Hb Bart's hydrops fetalis

Summary

Hb Bart’s hydrops fetalis (MONDO:0015579) is a disease with 2 cohort genes and 2 clinical trials.

At a glance

• Prevalence: >1 / 1000 (South East Asia) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 1
• Phenotypes (HPO): 12
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	>1 / 1000	275	South East Asia	Validated
Prevalence at birth	1-9 / 100 000	7.6	United States	Validated

Signs & symptoms

Clinical features (HPO)

12 HPO clinical features (Orphanet curated; top 12 by frequency):

HPO ID	Term	Frequency
HP:0000980	Pallor	Very frequent (80-99%)
HP:0001635	Congestive heart failure	Very frequent (80-99%)
HP:0001789	Hydrops fetalis	Very frequent (80-99%)
HP:0001903	Anemia	Very frequent (80-99%)
HP:0011902	Abnormal hemoglobin	Very frequent (80-99%)
HP:0000238	Hydrocephalus	Frequent (30-79%)
HP:0001561	Polyhydramnios	Frequent (30-79%)
HP:0001562	Oligohydramnios	Frequent (30-79%)
HP:0001744	Splenomegaly	Frequent (30-79%)
HP:0002240	Hepatomegaly	Frequent (30-79%)
HP:0100602	Preeclampsia	Frequent (30-79%)
HP:0001701	Pericarditis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Hb Bart’s hydrops fetalis
Mondo ID	MONDO:0015579
Orphanet	163596
SNOMED CT	5300004
UMLS	C0272005
MedGen	543726
GARD	0016992
Is cancer (heuristic)	no

Also known as: alpha-thalassemia hydrops fetalis · Alpha-thalassemia major · Haemoglobin Bart’s hydrops fetalis · Hb Bart’s hydrops fetalis caused by quadallelic variation in HBA1;HBA2 · Hb Bart’s hydrops fetalis related to quadallelic variation in HBA1 and HBA2 · HBA1;HBA2 digenic quadallelic Hb Bart’s hydrops fetalis · Hemoglobin Bart’s hydrops fetalis · homozygous alpha0-thalassemia

Data availability: 1 ClinVar variant · 2 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › hydrops fetalis › non-immune hydrops fetalis › Hb Bart’s hydrops fetalis

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

1 retrieved; paginated sample, class counts are floors:

1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
4074288	GRCh37/hg19 16p13.3(chr16:226678-227520)x1	HBA1	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 24 · Orphanet: 15 · 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
HBA1	Supportive	Autosomal recessive	Hb Bart’s hydrops fetalis	13
HBA2	Supportive	Autosomal recessive	Hb Bart’s hydrops fetalis	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HBA1	Orphanet:163596	Hemoglobin Bart’s fetalis syndrome
HBA1	Orphanet:247511	Autosomal dominant secondary polycythemia
HBA1	Orphanet:330041	Hemoglobin M disease
HBA1	Orphanet:707789	Unstable alpha globin chain variant disease
HBA1	Orphanet:715143	Heterozygous beta-thalassemia intermedia with supernumerary alpha-globin gene
HBA1	Orphanet:93616	Hemoglobin H disease
HBA1	Orphanet:98791	Alpha-thalassemia-intellectual disability syndrome linked to chromosome 16
HBA2	Orphanet:163596	Hemoglobin Bart’s fetalis syndrome
HBA2	Orphanet:247511	Autosomal dominant secondary polycythemia
HBA2	Orphanet:330041	Hemoglobin M disease
HBA2	Orphanet:707789	Unstable alpha globin chain variant disease
HBA2	Orphanet:715143	Heterozygous beta-thalassemia intermedia with supernumerary alpha-globin gene
HBA2	Orphanet:715154	Low oxygen affinity alpha chain hemoglobin disease
HBA2	Orphanet:93616	Hemoglobin H disease
HBA2	Orphanet:98791	Alpha-thalassemia-intellectual disability syndrome linked to chromosome 16

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HBA1	HGNC:4823	ENSG00000206172	P69905	Hemoglobin subunit alpha	gencc,clinvar
HBA2	HGNC:4824	ENSG00000188536	P69905	Hemoglobin subunit alpha	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HBA1	Hemoglobin subunit alpha	Involved in oxygen transport from the lung to the various peripheral tissues.
HBA2	Hemoglobin subunit alpha	Involved in oxygen transport from the lung to the various peripheral tissues.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HBA1	Other/Unknown	no		Globin, Hemoglobin_a-typ, Hemoglobin_pi
HBA2	Other/Unknown	no		Globin, Hemoglobin_a-typ, Hemoglobin_pi

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
blood	2
monocyte	2
bone marrow	1
bone element	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HBA1	133	tissue_specific	marker	monocyte, blood, bone marrow
HBA2	143	tissue_specific	marker	monocyte, blood, bone element

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HBA1	434
HBA2	434

Intra-cohort edges

A	B	Sources
HBA1	HBA2	biogrid_interaction, intact

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HBA1	P69905	356
HBA2	P69905	356

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Heme assimilation	2	3806.7×	3e-07	HBA1, HBA2
Erythrocytes take up oxygen and release carbon dioxide	2	1268.9×	2e-06	HBA1, HBA2
Erythrocytes take up carbon dioxide and release oxygen	2	878.5×	2e-06	HBA1, HBA2
Scavenging of heme from plasma	2	878.5×	2e-06	HBA1, HBA2
Heme signaling	2	215.5×	3e-05	HBA1, HBA2
Cytoprotection by HMOX1	2	184.2×	3e-05	HBA1, HBA2

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
nitric oxide transport	2	3370.4×	6e-07	HBA1, HBA2
cellular oxidant detoxification	2	1872.4×	1e-06	HBA1, HBA2
carbon dioxide transport	2	1296.3×	1e-06	HBA1, HBA2
oxygen transport	2	1053.2×	2e-06	HBA1, HBA2
hydrogen peroxide catabolic process	2	674.1×	3e-06	HBA1, HBA2
erythrocyte development	2	526.6×	5e-06	HBA1, HBA2
response to hydrogen peroxide	2	468.1×	5e-06	HBA1, HBA2
inflammatory response	2	37.7×	7e-04	HBA1, HBA2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HBA1	0	0
HBA2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
HBA1	59	Binding:46, Functional:13
HBA2	59	Binding:46, Functional:13

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

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	2	HBA1, HBA2

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)
HBA1	59	—
HBA2	59	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02986698	PHASE1	TERMINATED	In Utero Hematopoietic Stem Cell Transplantation for Alpha-thalassemia Major (ATM)
NCT04872179	Not specified	RECRUITING	International Registry of Patients With Alpha Thalassemia