Thrombocytopenia with congenital dyserythropoietic anemia

Summary

Thrombocytopenia with congenital dyserythropoietic anemia (MONDO:0019031) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 9

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0000028	Cryptorchidism	Very frequent (80-99%)
HP:0001931	Hypochromic anemia	Very frequent (80-99%)
HP:0004447	Poikilocytosis	Very frequent (80-99%)
HP:0010972	Anemia of inadequate production	Very frequent (80-99%)
HP:0011273	Anisocytosis	Very frequent (80-99%)
HP:0012143	Abnormal megakaryocyte morphology	Very frequent (80-99%)
HP:0012145	Abnormality of multiple cell lineages in the bone marrow	Very frequent (80-99%)
HP:0040185	Macrothrombocytopenia	Very frequent (80-99%)
HP:0045040	Abnormal lactate dehydrogenase activity	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	thrombocytopenia with congenital dyserythropoietic anemia
Mondo ID	MONDO:0019031
Orphanet	67044
SNOMED CT	722475006
UMLS	C4302508
MedGen	928177
GARD	0016676
Is cancer (heuristic)	no

Also known as: congenital dyserythropoietic anaemia with thombocytopenia · congenital dyserythropoietic anemia with thombocytopenia · X-linked congenital dyserythropoietic anaemia with thrombocytopenia · X-linked congenital dyserythropoietic anemia with thrombocytopenia · XDAT

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood platelet disease › thrombocytopenia › inherited thrombocytopenia › thrombocytopenia, X-linked, with or without dyserythropoietic anemia › thrombocytopenia with congenital dyserythropoietic anemia

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

No tiered GWAS variants or ClinVar records for this disease.

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	Strong	X-linked	thrombocytopenia, X-linked, with or without dyserythropoietic anemia	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

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.