HBA2

Summary

HBA2 (hemoglobin subunit alpha 2, HGNC:4824) is a protein-coding gene on chromosome 16p13.3, encoding Hemoglobin subunit alpha (P69905). Involved in oxygen transport from the lung to the various peripheral tissues.

The human alpha globin gene cluster located on chromosome 16 spans about 30 kb and includes seven loci: 5’- zeta - pseudozeta - mu - pseudoalpha-1 - alpha-2 - alpha-1 - theta - 3’. The alpha-2 (HBA2) and alpha-1 (HBA1) coding sequences are identical. These genes differ slightly over the 5’ untranslated regions and the introns, but they differ significantly over the 3’ untranslated regions. Two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin; alpha chains combine with delta chains to constitute HbA-2, which with HbF (fetal hemoglobin) makes up the remaining 3% of adult hemoglobin. Alpha thalassemias result from deletions of each of the alpha genes as well as deletions of both HBA2 and HBA1; some nondeletion alpha thalassemias have also been reported.

Source: NCBI Gene 3040 — RefSeq curated summary.

At a glance

• Gene–disease (curated): HBA2-related alpha thalassemia spectrum (Definitive, ClinGen) — +8 more curated relationships
• GWAS associations: 26
• Clinical variants (ClinVar): 360 total — 45 pathogenic, 80 likely-pathogenic
• Phenotypes (HPO): 54
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000517

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4824
Approved symbol	HBA2
Name	hemoglobin subunit alpha 2
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	HBA-T2
Ensembl gene	ENSG00000188536
Ensembl biotype	protein_coding
OMIM	141850
Entrez	3040

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000251595, ENST00000397806, ENST00000482565, ENST00000484216, ENST00000866237

RefSeq mRNA: 1 — MANE Select: NM_000517 NM_000517

CCDS: CCDS10398

Canonical transcript exons

ENST00000251595 — 3 exons

Exon	Start	End
ENSE00001143637	173472	173710
ENSE00002733732	172876	173007
ENSE00003626442	173125	173329

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 99.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.6898 / max 556.1188, expressed in 80 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151864	3.5460	99
151866	1.6898	80
151862	1.6196	76
151863	0.5936	48
151861	0.1002	11

Top tissues by expression

143 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.99	gold quality
blood	UBERON:0000178	99.98	gold quality
bone element	UBERON:0001474	99.94	gold quality
bone marrow	UBERON:0002371	99.94	gold quality
bone marrow cell	CL:0002092	99.93	gold quality
placenta	UBERON:0001987	99.88	gold quality
spleen	UBERON:0002106	99.78	gold quality
apex of heart	UBERON:0002098	99.73	gold quality
metanephros cortex	UBERON:0010533	99.61	gold quality
lower esophagus mucosa	UBERON:0035834	99.60	gold quality
ganglionic eminence	UBERON:0004023	99.59	gold quality
embryo	UBERON:0000922	99.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.56	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.53	gold quality
colonic epithelium	UBERON:0000397	99.49	gold quality
upper lobe of left lung	UBERON:0008952	99.43	gold quality
temporal lobe	UBERON:0001871	99.42	gold quality
amygdala	UBERON:0001876	99.42	gold quality
substantia nigra	UBERON:0002038	99.38	gold quality
lung	UBERON:0002048	99.38	gold quality
granulocyte	CL:0000094	99.37	gold quality
pituitary gland	UBERON:0000007	99.23	gold quality
right lobe of thyroid gland	UBERON:0001119	99.19	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.15	gold quality
adenohypophysis	UBERON:0002196	99.12	gold quality
primary visual cortex	UBERON:0002436	99.08	gold quality
caudate nucleus	UBERON:0001873	99.06	gold quality
anterior cingulate cortex	UBERON:0009835	99.00	gold quality
hypothalamus	UBERON:0001898	98.99	gold quality
putamen	UBERON:0001874	98.92	gold quality

Single-cell (SCXA)

Detected in 53 experiment(s), a significant marker in 48.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	323348.22
E-GEOD-149689	yes	321347.65
E-CURD-120	yes	317115.31
E-HCAD-36	yes	310596.84
E-MTAB-7407	yes	299850.73
E-MTAB-8207	yes	284915.14
E-CURD-55	yes	281308.90
E-MTAB-9221	yes	269419.82
E-MTAB-9467	yes	262338.85
E-HCAD-8	yes	247012.88
E-GEOD-139324	yes	241158.23
E-HCAD-4	yes	230692.35
E-MTAB-10042	yes	230211.49
E-MTAB-6653	yes	223511.31
E-MTAB-8495	yes	221731.78

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
TNF	Activation

Upstream regulators (CollecTRI, top): ATRX, GATA1, KLF1, MYC

miRNA regulators (miRDB)

5 targeting HBA2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-499B-5P	98.35	68.39	988
HSA-MIR-7160-3P	96.40	64.15	462
HSA-MIR-6781-5P	94.61	59.49	155

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Hb Pakse differs from Hb CS by having lysine at 142 instead of glutamine. It also seems to lead to an unstable alpha globin mRNA and slighter higher Hb H levels. (PMID:11836160)
• Allosteric effects of chloride ions at the interfaces between the alphabeta dimers. (PMID:12360531)
• Crystallization and X-ray structure of this protein, isolated from blood of beta-thalassemic patients. (PMID:12659864)
• Review. The effects of alpha-globin genotype on the pathophysiology of sickle cell anemia, HbSC disease, and sickle beta-thalassemia are studied. (PMID:12673836)
• in alpha-thalassemia, transcription of antisense RNA mediates silencing and methylation of the associated CpG island of the HBA2 gene (PMID:12730694)
• High frequency of the Hb A2 abnormality, reaching higher numbers among blacksmiths living in the same village in Mali. (PMID:12779272)
• Alpha-thalassemia mutations in Iranian individuals are not found in HBA2. (PMID:12779276)
• Hb Setif with Asp-to-Tyr missense mutation at codon 94 was studied. The abnormal hemoglobin comprised 15% of total Hb, tested negative for erythrocyte sickling, but exhibited pseudosickling in vitro. (PMID:14649316)
• the phenotype of the carrier state makes it likely that this codon 90 mutation will cause severe Hb H disease when inherited with a two gene deletion mutation (PMID:14649319)
• Sequencing of alpha-globin genes of 18 Sardinian heterozygotes for the Hb G-Philadelphia; identification of the C–>G mutation on the normal alpha alpha chromosome points to an undescribed genotype (PMID:15128423)
• Gene scanning of HBA2 genes in thalassemic patients revealed 3 new alleles: c.1A>G, c.79G>A, and c.281T>G. (PMID:15365991)
• A high-resolution crystal structure of ferrocyanide-bound HbA2 is presented that throws light on the location and mode of binding of ferrocyanide anion with hemoglobin. (PMID:15449937)
• Finds hemoglobin H disease involving the alpha-2-globin mutation (AATAAA–>AATAAG) is a mild thal intermedia phenotype among Kuwaitis (PMID:16103716)
• Data show the frequent juxtaposition of active alpha- and beta-globin genes and of homologous alpha-globin loci that occurs at nuclear speckles and correlates with transcription. (PMID:16418531)
• We proved that, in the human alpha-globin gene cluster, the normal order of structural genes relative to alpha-Upstream Regulatory Element plays a crucial role in the regulation of developmental switching. (PMID:16436049)
• Hb Al-Hammadi Riyadh [codon 75 (GAC–>GTC); alpha75(EF4)Asp–>Val (alpha2)] corresponds to an A–>T transversion in the second exon of the alpha2-globin gene. (PMID:16798639)
• Results describe the shared stabilization functions of pyrimidine-rich determinants in the erythroid 15-lipoxygenase and alpha-globin mRNAs. (PMID:16847316)
• family with a rare combination of two abnormal alpha-globin genes, a two-base deletion and a .7 kb alpha gene deletion. (PMID:17486499)
• interaction of the Hb Constant Spring EE Bart’s disease produces a tetrameric Hb molecule is formed between alpha(CS) and beta(E) chains leading to a hybrid Hb (PMID:17587614)
• multiple origins of the alpha(CS) and a single origin of the alpha(Pakse) mutations in Southeast Asia (PMID:17589844)
• mechanism by which the human globin genes are activated during erythropoiesis (PMID:17715390)
• This work describes the study of the interactions of different hemoglobin variants HbA, HbE and HbF and the globin subunits of HbA with the two aminophospholipids in the presence and absence of cholesterol. (PMID:17916326)
• In alpha-thalassemia, alpha/beta-globin mRNA ratio correlated with the number of functional alpha-globin genes present, whereas in beta-thalassemia, the ratio provided a good indicator of disease severity. (PMID:17920577)
• Our study suggests that the regulation of alpha-URE and beta-LCR on the expression level and developmental switching mode of downstream globin genes is cluster specific. (PMID:17996867)
• Coinheritance of alpha-thalassemia with beta 0-thalassemia/Hb E produces a milder clinical phenotype in contrast to an interaction of alpha-globin gene triplication in severe thalassemia (PMID:18026953)
• Hb Federico II is a novel hemoglobin variant [beta-106 (G8) Leu->Val] (PMID:18591626)
• REVIEW of the complex process of expression of alpha-globin and the complex interaction of factors which are required to balance necessary high expression against the negative impacts of overexpression (PMID:18768527)
• regulation of human alpha-globin synthesis, encoded by two adjacent genes (alpha(2) and alpha(1)) clustered on chromosome 16 (PMID:19048483)
• genotypes of individuals with unexplained hypochromia and/or microcytosis, as well patients with documented Hb H disease from the Dohuk region in northern Iraq were analyzed (PMID:19205971)
• To investigate dynamical differences between the alpha- and beta- globin chains, ligand recombination and heme structural evolution, following HbCO dissociation, was monitored with chain selectivity (PMID:19245215)
• Results report that hemoglobin chains alpha2 nad beta are expressed in mammalian brain neurons and are regulated by a mitochondrial toxin. (PMID:19479992)
• Studies present five new hemoglobin (Hb) variants, Hb Canuts, Hb Ambroise Pare, Hb Beaujolais, Hb Monplaisir and Hb(A2)-North Africa. (PMID:19657833)
• A duplication of the alpha-globin gene locus, including the upstream regulatory region, was present in all patients with thalassemia intermedia. (PMID:19794088)
• alpha-thalassaemia masked by beta gene defects and a new polyadenylation site mutation on the alpha2-globin gene. (PMID:19912309)
• In a cohort of 104 unrelated putative alpha-thal patients, nine carried the point mutation Hb Sallanches and two were homozygotes. The mutation occurred on both the alpha2- or alpha1-globin genes. (PMID:19958194)
• identification of two different mutations involving the first nucleotide of intron 1 of the alpha2-globin gene (PMID:19958200)
• Studies indicate that the interaction of alpha-Hb with AHSP involves surfaces normally employed in binding to beta-Hb. (PMID:20036801)
• Identification and molecular characterization of the –CAMPANIA deletion, a novel alpha degrees -thalassemic defect, in two unrelated Italian families. (PMID:20054848)
• We report four novel and five uncommon deletions that remove alpha-globin distal regulatory elements and/or the complete alpha-globin gene cluster. One of them occurred de novo and removes all HSs except HS-10, while other eliminates only the HS-40 site. (PMID:20580289)
• One hundred and ninety-one (53.3%) patients were diagnosed with HbH-Constant Spring, 19 were diagnosed with HbH Westmead in Guangxi province, China (PMID:20639625)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	hbae4	ENSDARG00000045144
mus_musculus	Hba-a2	ENSMUSG00000069917
mus_musculus	Hba-a1	ENSMUSG00000069919
rattus_norvegicus	Hba-a2	ENSRNOG00000029886
rattus_norvegicus	Hba-a3	ENSRNOG00000047321
rattus_norvegicus	Hba-a3	ENSRNOG00000088611
drosophila_melanogaster	glob1	FBGN0027657
caenorhabditis_elegans		WBGENE00008996
caenorhabditis_elegans		WBGENE00077763

Paralogs (11): HBQ1 (ENSG00000086506), HBZ (ENSG00000130656), CYGB (ENSG00000161544), HBG2 (ENSG00000196565), MB (ENSG00000198125), HBA1 (ENSG00000206172), HBM (ENSG00000206177), HBE1 (ENSG00000213931), HBG1 (ENSG00000213934), HBD (ENSG00000223609), HBB (ENSG00000244734)

Protein

Protein identifiers

Hemoglobin subunit alpha — P69905 (reviewed: P69905)

Alternative names: Alpha-globin, Hemoglobin alpha chain

All UniProt accessions (4): A0A2R8Y7C0, D1MGQ2, G3V1N2, P69905

UniProt curated annotations — full annotation on UniProt →

Function. Involved in oxygen transport from the lung to the various peripheral tissues. Hemopressin acts as an antagonist peptide of the cannabinoid receptor CNR1. Hemopressin-binding efficiently blocks cannabinoid receptor CNR1 and subsequent signaling.

Subunit / interactions. Heterotetramer of two alpha chains and two beta chains in adult hemoglobin A (HbA); two alpha chains and two delta chains in adult hemoglobin A2 (HbA2); two alpha chains and two epsilon chains in early embryonic hemoglobin Gower-2; two alpha chains and two gamma chains in fetal hemoglobin F (HbF). (Microbial infection) Interacts with Staphylococcus aureus protein isdB.

Tissue specificity. Red blood cells.

Post-translational modifications. The initiator Met is not cleaved in variant Thionville and is acetylated.

Disease relevance. Heinz body anemias (HEIBAN) [MIM:140700] Form of non-spherocytic hemolytic anemia of Dacie type 1. After splenectomy, which has little benefit, basophilic inclusions called Heinz bodies are demonstrable in the erythrocytes. Before splenectomy, diffuse or punctate basophilia may be evident. Most of these cases are probably instances of hemoglobinopathy. The hemoglobin demonstrates heat lability. Heinz bodies are observed also with the Ivemark syndrome (asplenia with cardiovascular anomalies) and with glutathione peroxidase deficiency. The disease may be caused by variants affecting the gene represented in this entry. Alpha-thalassemia (A-THAL) [MIM:604131] A form of thalassemia. Thalassemias are common monogenic diseases occurring mostly in Mediterranean and Southeast Asian populations. The hallmark of alpha-thalassemia is an imbalance in globin-chain production in the adult HbA molecule. The level of alpha chain production can range from none to very nearly normal levels. Deletion of both copies of each of the two alpha-globin genes causes alpha(0)-thalassemia, also known as homozygous alpha thalassemia. Due to the complete absence of alpha chains, the predominant fetal hemoglobin is a tetramer of gamma-chains (Bart hemoglobin) that has essentially no oxygen carrying capacity. This causes oxygen starvation in the fetal tissues leading to prenatal lethality or early neonatal death. The loss of two alpha genes results in mild alpha-thalassemia, also known as heterozygous alpha-thalassemia. Affected individuals have small red cells and a mild anemia (microcytosis). If three of the four alpha-globin genes are functional, individuals are completely asymptomatic. Some rare forms of alpha-thalassemia are due to point mutations (non-deletional alpha-thalassemia). The disease is caused by variants affecting the gene represented in this entry. Alpha(0)-thalassemia is associated with non-immune hydrops fetalis, a generalized edema of the fetus with fluid accumulation in the body cavities due to non-immune causes. Non-immune hydrops fetalis is not a diagnosis in itself but a symptom, a feature of many genetic disorders, and the end-stage of a wide variety of disorders. Hemoglobin H disease (HBH) [MIM:613978] A form of alpha-thalassemia due to the loss of three alpha genes. This results in high levels of a tetramer of four beta chains (hemoglobin H), causing a severe and life-threatening anemia. Untreated, most patients die in childhood or early adolescence. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Gives blood its red color.

Similarity. Belongs to the globin family.

RefSeq proteins (1): NP_000508* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000971	Globin	Domain
IPR002338	Hemoglobin_a-typ	Family
IPR002339	Hemoglobin_pi	Family
IPR009050	Globin-like_sf	Homologous_superfamily
IPR012292	Globin/Proto	Homologous_superfamily
IPR050056	Hemoglobin_oxygen_transport	Family

Pfam: PF00042

UniProt features (213 total): sequence variant 151, site 19, modified residue 17, helix 10, glycosylation site 4, turn 3, strand 2, binding site 2, initiator methionine 1, chain 1, sequence conflict 1, peptide 1, domain 1

Structure

Experimental structures (PDB)

356 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2W72	X-RAY DIFFRACTION	1.07
1IRD	X-RAY DIFFRACTION	1.25
2DN1	X-RAY DIFFRACTION	1.25
2DN2	X-RAY DIFFRACTION	1.25
2DN3	X-RAY DIFFRACTION	1.25
7DY4	X-RAY DIFFRACTION	1.3
6KA9	X-RAY DIFFRACTION	1.4
6KAO	X-RAY DIFFRACTION	1.4
6LCW	X-RAY DIFFRACTION	1.4
6LCX	X-RAY DIFFRACTION	1.4
7DY3	X-RAY DIFFRACTION	1.4
3S66	X-RAY DIFFRACTION	1.4
1J40	X-RAY DIFFRACTION	1.45
1J41	X-RAY DIFFRACTION	1.45
2D5Z	X-RAY DIFFRACTION	1.45
6KAE	X-RAY DIFFRACTION	1.45
6KAH	X-RAY DIFFRACTION	1.45
6KAI	X-RAY DIFFRACTION	1.45
6KAP	X-RAY DIFFRACTION	1.45
6L5V	X-RAY DIFFRACTION	1.45
7JY3	X-RAY DIFFRACTION	1.48
1BAB	X-RAY DIFFRACTION	1.5
1BZ0	X-RAY DIFFRACTION	1.5
1THB	X-RAY DIFFRACTION	1.5
1UIW	X-RAY DIFFRACTION	1.5
6KAQ	X-RAY DIFFRACTION	1.5
6L5W	X-RAY DIFFRACTION	1.5
9HBA	X-RAY DIFFRACTION	1.51
5WOG	X-RAY DIFFRACTION	1.54
1J3Y	X-RAY DIFFRACTION	1.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P69905-F1	98.04	0.99

Antibody-complex structures (SAbDab): 1 — 8VYL

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (19): 30–31 ((microbial infection) cleavage; by n.americanus apr-2); 46–47 ((microbial infection) cleavage; by n.americanus apr-2); 48–49 ((microbial infection) cleavage; by n.americanus apr-2); 53–54 ((microbial infection) cleavage; by n.americanus apr-2); 56–57 ((microbial infection) cleavage; by n.americanus apr-2); 57 (not glycated); 60–61 ((microbial infection) cleavage; by n.americanus apr-2); 61 (not glycated); 91 (not glycated); 92–93 ((microbial infection) cleavage; by n.americanus apr-2); 100 (not glycated); 107–108 ((microbial infection) cleavage; by n.americanus apr-2) …

Ligand- & substrate-binding residues (2): 59; 88 (proximal binding residue)

Post-translational modifications (17): 4, 8, 9, 12, 17, 17, 25, 36, 41, 50, 103, 109, 125, 132, 135, 138, 139

Glycosylation sites (4): 8, 17, 41, 62

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1237044	Erythrocytes take up carbon dioxide and release oxygen
R-HSA-1247673	Erythrocytes take up oxygen and release carbon dioxide
R-HSA-2168880	Scavenging of heme from plasma
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9707616	Heme signaling
R-HSA-9927020	Heme assimilation

MSigDB gene sets: 297 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, GOBP_HYDROGEN_PEROXIDE_CATABOLIC_PROCESS, GOBP_ERYTHROCYTE_HOMEOSTASIS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, MODULE_128, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_DN, HUMMERICH_MALIGNANT_SKIN_TUMOR_UP, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_ONE_CARBON_COMPOUND_TRANSPORT, GOBP_GAS_TRANSPORT, MODULE_171

GO Biological Process (8): inflammatory response (GO:0006954), carbon dioxide transport (GO:0015670), oxygen transport (GO:0015671), nitric oxide transport (GO:0030185), response to hydrogen peroxide (GO:0042542), hydrogen peroxide catabolic process (GO:0042744), erythrocyte development (GO:0048821), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (8): oxygen carrier activity (GO:0005344), iron ion binding (GO:0005506), oxygen binding (GO:0019825), heme binding (GO:0020037), peroxidase activity (GO:0004601), protein binding (GO:0005515), haptoglobin binding (GO:0031720), metal ion binding (GO:0046872)

GO Cellular Component (9): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytosol (GO:0005829), hemoglobin complex (GO:0005833), membrane (GO:0016020), haptoglobin-hemoglobin complex (GO:0031838), extracellular exosome (GO:0070062), endocytic vesicle lumen (GO:0071682), blood microparticle (GO:0072562)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
O2/CO2 exchange in erythrocytes	2
Binding and Uptake of Ligands by Scavenger Receptors	1
Cellular response to chemical stress	1
Cellular responses to stress	1
Metal ion assimilation from the host	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
gas transport	2
protein-containing complex	2
defense response	1
one-carbon compound transport	1
nitrogen compound transport	1
response to reactive oxygen species	1
catabolic process	1
hydrogen peroxide metabolic process	1
erythrocyte differentiation	1
myeloid cell development	1
cellular detoxification	1
oxygen transport	1
oxygen binding	1
molecular carrier activity	1
transition metal ion binding	1
small molecule binding	1
tetrapyrrole binding	1
antioxidant activity	1
oxidoreductase activity, acting on peroxide as acceptor	1
binding	1
protein binding	1
cation binding	1
cytoplasm	1
cytosol	1
extracellular vesicle	1
endocytic vesicle	1
intracellular organelle lumen	1
extracellular region	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

212 interactions, top by confidence:

A	B	Type	Score
HBB	HBA1	psi-mi:“MI:0407”(direct interaction)	0.970
HBA1	HBB	psi-mi:“MI:0407”(direct interaction)	0.970
HBA1	HBB	psi-mi:“MI:2364”(proximity)	0.970
HBA1	HBB	psi-mi:“MI:0915”(physical association)	0.970
HBB	HBA1	psi-mi:“MI:0915”(physical association)	0.970
HBB	HBA1	psi-mi:“MI:2364”(proximity)	0.970
UBE2V1	UBE2N	psi-mi:“MI:0914”(association)	0.910
MED4	MED19	psi-mi:“MI:0914”(association)	0.900

BioGRID (222): KRT40 (Two-hybrid), CCDC57 (Two-hybrid), HBA1 (Affinity Capture-MS), HBA2 (Affinity Capture-MS), HBA1 (Affinity Capture-MS), HBA2 (Affinity Capture-MS), HBA2 (Affinity Capture-MS), HBA2 (Affinity Capture-MS), HBA2 (Affinity Capture-MS), HBA2 (Affinity Capture-MS), HBA2 (Affinity Capture-MS), HBA2 (Affinity Capture-MS), HBA2 (Affinity Capture-MS), HBA2 (Affinity Capture-MS), HBA2 (Affinity Capture-MS)

ESM2 similar proteins: P01923, P01924, P01926, P01928, P01929, P01930, P01937, P01938, P01940, P01951, P01953, P01958, P01959, P01960, P01961, P01969, P06635, P07402, P07403, P07421, P08852, P09839, P09908, P10892, P18972, P19002, P20243, P20854, P21766, P21767, P21768, P23601, P24659, P28780, P63107, P63108, P67817, P67818, P69905, P69906

Diamond homologs: B3EWC7, B3EWC9, B3EWD1, B3EWD3, B3EWD5, B3EWD7, B3EWD9, B3EWE1, B3EWE3, D0VX09, P01923, P01924, P01926, P01928, P01929, P01930, P01933, P01934, P01935, P01936, P01937, P01938, P01939, P01940, P01941, P01942, P01943, P01945, P01948, P01951, P01953, P01956, P01958, P01962, P01963, P01968, P06635, P07402, P07403, P07421

SIGNOR signaling

29 interactions.

A	Effect	B	Mechanism
HBA1	“up-regulates activity”	CD163	binding
HBA1	“down-regulates activity”	ADAMTS13
HBA1	“down-regulates activity”	AHSP
HBA1	“up-regulates quantity by expression”	TNF	“transcriptional regulation”
HBA1	“up-regulates quantity by stabilization”	APOB
HBA1	“up-regulates activity”	CYP2E1
HBA1	“down-regulates activity”	EDN1
ACVR1B	“up-regulates quantity by stabilization”	HBA1
AHSP	“up-regulates quantity by stabilization”	HBA1	binding
ARSA	“up-regulates activity”	HBA1	acetylation
EIF2AK1	“down-regulates quantity by repression”	HBA1	“transcriptional regulation”
EPAS1	“up-regulates quantity by expression”	HBA1	“transcriptional regulation”
ETV6	“up-regulates quantity by expression”	HBA1	“transcriptional regulation”
FGF2	“down-regulates quantity by repression”	HBA1	“transcriptional regulation”
TGFB1	“up-regulates quantity by expression”	HBA1	“transcriptional regulation”
HMOX1	“down-regulates activity”	HBA1
HMOX2	“down-regulates activity”	HBA1
HP	“down-regulates quantity”	HBA1	binding
MIF	“down-regulates quantity by repression”	HBA1	“transcriptional regulation”
MAPK11	“up-regulates quantity by expression”	HBA1	“transcriptional regulation”
MAPK14	“up-regulates quantity by expression”	HBA1	“transcriptional regulation”
heme	“up-regulates activity”	HBA1	“chemical activation”
HBA1	“form complex”	Hemoglobin	binding
HOXB6	“down-regulates quantity by repression”	HBA1	“transcriptional regulation”
EGF	“up-regulates quantity by expression”	HBA1	“transcriptional regulation”
EPO	“up-regulates quantity by expression”	HBA1	“transcriptional regulation”
STAT5A	“up-regulates quantity by expression”	HBA1	“transcriptional regulation”
CPM	“down-regulates activity”	HBA1	cleavage
CPN1	“down-regulates activity”	HBA1	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 198 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Post-translational protein phosphorylation	10	7.9×	4e-04
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	10	6.8×	8e-04
Platelet degranulation	9	6.2×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
oxygen transport	6	35.5×	1e-05
erythrocyte development	6	17.8×	4e-04
protein folding	10	5.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

360 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	45
Likely pathogenic	80
Uncertain significance	111
Likely benign	38
Benign	9

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072684	NC_000016.9:g.(?163493)(163851_?)del	Pathogenic
1072685	NC_000016.9:g.(?163493)(193701_?)del	Pathogenic
1098491	NM_000517.6(HBA2):c.210_211insT (p.Val71fs)	Pathogenic
1330041	NM_000517.6(HBA2):c.283G>A (p.Asp95Asn)	Pathogenic
15626	NM_000517.4(HBA2):c.427T>A (p.Ter143Lys)	Pathogenic
15630	NM_000517.6(HBA2):c.377T>C (p.Leu126Pro)	Pathogenic
15643	NM_000517.6(HBA2):c.2T>C (p.Met1Thr)	Pathogenic
15651	NM_000517.6(HBA2):c.89T>C (p.Leu30Pro)	Pathogenic
15652	NM_000517.4(HBA2):c.429A>T (p.Ter143Tyr)	Pathogenic
15657	NM_000517.6(HBA2):c.118_124delinsTACTTC (p.Thr40fs)	Pathogenic
15678	NM_000517.6(HBA2):c.96G>Y (p.Arg32Ser)	Pathogenic
15679	NM_000517.6(HBA2):c.96-2A>G	Pathogenic
15692	NM_000517.6(HBA2):c.2del (p.Met1fs)	Pathogenic
2428504	NM_000517.6(HBA2):c.130T>G (p.Phe44Val)	Pathogenic
2628369	NM_000517.6(HBA2):c.320T>G (p.Leu107Arg)	Pathogenic
2691625	NM_000517.6(HBA2):c.389T>C (p.Leu130Pro)	Pathogenic
280127	NM_000517.6(HBA2):c.60del (p.His21fs)	Pathogenic
2921026	NM_000517.6(HBA2):c.95+1G>C	Pathogenic
3346945	NM_000517.6(HBA2):c.175C>T (p.His59Tyr)	Pathogenic
3385101	NM_000517.6(HBA2):c.428A>T (p.Ter143Leu)	Pathogenic
375746	NM_000517.6(HBA2):c.95+2_95+6del	Pathogenic
375752	Single allele	Pathogenic
3766787	NM_000517.6(HBA2):c.275T>C (p.Leu92Pro)	Pathogenic
3893268	NC_000016.10:g.169818_174075del	Pathogenic
4069082	NM_000517.6(HBA2):c.163del (p.Gln55fs)	Pathogenic
439112	NM_000517.6(HBA2):c.179G>A (p.Gly60Asp)	Pathogenic
439117	NM_000517.6(HBA2):c.379G>T (p.Asp127Tyr)	Pathogenic
439126	NM_000517.6(HBA2):c.95+1G>A	Pathogenic
4818622	NM_000517.6(HBA2):c.131del (p.Phe44fs)	Pathogenic
4818680	NM_000517.6(HBA2):c.95+2T>C	Pathogenic

SpliceAI

188 predictions. Top by Δscore:

Variant	Effect	Δscore
16:173121:GCA:G	acceptor_loss	1.0000
16:173122:CA:C	acceptor_loss	1.0000
16:173123:A:AG	acceptor_gain	1.0000
16:173123:AG:A	acceptor_gain	1.0000
16:173123:AGGAT:A	acceptor_gain	1.0000
16:173124:G:GT	acceptor_gain	1.0000
16:173124:GG:G	acceptor_gain	1.0000
16:173124:GGA:G	acceptor_gain	1.0000
16:173124:GGAT:G	acceptor_gain	1.0000
16:173124:GGATG:G	acceptor_gain	1.0000
16:173325:TCAAG:T	donor_gain	1.0000
16:173327:AAG:A	donor_gain	1.0000
16:173327:AAGG:A	donor_loss	1.0000
16:173328:AG:A	donor_gain	1.0000
16:173328:AGGT:A	donor_loss	1.0000
16:173329:GG:G	donor_gain	1.0000
16:173329:GGTG:G	donor_loss	1.0000
16:173330:G:GG	donor_gain	1.0000
16:173330:GTG:G	donor_loss	1.0000
16:173004:AGAG:A	donor_loss	0.9900
16:173005:GAG:G	donor_gain	0.9900
16:173008:G:A	donor_loss	0.9900
16:173009:T:A	donor_loss	0.9900
16:173331:T:A	donor_loss	0.9900
16:173467:CACA:C	acceptor_loss	0.9900
16:173468:ACAG:A	acceptor_loss	0.9900
16:173470:A:AG	acceptor_gain	0.9900
16:173470:A:AT	acceptor_loss	0.9900
16:173471:G:GG	acceptor_gain	0.9900
16:173471:GCTC:G	acceptor_gain	0.9900

AlphaMissense

921 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1002853503 (16:171579 G>A), RS1002884187 (16:171754 C>A,T), RS1003188977 (16:171354 T>C), RS1003598942 (16:173976 G>A,T), RS1004457469 (16:173118 C>T), RS1006988959 (16:171340 C>T), RS1007250809 (16:172083 A>G), RS1011492588 (16:171772 C>G,T), RS1016913082 (16:171131 A>C,G), RS1016987803 (16:171342 C>G,T), RS1017213698 (16:171824 A>T), RS1021488578 (16:171778 C>T), RS1023128758 (16:174078 G>C,T), RS1025568221 (16:171160 T>C), RS1025977498 (16:173046 C>G,T)

Disease associations

OMIM: gene MIM:141850 | disease phenotypes: MIM:140700, MIM:604131, MIM:613978, MIM:617981, MIM:236750

GenCC curated gene-disease

Disease	Classification	Inheritance
erythrocytosis, familial, 7	Strong	Autosomal dominant
Heinz body anemia	Strong	Autosomal dominant
alpha thalassemia spectrum	Strong	Autosomal recessive
Hb Bart’s hydrops fetalis	Supportive	Autosomal recessive
hemoglobin M disease	Supportive	Autosomal dominant
hemoglobin H disease	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (4)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
methemoglobinemia, alpha type	Limited	AD
erythrocytosis, familial, 7	Limited	AD
HBA2-related alpha thalassemia spectrum	Definitive	AR
unstable hemoglobin disease	Limited	AD

Mondo (9): Heinz body anemia (MONDO:0007705), alpha thalassemia spectrum (MONDO:0011399), hemoglobin H disease (MONDO:0013512), erythrocytosis, familial, 7 (MONDO:0054802), beta thalassemia (MONDO:0019402), thalassemia (MONDO:0000984), non-immune hydrops fetalis (MONDO:0009369), Hb Bart’s hydrops fetalis (MONDO:0015579), hemoglobin M disease (MONDO:0018023)

Orphanet (5): OBSOLETE: Heinz body anemia (Orphanet:178330), Alpha-thalassemia (Orphanet:846), Hemoglobin H disease (Orphanet:93616), Beta-thalassemia (Orphanet:848), Non-immune hydrops fetalis (Orphanet:363999)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000431	Wide nasal bridge
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000768	Pectus carinatum
HP:0000978	Bruising susceptibility
HP:0000980	Pallor
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001371	Flexion contracture
HP:0001508	Failure to thrive
HP:0001561	Polyhydramnios
HP:0001562	Oligohydramnios
HP:0001635	Congestive heart failure
HP:0001701	Pericarditis
HP:0001744	Splenomegaly
HP:0001762	Talipes equinovarus

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST000587_1	Mean corpuscular hemoglobin	3.000000e-09
GCST003122_1	Hemoglobin levels	6.000000e-18
GCST004334_1	Mean corpuscular hemoglobin	3.000000e-12
GCST004611_207	High light scatter reticulocyte count	2.000000e-18
GCST004612_198	High light scatter reticulocyte percentage of red cells	2.000000e-24
GCST004619_16	Reticulocyte fraction of red cells	1.000000e-30
GCST004621_81	Red cell distribution width	4.000000e-16
GCST004622_36	Reticulocyte count	2.000000e-20
GCST005951_12	Body mass index	5.000000e-11
GCST008034_20	Hemoglobin A1c levels	8.000000e-12
GCST008034_9	Hemoglobin A1c levels	3.000000e-12
GCST008038_1	Mean corpuscular hemoglobin concentration	3.000000e-78
GCST012126_11	hemolysis of donated blood (osmotic)	5.000000e-08
GCST012130_3	hemolysis of donated blood (osmotic)	3.000000e-14
GCST012131_2	hemolysis of donated blood (osmotic)	1.000000e-12
GCST012135_11	hemolysis of donated blood (osmotic)	3.000000e-14
GCST90002385_67	High light scatter reticulocyte count	2.000000e-16
GCST90002386_605	High light scatter reticulocyte percentage of red cells	2.000000e-16
GCST90002386_607	High light scatter reticulocyte percentage of red cells	5.000000e-19
GCST90002390_627	Mean corpuscular hemoglobin	9.000000e-41
GCST90002390_629	Mean corpuscular hemoglobin	5.000000e-14
GCST90002391_158	Mean corpuscular hemoglobin concentration	1.000000e-10
GCST90002392_475	Mean corpuscular volume	1.000000e-09
GCST90002405_349	Reticulocyte count	2.000000e-14
GCST90002405_351	Reticulocyte count	2.000000e-18
GCST90002406_401	Reticulocyte fraction of red cells	2.000000e-23

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0007629	hemoglobin A1 measurement
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width
EFO:0004340	body mass index
EFO:0004541	HbA1c measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0009473	hemolysis

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D013789	Thalassemia	C15.378.050.141.150.875; C15.378.420.826; C16.320.070.875; C16.320.365.826
D017085	alpha-Thalassemia	C15.378.050.141.150.875.100; C15.378.420.826.100; C16.320.070.875.100; C16.320.365.826.100
D017086	beta-Thalassemia	C15.378.050.141.150.875.150; C15.378.420.826.150; C16.320.070.875.150; C16.320.365.826.150
C563030	Heinz Body Anemias (supp.)
C581942	Hemoglobin M Disease (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2095168 (PROTEIN COMPLEX), CHEMBL2887 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, affects cotreatment, increases expression	2
Cadmium	increases palmitoylation, affects binding, decreases reaction, increases abundance	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
fluorene-9-bisphenol	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
tebuconazole	decreases expression	1
JP8 aviation fuel	decreases expression	1
deguelin	increases expression	1
corosolic acid	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
pyrimidifen	increases expression	1
pyrachlostrobin	increases expression	1
picoxystrobin	increases expression	1
Capecitabine	decreases expression	1
Acetaminophen	increases expression	1
Aldehydes	increases expression	1
Antimycin A	increases expression	1
Copper	affects binding	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	decreases expression	1

ChEMBL screening assays

59 unique, capped per target: 46 binding, 13 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3136831	Binding	Binding affinity to Hemoglobin (unknown origin) at 10 mM by circular dichroism spectroscopy	Synthesis of amphiphilic, chalcogen-based redox modulators with in vitro cytotoxic activity against cancer cells, macrophages and microbes — Medchemcomm
CHEMBL810680	Functional	Affinity towards oxygen by hemoglobin after modification by compound	Regioselective covalent modification of hemoglobin in search of antisickling agents. — J Med Chem

Cellosaurus cell lines

11 cell lines: 9 induced pluripotent stem cell, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1BY	HNMUi002-A	Induced pluripotent stem cell	Male
CVCL_A1CA	HNMUi004-A	Induced pluripotent stem cell	Male
CVCL_A1CB	HNMUi005-A	Induced pluripotent stem cell	Male
CVCL_A1CD	HNMUi007-A	Induced pluripotent stem cell	Male
CVCL_A7GC	GZHMCi007-A	Induced pluripotent stem cell	Male
CVCL_B7E8	MUi034-A	Induced pluripotent stem cell	Female
CVCL_E4G8	SU-iPS-1	Induced pluripotent stem cell	Male
CVCL_E4G9	C-SU-iPS-1	Induced pluripotent stem cell	Male
CVCL_F1VY	DUK66652	Transformed cell line	Sex unspecified
CVCL_F1W0	DUK71006	Transformed cell line	Sex unspecified

Clinical trials (associated diseases)

237 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00103753	PHASE4	UNKNOWN	Combined Chelation Treatment With Deferiprone and Deferoxamine in Thalassemia Major
NCT00564941	PHASE4	COMPLETED	Evaluating the Efficacy of Deferasirox in Transfusion Dependent Chronic Anaemias (Myelodysplastic Syndrome, Beta-thalassaemia Patients) With Chronic Iron Overload
NCT00733811	PHASE4	COMPLETED	Efficacy Study of the Use of Sequential DFP-DFO Versus DFP
NCT03961828	PHASE4	COMPLETED	Hyalornic Acid Level in β-Thalassemic Children Treated for Hepatitis C Virus
NCT00346242	PHASE4	COMPLETED	Evaluation of Efficacy of Zoledronic Acid in Patients With Haemoglobin Syndromes (Thalassemia and Sicle Cell Anaemia) and Risk of Skeletal Events
NCT00707850	PHASE4	COMPLETED	Pegasys® Plus Ribavirin in Thalassemic Patients With Hepatitis C Virus Infection
NCT01250951	PHASE4	COMPLETED	This Study Will Evaluate Efficacy and Safety of Deferasirox in Patients With Myelodysplastic Syndromes (MDS), Thalassemia and Rare Anemia Types Having Transfusion-induced Iron Overload.
NCT02069886	PHASE4	WITHDRAWN	Effect of Deferasirox on Endocrine Complications in Subjects With Transfusion Dependent Thalassemia
NCT02386800	PHASE4	ACTIVE_NOT_RECRUITING	CINC424A2X01B Rollover Protocol
NCT03032666	PHASE4	COMPLETED	Sofosbuvir/Ledipasvir for Hepatitis C Genotype 1-6 in Patients With Transfusion-Dependent Thalassemia: An Open Label Trial
NCT03095326	PHASE4	COMPLETED	Pneumococcal Vaccination for Splenectomised Thalassemia Major Patients in Indonesia
NCT03117192	PHASE4	COMPLETED	Zinc Supplementation on Cellular Immunity in Thalassemia Major
NCT03374111	PHASE4	UNKNOWN	Colla Corii Asini Treating Anemia in Pregnant Women With Thalassemia(Presenting the Syndrome of Blood Deficiency)
NCT03392298	PHASE4	UNKNOWN	Study on the Mechanism of Colla Corri Asini in the Treatment of Thalassemia Patients With Pregnancy Anemia
NCT03402191	PHASE4	UNKNOWN	L-arginine Versus Sildenafil in Children With Beta Thalassemia Associated With Pulmonary Hypertension
NCT00061750	PHASE3	COMPLETED	Safety & Efficacy of ICL670 vs. Deferoxamine in Beta-thalassemia Patients With Iron Overload Due to Blood Transfusions
NCT00171171	PHASE3	COMPLETED	A Study of Long-term Treatment With Deferasirox in Patients With Beta-thalassemia and Transfusional Hemosiderosis
NCT02604433	PHASE3	COMPLETED	An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Adults Who Require Regular Red Blood Cell Transfusions Due to Beta (β) Thalassemia
NCT02906202	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Participants With Transfusion-Dependent β-Thalassemia, Who do Not Have a β0/β0 Genotype
NCT03207009	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Participants With Transfusion-Dependent β-Thalassemia
NCT04064060	PHASE3	RECRUITING	A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials
NCT04208529	PHASE3	ENROLLING_BY_INVITATION	A Long-term Follow-up Study in Participants Who Received CTX001
NCT05356195	PHASE3	ACTIVE_NOT_RECRUITING	Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Transfusion-Dependent β-Thalassemia (TDT)
NCT05477563	PHASE3	RECRUITING	Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease
NCT07157722	PHASE3	NOT_YET_RECRUITING	Evaluating the Effect of N-Acetyl Cysteine and Alpha Lipoic Acid in Patients With Beta Thalassemia
NCT00235391	PHASE3	COMPLETED	Expanded Access of Deferasirox to Patients With Congenital Disorders of Red Blood Cells and Chronic Iron Overload
NCT01395199	PHASE3	COMPLETED	Amlodipine in the Prevention and Treatment of Iron Overload in Patients With Thalassemia Major
NCT06609226	PHASE3	RECRUITING	A Research Study Looking at Long-term Treatment With Etavopivat in People With Sickle Cell Disease or Thalassaemia
NCT00000588	PHASE2	COMPLETED	Chelation Therapy of Iron Overload With Pyridoxal Isonicotinoyl Hydrazone
NCT00000595	PHASE2	COMPLETED	Evaluation of Subcutaneous Desferrioxamine as Treatment for Transfusional Hemochromatosis
NCT00001958	PHASE2	COMPLETED	Hydroxyurea to Treat Beta-Thalassemia (Cooley’s Anemia)
NCT00005934	PHASE2	COMPLETED	5-Azacytidine and Phenylbutyrate to Treat Severe Thalassemia
NCT00006136	PHASE2	COMPLETED	Phase II Study of Arginine Butyrate With or Without Epoetin Alfa in Patients With Thalassemia Intermedia
NCT00029380	PHASE2	COMPLETED	Cord Blood Transplantation for Sickle Cell Anemia and Thalassemia
NCT00061763	PHASE2	COMPLETED	Study of Deferasirox in Iron Overload From Beta-thalassemia Unable to be Treated With Deferoxamine or Chronic Anemias
NCT00115349	PHASE2	TERMINATED	Combination Therapy Compared With Single-Drug Therapy in Patients With Cardiac Diseases
NCT00408447	PHASE2	ACTIVE_NOT_RECRUITING	Stem Cell Transplant in Sickle Cell Disease and Thalassemia
NCT00447694	PHASE2	COMPLETED	Cardiac T2* in Beta-thalassemia Patients on Deferasirox Treatment
NCT01049854	PHASE2	COMPLETED	CD34+Selection for Partially Matched Family or Matched Unrelated Adult Donor Transplant
NCT01186419	PHASE2	COMPLETED	Safety and Pharmacodynamic Study of an Oral Iron Chelator Given for 6 Months to Patients With Iron Overload