Frasier syndrome

Summary

Frasier syndrome (MONDO:0007635) is a disease with 3 cohort genes and 2 clinical trials.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 1,458
• Phenotypes (HPO): 16
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		150	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0000033	Ambiguous genitalia, male	Obligate (100%)
HP:0000037	Male pseudohermaphroditism	Obligate (100%)
HP:0100820	Glomerulopathy	Obligate (100%)
HP:0000093	Proteinuria	Very frequent (80-99%)
HP:0000097	Focal segmental glomerulosclerosis	Very frequent (80-99%)
HP:0000786	Primary amenorrhea	Very frequent (80-99%)
HP:0000815	Hypergonadotropic hypogonadism	Very frequent (80-99%)
HP:0000837	Increased circulating gonadotropin level	Very frequent (80-99%)
HP:0008214	Decreased serum estradiol	Very frequent (80-99%)
HP:0008723	Gonadal dysgenesis with female appearance, male	Very frequent (80-99%)
HP:0000083	Renal insufficiency	Frequent (30-79%)
HP:0000100	Nephrotic syndrome	Frequent (30-79%)
HP:0000150	Gonadoblastoma	Frequent (30-79%)
HP:0000822	Hypertension	Frequent (30-79%)
HP:0010464	Streak ovary	Frequent (30-79%)
HP:0002667	Nephroblastoma	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Frasier syndrome
Mondo ID	MONDO:0007635
MeSH	D052159
OMIM	136680
Orphanet	347
DOID	DOID:0050438
ICD-11	1659542949
NCIT	C122805
SNOMED CT	445431000
UMLS	C0950122
MedGen	215533
GARD	0002375
Is cancer (heuristic)	no

Also known as: Frasier syndrome · Frasier syndrome, autosomal dominant, somatic mutation

Data availability: 1,458 ClinVar variants · 1 GenCC gene-disease record · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › Frasier syndrome

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid 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:

280 uncertain significance, 262 likely benign, 31 conflicting classifications of pathogenicity, 16 pathogenic, 5 benign, 3 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: 7 · Orphanet: 9 · 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
WT1	Supportive	Autosomal dominant	Frasier syndrome	7

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

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WT1	HGNC:12796	ENSG00000184937	P19544	Wilms tumor protein	gencc,clinvar
ELP4	HGNC:1171	ENSG00000109911	Q96EB1	Elongator complex protein 4	clinvar
WT1-AS	HGNC:18135	ENSG00000183242	Q06250	Putative Wilms tumor upstream neighbor 1 gene protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WT1	Wilms tumor protein	Transcription factor that plays an important role in cellular development and cell survival.
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).

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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	1	2.8×	0.587
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WT1	Transcription factor	no		Wilms_tumour_N, Znf_C2H2_type, Znf_C2H2_sf
ELP4	Other/Unknown	no		Elongator_complex_protein_4, P-loop_NTPase
WT1-AS	Other/Unknown	no

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
germinal epithelium of ovary	1
metanephric glomerulus	1
renal glomerulus	1
calcaneal tendon	1
primordial germ cell in gonad	1
ventricular zone	1
left ovary	1
ovary	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WT1	168	broad	marker	germinal epithelium of ovary, renal glomerulus, metanephric glomerulus
ELP4	250	ubiquitous	marker	ventricular zone, calcaneal tendon, primordial germ cell in gonad
WT1-AS	106	tissue_specific	yes	right uterine tube, left ovary, ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WT1	3,938
ELP4	1,740
WT1-AS	35

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WT1	P19544	28

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: 4. Enrichment computed across 3 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
Nephron development	1	439.2×	0.006	WT1
Transcriptional regulation of testis differentiation	1	356.9×	0.006	WT1
Negative Regulation of CDH1 Gene Transcription	1	60.1×	0.022	WT1
HATs acetylate histones	1	39.6×	0.025	ELP4

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
negative regulation of metanephric glomerular mesangial cell proliferation	1	8426.0×	0.002	WT1
regulation of animal organ formation	1	4213.0×	0.002	WT1
adrenal cortex formation	1	4213.0×	0.002	WT1
visceral serous pericardium development	1	4213.0×	0.002	WT1
posterior mesonephric tubule development	1	4213.0×	0.002	WT1
positive regulation of metanephric ureteric bud development	1	4213.0×	0.002	WT1
positive regulation of heart growth	1	2106.5×	0.003	WT1
metanephric S-shaped body morphogenesis	1	2106.5×	0.003	WT1
negative regulation of female gonad development	1	2106.5×	0.003	WT1
thorax and anterior abdomen determination	1	1685.2×	0.003	WT1
cardiac muscle cell fate commitment	1	1685.2×	0.003	WT1
metanephric epithelium development	1	1685.2×	0.003	WT1
cellular response to gonadotropin stimulus	1	1404.3×	0.003	WT1
metanephric mesenchyme development	1	1203.7×	0.003	WT1
tissue development	1	936.2×	0.003	WT1
diaphragm development	1	936.2×	0.003	WT1
sex determination	1	842.6×	0.003	WT1
positive regulation of male gonad development	1	842.6×	0.003	WT1
glomerular basement membrane development	1	766.0×	0.003	WT1
mesenchymal to epithelial transition	1	766.0×	0.003	WT1
podocyte differentiation	1	702.2×	0.004	WT1
glomerulus development	1	648.1×	0.004	WT1
tRNA wobble uridine modification	1	601.9×	0.004	ELP4
gonad development	1	561.7×	0.004	WT1
negative regulation of gene expression via chromosomal CpG island methylation	1	526.6×	0.004	WT1
male genitalia development	1	443.5×	0.005	WT1
adrenal gland development	1	337.0×	0.006	WT1
ureteric bud development	1	227.7×	0.008	WT1
germ cell development	1	227.7×	0.008	WT1
branching involved in ureteric bud morphogenesis	1	183.2×	0.009	WT1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	WT1, ELP4, WT1-AS

Undrugged target profiles

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

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

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

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
NCT01252901	Not specified	COMPLETED	Registry for Patients With Wilms’ Tumor Suppressor Gene 1 (WT1) Mutation Associated Diseases