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

Sequence Viewer

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Publications / Origin

  1. 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 PubMed
  2. 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 PubMed
  3. 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 PubMed
Created on 2010-06-16 16:13:16, Last reviewed on 2023-06-09 10:35:41 (Show full history)

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