IthaID: 698
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | N/A |
|---|---|---|---|
| Common Name: | CD 103 CAC>CGC [His>Arg] | HGVS Name: | HBA1:c.311A>G | HBA2:c.311A>G |
| Hb Name: | Hb Contaldo | Protein Info: | α2 or α1 103(G10) His>Arg |
| Also known as: |
We follow the
HGVS sequence variant nomenclature
and
IUPAC standards.
Context nucleotide sequence:
CTCTTCTCTGCACAGCTCCTAAGCC [A/G/T] CTGCCTGCTGGTGACCCTGGCCGCC (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSRCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR
Comments: Replacement of histidine residue at position α103 in the G helix (G10) by a charged arginine residue, which disrturbs contact with the β chain residue Asn 108 (G10) across the α1β1 interface. Interference with α1β1 dimerization results in the accumulation of free globin subunits. It also destabilizes free α chains by disrupting binding to the chaperone AHSP. Unstable in isopropanol and heat denaturation tests. Discovered as a de novo mutation in a heterozygous proband from North Italy with moderate hemolytic anaemia (severe microcytosis and hypochromia, anisocytosis, isochromic and polychromatic cells, poikilocytosis, and Heinz bodies). The haematological abnormalities could be accentuated by the presence of an additionnal α-thalassemia variant (inferred, not confirmed).
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | α-chain variant |
| Allele Phenotype: | N/A |
| Stability: | Unstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | Haemolytic anaemia [HP:0001878] |
Location
| Chromosome: | 16 |
|---|---|
| Locus: | NG_000006.1 |
| Locus Location: | 34345 or 38156 |
| Size: | 1 bp or 1 bp |
| Located at: | α1 or α2 |
| Specific Location: | Exon 3 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | Italian |
| Molecular mechanism: | Altered α1β1 interface |
| Inheritance: | Recessive |
| DNA Sequence Determined: | No |
In silico pathogenicity prediction
Publications / Origin
- Sciarratta GV, Ivaldi G, Molaro GL, Sansone G, Salkie ML, Wilson JB, Reese AL, Huisman TH, The characterization of hemoglobin Manitoba or alpha (2)102(G9)Ser----Arg beta 2 and hemoglobin Contaldo or alpha (2)103(G10)His----Arg beta 2 by high performance liquid chromatography., Hemoglobin , 8(2), 169-81, 1984
- Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013