IthaID: 1052
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Variant of Uncertain Significance |
|---|---|---|---|
| Common Name: | CD 75 CTG>CGG | HGVS Name: | HBB:c.227T>G |
| Hb Name: | Hb Pasadena | Protein Info: | β 75(E19) Leu>Arg |
Context nucleotide sequence:
GTGCTCGGTGCCTTTAGTGATGGCC [T>G] GGCTCACCTGGACAACCTCAAGGGC (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGRAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Also known as:
Comments: The hydrophobic leucyl residue at β75(E19) is the second residue from the C-terminus of the E helix. It makes neither heme nor interchain contacts, but is part of the interlocking residues that link helices E and A (with Val β11(A8) and Trp β15(A12)). Its substitution by the relatively large, hydrophylic arginyl residue leaves a gap that allows water penetration in the protein interior, loosening the tertiary structure. Also, the arginyl side chain would protrude at the surface so that its guanidium group could be hydrated. The bulky volume of the arginyl residue at βE19 may also disturb the adjacent phenylalanyl residue in the helix at βE15, which ordinarily makes contact with the distal side of the heme in the normal β chain. These changes could account for the instability, increased autoxidation rate and altered oxygen binding properties of Hb Pasadena.
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: | Increased Oxygen Affinity |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 70951 |
| 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: | French |
| Molecular mechanism: | N/A |
| Inheritance: | Recessive |
| DNA Sequence Determined: | No |
In silico pathogenicity prediction
Publications / Origin
- Johnson CS, Moyes D, Schroeder WA, Shelton JB, Shelton JR, Beutler E, Hemoglobin Pasadena,alpha 2 beta 275(E19)Leu leads to Arg. Identification by high performance liquid chromatography of a new unstable variant with increased oxygen affinity., Biochimica et biophysica acta, 623(2), 360-7, 1980
- Shih TB, Jones RT, Johnson CS, Functional properties of Hb Pasadena, alpha 2 beta 2 75(E 19) Leu replaced by Arg., Hemoglobin, 6(2), 153-67, 1982