beta-thalassemia-X-linked thrombocytopenia syndrome

Summary

beta-thalassemia-X-linked thrombocytopenia syndrome (MONDO:0010745) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 16
• Phenotypes (HPO): 6

Clinical features

Signs & symptoms

Clinical features (HPO)

6 HPO clinical features (Orphanet curated; top 6 by frequency):

HPO ID	Term	Frequency
HP:0001744	Splenomegaly	Very frequent (80-99%)
HP:0001873	Thrombocytopenia	Very frequent (80-99%)
HP:0001892	Abnormal bleeding	Very frequent (80-99%)
HP:0001903	Anemia	Very frequent (80-99%)
HP:0011869	Abnormal platelet function	Very frequent (80-99%)
HP:0011902	Abnormal hemoglobin	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	beta-thalassemia-X-linked thrombocytopenia syndrome
Mondo ID	MONDO:0010745
MeSH	C564050
OMIM	314050
Orphanet	231393
DOID	DOID:0111767
ICD-11	905057212
NCIT	C134941
SNOMED CT	718196002
UMLS	C1839161
MedGen	326415
GARD	0017166
Is cancer (heuristic)	no

Also known as: thrombocytopenia with BETA-thalassemia, X-linked · thrombocytopenia with beta-thalassemia, X-linked, X-linked recessive · X-linked thrombocytopenia with Beta-thalassemia · XLTT

Data availability: 16 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › beta-thalassemia and related diseases › beta-thalassemia-X-linked thrombocytopenia syndrome

Related subtypes (6): delta-beta-thalassemia, hemoglobin C-beta-thalassemia syndrome, hemoglobin E-beta-thalassemia syndrome, hemoglobin Lepore-beta-thalassemia syndrome, hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome, beta thalassemia

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

16 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 3 conflicting classifications of pathogenicity, 2 benign/likely benign, 1 pathogenic, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
10428	NM_002049.4(GATA1):c.647G>A (p.Arg216Gln)	GATA1	Pathogenic	criteria provided, multiple submitters, no conflicts
952388	NM_002049.4(GATA1):c.35C>G (p.Ser12Ter)	GATA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31943	NM_002049.4(GATA1):c.646C>T (p.Arg216Trp)	GATA1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1018362	NM_002049.4(GATA1):c.283G>A (p.Gly95Ser)	GATA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2082310	NM_002049.4(GATA1):c.340G>A (p.Glu114Lys)	GATA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
465135	NM_002049.4(GATA1):c.94G>A (p.Val32Ile)	GATA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1429222	NM_002049.4(GATA1):c.893G>A (p.Arg298Gln)	GATA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2937136	NM_002049.4(GATA1):c.550_551delinsAA (p.Ala184Asn)	GATA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3598344	NM_002049.4(GATA1):c.499G>C (p.Asp167His)	GATA1	Uncertain significance	criteria provided, single submitter
3598345	NM_002049.4(GATA1):c.748G>A (p.Val250Ile)	GATA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3598346	NM_002049.4(GATA1):c.1003A>C (p.Met335Leu)	GATA1	Uncertain significance	criteria provided, single submitter
3893065	NM_002049.4(GATA1):c.528C>A (p.Thr176=)	GATA1	Uncertain significance	criteria provided, single submitter
533694	NM_002049.4(GATA1):c.419G>A (p.Arg140Gln)	GATA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
945514	NM_002049.4(GATA1):c.944A>G (p.Lys315Arg)	GATA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1563494	NM_002049.4(GATA1):c.599-9C>T	GATA1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
258542	NM_002049.4(GATA1):c.174G>A (p.Ala58=)	GATA1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 8 · 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
GATA1	Definitive	X-linked	GATA1-Related X-Linked Cytopenia	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GATA1	Orphanet:124	Diamond-Blackfan anemia
GATA1	Orphanet:231393	Beta-thalassemia-X-linked thrombocytopenia syndrome
GATA1	Orphanet:363727	X-linked dyserythropoietic anemia with abnormal platelets and neutropenia
GATA1	Orphanet:420611	Transient myeloproliferative syndrome
GATA1	Orphanet:67044	Thrombocytopenia with congenital dyserythropoietic anemia
GATA1	Orphanet:79277	Congenital erythropoietic porphyria
GATA1	Orphanet:86849	Acute basophilic leukemia
GATA1	Orphanet:99887	Acute megakaryoblastic leukemia in children with Down syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GATA1	HGNC:4170	ENSG00000102145	P15976	Erythroid transcription factor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GATA1	Erythroid transcription factor	Transcriptional activator or repressor which serves as a general switch factor for erythroid development.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GATA1	Transcription factor	no		Znf_GATA, Znf_NHR/GATA, Transcription_factor_GATA

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
blood	1
bone marrow	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GATA1	138	tissue_specific	marker	trabecular bone tissue, blood, bone marrow

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GATA1	4,810

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GATA1	P15976	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 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
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	120.2×	0.015	GATA1
RUNX1 regulates transcription of genes involved in differentiation of HSCs	1	95.2×	0.015	GATA1
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.015	GATA1

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of primitive erythrocyte differentiation	1	8426.0×	0.001	GATA1
basophil differentiation	1	8426.0×	0.001	GATA1
eosinophil fate commitment	1	8426.0×	0.001	GATA1
regulation of definitive erythrocyte differentiation	1	5617.3×	0.001	GATA1
regulation of glycoprotein biosynthetic process	1	4213.0×	0.001	GATA1
eosinophil differentiation	1	4213.0×	0.001	GATA1
primitive erythrocyte differentiation	1	4213.0×	0.001	GATA1
myeloid cell apoptotic process	1	2106.5×	0.002	GATA1
negative regulation of myeloid cell apoptotic process	1	1872.4×	0.002	GATA1
positive regulation of mast cell degranulation	1	1532.0×	0.002	GATA1
osteoblast proliferation	1	1404.3×	0.002	GATA1
cellular response to follicle-stimulating hormone stimulus	1	1404.3×	0.002	GATA1
megakaryocyte differentiation	1	1203.7×	0.002	GATA1
positive regulation of osteoblast proliferation	1	1203.7×	0.002	GATA1
Sertoli cell development	1	1123.5×	0.002	GATA1
dendritic cell differentiation	1	1053.2×	0.002	GATA1
negative regulation of bone mineralization	1	936.2×	0.002	GATA1
platelet formation	1	702.2×	0.003	GATA1
animal organ regeneration	1	601.9×	0.003	GATA1
erythrocyte development	1	526.6×	0.004	GATA1
positive regulation of erythrocyte differentiation	1	510.7×	0.004	GATA1
homeostasis of number of cells within a tissue	1	443.5×	0.004	GATA1
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	411.0×	0.004	GATA1
platelet aggregation	1	337.0×	0.005	GATA1
cell fate commitment	1	295.6×	0.005	GATA1
cellular response to cAMP	1	290.6×	0.005	GATA1
bone mineralization	1	271.8×	0.005	GATA1
erythrocyte differentiation	1	267.5×	0.005	GATA1
male gonad development	1	156.0×	0.009	GATA1
positive regulation of cytosolic calcium ion concentration	1	117.0×	0.011	GATA1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GATA1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	GATA1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GATA1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.