Hemolytic anemia due to erythrocyte adenosine deaminase overproduction

Summary

Hemolytic anemia due to erythrocyte adenosine deaminase overproduction (MONDO:0020458) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hemolytic anemia due to erythrocyte adenosine deaminase overproduction
Mondo ID	MONDO:0020458
MeSH	C566314
OMIM	102730, 301083
Orphanet	99138
DOID	DOID:0051008
ICD-11	1200845933
UMLS	C1863235
MedGen	400240
GARD	0019669
Is cancer (heuristic)	no

Also known as: adenosine deaminase, elevated, hemolytic anaemia due to · adenosine deaminase, elevated, hemolytic anemia due to · anemia, congenital, nonspherocytic hemolytic, 9

Data availability: 9 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › congenital anemia › congenital nonspherocytic hemolytic anemia › hemolytic anemia due to erythrocyte adenosine deaminase overproduction

Related subtypes (9): anemia, nonspherocytic hemolytic, gamma-glutamylcysteine synthetase deficiency, glutathione synthetase deficiency without 5-oxoprolinuria, non-spherocytic hemolytic anemia due to hexokinase deficiency, hemolytic anemia due to pyrimidine 5’ nucleotidase deficiency, pyruvate kinase deficiency of red cells, hemolytic anemia due to adenylate kinase deficiency, hemolytic anemia due to glucophosphate isomerase deficiency, hemolytic anemia due to glutathione reductase deficiency

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

9 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
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
1399872	NM_002049.4(GATA1):c.920G>A (p.Arg307His)	GATA1	Uncertain significance	criteria provided, single submitter
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
373400	NM_002049.4(GATA1):c.919C>T (p.Arg307Cys)	GATA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3893065	NM_002049.4(GATA1):c.528C>A (p.Thr176=)	GATA1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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	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.