IthaID: 1180
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Variant of Uncertain Significance |
|---|---|---|---|
| Common Name: | CD 111 GTC>TTC [Val>Phe] | HGVS Name: | HBB:c.334G>T |
| Hb Name: | Hb Peterborough | Protein Info: | β 111(G13) Val>Phe |
Context nucleotide sequence:
CCCACAGCTCCTGGGCAACGTGCTG [C/G/T] TCTGTGTGCTGGCCCATCACTTTGG (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLFCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Also known as:
Comments: Described as an unstable haemoglobin (Hb) with reduced oxygen affinity in a family heterozygous for Hb A/Hb Lepore. Alteration of the α1β1 interface, favouring the formation of monomers with subsequent accumulation of free globin subunits. The bulkier residue of phenylalanine at position G13 can be accomodated in the α1β1 interface by displacing the side chain of glutamine β127 (H5) in the deoxy-form of haemoglobin. This is not possible in the oxy-form of haemoglobin. Hence, Phe substitution favours the deoxy-form, causing Hb Peterborough to have a low oxygen affinity.
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: | Decreased Oxygen Affinity |
| Associated Phenotypes: | Haemolytic anaemia [HP:0001878] |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 71908 |
| 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: | Italian |
| Molecular mechanism: | Altered α1β1 interface |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- King MA, Wiltshire BG, Lehmann H, Morimoto H, An unstable haemoglobin with reduced oxygen affinity: haemoglobin Peterborough, 3 (GI3) Valine lead to Phenylalanine, its interaction with normal haemoglobin and with haemoglobin Lepore., British journal of haematology, 22(2), 125-34, 1972
- Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013