Affinage

HBA1

Hemoglobin subunit alpha · UniProt P69905

Round 2 corrected
Length
142 aa
Mass
15.3 kDa
Annotated
2026-04-28
120 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HBA1 encodes the alpha subunit of the adult hemoglobin tetramer (HbA, α₂β₂), an oxygen-transport hemoprotein whose cooperative ligand binding is governed by allosteric R↔T quaternary transitions defined by atomic-resolution crystal structures of the deoxy (T), oxy (R), and a third stable R2 quaternary state (PMID:1177322, PMID:6644819, PMID:1512262, PMID:16765986). In the alpha subunit, the distal histidine (HisE7) hydrogen-bonds the O₂ ligand, the iron atom sits near the porphyrin plane in the R-state, and C-terminal Arg141α participates in intersubunit salt bridges that stabilize the T-state; nonenzymatic glycosylation occurs preferentially at Lys16α and other surface lysines, generating HbA1c species (PMID:6644819, PMID:7358733). Beyond erythrocytes, hemoglobin α is expressed in arterial endothelial cells and enriched at the myoendothelial junction, where its Fe³⁺/Fe²⁺ redox state—regulated by CYB5R3—gates eNOS-derived nitric oxide diffusion to vascular smooth muscle, establishing a non-canonical role in vascular tone regulation (PMID:23123858). Loss-of-function mutations in HBA1 cause alpha-thalassemia, as demonstrated by chromosomal truncations removing the locus and by hyperunstable variants that undergo post-translational degradation during erythroid maturation (PMID:1975428, PMID:31190578).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1975 High

    The first atomic model of the T-state (deoxy) hemoglobin quaternary structure established how the alpha and beta subunits are arranged in the low-affinity conformation, providing the structural foundation for understanding cooperative oxygen binding.

    Evidence X-ray crystallography of human deoxyhemoglobin at 2.5 Å resolution

    PMID:1177322

    Open questions at the time
    • R-state (oxy) structure not yet determined at comparable resolution
    • No structural basis for the T→R transition mechanism
  2. 1976 High

    Identification of the AAUAAA hexanucleotide as the conserved polyadenylation signal in alpha- and beta-globin mRNAs established how the 3' end of HBA1 mRNA is processed, a mechanism later shown to be universal for eukaryotic mRNAs.

    Evidence Direct RNA sequencing of purified human and rabbit globin mRNAs

    PMID:822353

    Open questions at the time
    • Protein factors recognizing AAUAAA not yet identified
    • Functional consequence of signal disruption on alpha-globin expression not tested
  3. 1980 High

    Mapping nonenzymatic glycosylation to specific lysine residues (preferentially Lys16α) on the alpha chain defined the molecular basis for glycated hemoglobin species (HbA1c), explaining how post-translational modification occurs on HBA1-encoded protein.

    Evidence In vitro glycosylation with [¹⁴C]-glucose, peptide mapping, and sequencing

    PMID:7358733

    Open questions at the time
    • Effect of glycosylation on oxygen affinity or allosteric cooperativity not quantified
    • In vivo glycosylation kinetics not measured
  4. 1983 High

    The R-state (oxy) crystal structure at 2.1 Å revealed the alpha subunit iron-oxygen geometry, the distal HisE7 hydrogen bond to O₂, and the loss of T-state salt bridges at Arg141α, completing the structural picture of the allosteric mechanism.

    Evidence Single-crystal X-ray analysis of human oxyhemoglobin

    PMID:6644819

    Open questions at the time
    • Whether additional quaternary intermediates exist between T and R states was unknown
    • Dynamic pathway of the T→R transition unresolved
  5. 1990 High

    A chromosome 16p13.3 terminal truncation that deleted the alpha-globin regulatory region demonstrated that the chromosomal context upstream of HBA1 is essential for expression, and linked disruption of this locus to alpha-thalassemia.

    Evidence Southern blotting, PFGE, DNA sequencing of breakpoint, and family studies

    PMID:1975428

    Open questions at the time
    • Specific cis-regulatory elements required for HBA1 expression not delineated
    • Mechanism by which telomeric healing stabilized the truncation not fully explored
  6. 1992 High

    Discovery of the R2 quaternary state and engineering of di-alpha hemoglobin answered two long-standing questions: whether additional stable allosteric conformations exist (yes—the R2 state differs at the α1β2 interface), and whether preventing αβ-dimer dissociation could eliminate renal toxicity of cell-free hemoglobin (yes—tandem alpha-globin fusion extended in vivo half-life).

    Evidence X-ray crystallography at 1.7 Å (R2 state); recombinant di-alpha Hb expression in E. coli with oxygen affinity and pharmacokinetic validation

    PMID:1512262 PMID:1552945

    Open questions at the time
    • Physiological relevance of R2 state in vivo not demonstrated
    • Whether additional quaternary intermediates exist beyond R, R2, and T
  7. 2006 High

    Ultra-high-resolution structures (1.25 Å) of oxy-, deoxy-, and CO-hemoglobin resolved subtle differences in distal HisE7 hydrogen-bond geometry between alpha and beta subunits, explaining why HisE7 mutations produce different phenotypes in each chain.

    Evidence X-ray crystallography at 1.25 Å for three ligation states

    PMID:16765986

    Open questions at the time
    • Dynamic motions of HisE7 during ligand entry and exit not captured by crystallography
    • Contribution of each subunit to overall cooperativity still debated
  8. 2012 High

    Discovery that hemoglobin α is expressed in arterial endothelial cells and enriched at the myoendothelial junction—where its redox state controlled by CYB5R3 gates NO diffusion to smooth muscle—established a non-canonical vascular signaling role entirely distinct from erythrocyte oxygen transport.

    Evidence Co-immunoprecipitation, subcellular fractionation, immunofluorescence, siRNA/knockout mice, pharmacological inhibition, ex vivo vascular reactivity

    PMID:23123858

    Open questions at the time
    • Mechanism of Hbα targeting to the myoendothelial junction unknown
    • Whether endothelial Hbα expression is regulated independently of erythroid Hbα
    • Structural basis for the Hbα–eNOS interaction not defined
  9. 2017 Medium

    Characterization of hyperunstable HBA1 variants (Hb Amsterdam-A1 and others) showed that specific missense mutations cause rapid post-translational degradation of alpha-globin protein despite normal mRNA levels, demonstrating that heme pocket and subunit-interface integrity are critical for alpha-globin proteostatic stability during erythroid maturation.

    Evidence Isopropanol stability testing, mass spectrometry of precipitate and lysate fractions, qPCR of mRNA in erythroid progenitors

    PMID:28696843 PMID:31190578

    Open questions at the time
    • Proteolytic pathway responsible for degradation of hyperunstable alpha-globin not identified
    • Whether AHSP stabilizes these variants in vivo not tested
  10. 2022 Medium

    Overexpression of HBA1 in AML cells inhibited proliferation and induced apoptosis, raising the possibility of a tumor-suppressive role outside erythroid lineages, though the downstream pathway remains uncharacterized.

    Evidence RT-qPCR in patient samples, transfection/overexpression in K562 cells, CCK-8 assay, flow cytometry

    PMID:36117408

    Open questions at the time
    • Mechanism linking HBA1 expression to apoptosis and G2/M arrest not defined
    • Not independently replicated in non-K562 AML models
    • Whether this reflects an oxygen/NO-dependent or novel function is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the molecular basis for Hbα targeting to the myoendothelial junction, whether endothelial and erythroid Hbα transcription is controlled by distinct regulatory programs, and the identity of the proteolytic machinery that degrades hyperunstable alpha-globin variants during erythropoiesis.
  • Mechanism of Hbα localization to myoendothelial junctions unknown
  • Proteolytic pathway for hyperunstable alpha-globin variants unidentified
  • Non-canonical (non-erythroid) functions of Hbα lack systematic characterization

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140104 molecular carrier activity 4 GO:0098772 molecular function regulator activity 1
Localization
GO:0005829 cytosol 2 GO:0005576 extracellular region 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-382551 Transport of small molecules 3 R-HSA-162582 Signal Transduction 1
Partners
CYB5R3HBBNOS3
Complex memberships
Hemoglobin tetramer (α₂β₂)

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1976 The hexanucleotide sequence AAUAAA (encoded by the HBA1/HBA2 and HBB mRNAs, as well as other eukaryotic mRNAs) is located approximately 20 residues upstream of the 3'-terminal poly(A) sequence and is conserved across alpha- and beta-globin mRNAs of rabbit and human, establishing it as the canonical polyadenylation signal in eukaryotic mRNAs. RNA sequencing of purified mRNAs including human and rabbit alpha- and beta-globin mRNAs Nature High 822353
1975 Three-dimensional X-ray crystallographic refinement of human deoxyhaemoglobin at 2.5 Å resolution established the atomic model of the T-state (deoxy) quaternary structure of HbA, defining the spatial arrangement of the alpha (HBA1/HBA2) and beta subunits in the low-affinity conformation. X-ray crystallography, atomic model refinement Journal of molecular biology High 1177322
1983 Crystal structure of human oxyhaemoglobin at 2.1 Å resolution revealed that the iron atom in the alpha subunit (HBA1/HBA2) is 0.16 Å from the porphyrin plane, the Fe–O bond length is 1.66 Å, and a hydrogen bond from the oxygen ligand to the distal HisE7 is present in the alpha subunit; the R-state (oxy) quaternary structure was confirmed, with the C-terminal ArgHC3(141α) unable to form T-state intersubunit salt bridges. Single crystal X-ray analysis, Jack-Levitt refinement Journal of molecular biology High 6644819
1980 Nonenzymatic glycosylation of human haemoglobin A occurs at multiple specific lysine residues on both the alpha (HBA1) and beta chains; the alpha chain is glycosylated preferentially at LysA16(α16) and other surface lysines, establishing the molecular basis for HbA1c and related glycated haemoglobin species. In vitro glycosylation assay with [14C]-glucose followed by peptide mapping and sequencing of glycated peptides The Journal of biological chemistry High 7358733
1992 Human haemoglobin adopts a third stable quaternary structure (R2-state) for liganded HbA at 1.7 Å resolution; in the R2-state the α1β2 interface 'switch' region (His97β) rotates away from Thr38α1 and Thr41α1, opening the interface and potentially functioning as a stable intermediate on an R→R2→T pathway during allosteric transition of the alpha (HBA1) and beta subunits. X-ray crystallography at 1.7 Å resolution The Journal of biological chemistry High 1512262
1992 A recombinant human haemoglobin with tandemly fused (di-alpha) alpha-globin subunits (encoded by HBA1) and a mutant beta-globin with reduced oxygen affinity was expressed in E. coli and shown to function as a blood substitute: fusion of the two alpha subunits prevented dissociation into αβ dimers (increasing in vivo half-life and eliminating renal toxicity) and the beta mutation restored physiologically appropriate oxygen unloading. Recombinant protein expression in E. coli, in vitro oxygen affinity measurements, in vivo pharmacokinetic studies Nature High 1552945
2006 Crystal structures of human haemoglobin in oxy, deoxy, and carbonmonoxy forms refined to 1.25 Å resolution clarified that the distal histidine (HisE7) forms a hydrogen bond to the oxygen ligand in both the alpha (HBA1) and beta subunits in the R-state, and revealed subtle geometric differences in the hydrogen-bond geometry between subunits that explain differential phenotypes when HisE7 is mutated in alpha versus beta globin. High-resolution X-ray crystallography (1.25 Å) for three liganded states Journal of molecular biology High 16765986
2012 Haemoglobin alpha (encoded by HBA1/HBA2) is expressed in arterial endothelial cells and is enriched at the myoendothelial junction, where it regulates nitric oxide (NO) signalling: Hb α in the Fe(3+) (met) state permits eNOS-derived NO to reach vascular smooth muscle, whereas reduction to Fe(2+) by endothelial cytochrome b5 reductase 3 (CYB5R3) quenches NO bioactivity. Genetic depletion of Hb α or pharmacological inhibition of CYB5R3 altered vascular reactivity in small arteries. Co-immunoprecipitation, subcellular fractionation/immunofluorescence localization, genetic knockdown (siRNA/knockout mice), pharmacological inhibition, ex vivo vascular reactivity assays Nature High 23123858
1990 A terminal truncation of chromosome 16p13.3 to a site 50 kb distal to the alpha-globin gene cluster (causing alpha-thalassaemia) was stabilized by direct addition of telomeric (TTAGGG)n repeats to the break site, demonstrating that telomeric DNA alone is sufficient to cap and stabilize a broken chromosome end; this also defined the chromosomal context essential for normal HBA1 expression. Southern blotting, pulsed-field gel electrophoresis, DNA sequencing of the truncation breakpoint, stable inheritance confirmed by family studies Nature High 1975428
2022 Overexpression of HBA1 in K562 AML cells inhibited proliferation, induced apoptosis, and arrested the cell cycle at G2/M phase, whereas endogenous HBA1 expression was significantly reduced in AML patient samples and cell lines, implicating HBA1 as a potential tumour suppressor in acute myeloid leukaemia. RT-qPCR in patient samples, transfection/overexpression in K562 cells, CCK-8 proliferation assay, flow cytometry (apoptosis and cell cycle) Hematology (Amsterdam, Netherlands) Medium 36117408
2017 The HBA1 variant Hb Amsterdam-A1 [α32(B13)Met→Ile; HBA1:c.99G>A] is hyperunstable due to perturbation of globin–heme and potentially α1β1 subunit interactions; the variant was detectable in erythrocyte precipitates (55% of alpha chains) but only 2.5% in the lysate, confirmed by isopropanol stability test and mass spectrometry, demonstrating rapid co-translational or early post-translational degradation. Isopropanol stability test, mass spectrometry of precipitate and lysate fractions Hemoglobin Medium 28696843
2017 The HBA1 insertion variant Hb Bakersfield [HBA1:c.151_152insGGAGCC, inserting Arg-Ser between α49 and α51] produces a stable haemoglobin with increased oxygen affinity, as demonstrated by oxygen affinity testing and isopropanol stability assay in the heterozygous carrier. HPLC quantification, isopropanol stability test, oxygen affinity testing Hemoglobin Low 28532286
2015 A novel HBA1 variant Hb G-Waimanalo [A1] [α64(E13)Asp→Asn; HBA1:c.193G>A] was found to have decreased oxygen affinity compared to normal haemoglobin, as shown by direct oxygen dissociation curve analysis. Cation exchange HPLC, DNA sequencing, oxygen affinity measurement (oxygen dissociation curve) Hemoglobin Low 26291968
2019 Homozygosity for Hb Charlieu [α106(G13)Leu→Pro; HBA1:c.320T>C] causes a hyperunstable alpha-globin protein: qPCR confirmed normal αCharlieu mRNA levels, but the protein was undetectable by standard electrophoretic methods in erythrocytes and only detectable by mass spectrometry in erythroid progenitors, indicating the mutation causes post-translational protein instability (likely during RBC maturation). New methylene blue-stained aggregates in reticulocytes suggested that incorporation of αCharlieu destabilizes haemoglobin tetramers. qPCR (mRNA stability), capillary electrophoresis, reverse-phase electrophoresis, isoelectric focusing, mass spectrometry of erythroid progenitors, heat stability test, reticulocyte inclusion body staining Hemoglobin Medium 31190578
2025 Two novel HBA1 mutations in the 3'UTR (c.*119_120insT and c.*150C>A) cause alpha-thalassaemia; in silico structural modelling predicted disruption of RNA secondary structure, impaired binding of RNA-stabilising proteins HuR and AUF1, altered microRNA (miR-16-5p) binding sites, and interference with polyadenylation signals, collectively resulting in mRNA instability and reduced alpha-globin synthesis. Direct Sanger sequencing, in silico RNA secondary structure prediction, in silico protein–RNA interaction modelling (HuR, AUF1), in silico miRNA binding prediction Annals of hematology Low 41388082
2025 A novel HBA1 missense mutation (NM_000558.5:c.85G>C, p.Ala29Pro) designated Hb Tozeur was predicted by in silico structural modelling (Swiss-PdbViewer, DynaMut) to destabilize the alpha-globin protein, reduce thermodynamic stability, and alter flexibility near the heme-binding region, consistent with its clinical presentation as alpha-thalassaemia. In silico pathogenicity prediction (PolyPhen-2, SIFT, MutationTaster), structural homology modelling, DynaMut stability prediction Annals of hematology Low 40484869

Source papers

Stage 0 corpus · 120 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1976 3' non-coding region sequences in eukaryotic messenger RNA. Nature 2913 822353
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
1966 Abnormal human haemoglobins. Separation and characterization of the alpha and beta chains by chromatography, and the determination of two new variants, hb Chesapeak and hb J (Bangkok). Journal of molecular biology 1562 5967288
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1983 Structure of human oxyhaemoglobin at 2.1 A resolution. Journal of molecular biology 505 6644819
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2003 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nature biotechnology 485 12665801
1989 A review of the molecular genetics of the human alpha-globin gene cluster. Blood 479 2649166
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2010 Genome-wide association study of hematological and biochemical traits in a Japanese population. Nature genetics 406 20139978
1975 Three-dimensional fourier synthesis of human deoxyhaemoglobin at 2-5 A resolution: refinement of the atomic model. Journal of molecular biology 387 1177322
2008 Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c. Blood 363 18694998
2017 Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis. PLoS medicine 320 28898252
1961 [The structure of normal adult human hemoglobins]. Hoppe-Seyler's Zeitschrift fur physiologische Chemie 316 13872627
1980 Sites of nonenzymatic glycosylation of human hemoglobin A. The Journal of biological chemistry 303 7358733
1982 The structure of the human zeta-globin gene and a closely linked, nearly identical pseudogene. Cell 290 6297773
2012 Endothelial cell expression of haemoglobin α regulates nitric oxide signalling. Nature 272 23123858
2016 The cell proliferation antigen Ki-67 organises heterochromatin. eLife 265 26949251
2002 High and low hemoglobin glycation phenotypes in type 1 diabetes: a challenge for interpretation of glycemic control. Journal of diabetes and its complications 259 12200073
2011 A directed protein interaction network for investigating intracellular signal transduction. Science signaling 258 21900206
1990 A truncated human chromosome 16 associated with alpha thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n. Nature 258 1975428
2022 EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3. Molecular cancer 257 35031058
1992 A human recombinant haemoglobin designed for use as a blood substitute. Nature 249 1552945
2004 An investigation into the human serum "interactome". Electrophoresis 247 15174051
1992 A third quaternary structure of human hemoglobin A at 1.7-A resolution. The Journal of biological chemistry 247 1512262
2006 1.25 A resolution crystal structures of human haemoglobin in the oxy, deoxy and carbonmonoxy forms. Journal of molecular biology 235 16765986
2010 Pitfalls in the use of HbA₁(c) as a diagnostic test: the ethnic conundrum. Nature reviews. Endocrinology 106 20680035
2010 HbA₁(c) and mean blood glucose show stronger associations with cardiovascular disease risk factors than do postprandial glycaemia or glucose variability in persons with diabetes: the A1C-Derived Average Glucose (ADAG) study. Diabetologia 67 20886203
2003 Schizosaccharomyces pombe cells lacking the Ran-binding protein Hba1 show a multidrug resistance phenotype due to constitutive nuclear accumulation of Pap1. The Journal of biological chemistry 34 12896976
2016 In-Silico Computing of the Most Deleterious nsSNPs in HBA1 Gene. PloS one 33 26824843
2010 The TCF7L2 diabetes risk variant is associated with HbA₁(C) levels: a genome-wide association meta-analysis. Annals of human genetics 27 20849430
1987 The value of HbA1 and fructosamine in predicting impaired glucose tolerance--an alternative to OGTT to detect diabetes mellitus or gestational diabetes. Annals of clinical biochemistry 27 3662394
2006 Determining the cause of patchwork HBA1 and HBA2 genes: recurrent gene conversion or crossing over fixation events. Haematologica 21 16503550
1985 Apolipoproteins and lipoproteins in children with type I diabetes: relation to glycosylated serum protein and HbA1. Acta paediatrica Scandinavica 17 4090971
2010 Two new alpha1-globin gene point mutations: Hb Nedlands (HBA1:c.86C>T) [alpha28(B9)Ala-->Val] and Hb Queens Park (HBA1:c.98T>A) [alpha32(B13)Met-->Lys]. Hemoglobin 16 20353346
2018 Hb Adana (HBA2 or HBA1: c.179G > A) and alpha thalassemia: Genotype-phenotype correlation. Pediatric blood & cancer 15 29749692
2013 Clinical presentation and molecular identification of four uncommon alpha globin variants in Thailand. Initiation codon mutation of α2-globin Gene (HBA2:c.1delA), donor splice site mutation of α1-globin gene (IVSI-1, HBA1:c.95 + 1G>A), hemoglobin Queens Park/Chao Pra Ya (HBA1:c.98T>A) and hemoglobin Westmead (HBA2:c.369C>G). Acta haematologica 15 24081251
2022 Decreased expression of HBA1 and HBB genes in acute myeloid leukemia patients and their inhibitory effects on growth of K562 cells. Hematology (Amsterdam, Netherlands) 13 36117408
2014 A case series of α-thalassemia intermedia due to compound heterozygosity for Hb Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] with other α-thalassemias in Malay families. Hemoglobin 12 24829075
2014 Screening and diagnosis of Hb Quong Sze [HBA2: c.377T > C (or HBA1)] in a prenatal control program for thalassemia. Hemoglobin 11 24826791
2022 Evaluation of in silico predictors on short nucleotide variants in HBA1, HBA2, and HBB associated with haemoglobinopathies. eLife 10 36453528
1985 Comparison of three different assay procedures for the determination of HbA1 with special attention to the influence of pre-HbA1c, temperature and haemoglobin concentration. Annals of clinical biochemistry 9 4026185
2022 Importance of Sequencing HBA1, HBA2 and HBB Genes to Confirm the Diagnosis of High Oxygen Affinity Hemoglobin. Genes 8 35052472
2020 Identification of a new hemoglobin variant Hb Liuzhou [HBA1:C.182A→G] by MALDI-TOF mass spectrometry during HbA1c measurement. Scandinavian journal of clinical and laboratory investigation 7 32597240
2014 Homozygosity for HBA1: c.179G > A: Hb Adana in an infant. Hemoglobin 7 25342395
1984 Haemoglobinopathies, malaria, and other interferences with HBA1 assessment. Diabete & metabolisme 7 6530003
2017 Hb Amsterdam-A1 [α32(B13)Met→Ile; HBA1: c.99G>A]: A Hyperunstable Variant Due to a New Mutation on the α1 Gene. Hemoglobin 6 28696843
2014 A combination of two novel alpha globin variants Hb Bridlington (HBA1) and Hb Taybe (HBA2) resulting in severe hemolysis, pulmonary hypertension, and death. Hematology (Amsterdam, Netherlands) 6 24716903
2020 Fifteen Cases of Hb J-Meerut: The Rare Association with Hb E and/or HBA1: c.-24C>G (or HBA2) Variants. Hemoglobin 5 32924661
2018 Hb Nouakchott [α114(GH2)Pro→Leu; HBA1: c.344C>T], A Second and Third Case Described in Two Unrelated Dutch Families. Hemoglobin 5 29405838
2018 Falsely high HbA1c value due to a novel α1-globin gene mutation: Hb shantou [α127(H10)Lys > Glu; HBA1: c.382 A > G]. Scandinavian journal of clinical and laboratory investigation 5 30375897
2017 Hb Bakersfield (HBA1: c.151_152insGGAGCC): The Insertion of Arg-His Between Codons 49 and 50 of the α1-Globin Chain Leads to Increased Oxygen Affinity. Hemoglobin 5 28532286
2016 FIRST IDENTIFICATION OF HEMOGLOBIN LANSINGRAMATHIBODI [α87(F8)His → Gln; CAC>CAG (HBA1: c.264C>G)] IN A THAI FAMILY WITH SPURIOUS HYPOXEMIA. The Southeast Asian journal of tropical medicine and public health 5 29620819
2015 Development and validation of a high throughput, closed tube method for the determination of haemoglobin alpha gene (HBA1 and HBA2) numbers by gene ratio assay copy enumeration-PCR (GRACE-PCR). BMC medical genetics 5 26683685
2014 Novel point mutation of the α2-globin gene (HBA2) and a rare 2.4 kb deletion of the α1-globin gene (HBA1), identified in two chinese patients with Hb H disease. Hemoglobin 5 24826793
2012 Identification of a new HBA1 gene mutation (HBA1:c.301-2A>T) in cis with Hb Riccarton (HBA1:c.154G>A) [α51(CE9)Gly→Ser]. Hemoglobin 5 22738642
2024 A clinical update of compound heterozygosity for hemoglobin Hekinan II [a27(B8)Glu-Asp; HBA1: c.84G>T] variant in China. Laboratory medicine 4 38581097
2022 Effects of Senegal haplotype (Xmn1-rs7412844), alpha-thalassemia (3.7kb HBA1/HBA2 deletion), NPRL3-rs11248850 and BCL11A-rs4671393 variants on sickle cell nephropathy. International journal of biochemistry and molecular biology 4 35611053
2020 Pedigree Analysis of Nonhomologous Sequence Recombination of HBA1 and HBA2 Genes. Hemoglobin 4 32811243
2018 Hb Hubei [α114(GH2)Pro→His, HBA1: c.344C>A]: A Novel Hemoglobin Variant of the α1-Globin Chain. Hemoglobin 4 30277418
2015 Description of Three New α Variants and Four New β Variants: Hb Montluel [α110(G17)Ala → Val; HBA1: c.332C > T], Hb Cap d'Agde [α131(H14)Ser → Cys; HBA2: c.395C > G] and Hb Corsica [α100(G7)Leu → Pro; HBA1: 302T > C]; Hb Nîmes [β104(G6)Arg → Gly; HBB: c.313A > G], Hb Saint Marcellin [β112(G14)Cys → Gly; HBB: c.337T > G], Hb Saint Chamond [β80(EF4)Asn → 0; HBB: c.241_243delAAC] and Hb Dompierre [β29(B11)Gly → Arg; HBB: c.88G > C]. Hemoglobin 4 26100115
2014 Variable genotype-phenotype correlations in patients with a rare nondeletional α-thalassemia; Hb Pak Num Po (HBA1: c.396_397insT). Journal of pediatric hematology/oncology 4 24136020
2014 Hb Memphis [HBA2: c.70G>C (or HBA1)] in a Turkish child: a case report and comparison to Hb Q-Thailand (HBA1: c.223G>C). Hemoglobin 4 24432778
2018 Complex Interaction of Hb Q-Thailand (HBA1: c.223G>C) with β-Thalassemia/Hb E (HBB: c.79G>A) Disease. Hemoglobin 3 29484903
2015 A novel hemoglobin variant found on the α1 chain: Hb KSVGH (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys). Hemoglobin 3 25669128
2015 Multi-allele DNA biosensor for the rapid genotyping of 'nondeletion' alpha thalassaemia mutations in HBA1 and HBA2 genes by means of multiplex primer extension reaction. Clinica chimica acta; international journal of clinical chemistry 3 25892676
2015 Screening non-deletion α-thalassaemia mutations in the HBA1 and HBA2 genes by high-resolution melting analysis. Clinical chemistry and laboratory medicine 3 26035111
2015 Identification of Mutations Causing Aberrant Termination and Deficient Splice Donor Site on the HBA1 Gene. Hemoglobin 3 26531168
1983 Glycosylated haemoglobin (HbA1) for diabetic control in Africans; preliminary findings with the microcolumn technique. Tropical and geographical medicine 3 6670118
2025 Revealing silent alpha-thalassemia: characterization of novel HBA1 deletion and missense mutation in Tunisian families. Annals of hematology 2 40484869
2024 Interactions of electrophoretically silent hemoglobin Hekinan II [HBA1:c.84G>T] with various forms of α-thalassemias and other hemoglobinopathies: novel insights into the molecular and hematological characteristics and genetic origins. The Libyan journal of medicine 2 39312720
2022 A New Hemoglobin Variant, Hb Natal (HBA1: c.423C>A), Found in a Greek Family. Hemoglobin 2 36000508
2021 A Novel Mutation at HBA1: c.349G>T Causing α-Thalassemia in a Chinese Family. Hemoglobin 2 34082638
2021 Eleven Cases of Hb J-Paris-I [HBA2: c.38C>A (or HBA1)]: A Stable α Chain Variant Elutes in the P3 Window on High-Performance Liquid Chromatography. Hemoglobin 2 34784833
2020 α-Thalassemia Intermedia Results from Interactions of Unstable Hb Prato [α31(B12)Arg→Ser (HBA1 or HBA2 c.96G>T or C)] with the α-Thalassemia-1 [- -SEA (Southeast Asian)] Deletion in Thailand. Hemoglobin 2 32727229
2019 Compound Heterozygosity for an Unstable Novel Hemoglobin Variant, Hb Dongguan [α52(E1)Ser→Cys (TCT>TGT); HBA1: c.158C>G], and the - -SEA (Southeast Asian) α-Thalassemia Deletion. Hemoglobin 2 31650882
2017 Hematological Characterizations and Molecular Diagnostic Aspects of Hb Wiangpapao [α44(CE2)Pro→Ser (α1), CCG>TCG; HBA1: c.133C>T], a New α-Globin Variant Found in a Pregnant Thai Woman. Hemoglobin 2 28641501
2013 Coinheritance of a novel mutation on the HBA1 gene: c.187delG (p.W62fsX66) [codon 62 (-G) (α1)] with the α212 patchwork allele and Hb S [β6(A3)Glu→Val, GAG>GTG; HBB: c.20A>T]. Hemoglobin 2 23806041
2013 Hb Fulton-Georgia [α20(B1)His→Pro; HBA1: c.62A>C]: a new α-globin variant coinherited with α-thalassemia-2 (3.7 kb deletion) and Hb SC disease. Hemoglobin 2 24006930
1983 Genetic control of the immune response to human adult haemoglobin (HbA1) and sickle cell haemoglobin (HbS). Journal of immunogenetics 2 6404988
2025 Comprehensive Hematological and molecular Characterization of hemoglobin Hekinan [α27(B8)Glu→Asp(α1), HBA1:c.84G > T] in a Large Thai cohort. Hematology (Amsterdam, Netherlands) 1 39878036
2023 Hb Nivaria: A New Hemoglobin Variant with a Shortened α-Globin Chain [α139(HC1)Lys→Stop; HBA1: c.418A>T]. Hemoglobin 1 36847654
2021 Hb Maruchi [α165 (E14) Ala>Pro; HBA1: c.196G>C]: A new thalassemia hemoglobinopathy related to the alpha1 globin gene. Clinical biochemistry 1 33675809
2021 Eight Cases of Hb Winnipeg [HBA2: c.226G>T (or HBA1)]: A Detailed Study. Hemoglobin 1 34496687
2020 Association of Hb Shenyang [α26(B7)Ala→Glu, GCG>GAG, HBA2: c.80C>A (or HBA1)] with Several Types of α-Thalassemia in Thailand. Hemoglobin 1 33023349
2019 A Homozygous Mutation on the HBA1 Gene Coding for Hb Charlieu (HBA1: c.320T>C) Together with β-Thalassemia Trait Results in Severe Hemolytic Anemia. Hemoglobin 1 31190578
2016 Symptomatic Erythrocytosis Due to Homozygosity for Hb Luton [HBA2: c.269A>T (or HBA1)] and α-Thalassemia: A Clinical Update. Hemoglobin 1 26852627
2016 Novel Mutation of the Translation Initiation Codon of the α1-Globin Gene (ATG>AAG or HBA1:c.2T>A). Hemoglobin 1 27821014
2015 Hb G-Waimanalo [A1] or α64(E13)Asp→Asn (α1) (HBA1: c.193G>A) Observed in a Bulgarian Family. Hemoglobin 1 26212674
2015 Hb G-Waimanalo [A1] [α64(E13)Asp→Asn; HBA1: c.193 G > A] with Decreased Oxygen Affinity. Hemoglobin 1 26291968
2013 Codon 62 (GTG>GCG, Val→Ala) (α1) (HBA1: c.188T>C) causing nondeletional α-thalassemia in a Chinese family. Hemoglobin 1 23470151
2013 Description of the phenotypes of 63 heterozygous, homozygous and compound heterozygous patients carrying the Hb Groene Hart [α119(H2)Pro→Ser; HBA1: c.358C>T] variant. Hemoglobin 1 24111644
2026 A Novel Alpha1-Variant (HBA1:c.-35T>C) Complexed With the First Reported Hb M-Saskatoon in the Chinese Population. Molecular genetics & genomic medicine 0 41498364
2025 Rare Hemoglobin Variant Hb Handsworth (HBA1:c.55 G>C): Leads to False Positive Diagnosis of Hb S. Clinical laboratory 0 40497600
2025 Novel Double Heterozygosity: HBA2: c.70G > A (Hb Chad)/HBB: c.-78A > G and Novel Compound Heterozygosity: HBA2: c.70G > A (Hb Chad)/HBA1: c.84G > T (Hb Hekinan II) Hemoglobinopathy in a Chinese Family. Hemoglobin 0 40685501
2025 Molecular Diagnosis and Stability Testing of Hemoglobin Phnom Penh [HBA1: C.353_355dup (p.Phe118_Thr119insIle)] - The First Northern Thai Case. Hemoglobin 0 40887457
2025 Genetic Analysis and Clinical Relevance of :c.305T > C (Leu > Pro): A Novel Variant Linked to α-Thalassemia. Hemoglobin 0 41236345
2025 Importance of the 3'UTR region in globin synthesis: identification of two novel HBA1 mutations causing α-Thalassemia. Annals of hematology 0 41388082
2024 Severe Transfusion-Dependent Thalassemia in Compound Heterozygote Palestinian Siblings with Two α-Globin Gene Defects, Hb Taybe D HBA1: C.119_121delCCA Mutation and HBA2: C.*94A > G Mutation. Hemoglobin 0 38626925
2024 A New α1-Globin Variant, Hb Ormylia [HBA1:c.63C > G; p.His21Gln]. Report of Eleven Cases in Northern Greece. Hemoglobin 0 38632978
2024 Hb Guigang [α90 (FG2)Lys→Asn; HBA1:c.273G˃T]: a Novel α-Globin Chain Variant. Clinical laboratory 0 38965958
2024 Alpha-Thalassemia Caused by ααIVSI-1(AGGT> AGAT) (HBA1: c.95 + 1G > A) Mutation and its Combinations with Other Forms of Thalassemia or Hemoglobinopathy in Northern Thailand. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 0 40687478
2023 Severe Hb H Disease Caused by Hb Zürich-Albisrieden (HBA1: c.178G>C): Another Case Report. Hemoglobin 0 36815319
2023 Hb Qinzhou [α1 78 (EF7) Asn→Lys (AAC>AAA); HBA1:c.237C>A]: a Novel α-Globin Variant in a Chinese Family. Clinical laboratory 0 37145073
2023 A New Hemoglobin Variant: Hb Tangshan [HBA1: c.239C > T, CD79(GCG > GTG)(Ala > Val)] Detected by MALDI-TOF MS. Hemoglobin 0 37909121
2021 Hb Waikato [α127(H10)Lys→Gln; HBA1: c.382A>C]: A Novel High Oxygen Affinity Variant. Hemoglobin 0 33478272
2021 Identification of Two Novel Thalassemia Variants, HBA1: c.263delA and HBA2: c.376dupC, in Chinese Individuals. Hemoglobin 0 33792465
2021 Report of Two Novel Thalassemia Variants, HBB: c.181delG and HBA1: c.121_126delAAGACC, in Chinese Individuals. Hemoglobin 0 33792470
2021 Hb Jishui [HBA1: c.225C>G, Codon 74 (GAC>GAG), Asp→Glu]: A Novel α Chain Hemoglobin Variant Detected During Hb A1c Measurement. Hemoglobin 0 34802367
2020 Hb broomhill [α1 or α2 114(GH2) pro > ala;HBA1 or HBA2:c.343C > G]: a rare Hb variant found in a diabetic chinese individual. Scandinavian journal of clinical and laboratory investigation 0 32783538
2019 Hb Milano [α109(G16)Leu→Pro (CTG>CCG); HBA1: c.329T>C]: A Novel Variant on the α1-Globin Gene in an Italian Family. Hemoglobin 0 31084368
2018 Novel nonsense mutation in the α1-globin gene [HBA1:C.49A>T] is responsible for non-deletion α-thalassemia. Clinical biochemistry 0 30595158
2018 First Report of Association Between Rare α-Thalassemia Mutation (HBA1: c.298A>T) and Hb Fontainebleau (HBA2: c.64G>C). Indian journal of clinical biochemistry : IJCB 0 30728682
2001 Chromosomal mapping of calmodulin 1 (CALM1) and alpha-globin 1 genes (HBA1) in the bovine. Animal biotechnology 0 11808628
1990 Clinical usefulness of serum fructosamine and HbA1 as markers for metabolic control in patients with changing insulin regimens. Diabetes research (Edinburgh, Scotland) 0 2134209
1990 [The significance of HbA1 determination in children]. Padiatrie und Grenzgebiete 0 2188196