Thrombocytopenia 1

Summary

Thrombocytopenia 1 (MONDO:0010743) is a disease caused by WAS (GenCC Strong), with 3 cohort genes and 22 clinical trials. Top therapeutic interventions include dronabinol, nicotine, and d-limonene.

At a glance

• Causal gene: WAS (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 614
• Clinical trials: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	thrombocytopenia 1
Mondo ID	MONDO:0010743
MeSH	C564052
OMIM	313900
Orphanet	852
NCIT	C176617
UMLS	C1839163
MedGen	326416
GARD	0005176
Is cancer (heuristic)	no

Also known as: THC · THC1 · thrombocytopenia 1 · thrombocytopenia type 1 · thrombocytopenia, X-linked, intermittent, X-linked recessive · thrombocytopenia, X-linked, X-linked recessive · X-linked thrombocytopenia · X-linked thrombocytopenia with normal platelets · XLT

Data availability: 614 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood platelet disease › thrombocytopenia › inherited thrombocytopenia › thrombocytopenia 1

Related subtypes (20): thrombocytopenia 2, thrombocytopenia, cyclic, thrombocytopenia 3, congenital thrombotic thrombocytopenic purpura, thrombocytopenia, X-linked, with or without dyserythropoietic anemia, thrombocytopenia 4, thrombocytopenia 5, autosomal dominant macrothrombocytopenia, isolated delta-storage pool disease, syndromic constitutional thrombocytopenia, alpha granule disease, thrombocytopenia 7, macrothrombocytopenia, isolated, congenital autosomal recessive small-platelet thrombocytopenia, congenital amegakaryocytic thrombocytopenia, thrombocytopenia 9, thrombocytopenia 10, thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies, thrombocytopenia 12 with or without myopathy, thrombocytopenia 13, syndromic

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:

237 likely benign, 169 uncertain significance, 100 pathogenic, 33 conflicting classifications of pathogenicity, 26 benign, 17 benign/likely benign, 10 likely pathogenic, 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
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
11117	NM_000377.3(WAS):c.707C>G (p.Ala236Gly)	WAS	Pathogenic	no assertion criteria provided
11118	NM_000377.3(WAS):c.482dup (p.Pro162fs)	WAS	Pathogenic	no assertion criteria provided
11119	NM_000377.3(WAS):c.100C>T (p.Arg34Ter)	WAS	Pathogenic	criteria provided, single submitter
11123	NM_000377.3(WAS):c.134C>T (p.Thr45Met)	WAS	Pathogenic	criteria provided, multiple submitters, no conflicts
11125	NM_000377.3(WAS):c.809T>C (p.Leu270Pro)	WAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11132	NM_000377.3(WAS):c.11del (p.Gly4fs)	WAS	Pathogenic	criteria provided, single submitter
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
1723230	NM_000377.3(WAS):c.464-11T>G	WAS	Pathogenic	criteria provided, single submitter
1810240	NM_000377.3(WAS):c.383T>C (p.Phe128Ser)	WAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2005814	NM_000377.3(WAS):c.701del (p.Ser234fs)	WAS	Pathogenic	criteria provided, single submitter
2013847	NM_000377.3(WAS):c.964G>T (p.Gly322Ter)	WAS	Pathogenic	criteria provided, single submitter
2022929	NM_000377.3(WAS):c.1266del (p.Gly424fs)	WAS	Pathogenic	criteria provided, single submitter
2029720	NM_000377.3(WAS):c.412dup (p.Arg138fs)	WAS	Pathogenic	criteria provided, single submitter
2030805	NM_000377.3(WAS):c.19_41del (p.Gly7fs)	WAS	Pathogenic	criteria provided, single submitter
2033777	NM_000377.3(WAS):c.295del (p.Gln99fs)	WAS	Pathogenic	criteria provided, single submitter
2091421	NM_000377.3(WAS):c.735-2A>T	WAS	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 3 · 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	Strong	X-linked	thrombocytopenia 1	11

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

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
WAS	HGNC:12731	ENSG00000015285	P42768	Actin nucleation-promoting factor WAS	gencc,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.
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: 0 · Difficult: 0 · 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
Other/Unknown	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WAS	Other/Unknown	no		CRIB_dom, WH1/EVH1_dom, WH2_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.

1 cohort gene 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
primordial germ cell in gonad	2
granulocyte	1
leukocyte	1
mononuclear cell	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
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: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WAS	3,320
CCNB3	2,576
LINC01560	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WAS	P42768	6

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: 7. Enrichment computed across 3 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Generation of second messenger molecules	1	346.1×	0.008	WAS
RHO GTPases Activate WASPs and WAVEs	1	317.2×	0.008	WAS
RHOJ GTPase cycle	1	200.3×	0.008	WAS
FCGR3A-mediated phagocytosis	1	187.2×	0.008	WAS
Regulation of actin dynamics for phagocytic cup formation	1	184.2×	0.008	WAS
CDC42 GTPase cycle	1	72.3×	0.016	WAS
RAC1 GTPase cycle	1	61.1×	0.016	WAS

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
regulation of T cell antigen processing and presentation	1	8426.0×	0.003	WAS
Cdc42 protein signal transduction	1	2106.5×	0.005	WAS
regulation of actin polymerization or depolymerization	1	1404.3×	0.005	WAS
regulation of lamellipodium assembly	1	936.2×	0.006	WAS
negative regulation of cell motility	1	648.1×	0.007	WAS
regulation of stress fiber assembly	1	495.6×	0.008	WAS
actin filament-based movement	1	401.2×	0.008	WAS
actin polymerization or depolymerization	1	383.0×	0.008	WAS
negative regulation of stress fiber assembly	1	290.6×	0.009	WAS
actin filament polymerization	1	240.7×	0.010	WAS
positive regulation of double-strand break repair via homologous recombination	1	191.5×	0.011	WAS
T cell activation	1	129.6×	0.013	WAS
endosomal transport	1	122.1×	0.013	WAS
meiotic cell cycle	1	122.1×	0.013	CCNB3
defense response	1	108.0×	0.013	WAS
epidermis development	1	105.3×	0.013	WAS
cellular response to type II interferon	1	104.0×	0.013	WAS
G1/S transition of mitotic cell cycle	1	100.3×	0.013	CCNB3
blood coagulation	1	86.9×	0.014	WAS
protein-containing complex assembly	1	56.9×	0.020	WAS
immune response	1	23.5×	0.045	WAS
cell division	1	23.1×	0.045	CCNB3
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	WAS

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
CCNB3	PALBOCICLIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CCNB3	17	4
WAS	0	0
LINC01560	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
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
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): 0.

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

Symbol	Assays	Type breakdown
CCNB3	148	Binding:147, Functional:1

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: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

17 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)
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
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)	1	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	2	WAS, LINC01560

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
WAS	0	—
LINC01560	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 22.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	6
PHASE1	5
Not specified	4
PHASE1/PHASE2	3
EARLY_PHASE1	3
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04340700	PHASE3	WITHDRAWN	Characterization of the Pharmacodynamic Response to Vaped THC
NCT05514899	PHASE2	RECRUITING	Effects of Cannabidiol and Tetrahydrocannabinol on Microbiome and Neuroinflammation in HIV
NCT05641766	PHASE2	NOT_YET_RECRUITING	Multimodal Magnetoencephalography and Electroencephalography Exploration of the Acute Effects of THC Exposure on Neural Noise and Information Transmission Within Working Memory Networks
NCT05999383	PHASE2	RECRUITING	Understanding the Clinical Pharmacology of Marijuana-Tobacco Co-administration
NCT06099379	PHASE1/PHASE2	RECRUITING	Modulation of THC Effects by CBD: a Dose-ranging Study
NCT06647524	PHASE2	RECRUITING	Pilot fMRI Studies of Aging-Related Effects of THC
NCT04360044	PHASE2	COMPLETED	Efficacy of Inhaled Cannabis for Acute Migraine Treatment
NCT04976738	PHASE1/PHASE2	COMPLETED	A Study of Cybis™ 10:25 THC:CBD Oil in Adults With Chronic Back/Neck Pain
NCT05116527	PHASE1/PHASE2	UNKNOWN	THC Memory & Reward Learning Pilot
NCT05427630	PHASE2	SUSPENDED	Dose-Ranging Trial of Inhaled Cannabis for Acute Migraine Treatment
NCT06378957	PHASE1	RECRUITING	Behavioral Pharmacology of Orally Administered THC and D-limonene
NCT00774358	PHASE1	COMPLETED	Interleukin-2 Treatment for Wiskott-Aldrich Syndrome
NCT03098940	PHASE1	UNKNOWN	A Bioavailability Study on Dronabinol
NCT04130633	PHASE1	COMPLETED	Behavioral Pharmacology of THC and Alpha-pinene
NCT05121506	PHASE1	COMPLETED	A Study to Investigate the Bioavailability and Skin Absorption of CBD and THC From GT4 Technology in Healthy Adults
NCT02102113	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Probing the Cannabinoid System in Individuals With a Family History of Psychosis
NCT03560934	EARLY_PHASE1	COMPLETED	Tetrahydrocannabinol (THC) and Sleep
NCT04294966	EARLY_PHASE1	COMPLETED	Age-Related Effects of THC
NCT07105449	Not specified	NOT_YET_RECRUITING	THC Titration of High-Potency Cannabis Concentrates
NCT04429568	Not specified	COMPLETED	THC Crossover Study
NCT04851392	Not specified	COMPLETED	Do Adolescents and Adults Differ in Their Acute Response to Cannabis?
NCT06077292	Not specified	SUSPENDED	Cannabis THC Potency, Metabolism, and Cognitive Impairment in Young Adults

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DRONABINOL	4	2
NICOTINE	4	1
D-LIMONENE	2	1
ALPHA-PINENE	1	1
CHEMBL423707	0	1
1R-(+)-ALPHA-PINENE	0	1
BETA-PINENE	0	1