IthaID: 922
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 35 TAC>TTC [Tyr>Phe] | HGVS Name: | HBB:c.107A>T |
| Hb Name: | Hb Philly | Protein Info: | β 35(C1) Tyr>Phe |
| Also known as: |
We follow the
HGVS sequence variant nomenclature
and
IUPAC standards.
Context nucleotide sequence:
CCCACCCTTAGGCTGCTGGTGGTCT [A/T] CCCTTGGACCCAGAGGTTCTTTGAG (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVFPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Comments: The phenylalanine substitution results in the loss of the normal hydrogen bond between the tyrosine hydroxyl group β35 and the carboxyl group of aspartic acid α126 at the α1β1 contact. Alteration of the α1β1 interface favours the formation of monomers with subsequent accumulation of free globin subunits. Positive heinz body test and increased heat precipitability of the haemoglobin (Hb). No abnormal Hb detected by electrophoresis or column chromatography; phenylalanine is an almost perfect isomorphous replacement of tyrosine.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-chain variant |
| Allele Phenotype: | N/A |
| Stability: | Unstable |
| Oxygen Affinity: | Increased Oxygen Affinity |
| Associated Phenotypes: | Haemolytic anaemia [HP:0001878] |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 70831 |
| Size: | 1 bp |
| Located at: | β |
| Specific Location: | Exon 2 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | French, German, Italian |
| Molecular mechanism: | Altered α1β1 interface |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Rieder RF, Oski FA, Clegg JB, Hemoglobin Philly (beta 35 tyrosine phenylalanine): studies in the molecular pathology of hemoglobin., The Journal of clinical investigation, 48(9), 1627-42, 1969
- Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013