HBA1

Summary

HBA1 (hemoglobin subunit alpha 1, HGNC:4823) 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 3039 — RefSeq curated summary.

At a glance

• Gene–disease (curated): HBA1-related alpha thalassemia spectrum (Definitive, ClinGen) — +8 more curated relationships
• GWAS associations: 20
• Clinical variants (ClinVar): 387 total — 38 pathogenic, 83 likely-pathogenic
• Phenotypes (HPO): 57
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000558

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4823
Approved symbol	HBA1
Name	hemoglobin subunit alpha 1
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	HBA-T3
Ensembl gene	ENSG00000206172
Ensembl biotype	protein_coding
OMIM	141800
Entrez	3039

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 retained_intron

ENST00000320868, ENST00000397797, ENST00000472694, ENST00000487791, ENST00000875767

RefSeq mRNA: 1 — MANE Select: NM_000558 NM_000558

CCDS: CCDS10399

Canonical transcript exons

ENST00000320868 — 3 exons

Exon	Start	End
ENSE00001261694	177283	177522
ENSE00001723291	176680	176811
ENSE00003664042	176929	177133

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 99.97.

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

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151866	1.6898	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.97	gold quality
blood	UBERON:0000178	99.95	gold quality
bone marrow	UBERON:0002371	99.91	gold quality
bone marrow cell	CL:0002092	99.89	gold quality
placenta	UBERON:0001987	99.80	gold quality
spleen	UBERON:0002106	99.53	gold quality
ganglionic eminence	UBERON:0004023	99.50	gold quality
lower esophagus mucosa	UBERON:0035834	99.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.98	gold quality
leukocyte	CL:0000738	98.85	gold quality
apex of heart	UBERON:0002098	98.63	gold quality
metanephros cortex	UBERON:0010533	98.54	gold quality
temporal lobe	UBERON:0001871	98.53	gold quality
amygdala	UBERON:0001876	98.52	gold quality
upper lobe of left lung	UBERON:0008952	98.51	gold quality
lung	UBERON:0002048	98.44	gold quality
granulocyte	CL:0000094	98.30	gold quality
substantia nigra	UBERON:0002038	98.09	gold quality
primary visual cortex	UBERON:0002436	97.94	gold quality
anterior cingulate cortex	UBERON:0009835	97.75	gold quality
pituitary gland	UBERON:0000007	97.57	gold quality
adenohypophysis	UBERON:0002196	97.51	gold quality
ventricular zone	UBERON:0003053	97.51	gold quality
right lobe of thyroid gland	UBERON:0001119	97.47	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.38	gold quality
adrenal tissue	UBERON:0018303	97.32	gold quality
hypothalamus	UBERON:0001898	97.12	gold quality
Ammon’s horn	UBERON:0001954	96.98	gold quality
right lobe of liver	UBERON:0001114	96.90	gold quality

Single-cell (SCXA)

Detected in 50 experiment(s), a significant marker in 47.

Experiment	Marker?	Max mean expression
E-MTAB-9467	yes	276973.49
E-MTAB-9221	yes	253113.11
E-CURD-120	yes	244578.80
E-CURD-122	yes	232958.00
E-CURD-55	yes	213156.69
E-GEOD-149689	yes	201705.74
E-MTAB-6653	yes	194392.64
E-HCAD-4	yes	193013.44
E-MTAB-10042	yes	189866.47
E-MTAB-8207	yes	182816.30
E-MTAB-7407	yes	181209.22
E-HCAD-9	yes	158139.36
E-HCAD-15	yes	141102.68
E-HCAD-36	yes	138773.84
E-MTAB-8221	yes	133334.91

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
TNF	Activation

Upstream regulators (CollecTRI, top): AP1, ATRX, BACH1, CTCF, E2F1, EGF, EIF2AK1, EPAS1, EPO, ETV6, FGF2, FLI1, GATA1, GATA2, HESX1, HOXB6, JUN, KLF3, MAPK11, MAPK14, MIF, MIXL1, MYC, NFE2, NFIC, RNF2, SP1, STAT5A, TFCP2, TGFB1

miRNA regulators (miRDB)

4 targeting HBA1, 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-12123	99.52	71.79	2990
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-499B-5P	98.35	68.39	988
HSA-MIR-4787-5P	89.08	66.18	88

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• study of mutations on severity in beta-thalassemia patints: efffects of alpha- thalassemia (PMID:11833853)
• Hb Siam [alpha15(A13)Gly–>Arg (alpha1) (GGT–>CGT)] is a typical alpha chain hemoglobinopathy without an alpha-thalassemic effect. (PMID:11939517)
• Esterification of the propionate groups promotes alpha/beta hemoglobin chain homogeneity of CN-hemin binding (PMID:12054662)
• High and low glycation phenotypes are found in type I diabetes (PMID:12200073)
• Quaternary structure of hemoglobin in solution. (PMID:12525687)
• Review. The effects of alpha-globin genotype on the pathophysiology of sickle cell anemia, HbSC disease, and sickle beta-thalassemia are studied. (PMID:12673836)
• Three novel mutations: alpha2 cd19 (-G) frameshift mutation, alpha1 IVS1-148(A–>G), and cd14 (TGG–>TAG). Fourth mutation, IVS1-38 (C–>T) in heterozygote for alpha2 cd19(-G) mutation. (PMID:14508795)
• A Lys to Asn substitution at codon 40 is reported for a new variant (Hb Saratoga Springs) associated with erythrocytosis; quaternary protein structure and oxygen binding are discussed (PMID:14649314)
• Gene scanning of HBA1 genes in thalassemic patients revealed a new allele: c.475C>A. (PMID:15365991)
• These data demonstrate that S-nitrosothiol content and oxygen saturation are tightly coupled in hemoglobin in intact erythrocytes and that this coupling is likely to be of pathophysiological significance. (PMID:15824313)
• Amino acid residues in the B10 helix of the alpha- and beta-chains of hemoglobin A can play different roles in regulating the functional properties and stability of the hemoglobin molecule. (PMID:15882059)
• differences in dizygotic twins with type 1 diabetes in hla identical twins. (PMID:16123516)
• Data describe the different effects of pH and NaCl on individual O2-binding properties of alpha and beta subunits within liganded tetramer and dimer of human hemoglobin. (PMID:16302974)
• searched for -alpha(3.7) and -alpha(4.2) alpha(+)-thalassemia deletion alleles, as well as the alpha alpha alpha(anti3.7) triplication through long-gap PCR (PMID:16466950)
• Consumption of GSH noted in thalassemic red blood cells may be via a prooxidant pathway as augmentation of cellular GSH levels actually enhances alpha-hemoglobin chain-mediated injury. (PMID:16545695)
• Results support the global allostery model for hemoglobin A by showing that conformational changes propagate from the effector binding site to the interdimeric interfaces in both quaternary states. (PMID:16822864)
• Each blood glucose value at baseline and after treatment optimization significantly correlated with baseline and follow-up Hb (A1c), respectively. (PMID:16933182)
• comparison of HbA and HbS, and demonstration that HbS polymerization can be controlled by varying the cluster properties (PMID:17040989)
• Increased tendency of LDL to undergo lipid peroxidation in diabetic patients contributes to increased levels of blood HbA1c (PMID:17070510)
• analysis of the interaction between human apohemoglobin A and CN-Mesohemin (PMID:17191128)
• Aasociated with cardiovascular disease and coronary diseasse risk in Asian-Indian subjects with normal glucose tolerance. (PMID:17351274)
• Our RDC analysis suggests that the quaternary and tertiary structures of deoxy-Hb A in solution differ from its recently determined high-resolution crystal structures (PMID:17691822)
• This work therefore 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)
• Metabolic disturbances related to metabolic syndrome or diabetes affect the ability to detect early-stage prostate cancer. (PMID:17938644)
• the alpha2-globin mutation cod 117 TTC>TCC or alpha 117(GH5)Phe>Ser impairs the interaction of the alpha-chain variant with the AHSP and prevents its stabilizing effect, thus leading to the alpha-chain pool reduction (PMID:18166800)
• Used as an index of glycemic control in adolescents with type 1 diabetes who attended or did not attend a diabetes camp. (PMID:18211634)
• A retrospective analysis of the fasting plasma glucose and glycosylated hemoglobin and pharmacotherapy change patterns among type 2 diabetes mellitus patients. (PMID:18343267)
• HbA1 provides an easy-to-assess, accurate measure of lecithin acyltransferase activity in type 2 diabetes. (PMID:18485513)
• The insertion 45 nucleotides probably results from replication slippage during DNA synthesis and the 15-residue repeat results in full repetition of the heme-linked F helix. (PMID:18571503)
• Elevated glycosylated haemoglobin (HbA1c) is a risk marker in coronary artery bypass surgery. (PMID:18609043)
• four Greek cases with a similar atypical thalassemia intermedia phenotype; in all four cases, alpha(+)-thalassemia (alpha(+)-thal) mutations in trans to the in frame 3 bp deletion (-CCC) on the alpha1-globin gene between codons 36 & 37 was identified (PMID:18654888)
• Report Glycated HbA1c levels and risk of stroke, ischemic and hemorrhagic, in Japanese men and women. (PMID:18667812)
• HbA1c has a role in progression of diabetes (PMID:18689979)
• Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c. (PMID:18694998)
• Findings show that PAI-1 and HbA1c are singularly linked to metabolic syndrome. (PMID:18809301)
• Glycated hemoglobin levels are associated with genetic variation of HK1. (PMID:19096518)
• The polyethylene glycol chains conjugated at Val-1(alpha) decrease the Hill coefficient, the Bohr effect of Hb and the sensitization to the presence of the allosteric effectors. (PMID:19119852)
• HBA1 is a clinically useful parameter for identifying the risk for mortality, both for cardiovascular and non-cardiovascular mortality in diabetic hemodialysis patients. (PMID:19135755)
• Periodontal treatment with topical antibiotics improves HbA1c through reduction of C reactive protein in type 2 diabetics. (PMID:19168253)
• HBA1 level may be a predict aggressive tumor profile of prostate cancer in patients with diabetes mellitus. (PMID:19189299)

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), HBA2 (ENSG00000188536), HBG2 (ENSG00000196565), MB (ENSG00000198125), 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 (3): D1MGQ2, P69905, G3V1N2

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_000549* (*=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: 288 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, PEREZ_TP63_TARGETS, GOBP_HYDROGEN_PEROXIDE_CATABOLIC_PROCESS, MATTIOLI_MGUS_VS_PCL, GOBP_ERYTHROCYTE_HOMEOSTASIS, SATO_SILENCED_BY_DEACETYLATION_IN_PANCREATIC_CANCER, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, ADDYA_ERYTHROID_DIFFERENTIATION_BY_HEMIN, HANN_RESISTANCE_TO_BCL2_INHIBITOR_UP, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_DN, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE

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 197 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	8.0×	4e-04
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	10	6.9×	7e-04
Platelet degranulation	9	6.3×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
oxygen transport	5	29.8×	6e-04
erythrocyte development	5	14.9×	6e-03
protein folding	10	5.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	38
Likely pathogenic	83
Uncertain significance	78
Likely benign	31
Benign	4

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1328438	GRCh37/hg19 16p13.3(chr16:212275-234987)x1	Pathogenic
148582	GRCh38/hg38 16p13.3(chr16:165500-184338)x1	Pathogenic
149973	GRCh38/hg38 16p13.3(chr16:165500-183438)x1	Pathogenic
15655	NM_000517.6(HBA2):c.410T>C (p.Leu137Pro)	Pathogenic
15779	NM_000558.5(HBA1):c.262C>T (p.His88Tyr)	Pathogenic
15849	NM_000558.3(HBA1):c.179G>A (p.Gly60Asp)	Pathogenic
15880	NM_000558.5(HBA1):c.196_228del (p.Ala66_Asp76del)	Pathogenic
2423327	NC_000016.9:g.(?222912)(226810_?)del	Pathogenic
2428673	NM_000558.5(HBA1):c.1A>G (p.Met1Val)	Pathogenic
2580349	GRCh37/hg19 16p13.3(chr16:215947-231157)x1	Pathogenic
2681961	NM_000558.5(HBA1):c.95+1G>A	Pathogenic
3220863	Single allele	Pathogenic
375753	NC_000016.10:g.172005_177200del	Pathogenic
38635	NM_005332.2(HBZ):c.330_*22601del	Pathogenic
38636	NG_000006.1(HBA1):g.34247_38050del	Pathogenic
3893661	NC_000016.10:g.173384_177187dup	Pathogenic
3903433	NC_000016.10:g.175997_178388del	Pathogenic
4685967	NM_000558.5(HBA1):c.247_254delinsTGCA (p.Ala83fs)	Pathogenic
4814422	NM_000558.5(HBA1):c.95+1G>C	Pathogenic
487448	NC_000016.10:g.(?169780)(182142_?)del	Pathogenic
57278	GRCh38/hg38 16p13.3(chr16:165725-180586)x1	Pathogenic
625828	GRCh37/hg19 16p13.3(chr16:221962-228406)	Pathogenic
625829	GRCh37/hg19 16p13.3(chr16:216075-231021)	Pathogenic
638132	GRCh37/hg19 16p13.3(chr16:216742-233272)x0	Pathogenic
643713	NC_000016.10:g.(?176012)(177299_?)del	Pathogenic
648517	NC_000016.10:g.(?172913)(177411_?)del	Pathogenic
665057	NC_000016.10:g.(?176717)(177411_?)del	Pathogenic
811900	NM_000558.5(HBA1):c.358C>T (p.Pro120Ser)	Pathogenic
869215	NC_000016.10:g.158101_179001del	Pathogenic
869216	NC_000016.10:g.169197_259919delinsCACCCAGCACCCAGTACCA	Pathogenic

SpliceAI

181 predictions. Top by Δscore:

Variant	Effect	Δscore
16:176925:GCAG:G	acceptor_loss	1.0000
16:176926:CA:C	acceptor_loss	1.0000
16:176927:A:AC	acceptor_loss	1.0000
16:176927:A:AG	acceptor_gain	1.0000
16:176927:AG:A	acceptor_gain	1.0000
16:176927:AGGAT:A	acceptor_gain	1.0000
16:176928:G:GC	acceptor_gain	1.0000
16:176928:GG:G	acceptor_gain	1.0000
16:176928:GGA:G	acceptor_gain	1.0000
16:176928:GGAT:G	acceptor_gain	1.0000
16:176928:GGATG:G	acceptor_gain	1.0000
16:177129:TCAAG:T	donor_gain	1.0000
16:177132:AG:A	donor_gain	1.0000
16:177133:GG:G	donor_gain	1.0000
16:177134:G:GG	donor_gain	1.0000
16:177134:GTG:G	donor_loss	1.0000
16:176809:GAG:G	donor_gain	0.9900
16:176810:AGGTG:A	donor_loss	0.9900
16:176811:GG:G	donor_loss	0.9900
16:176813:T:A	donor_loss	0.9900
16:177131:AAG:A	donor_gain	0.9900
16:177135:T:G	donor_loss	0.9900
16:177278:CACA:C	acceptor_loss	0.9900
16:177280:CA:C	acceptor_loss	0.9900
16:177281:A:AG	acceptor_gain	0.9900
16:177282:G:GA	acceptor_gain	0.9900
16:177282:GC:G	acceptor_gain	0.9900
16:177282:GCTC:G	acceptor_gain	0.9900
16:177282:GCTCC:G	acceptor_gain	0.9900
16:176924:C:CA	acceptor_gain	0.9800

AlphaMissense

921 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:176963:T:C	F44L	0.999
16:176965:C:A	F44L	0.999
16:176965:C:G	F44L	0.999
16:177128:T:C	F99L	0.999
16:177130:C:A	F99L	0.999
16:177130:C:G	F99L	0.999
16:177095:C:A	H88N	0.998
16:177095:C:G	H88D	0.998
16:177012:G:A	G60D	0.997
16:177097:C:A	H88Q	0.997
16:177097:C:G	H88Q	0.997
16:177129:T:C	F99S	0.997
16:176748:T:A	V11D	0.996
16:176964:T:C	F44S	0.996
16:177108:T:C	L92P	0.996
16:177127:C:A	N98K	0.996
16:177127:C:G	N98K	0.996
16:177403:T:C	Y141H	0.996
16:176964:T:G	F44C	0.995
16:177008:C:G	H59D	0.995
16:177041:G:C	A70P	0.995
16:177093:T:C	L87P	0.995
16:177406:C:A	R142S	0.995
16:176759:T:A	W15R	0.994
16:176759:T:C	W15R	0.994
16:177000:T:A	V56D	0.994
16:177029:G:C	A66P	0.994
16:177042:C:A	A70D	0.994
16:177096:A:G	H88R	0.994
16:177099:C:A	A89E	0.994

dbSNP variants (sampled 300 via entrez): RS1000675994 (16:177247 G>A,T), RS1000893343 (16:177957 A>G), RS1004854583 (16:176145 G>A,T), RS1007190118 (16:177997 G>A), RS1008924513 (16:175216 A>C,G), RS1008999588 (16:175445 G>T), RS1009251270 (16:177659 G>A), RS1009323484 (16:177937 G>T), RS1013463922 (16:176219 C>T), RS1014549550 (16:177475 C>T), RS1014818135 (16:175646 C>A), RS1015263543 (16:176169 C>T), RS1018671676 (16:177749 A>T), RS1018724078 (16:178002 C>A,G), RS1023498045 (16:177217 A>T)

Disease associations

OMIM: gene MIM:141800 | disease phenotypes: MIM:604131, MIM:617981, MIM:140700, MIM:613978, MIM:617973

GenCC curated gene-disease

Disease	Classification	Inheritance
alpha thalassemia spectrum	Definitive	Semidominant
erythrocytosis, familial, 7	Strong	Autosomal dominant
Heinz body anemia	Strong	Autosomal dominant
methemoglobinemia, alpha type	Strong	Autosomal dominant
unstable hemoglobin disease	Moderate	Autosomal dominant
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
HBA1-related alpha thalassemia spectrum	Definitive	AR
methemoglobinemia, alpha type	Limited	AD
unstable hemoglobin disease	Moderate	AD
erythrocytosis, familial, 7	Moderate	AD

Mondo (10): alpha thalassemia spectrum (MONDO:0011399), erythrocytosis, familial, 7 (MONDO:0054802), Heinz body anemia (MONDO:0007705), hemoglobin H disease (MONDO:0013512), methemoglobinemia, alpha type (MONDO:0020835), anemia (MONDO:0002280), thalassemia (MONDO:0000984), Hb Bart’s hydrops fetalis (MONDO:0015579), unstable hemoglobin disease (MONDO:0020459), hemoglobin M disease (MONDO:0018023)

Orphanet (5): Alpha-thalassemia (Orphanet:846), OBSOLETE: Heinz body anemia (Orphanet:178330), Hemoglobin H disease (Orphanet:93616), Alpha-thalassemia and related disorders (Orphanet:275745), Hemoglobin Bart’s fetalis syndrome (Orphanet:163596)

HPO phenotypes

57 total (30 of 57 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:0000961	Cyanosis
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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST000587_1	Mean corpuscular hemoglobin	3.000000e-09
GCST003122_1	Hemoglobin levels	6.000000e-18
GCST004601_134	Red blood cell count	7.000000e-31
GCST004602_220	Mean corpuscular volume	1.000000e-85
GCST004605_10	Mean corpuscular hemoglobin concentration	3.000000e-52
GCST004619_59	Reticulocyte fraction of red cells	4.000000e-11
GCST004630_168	Mean corpuscular hemoglobin	2.000000e-12
GCST004630_169	Mean corpuscular hemoglobin	1.000000e-109
GCST005951_12	Body mass index	5.000000e-11
GCST010083_266	Hemoglobin levels	2.000000e-16
GCST90002384_354	Hemoglobin	1.000000e-24
GCST90002386_276	High light scatter reticulocyte percentage of red cells	1.000000e-27
GCST90002390_630	Mean corpuscular hemoglobin	2.000000e-214
GCST90002391_160	Mean corpuscular hemoglobin concentration	4.000000e-90
GCST90002392_476	Mean corpuscular volume	3.000000e-179
GCST90002396_645	Mean reticulocyte volume	4.000000e-12
GCST90002397_273	Mean spheric corpuscular volume	5.000000e-37
GCST90002403_657	Red blood cell count	4.000000e-119
GCST90002404_332	Red cell distribution width	1.000000e-32
GCST90002406_402	Reticulocyte fraction of red cells	2.000000e-49

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:0004305	erythrocyte count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007986	reticulocyte count
EFO:0004340	body mass index
EFO:0010701	mean reticulocyte volume
EFO:0009188	Red cell distribution width

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D000740	Anemia	C15.378.050
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
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

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

Chemical	Actions (top 5)	PubMed papers
Orlistat	decreases expression	2
Chromium	affects cotreatment, decreases expression, decreases glycation	2
Disulfiram	affects binding, decreases expression, increases expression	2
fluorene-9-bisphenol	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects binding, increases reaction	1
perfluorooctanoic acid	increases expression	1
picolinic acid	decreases glycation	1
hydroquinone	affects binding, decreases reaction	1
epigallocatechin gallate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium tripicolinate	decreases expression, affects cotreatment	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	increases expression	1
cetilistat	decreases expression	1
licochalcone B	increases expression	1
Capecitabine	decreases expression	1
Resveratrol	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Biotin	affects cotreatment, decreases expression	1
Cisplatin	increases expression	1
Copper	affects binding, decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Dichlorodiphenyl Dichloroethylene	affects binding	1
Diethylnitrosamine	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Fluorouracil	affects reaction, decreases expression	1
Glucose	increases glycation	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

3 cell lines: 3 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_BT08	LAZ-149	Transformed cell line	Female
CVCL_F1VY	DUK66652	Transformed cell line	Sex unspecified
CVCL_F1W0	DUK71006	Transformed cell line	Sex unspecified

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00003398	PHASE4	COMPLETED	Bone Marrow Transplantation in Treating Patients With Hematologic Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00046969	PHASE4	COMPLETED	Epoetin Beta in Treating Anemia in Patients With Cervical Cancer
NCT00111995	PHASE4	COMPLETED	Evaluating Aranesp® for the Treatment of Anemia in African-American Subjects With Chronic Renal Failure (CRF) Receiving Hemodialysis
NCT00117039	PHASE4	COMPLETED	A Study to Evaluate the Effectiveness of Aranesp® for Cancer Patients With Anemia
NCT00117065	PHASE4	COMPLETED	Study of Transplant Related Anemia Treated With Aranesp® (STRATA)
NCT00117117	PHASE4	COMPLETED	A Study to Assess Symptom Burden in Subjects With Nonmyeloid Malignancies Receiving Chemotherapy and Aranesp®
NCT00126334	PHASE4	COMPLETED	Conservative Versus Liberal Red Cell Transfusion in Myocardial Infarction Trial: The CRIT Pilot
NCT00153868	PHASE4	COMPLETED	A Web-based Study of Quality of Life Benefits Associated Aranesp in Anemic Patients With Cancer
NCT00168948	PHASE4	UNKNOWN	Intermittent Antimalaria Treatment With SP in African Children
NCT00173706	PHASE4	UNKNOWN	Evaluation of the Effects of L-Carnitine Injection in Patients Undergoing Hemodialysis
NCT00194857	PHASE4	TERMINATED	Treatment of Anemia and Neutropenia in HIV/HCV Coinfected Patients Treated With Pegylated Interferon and Ribavirin
NCT00204334	PHASE4	COMPLETED	Effects of Anemia Correction on Vascular and Monocyte Function in Renal Transplant Recipients
NCT00206739	PHASE4	COMPLETED	Intermittent Treatment With Sulfadoxine-pyrimethamine for Malaria Control in Infants
NCT00211120	PHASE4	TERMINATED	Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR)
NCT00216541	PHASE4	COMPLETED	A Study of the Safety and Effectiveness of Epoetin Alfa on Hemoglobin Levels and Blood Transfusions in Cancer Patients Receiving Chemotherapy
NCT00223938	PHASE4	TERMINATED	Study of the Efficacy and Safety of Ferrlecit in the Maintenance Dosing in Hemodialysis Patients.
NCT00223964	PHASE4	COMPLETED	Study of the Efficacy of Two Doses of Ferrlecit in the Treatment of Iron Deficiency in Pediatric Hemodialysis Patients
NCT00224003	PHASE4	COMPLETED	Study of the Safety and Efficacy of Ferrlecit® Maintenance Dosing in Pediatric Hemodialysis Patients
NCT00224068	PHASE4	COMPLETED	Effect of Iron Therapy as an Adjunct to Epoetin Alfa in the Anemia of Cancer Chemotherapy
NCT00239642	PHASE4	COMPLETED	Safety and Efficacy of Iron Sucrose in Children
NCT00247507	PHASE4	UNKNOWN	The Effects of Acetylcysteine on Alleviating Damage of Oxidative Stress in Hemodialysis Patients
NCT00248716	PHASE4	UNKNOWN	Treatment of Anemia in the 2nd Year of Life. Comparison of the Efficacy of Two Different Iron Preparations.
NCT00283465	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Treatment With Epoetin Alfa on Hemoglobin Levels, Red Blood Cell Transfusions, and Quality of Life in Patients With Cancer Receiving Platinum-containing Chemotherapy
NCT00312871	PHASE4	TERMINATED	Effects of Early Correction of Anemia in Patients With Chronic Renal Insufficiency
NCT00315484	PHASE4	COMPLETED	Hematologic Response of Epoetin Alfa (PROCRIT) Versus Darbepoetin Alfa (ARANESP) in Chemotherapy Induced Anemia
NCT00317902	PHASE4	COMPLETED	An Open-Label Study to Evaluate the Effect of Every Other Week PROCRIT� (Epoetin Alfa) Dosing (40,000-60,000 Units) On Maintaining Quality of Life and Target Hemoglobin Levels in Anemic HIV-Infected Patients (CHAMPS II)
NCT00335023	PHASE4	COMPLETED	Well Being of Obstetric Patients on Minimal Blood Transfusions
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00377481	PHASE4	COMPLETED	COMFORT Study: A Crossover Study of NeoRecormon (Epoetin Beta) and Darbepoetin Alfa in Patients With Renal Anemia.
NCT00396435	PHASE4	COMPLETED	Correction of Anaemia and Progression of Renal Failure on Transplanted Patients
NCT00401869	PHASE4	COMPLETED	The Effect of PROCRIT (Epoetin Alfa) on Postoperative Vigor and Handgrip Strength (VIGOR Study)
NCT00413101	PHASE4	COMPLETED	A Study of NeoRecormon (Epoetin Beta) in Patients With End Stage Renal Disease.
NCT00431496	PHASE4	COMPLETED	A Study of Cinacalcet to Improve Achievement of National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) Targets in Patients With End Stage Renal Disease (ESRD)
NCT00437723	PHASE4	COMPLETED	A Study of NeoRecormon in Patients With Chronic Kidney Disease.
NCT00440063	PHASE4	TERMINATED	A Study of NeoRecormon (Epoetin Beta) in Patients With Renal Anemia.
NCT00470158	PHASE4	COMPLETED	Delivery of Iron and Zinc Supplements: Evaluation of Interaction Effect on Biochemical and Clinical Outcomes
NCT00479102	PHASE4	UNKNOWN	Prevention of Iron Deficiency in 2nd Year of Life
NCT00495365	PHASE4	TERMINATED	A Dose Conversion Study of Epoetin Alfa in Subjects With the Anemia of Chronic Kidney Disease.
NCT00495378	PHASE4	TERMINATED	RAPID-2. A Study to Evaluate the Effectiveness of Alternate Dosing of PROCRIT (Epoetin Alfa) in Maintaining Hemoglobin Levels in Patients With Chemotherapy Related Anemia