticospinal tracts	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	WAGR syndrome
Mondo ID	MONDO:0008681
MeSH	D017624
OMIM	194072
Orphanet	893
DOID	DOID:14515
ICD-11	1858307812
NCIT	C3718
SNOMED CT	715215007
UMLS	C0206115
MedGen	64512
GARD	0005528
NORD	1833
Is cancer (heuristic)	no

Also known as: 11p deletion · 11p deletion syndrome · 11p monosomy · 11p partial monosomy syndrome · AGR triad · chromosome 11p deletion · chromosome 11p deletion syndrome · chromosome 11p13 deletion syndrome · Del(11)(p13) · deletion 11p · deletion 11p13 · monosomy 11p · monosomy 11p13 · partial monosomy 11p · WAGR · WAGR 11p13 deletion syndrome · WAGR Complex · WAGR syndrome · WAGR Syndrome/11p Deletion Syndrome · Wilms tumor, aniridia, genitourinary anomalies and developmental delay syndrome (+9 more)

Data availability: 1,475 ClinVar variants · 14 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › WAGR syndrome

Related subtypes (116): mosaic variegated aneuploidy syndrome, tuberous sclerosis, hereditary breast ovarian cancer syndrome, hereditary multiple osteochondromas, nevoid basal cell carcinoma syndrome, leukemia, chronic lymphocytic, susceptibility to, 2, blue rubber bleb nevus, cherubism, Beckwith-Wiedemann syndrome, multiple self-healing squamous epithelioma, erythroleukemia, familial, susceptibility to, goiter, multinodular 1, with or without Sertoli-Leydig cell tumors, hyperparathyroidism 2 with jaw tumors, Kaposi sarcoma, susceptibility to, hereditary leiomyomatosis and renal cell cancer, susceptibility to uveal melanoma, melanoma and neural system tumor syndrome, nasopharyngeal carcinoma, susceptibility to, 2, neuroblastoma, susceptibility to, 1, Rothmund-Thomson syndrome, mismatch repair cancer syndrome 1, Wiskott-Aldrich syndrome, N syndrome, hereditary thrombocytopenia and hematologic cancer predisposition syndrome, prostate cancer/brain cancer susceptibility, Brooke-Spiegler syndrome, pancreatic cancer, susceptibility to, 1, Carney-Stratakis syndrome, nasopharyngeal carcinoma, susceptibility to, 1, ovarian cancer, susceptibility to, 1, colorectal cancer, susceptibility to, 1, lung cancer susceptibility 1, leukemia, chronic lymphocytic, susceptibility to, 1, Kostmann syndrome, colorectal cancer, susceptibility to, 2, colorectal cancer, susceptibility to, 3, colorectal cancer, susceptibility to, 5, colorectal cancer, susceptibility to, 6, colorectal cancer, susceptibility to, 7, leukemia, chronic lymphocytic, susceptibility to, 3, leukemia, chronic lymphocytic, susceptibility to, 4, leukemia, chronic lymphocytic, susceptibility to, 5, lung cancer susceptibility 3, colorectal cancer, susceptibility to, 8, colorectal cancer, susceptibility to, 9, colorectal cancer, susceptibility to, 10, colorectal cancer, susceptibility to, 11, lung cancer susceptibility 4, neuroblastoma, susceptibility to, 3, neuroblastoma, susceptibility to, 4, neuroblastoma, susceptibility to, 5, neuroblastoma, susceptibility to, 6, leukemia, acute lymphocytic, susceptibility to, 1, leukemia, acute lymphocytic, susceptibility to, 2, lung cancer susceptibility 5, BAP1-related tumor predisposition syndrome, familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome, Maffucci syndrome, basal cell carcinoma, susceptibility to, 7, colorectal cancer, susceptibility to, 12, leukemia, acute lymphoblastic, susceptibility to, 3, cholangiocarcinoma, susceptibility to, progeroid features-hepatocellular carcinoma predisposition syndrome, neuroblastoma, susceptibility to, 7, DDX41-related hematologic malignancy predisposition syndrome, nasopharyngeal carcinoma, susceptibility to, 3, familial isolated hyperparathyroidism, intestinal polyposis syndrome, dyskeratosis congenita, familial rhabdoid tumor, multiple endocrine neoplasia, hereditary pheochromocytoma-paraganglioma, PTEN hamartoma tumor syndrome, familial multiple fibrofolliculoma, hereditary retinoblastoma, familial atypical multiple mole melanoma syndrome, hereditary nonpolyposis colon cancer, Li-Fraumeni syndrome, Cobb syndrome, neurofibromatosis, susceptibility to familial cutaneous melanoma, pancreatic cancer, susceptibility to, 5, leukemia, acute myeloid, susceptibility to, diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate, glioma susceptibility, hemangioma, capillary infantile, susceptibility to, CDH1-related diffuse gastric and lobular breast cancer syndrome, NTHL1-deficiency tumor predisposition syndrome, SAMD9-related spectrum and myeloid neoplasm risk, neuroblastoma, susceptibility to, 2, BARD1-related cancer predisposition, BRCA1-related cancer predisposition, BRCA2-related cancer predisposition, ATM-related cancer predisposition, CHEK2-related cancer predisposition, PALB2-related cancer predisposition, RAD51C-related cancer predisposition, RAD51D-related cancer predisposition, Li-fraumeni-like syndrome, breast cancer, familial, susceptibility to, 1, breast cancer, familial, susceptibility to, 2, breast cancer, familial, susceptibility to, 3, colorectal cancer, susceptibility to, 4, colorectal cancer, susceptibility to, on chromosome 15, ovarian cancer, familial, susceptibility to, 1, ovarian cancer, familial, susceptibility to, 2, ovarian cancer, familial, susceptibility to, 3, inherited hematologic cancer-predisposing syndrome, mosaic neurofibromatosis/schwannomatosis, tumor predisposition syndrome 2, prostate cancer, hereditary, X-linked 3, follicular lymphoma, susceptibility to, GPR161-related medulloblastoma predisposition, SAMD9L-related spectrum and myeloid neoplasm risk, HAVCR2-related cancer predisposition, EGLN1-related erythrocytosis and pheochromocytoma/paraganglioma predisposition

Subtypes (1): Wilms tumor, aniridia, genitourinary anomalies, intellectual disability, and obesity syndrome

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:

279 uncertain significance, 262 likely benign, 31 conflicting classifications of pathogenicity, 16 pathogenic, 5 benign, 4 benign/likely benign, 2 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1075590	NM_024426.6(WT1):c.455del (p.Gly152fs)	LOC107982234	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453898	NM_024426.6(WT1):c.276del (p.Gly93fs)	LOC107982234	Pathogenic	criteria provided, single submitter
1456851	NM_024426.6(WT1):c.314_318dup (p.Trp107fs)	LOC107982234	Pathogenic	criteria provided, single submitter
2036794	NM_024426.6(WT1):c.453G>A (p.Trp151Ter)	LOC107982234	Pathogenic	criteria provided, single submitter
2099254	NM_024426.6(WT1):c.507_511delinsCACTGT (p.Ser170fs)	LOC107982234	Pathogenic	criteria provided, single submitter
2134883	NM_024426.6(WT1):c.514C>T (p.Gln172Ter)	LOC107982234	Pathogenic	criteria provided, single submitter
1069921	NC_000011.10:g.32396408del	WT1	Pathogenic	criteria provided, single submitter
1073615	NC_000011.9:g.(?32456236)(32460464_?)del	WT1	Pathogenic	criteria provided, single submitter
1073616	NC_000011.9:g.(?32421484)(32421600_?)del	WT1	Pathogenic	criteria provided, single submitter
1076730	NM_024426.6(WT1):c.798C>G (p.Tyr266Ter)	WT1	Pathogenic	criteria provided, single submitter
1378543	NM_024426.6(WT1):c.1121_1122insGGGG (p.Arg375fs)	WT1	Pathogenic	criteria provided, single submitter
1457778	NM_024426.6(WT1):c.1240C>T (p.Gln414Ter)	WT1	Pathogenic	criteria provided, single submitter
1503278	NM_024426.6(WT1):c.882_887+3del	WT1	Pathogenic	criteria provided, single submitter
2028955	NM_024426.6(WT1):c.1077C>G (p.Tyr359Ter)	WT1	Pathogenic	criteria provided, single submitter
2033498	NM_024426.6(WT1):c.1299T>A (p.Cys433Ter)	WT1	Pathogenic	criteria provided, single submitter
2100281	NM_024426.6(WT1):c.913C>T (p.Gln305Ter)	WT1	Pathogenic	criteria provided, single submitter
2137049	NM_024426.6(WT1):c.1372T>C (p.Cys458Arg)	WT1	Pathogenic	criteria provided, single submitter
1489927	NM_024426.6(WT1):c.1016+2T>G	WT1	Likely pathogenic	criteria provided, single submitter
1518490	NM_024426.6(WT1):c.1016+1G>A	WT1	Likely pathogenic	criteria provided, single submitter
1409524	NM_024426.6(WT1):c.459C>T (p.Gly153=)	LOC107982234	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1479531	NM_024426.6(WT1):c.19C>A (p.Gln7Lys)	LOC107982234	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1495132	NM_024426.6(WT1):c.661+15G>T	LOC107982234	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1534604	NM_024426.6(WT1):c.66G>T (p.Thr22=)	LOC107982234	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2093007	NM_024426.6(WT1):c.161G>C (p.Ser54Thr)	LOC107982234	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1008768	NM_024426.6(WT1):c.1376A>G (p.Lys459Arg)	WT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1014150	NM_024426.6(WT1):c.968T>C (p.Val323Ala)	WT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1018611	NM_024426.6(WT1):c.996A>T (p.Lys332Asn)	WT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1019449	NM_024426.6(WT1):c.677C>A (p.Thr226Asn)	WT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1055328	NM_024426.6(WT1):c.76G>C (p.Gly26Arg)	WT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1113403	NM_024426.6(WT1):c.978G>A (p.Gly326=)	WT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 23 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WT1	Orphanet:220	Denys-Drash syndrome
WT1	Orphanet:242	46,XY complete gonadal dysgenesis
WT1	Orphanet:251510	46,XY partial gonadal dysgenesis
WT1	Orphanet:3097	Meacham syndrome
WT1	Orphanet:347	Frasier syndrome
WT1	Orphanet:654	Nephroblastoma
WT1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
WT1	Orphanet:83469	Desmoplastic small round cell tumor
WT1	Orphanet:893	WAGR syndrome
FSHB	Orphanet:52901	Isolated follicle stimulating hormone deficiency
PAX6	Orphanet:1065	Aniridia-cerebellar ataxia-intellectual disability syndrome
PAX6	Orphanet:2253	Foveal hypoplasia-presenile cataract syndrome
PAX6	Orphanet:2334	Autosomal dominant keratitis
PAX6	Orphanet:250923	Isolated aniridia
PAX6	Orphanet:35737	Morning glory disc anomaly
PAX6	Orphanet:708	Peters anomaly
PAX6	Orphanet:893	WAGR syndrome
PAX6	Orphanet:98942	Coloboma of choroid and retina
PAX6	Orphanet:98943	Coloboma of eye lens
PAX6	Orphanet:98944	Coloboma of iris
PAX6	Orphanet:98945	Coloboma of macula
PAX6	Orphanet:98946	Coloboma of eyelid
PAX6	Orphanet:98947	Coloboma of optic disc

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ELP4	HGNC:1171	ENSG00000109911	Q96EB1	Elongator complex protein 4	clinvar
WT1	HGNC:12796	ENSG00000184937	P19544	Wilms tumor protein	clinvar
WT1-AS	HGNC:18135	ENSG00000183242	Q06250	Putative Wilms tumor upstream neighbor 1 gene protein	clinvar
FSHB	HGNC:3964	ENSG00000131808	P01225	Follitropin subunit beta	clinvar
PAX6	HGNC:8620	ENSG00000007372	P26367	Paired box protein Pax-6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ELP4	Elongator complex protein 4	Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine).
WT1	Wilms tumor protein	Transcription factor that plays an important role in cellular development and cell survival.
FSHB	Follitropin subunit beta	Together with the alpha chain CGA constitutes follitropin, the follicle-stimulating hormone, and provides its biological specificity to the hormone heterodimer.
PAX6	Paired box protein Pax-6	Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 3 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	2	3.3×	0.229
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ELP4	Other/Unknown	no		Elongator_complex_protein_4, P-loop_NTPase
WT1	Transcription factor	no		Wilms_tumour_N, Znf_C2H2_type, Znf_C2H2_sf
WT1-AS	Other/Unknown	no
FSHB	Other/Unknown	no		Gonadotropin_bsu, Glyco_hormone_CN, Gonadotropin_bsu_CS
PAX6	Transcription factor	no		HD, Paired_dom, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 0.

3 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
calcaneal tendon	1
primordial germ cell in gonad	1
germinal epithelium of ovary	1
metanephric glomerulus	1
renal glomerulus	1
left ovary	1
ovary	1
right uterine tube	1
adenohypophysis	1
male germ line stem cell (sensu Vertebrata) in testis	1
pituitary gland	1
palpebral conjunctiva	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ELP4	250	ubiquitous	marker	ventricular zone, calcaneal tendon, primordial germ cell in gonad
WT1	168	broad	marker	germinal epithelium of ovary, renal glomerulus, metanephric glomerulus
WT1-AS	106	tissue_specific	yes	right uterine tube, left ovary, ovary
FSHB	52	tissue_specific	yes	adenohypophysis, pituitary gland, male germ line stem cell (sensu Vertebrata) in testis
PAX6	201	broad	marker	palpebral conjunctiva, type B pancreatic cell, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAX6	4,971
WT1	3,938
ELP4	1,740
FSHB	1,333
WT1-AS	35

Intra-cohort edges

A	B	Sources
ELP4	PAX6	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WT1	P19544	28
FSHB	P01225	6
PAX6	P26367	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ELP4	Q96EB1	74.49
WT1-AS	Q06250	61.60

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 5 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
Formation of the anterior neural plate	1	259.6×	0.011	PAX6
Glycoprotein hormones	1	237.9×	0.011	FSHB
Hormone ligand-binding receptors	1	237.9×	0.011	FSHB
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)	1	219.6×	0.011	PAX6
Nephron development	1	219.6×	0.011	WT1
Transcriptional regulation of testis differentiation	1	178.4×	0.011	WT1
Regulation of gene expression in beta cells	1	129.8×	0.012	PAX6
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	129.8×	0.012	PAX6
Negative Regulation of CDH1 Gene Transcription	1	30.1×	0.044	WT1
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	22.8×	0.052	PAX6
HATs acetylate histones	1	19.8×	0.054	ELP4
G alpha (s) signalling events	1	18.3×	0.054	FSHB

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
pancreatic A cell development	1	4213.0×	0.004	PAX6
oligodendrocyte cell fate specification	1	4213.0×	0.004	PAX6
forebrain-midbrain boundary formation	1	4213.0×	0.004	PAX6
somatic motor neuron fate commitment	1	4213.0×	0.004	PAX6
negative regulation of metanephric glomerular mesangial cell proliferation	1	4213.0×	0.004	WT1
positive regulation of miRNA transcription	2	145.3×	0.004	WT1, PAX6
positive regulation of gene expression	3	29.1×	0.004	WT1, FSHB, PAX6
regulation of animal organ formation	1	2106.5×	0.004	WT1
positive regulation of steroid biosynthetic process	1	2106.5×	0.004	FSHB
adrenal cortex formation	1	2106.5×	0.004	WT1
visceral serous pericardium development	1	2106.5×	0.004	WT1
posterior mesonephric tubule development	1	2106.5×	0.004	WT1
positive regulation of metanephric ureteric bud development	1	2106.5×	0.004	WT1
habenula development	1	1404.3×	0.006	PAX6
follicle-stimulating hormone signaling pathway	1	1404.3×	0.006	FSHB
regulation of asymmetric cell division	1	1053.2×	0.006	PAX6
regulation of timing of cell differentiation	1	1053.2×	0.006	PAX6
positive regulation of heart growth	1	1053.2×	0.006	WT1
metanephric S-shaped body morphogenesis	1	1053.2×	0.006	WT1
negative regulation of female gonad development	1	1053.2×	0.006	WT1
progesterone biosynthetic process	1	842.6×	0.006	FSHB
thorax and anterior abdomen determination	1	842.6×	0.006	WT1
cardiac muscle cell fate commitment	1	842.6×	0.006	WT1
metanephric epithelium development	1	842.6×	0.006	WT1
positive regulation of transcription by RNA polymerase II	3	11.2×	0.006	WT1, FSHB, PAX6
ventral spinal cord interneuron specification	1	702.2×	0.006	PAX6
commitment of neuronal cell to specific neuron type in forebrain	1	702.2×	0.006	PAX6
Sertoli cell proliferation	1	702.2×	0.006	FSHB
cellular response to gonadotropin stimulus	1	702.2×	0.006	WT1
salivary gland morphogenesis	1	601.9×	0.006	PAX6

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 1 of 5 evidence-associated genes (20%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ELP4	0	0
WT1	0	0
WT1-AS	0	0
FSHB	0	0
PAX6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	5	ELP4, WT1, WT1-AS, FSHB, PAX6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ELP4	0	—
WT1	0	—
WT1-AS	0	—
FSHB	0	—
PAX6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT06740162	Not specified	RECRUITING	Physical Activity and Community EmPOWERment Project
NCT00758108	Not specified	COMPLETED	Characterization of WAGR Syndrome and Other Chromosome 11 Gene Deletions

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LUFENURON	2	1