Wiskott-Aldrich syndrome

Summary

Wiskott-Aldrich syndrome (MONDO:0010518) is a disease caused by WAS (GenCC Definitive), with 5 cohort genes and 34 clinical trials. Top therapeutic interventions include romiplostim, alefacept, and dextrose.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: WAS (GenCC Definitive)
• Cohort genes: 5
• ClinVar variants: 694
• Phenotypes (HPO): 57
• Clinical trials: 34

Clinical features

Epidemiology

Prevalence records

8 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.1	Europe	Validated
Point prevalence	1-9 / 1 000 000	0.18	France	Validated
Point prevalence	<1 / 1 000 000	0.07	Australia	Validated
Point prevalence	<1 / 1 000 000	0.03	Korea, Republic of	Validated
Point prevalence	<1 / 1 000 000	0.0278	China	Validated
Prevalence at birth	1-9 / 1 000 000	0.2	Switzerland	Validated
Prevalence at birth	1-9 / 1 000 000	0.2	United States	Validated
Point prevalence	1-9 / 1 000 000	0.55	Norway	Not yet validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000246	Sinusitis	Very frequent (80-99%)
HP:0000388	Otitis media	Very frequent (80-99%)
HP:0000389	Chronic otitis media	Very frequent (80-99%)
HP:0000978	Bruising susceptibility	Very frequent (80-99%)
HP:0001873	Thrombocytopenia	Very frequent (80-99%)
HP:0001888	Lymphopenia	Very frequent (80-99%)
HP:0001945	Fever	Very frequent (80-99%)
HP:0002028	Chronic diarrhea	Very frequent (80-99%)
HP:0002205	Recurrent respiratory infections	Very frequent (80-99%)
HP:0002721	Immunodeficiency	Very frequent (80-99%)
HP:0003010	Prolonged bleeding time	Very frequent (80-99%)
HP:0006510	Chronic pulmonary obstruction	Very frequent (80-99%)
HP:0007420	Spontaneous hematomas	Very frequent (80-99%)
HP:0011029	Internal hemorrhage	Very frequent (80-99%)
HP:0011875	Abnormal platelet morphology	Very frequent (80-99%)
HP:0000967	Petechiae	Frequent (30-79%)
HP:0000979	Purpura	Frequent (30-79%)
HP:0001328	Specific learning disability	Frequent (30-79%)
HP:0001878	Hemolytic anemia	Frequent (30-79%)
HP:0001879	Abnormality of eosinophils	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0001935	Microcytic anemia	Frequent (30-79%)
HP:0002037	Inflammation of the large intestine	Frequent (30-79%)
HP:0002094	Dyspnea	Frequent (30-79%)
HP:0002248	Hematemesis	Frequent (30-79%)
HP:0002573	Hematochezia	Frequent (30-79%)
HP:0002960	Autoimmunity	Frequent (30-79%)
HP:0011675	Arrhythmia	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0000112	Nephropathy	Occasional (5-29%)
HP:0000140	Abnormality of the menstrual cycle	Occasional (5-29%)
HP:0000225	Gingival bleeding	Occasional (5-29%)
HP:0000421	Epistaxis	Occasional (5-29%)
HP:0000491	Keratitis	Occasional (5-29%)
HP:0000498	Blepharitis	Occasional (5-29%)
HP:0000509	Conjunctivitis	Occasional (5-29%)
HP:0000778	Hypoplasia of the thymus	Occasional (5-29%)
HP:0000964	Eczematoid dermatitis	Occasional (5-29%)
HP:0001025	Urticaria	Occasional (5-29%)
HP:0001287	Meningitis	Occasional (5-29%)
HP:0001369	Arthritis	Occasional (5-29%)
HP:0001645	Sudden cardiac death	Occasional (5-29%)
HP:0001875	Decreased total neutrophil count	Occasional (5-29%)
HP:0002170	Intracranial hemorrhage	Occasional (5-29%)
HP:0002488	Acute leukemia	Occasional (5-29%)
HP:0002633	Vasculitis	Occasional (5-29%)
HP:0002664	Neoplasm	Occasional (5-29%)
HP:0002665	Lymphoma	Occasional (5-29%)
HP:0005558	Chronic leukemia	Occasional (5-29%)
HP:0006535	Recurrent intrapulmonary hemorrhage	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Wiskott-Aldrich syndrome
Mondo ID	MONDO:0010518
MeSH	D014923
OMIM	301000
Orphanet	906
DOID	DOID:9169
ICD-10-CM	D82.0
ICD-11	168952525
NCIT	C3448
SNOMED CT	36070007
UMLS	C0043194
MedGen	21921
GARD	0007895
MedDRA	10047992
Is cancer (heuristic)	no

Also known as: eczema thrombocytopenia immunodeficiency syndrome · eczema-thrombocytopenia-immunodeficiency syndrome · Imd 2 · immunodeficiency 2 · WAS · Wiskott Aldrich syndrome · Wiskott-Aldrich syndrome · Wiskott-Aldrich syndrome 1 · Wiskott-Aldrich syndrome, X-linked recessive

Data availability: 694 ClinVar variants · 6 GenCC gene-disease records · 11 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › X-linked disease › Wiskott-Aldrich syndrome

Related subtypes (49): X-linked Opitz G/BBB syndrome, X-linked immunoneurologic disorder, X-linked adrenal hypoplasia congenita, X-linked lissencephaly with abnormal genitalia, X-linked severe congenital neutropenia, X-linked distal spinal muscular atrophy type 3, epilepsy, X-linked 1, with variable learning disabilities and behavior disorders, Aland island eye disease, X-linked erythropoietic protoporphyria, X-linked central congenital hypothyroidism with late-onset testicular enlargement, X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome, X-linked acrogigantism due to Xq26 microduplication, X-linked Alport syndrome, X-linked mandibulofacial dysostosis, X-linked chondrodysplasia punctata, choroideremia, cone dystrophy, X-linked, with tapetal-like sheen, diabetes insipidus, nephrogenic, X-linked, Dyggve-Melchior-Clausen syndrome, X-linked, dyskeratosis congenita, X-linked, X-linked hypohidrotic ectodermal dysplasia, X-linked Ehlers-Danlos syndrome, epidermodysplasia verruciformis, X-linked, exudative vitreoretinopathy 2, X-linked, Aarskog-Scott syndrome, X-linked, hemophilia A, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius, hyper-IgM syndrome type 1, X-linked lymphoproliferative syndrome, macular dystrophy, X-linked, X-linked Emery-Dreifuss muscular dystrophy, X-linked myotubular myopathy, X-linked lethal multiple pterygium syndrome, X-linked retinoschisis, spondyloepiphyseal dysplasia tarda, X-linked, X-linked cerebellar ataxia, adrenoleukodystrophy, Charcot-Marie-Tooth disease type X, X-linked dominant disease, X-linked recessive disease, X-linked hypophosphatemic rickets, X-linked sideroblastic anemia 1, X-linked deafness, X-linked cone-rod dystrophy, X-linked congenital stationary night blindness, X-linked congenital hemolytic anemia, X-linked complex neurodevelopmental disorder, X-linked intellectual disability, leukemia, acute, X-linked

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:

223 likely benign, 154 uncertain significance, 89 pathogenic, 34 benign, 33 likely pathogenic, 31 conflicting classifications of pathogenicity, 28 benign/likely benign, 8 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2422978	NC_000023.10:g.(?46618120)(48549553_?)del	LINC01560	Pathogenic	criteria provided, single submitter
1073358	NM_000377.3(WAS):c.753dup (p.Trp252fs)	WAS	Pathogenic	criteria provided, single submitter
1074326	NM_000377.3(WAS):c.827_828insGGGCCTTCTCCAGGGCAGGAAT (p.Ile276fs)	WAS	Pathogenic	criteria provided, single submitter
1074601	NM_000377.3(WAS):c.1453+2T>G	WAS	Pathogenic	criteria provided, single submitter
1074623	NM_000377.3(WAS):c.539dup (p.His180fs)	WAS	Pathogenic	criteria provided, single submitter
1076500	NM_000377.3(WAS):c.723del (p.Ser242fs)	WAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11113	NM_000377.3(WAS):c.177del (p.Gly60fs)	WAS	Pathogenic	no assertion criteria provided
11114	NM_000377.3(WAS):c.257G>T (p.Arg86Leu)	WAS	Pathogenic	no assertion criteria provided
11115	NM_000377.3(WAS):c.257G>A (p.Arg86His)	WAS	Pathogenic	criteria provided, multiple submitters, no conflicts
11116	NM_000377.3(WAS):c.167C>T (p.Ala56Val)	WAS	Pathogenic	criteria provided, multiple submitters, no conflicts
11119	NM_000377.3(WAS):c.100C>T (p.Arg34Ter)	WAS	Pathogenic	criteria provided, single submitter
11120	NM_000377.3(WAS):c.1A>T (p.Met1Leu)	WAS	Pathogenic	no assertion criteria provided
11121	NM_000377.3(WAS):c.389ACGAGG[3] (p.130DE[3])	WAS	Pathogenic	no assertion criteria provided
11123	NM_000377.3(WAS):c.134C>T (p.Thr45Met)	WAS	Pathogenic	criteria provided, multiple submitters, no conflicts
11124	NM_000377.3(WAS):c.1097del (p.Gly366fs)	WAS	Pathogenic	no assertion criteria provided
11125	NM_000377.3(WAS):c.809T>C (p.Leu270Pro)	WAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11128	WAS, 15,800-BP DEL	WAS	Pathogenic	no assertion criteria provided
11130	NM_000377.3(WAS):c.560-1G>A	WAS	Pathogenic	no assertion criteria provided
11131	NM_000377.3(WAS):c.559+2T>G	WAS	Pathogenic	no assertion criteria provided
11132	NM_000377.3(WAS):c.11del (p.Gly4fs)	WAS	Pathogenic	criteria provided, single submitter
11133	NM_000377.3(WAS):c.73_74del (p.Thr25fs)	WAS	Pathogenic	no assertion criteria provided
1200930	NM_000377.3(WAS):c.724del (p.Ser242fs)	WAS	Pathogenic	criteria provided, single submitter
1321313	NM_000377.3(WAS):c.990del (p.Ile331fs)	WAS	Pathogenic	no assertion criteria provided
1338374	NM_000377.3(WAS):c.192G>A (p.Trp64Ter)	WAS	Pathogenic	criteria provided, multiple submitters, no conflicts
1360224	NM_000377.3(WAS):c.176del (p.Pro59fs)	WAS	Pathogenic	criteria provided, multiple submitters, no conflicts
1410526	NM_000377.3(WAS):c.382T>C (p.Phe128Leu)	WAS	Pathogenic	criteria provided, single submitter
1418621	NM_000377.3(WAS):c.1021_1022insT (p.Pro341fs)	WAS	Pathogenic	criteria provided, single submitter
1441543	NM_000377.3(WAS):c.1085del (p.Pro362fs)	WAS	Pathogenic	criteria provided, single submitter
1466589	NM_000377.3(WAS):c.777+3_777+6del	WAS	Pathogenic	criteria provided, multiple submitters, no conflicts
1493038	NM_000377.3(WAS):c.1339-2A>G	WAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 5 · 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
WAS	Definitive	X-linked	Wiskott-Aldrich syndrome	11
WIPF1	Strong	Autosomal recessive	Wiskott-Aldrich syndrome 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WAS	Orphanet:852	X-linked thrombocytopenia with normal platelets
WAS	Orphanet:86788	X-linked severe congenital neutropenia
WAS	Orphanet:906	Wiskott-Aldrich syndrome
WIPF1	Orphanet:714493	Congenital thrombocytopenia-recurrent infections syndrome due to WIP deficiency
WRN	Orphanet:902	Werner syndrome

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
WAS	HGNC:12731	ENSG00000015285	P42768	Actin nucleation-promoting factor WAS	gencc,clinvar
WIPF1	HGNC:12736	ENSG00000115935	O43516	WAS/WASL-interacting protein family member 1	gencc
WRN	HGNC:12791	ENSG00000165392	Q14191	Bifunctional 3’-5’ exonuclease/ATP-dependent helicase WRN	clinvar
CCNB3	HGNC:18709	ENSG00000147082	Q8WWL7	G2/mitotic-specific cyclin-B3	clinvar
LINC01560	HGNC:27333	ENSG00000196741	Q8TB33	Putative uncharacterized protein encoded by LINC01560	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WAS	Actin nucleation-promoting factor WAS	Effector protein for Rho-type GTPases that regulates actin filament reorganization via its interaction with the Arp2/3 complex.
WIPF1	WAS/WASL-interacting protein family member 1	Plays a role in the reorganization of the actin cytoskeleton.
WRN	Bifunctional 3’-5’ exonuclease/ATP-dependent helicase WRN	Multifunctional enzyme that has magnesium and ATP-dependent 3’-5’ DNA-helicase activity on partially duplex substrates.
CCNB3	G2/mitotic-specific cyclin-B3	Cyclins are positive regulatory subunits of the cyclin-dependent kinases (CDKs), and thereby play an essential role in the control of the cell cycle, notably via their destruction during cell division.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.2

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	2.4×	0.353
Other/Unknown	4	1.4×	0.353

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WAS	Other/Unknown	no		CRIB_dom, WH1/EVH1_dom, WH2_dom
WIPF1	Other/Unknown	no		WH2_dom, PH-like_dom_sf, WAS/WASL-interacting_domain
WRN	Enzyme (other)	yes	3.6.4.12	Helicase_C-like, HRDC_dom, 3’-5’_exonuclease_dom
CCNB3	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
LINC01560	Other/Unknown	no

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
leukocyte	2
primordial germ cell in gonad	2
granulocyte	1
mononuclear cell	1
blood	1
monocyte	1
calcaneal tendon	1
male germ cell	1
sperm	1
male germ line stem cell (sensu Vertebrata) in testis	1
secondary oocyte	1
buccal mucosa cell	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WAS	246	broad	marker	granulocyte, leukocyte, mononuclear cell
WIPF1	284	ubiquitous	marker	blood, monocyte, leukocyte
WRN	252	ubiquitous	marker	calcaneal tendon, sperm, male germ cell
CCNB3	156	tissue_specific	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte
LINC01560	207	ubiquitous	yes	buccal mucosa cell, primordial germ cell in gonad, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WAS	3,320
WRN	3,258
CCNB3	2,576
WIPF1	1,600
LINC01560	0

Intra-cohort edges

A	B	Sources
WAS	WIPF1	biogrid_interaction, intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WRN	Q14191	51
WAS	P42768	6
WIPF1	O43516	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CCNB3	Q8WWL7	42.25
LINC01560	Q8TB33	40.36

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 5 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RHO GTPases Activate WASPs and WAVEs	2	211.5×	7e-04	WAS, WIPF1
FCGR3A-mediated phagocytosis	2	124.8×	7e-04	WAS, WIPF1
Regulation of actin dynamics for phagocytic cup formation	2	122.8×	7e-04	WAS, WIPF1
CDC42 GTPase cycle	2	48.2×	0.003	WAS, WIPF1
RAC1 GTPase cycle	2	40.7×	0.004	WAS, WIPF1
Processive synthesis on the C-strand of the telomere	1	253.8×	0.014	WRN
Removal of the Flap Intermediate from the C-strand	1	211.5×	0.014	WRN
Impaired BRCA2 binding to PALB2	1	152.3×	0.014	WRN
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	141.0×	0.014	WRN
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	141.0×	0.014	WRN
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	141.0×	0.014	WRN
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	131.3×	0.014	WRN
Homologous DNA Pairing and Strand Exchange	1	126.9×	0.014	WRN
Generation of second messenger molecules	1	115.3×	0.014	WAS
Impaired BRCA2 binding to RAD51	1	102.9×	0.014	WRN
Resolution of D-loop Structures through Holliday Junction Intermediates	1	100.2×	0.014	WRN
HDR through Single Strand Annealing (SSA)	1	97.6×	0.014	WRN
Presynaptic phase of homologous DNA pairing and strand exchange	1	90.6×	0.015	WRN
RHOJ GTPase cycle	1	66.8×	0.019	WAS
HDR through Homologous Recombination (HRR)	1	63.4×	0.019	WRN
SUMOylation of DNA damage response and repair proteins	1	48.8×	0.023	WRN
G2/M DNA damage checkpoint	1	40.1×	0.026	WRN
Regulation of TP53 Activity through Phosphorylation	1	39.2×	0.026	WRN
Processing of DNA double-strand break ends	1	38.1×	0.026	WRN

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
actin filament-based movement	2	401.2×	2e-04	WAS, WIPF1
actin polymerization or depolymerization	2	383.0×	2e-04	WAS, WIPF1
regulation of T cell antigen processing and presentation	1	4213.0×	0.002	WAS
positive regulation of hydrolase activity	1	4213.0×	0.002	WRN
positive regulation of strand invasion	1	4213.0×	0.002	WRN
regulation of growth rate	1	2106.5×	0.003	WRN
protein-containing complex assembly	2	56.9×	0.003	WAS, WIPF1
response to other organism	1	1404.3×	0.004	WIPF1
Cdc42 protein signal transduction	1	1053.2×	0.005	WAS
regulation of actin polymerization or depolymerization	1	702.2×	0.006	WAS
telomere maintenance via semi-conservative replication	1	702.2×	0.006	WRN
DNA geometric change	1	526.6×	0.007	WRN
regulation of lamellipodium assembly	1	468.1×	0.007	WAS
telomeric D-loop disassembly	1	468.1×	0.007	WRN
response to UV-C	1	421.3×	0.008	WRN
protein localization to nucleolus	1	383.0×	0.008	WRN
t-circle formation	1	351.1×	0.008	WRN
negative regulation of cell motility	1	324.1×	0.008	WAS
DNA metabolic process	1	263.3×	0.009	WRN
regulation of stress fiber assembly	1	247.8×	0.009	WAS
replicative senescence	1	247.8×	0.009	WRN
DNA synthesis involved in DNA repair	1	234.1×	0.010	WRN
mismatch repair	1	162.0×	0.013	WRN
cellular response to gamma radiation	1	150.5×	0.013	WRN
negative regulation of stress fiber assembly	1	145.3×	0.013	WAS
actin filament polymerization	1	120.4×	0.015	WAS
base-excision repair	1	117.0×	0.015	WRN
determination of adult lifespan	1	108.0×	0.016	WRN
replication fork processing	1	105.3×	0.016	WRN
positive regulation of double-strand break repair via homologous recombination	1	95.8×	0.017	WAS

Therapeutics

Drugs indicated for this disease

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

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Eltrombopag, Fludarabine Phosphate, Melphalan, Methotrexate, Mycophenolate Mofetil, Romiplostim, Tacrolimus Anhydrous.

Drug target analysis

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

Druggability breadth: 2 of 5 evidence-associated genes (40%) 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
WRN	INDIGOTINDISULFONATE
CCNB3	PALBOCICLIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CCNB3	17	4
WRN	2	4
WAS	0	0
WIPF1	0	0
LINC01560	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INDIGOTINDISULFONATE	4	WRN
PALBOCICLIB	4	CCNB3
DINACICLIB	3	CCNB3
ALVOCIDIB	3	CCNB3
QUERCETIN	3	CCNB3
SILMITASERTIB	2	CCNB3
INDIRUBIN	2	CCNB3
SELICICLIB	2	CCNB3
LUTEOLIN	2	CCNB3
ASNUCICLIB	2	CCNB3
FISETIN	2	CCNB3
RIVICICLIB	2	CCNB3
AT-7519	2	CCNB3
HRO-761	1	WRN
KAEMPFEROL	1	CCNB3
SU-9516	1	CCNB3
HARMINE	1	CCNB3
BMS-387032	1	CCNB3
LADUVIGLUSIB	1	CCNB3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CCNB3	148	Binding:147, Functional:1
WRN	32	Binding:30, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
WRN	3.6.4.12	DNA helicase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CCNB3	148

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

19 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)
INDIGOTINDISULFONATE	4	WRN
PALBOCICLIB	4	CCNB3
DINACICLIB	3	CCNB3
ALVOCIDIB	3	CCNB3
QUERCETIN	3	CCNB3
SILMITASERTIB	2	CCNB3
INDIRUBIN	2	CCNB3
SELICICLIB	2	CCNB3
LUTEOLIN	2	CCNB3
ASNUCICLIB	2	CCNB3
FISETIN	2	CCNB3
RIVICICLIB	2	CCNB3
AT-7519	2	CCNB3
HRO-761	1	WRN
KAEMPFEROL	1	CCNB3
SU-9516	1	CCNB3
HARMINE	1	CCNB3
BMS-387032	1	CCNB3
LADUVIGLUSIB	1	CCNB3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	WRN, CCNB3
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	WAS, WIPF1, LINC01560

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)
WAS	0	—
WIPF1	0	—
LINC01560	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 34.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	11
PHASE1/PHASE2	9
PHASE2	7
PHASE3	3
PHASE1	3
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01289847	PHASE4	COMPLETED	A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency
NCT03837483	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study to Evaluate the Use of a Cryopreserved Formulation of OTL-103 in Subjects With Wiskott-Aldrich Syndrome
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT00278954	PHASE3	COMPLETED	Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT02333760	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Long Term Safety Follow up of Haematopoietic Stem Cell Gene Therapy for the Wiskott Aldrich Syndrome
NCT00730314	PHASE1/PHASE2	COMPLETED	Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells
NCT00885833	PHASE1/PHASE2	COMPLETED	Study of Reduced Toxicity Myeloablative Conditioning Regimen for Wiskott-Aldrich Syndrome (WAS)
NCT00909363	PHASE2	TERMINATED	Thrombocytopenia and Bleeding in Wiskott-Aldrich Syndrome (WAS) Patients
NCT01347242	PHASE1/PHASE2	COMPLETED	Gene Therapy for Wiskott-Aldrich Syndrome (WAS)
NCT01347346	PHASE1/PHASE2	COMPLETED	Gene Therapy for WAS
NCT01410825	PHASE1/PHASE2	COMPLETED	Pilot and Feasibility Study of Hematopoietic Stem Cell Gene Transfer for the Wiskott-Aldrich Syndrome
NCT01515462	PHASE1/PHASE2	COMPLETED	Gene Therapy for Wiskott-Aldrich Syndrome
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT02512679	PHASE2	TERMINATED	Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells
NCT03019809	PHASE2	UNKNOWN	A Trial of Plerixafor/G-CSF as Additional Agents for Conditioning Before TCR Alpha/Beta Depleted HSCT in WAS Patients
NCT03333486	PHASE2	TERMINATED	Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT04371939	PHASE2	UNKNOWN	Efficacy and Safety of Romiplostim Versus Eltrombopag in the Treatment of Thrombocytopenia in Patients With Wiskott-Aldrich Syndrome
NCT00160355	PHASE1	COMPLETED	Haploidentical Hematopoietic Stem Cell Transplantation Patients With Wiskott-Aldrich Syndrome
NCT00774358	PHASE1	COMPLETED	Interleukin-2 Treatment for Wiskott-Aldrich Syndrome
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT00004341	Not specified	UNKNOWN	Study of Genetic and Molecular Defects in Primary Immunodeficiency Disorders
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00006319	Not specified	UNKNOWN	Molecular and Clinical Studies of Primary Immunodeficiency Diseases
NCT01319851	Not specified	TERMINATED	Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
NCT01953016	Not specified	COMPLETED	Participation in a Research Registry for Immune Disorders
NCT02064933	Not specified	COMPLETED	Patients Treated for Wiskott-Aldrich Syndrome (WAS) Since 1990
NCT03198195	Not specified	UNKNOWN	Post-transplant Cyclophosphamide in Wiskott-Aldrich Syndrome
NCT03399461	Not specified	COMPLETED	Targeted Literature Review and Subject Interviews in Wiskott-Aldrich Syndrome (WAS)
NCT04350164	Not specified	COMPLETED	Romiplostim Treatment for Thrombocytopenia in Patients With Wiskott-Aldrich Syndrome.
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ROMIPLOSTIM	4	2
ALEFACEPT	4	1
DEXTROSE	4	1
ELTROMBOPAG	4	1
HUMAN IMMUNOGLOBULIN G	4	1
CHEMBL423707	0	1