IthaID: 1141
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 99 GAT>GAA [Asp>Glu] | HGVS Name: | HBB:c.300T>A |
| Hb Name: | Hb Coimbra | Protein Info: | β 99(G1) Asp>Glu |
Context nucleotide sequence:
TGCACTGTGACAAGCTGCACGTGGA [T>A] CCTGAGAACTTCAGGGTGAGTCTAT (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVEPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Also known as:
Comments: The position βAsp99 forms hydrogen bonds with αTyr42 and αAsn97, stabilizing the T state (low O2 affinity). This position plays an important role in the allosteric α1β2 interface. Hb Coimbra (βAsp99Glu) is characterized by the insertion of a methylene group (CH2) in the α1β2 interface. This change affects the stability of the deoxy form of the Hb molecule, resulting in increased affinity for O2 and decreased heme-heme cooperativity. Carriers are clinically characterized by erythrocytocis caused by tissue hypoxia that prompts higher levels of erythropoietin and consequently intensive erythropoiesis. This Hb variant was identified in a Portuguese family by DNA analysis.
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: | N/A |
| Oxygen Affinity: | Increased Oxygen Affinity |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 71024 |
| Size: | 1 bp |
| Located at: | β |
| Specific Location: | Exon 2 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | N/A |
| Ethnic Origin: | Portuguese | Brazilian |
| Molecular mechanism: | Unstable T state |
| Inheritance: | Dominant |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Tamagnini GP, Ribeiro ML, Valente V, Ramachandran M, Wilson JB, Baysal E, Gu LH, Huisman TH, Hb Coimbra or alpha 2 beta (2)99(G1)Asp----Glu, a newly discovered highoxygen affinity variant., Hemoglobin, 15(6), 487-96, 1991
- Jorge SE, Bringas M, Petruk AA, Arrar M, Marti MA, Skaf MS, Costa FF, Capece L, Sonati MF, Estrin D, Understanding the molecular basis of the high oxygen affinity variant human hemoglobin Coimbra., Arch Biochem Biophys, 637(0), 73-78, 2018
- Santos BC, Jorge SE, de Albuquerque DM, Gilli SCO, Sonati MF, Fertrin KY, Costa FF, High erythropoietin may be associated with vascular complications in patients with secondary erythrocytosis caused by high oxygen affinity variant hemoglobin Coimbra., Blood Cells Mol Dis, 79(0), 102353, 2019