IthaID: 88
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 26 GAG>AAG [Glu>Lys] | HGVS Name: | HBB:c.79G>A |
| Hb Name: | HbE | Protein Info: | β 26(B8) Glu>Lys |
Context nucleotide sequence:
GGTGAACGTGGATGAAGTTGGTGGT [G>A] AGGCCCTGGGCAGGTTGGTATCAAG (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGKALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Also known as:
Comments: β codon 26 GAC>AAG [Glu>Lys] change gives rise to HbE, which also activates a cryptic splice site at the junction of exon 1 and intron 1 that causes abnormal alternative splicing and decreased transcription of functional mRNA for the HbE globin chain. Thus the Hb E mutation is both a qualitative defect (because of the amino acid substitution in the globin chain) and a quantitative defect with a β-thalassemia phenotype (because of decreased production of the mutated globin chain). Reduced Hb E synthesis explains Hb E levels in heterozygotes of between 25% to 30%. The homozygous state (Hb EE) manifests as a mild anemia with microcytes and target cells. Coihneritance with other hemoglobin variants (e.g., Hb S, forming Hb SE disease) or beta-thalassemia alleles (i.e., Hb E-β-thalassemia) creates a wide range of clinical severities. For example, Hb E-β0-thalassemia results in symptoms more severe than Hb EE and more closely resembles the severity of β-thalassemia major, requiring regular blood transfusions.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Thalassaemia and Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-thalassaemia, β-chain variant |
| Allele Phenotype: | β+ Thalassaemia |
| Stability: | Unstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: |
Haemolytic anaemia [HP:0001878] Ineffective erythropoiesis [HP:0010972] |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 70673 |
| Size: | 1 bp |
| Located at: | β |
| Specific Location: | Exon 1 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Cryptic splice site (mRNA Processing), Missense codons (Protein Structure) |
| Ethnic Origin: | SE Asian, European, Far East |
| Molecular mechanism: | N/A |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
HPLC
| ID | Hb Variant | Gene | Instrument | Method | Area (%) | Ret Time (min) | Comments | ||
|---|---|---|---|---|---|---|---|---|---|
| 564 | HbE | β | D-10 | Dual Kit Program | 41.2 | 2.78 | Association of HbE and beta-thalassaemia. | [PDF] | |
| 462 | HbE | β | D-10 | Dual Kit Program | 28.8 | 2.92 | Association of HbE and Hb Constant Spring | [PDF] | |
| 458 | HbE | β | D-10 | Dual Kit Program | 19.9 | 2.96 | HbE heterozygote with alpha-thal 1 heterozygote. | [PDF] | |
| 433 | HbE | β | D-10 | Dual Kit Program | 29.6 | 2.96 | heterozygote | [PDF] | |
| 335 | HbE | β | D-10 | Dual Kit Program | 87.3 | 2.87 | Homozygote. | [PDF] | |
| 26 | HbE | β | D-10 | Dual Kit Program | 28.9 | 3.15 | Heterozygous | [PDF] | |
| 20 | HbE | β | D-10 | HbA1c Program | 80.8 | 1.58 | Homozygous | [PDF] | |
| 18 | HbE | β | D-10 | HbA1c Program | 31.4 | 1.59 | Heterozygous | [PDF] | |
| 565 | HbE | β | VARIANT | β-thal Short Program | 47 | 3.73 | Association of HbE and beta-thalassaemia. | [PDF] | |
| 463 | HbE | β | VARIANT | β-thal Short Program | 25.3 | 3.68 | Association of HbE and Hb Constant Spring | [PDF] | |
| 459 | HbE | β | VARIANT | β-thal Short Program | 17.7 | 3.64 | HbE heterozygote with alpha-thal 1 heterozygote. | [PDF] | |
| 434 | HbE | β | VARIANT | β-thal Short Program | 25 | 3.63 | heterozygote | [PDF] | |
| 336 | HbE | β | VARIANT | β-thal Short Program | 76.4 | 3.65 | Homozygote. | [PDF] | |
| 567 | HbE | β | VARIANT II | Dual Kit Program | 42.6 | 2.885 | Association of HbE and beta-thalassaemia. | [PDF] | |
| 566 | HbE | β | VARIANT II | β-thal Short Program | 51.6 | 3.69 | Association of HbE and beta-thalassaemia. | [PDF] | |
| 465 | HbE | β | VARIANT II | Dual Kit Program | 27.2 | 2.899 | Association of HbE and Hb Constant Spring | [PDF] | |
| 464 | HbE | β | VARIANT II | β-thal Short Program | 27.1 | 3.68 | Association of HbE and Hb Constant Spring | [PDF] | |
| 461 | HbE | β | VARIANT II | Dual Kit Program | 18.9 | 2.91 | HbE heterozygote with alpha-thal 1 heterozygote. | [PDF] | |
| 460 | HbE | β | VARIANT II | β-thal Short Program | 19.4 | 3.68 | HbE heterozygote with alpha-thal 1 heterozygote. | [PDF] | |
| 436 | HbE | β | VARIANT II | Dual Kit Program | 25.9 | 2.926 | heterozygote | [PDF] | |
| 435 | HbE | β | VARIANT II | β-thal Short Program | 25.1 | 3.65 | heterozygote | [PDF] | |
| 338 | HbE | β | VARIANT II | Dual Kit Program | 69.4 | 2.9 | Homozygote. | [PDF] | |
| 337 | HbE | β | VARIANT II | β-thal Short Program | 69.5 | 3.64 | Homozygote. | [PDF] | |
| 64 | HbE | β | VARIANT II | Dual Kit Program - HbA1c | 85.9 | 1.737 | homozygote | [PDF] | |
| 39 | HbE | β | VARIANT II | Dual Kit Program | 22.4 | 2.969 | Heterozygous | [PDF] | |
| 38 | HbE | β | VARIANT II | Dual Kit Program | 27.6 | 3.65 | Heterozygous | [PDF] | |
| 37 | HbE | β | VARIANT II | β-thal Short Program | 25.1 | 3.66 | Heterozygous | [PDF] | |
| 21 | HbE | β | VARIANT II | HbA1c Program | 80.1 | 1.84 | Homozygous | [PDF] | |
| 19 | HbE | β | VARIANT II | HbA1c Program | 30.3 | 1.86 | Heterozygous | [PDF] |
In silico pathogenicity prediction
Frequencies
Publications / Origin
- Flatz G, Pik C, Sringam S, Haemoglobin E and beta-thalassaemia: their distribution in Thailand., Annals of human genetics, 29(2), 151-70, 1965
- Fairbanks VF, Oliveros R, Brandabur JH, Willis RR, Fiester RF, Homozygous hemoglobin E mimics beta-thalassemia minor without anemia or hemolysis: hematologic, functional, and biosynthetic studies of first North American cases., American journal of hematology, 8(1), 109-21, 1980
- Orkin SH, Kazazian HH, Antonarakis SE, Ostrer H, Goff SC, Sexton JP, Abnormal RNA processing due to the exon mutation of beta E-globin gene., Nature, 300(5894), 768-9, 1982
- Kazazian HH, Waber PG, Boehm CD, Lee JI, Antonarakis SE, Fairbanks VF, Hemoglobin E in Europeans: further evidence for multiple origins of the beta E-globin gene., American journal of human genetics, 36(1), 212-7, 1984