IthaID: 1243
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Variant of Uncertain Significance |
|---|---|---|---|
| Common Name: | CD 128 GCT>GAT [Ala>Asp] | HGVS Name: | HBB:c.386C>A |
| Hb Name: | Hb J-Guantanamo | Protein Info: | β 128(H6) Ala>Asp |
Context nucleotide sequence:
AAAGAATTCACCCCACCAGTGCAGG [A/C/T] TGCCTATCAGAAAGTGGTGGCTGGT (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQDAYQKVVAGVANALAHKYH
Also known as:
Comments: Asp is a negatively charged group in a site normally occupied by a hydrophobic residue. As a result, the presence of Asp at the position β128 (H6) weakens the α1β1 contact between Leu residue 34 and Gly residue 35 of the α-chain. Alteration of the α1β1 interface inhibits dimer formation with subsequent accumulation of free globin subunits. Hb J-Guantanamo is slightly unstable with a high number of target cells in the peripheral blood and reduced osmotic fragility.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-chain variant |
| Allele Phenotype: | N/A |
| Stability: | Unstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | Haemolytic anaemia [HP:0001878] |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 71960 |
| Size: | 1 bp |
| Located at: | β |
| Specific Location: | Exon 3 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | Benin, Chilean, Chinese, Cuban, Japanese |
| Molecular mechanism: | Altered α1β1 interface |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Martínez G, Lima F, Colombo B, Haemoglobin J Guantanamo (alpha 2 beta 2 128 (H6) Ala replaced by Asp). A new fast unstable haemoglobin found in a Cuban family., Biochimica et biophysica acta, 491(1), 1-6, 1977
- Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013