IthaID: 506
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 31 AGG>AGC [Arg>Ser] | HGVS Name: | HBA2:c.96G>C |
| Hb Name: | Hb Prato | Protein Info: | α2 31(B12) Arg>Ser |
Context nucleotide sequence:
CCCCTCACTCTGCTTCTCCCCGCAG [G/C] ATGTTCCTGTCCTTCCCCACCACCA (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALESMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR
Also known as:
Comments: Replacement of the arginine residue (charged) by serine (uncharged) at position α31 of the B-helix (B12), which lies in the α1β1 interface. The mutation weakens α31 contacts with residues of the β chain, thereby disrupting α1β1 dimerization with subsequent accumulation of free globin subunits. The mutation also destabilizes free α chains by inhibiting their binding to the chaperone AHSP. Unstable in isopropanol and heat denaturation tests. Near normal red cell indices (anisocytosis and hypochromia) and some evidence of inclusion bodies. Normal values for P50 O2, cooperativitiy and Bohr effect. Does not appear to cause clinical abnormalities. Discovered initially in two Italian families (from Tuscany and Calabria) and co-inherited with α-thalassaemia in a Taiwanese.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | α-chain variant |
| Allele Phenotype: | N/A |
| Stability: | Unstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 16 |
|---|---|
| Locus: | NG_000006.1 |
| Locus Location: | 33988 |
| Size: | 1 bp |
| Located at: | α2 |
| Specific Location: | Exon 2 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | Italian, Taiwanese |
| Molecular mechanism: | Altered α1β1 interface |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Marinucci M, Mavilio F, Massa A, Gabbianelli M, Fontanarosa PP, Camagna A, Ignesti C, Tentori L, A new abnormal human hemoglobin: Hb Prato (alpha 2 31 (B12) Arg leads to Ser beta 2)., Biochim. Biophys. Acta , 578(2), 534-40, 1979
- De Marco EV, Crescibene L, Pasqua A, Brancati C, Bria M, Qualtieri A, HB Prato [alpha 31(B12)Arg----Ser] in a Calabrian family., Hemoglobin , 16(4), 275-9, 1992
- Shih MC, Peng CT, Chang JY, Liu SC, Kuo PL, Chang JG, Hb Prato [alpha31(B12)Arg --> Ser (A2)] and alpha-thalassemia in a Taiwanese., Hemoglobin , 27(1), 45-7, 2003
- Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013