IthaID: 669
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 92 CGG>CTG [Arg>Leu] | HGVS Name: | HBA2:c.278G>T |
| Hb Name: | Hb Chesapeake | Protein Info: | α2 92(FG4) Arg>Leu |
Context nucleotide sequence:
AGCGACCTGCACGCGCACAAGCTTC [G/T] GGTGGACCCGGTCAACTTCAAGGTG (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLLVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR
Also known as:
Comments: Hb Chesapeake displays high oxygen affinity and presents with erythrocytosis in heterozygous individuals. It affects the amino acids involved in the α1-β2 chains’ contact, and impairs the normal rotational transition from the deoxygenated low-affinity state to the oxygenated high-affinity state, tending to lock the hemoglobin into the high-affinity relaxed state. It has been described in
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: | Increased Oxygen Affinity |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 16 |
|---|---|
| Locus: | NG_000006.1 |
| Locus Location: | 34170 |
| 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: | German, Irish, Japanese, French |
| Molecular mechanism: | N/A |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Clegg JB, Naughton MA, Weatherball DJ, Abnormal human haemoglobins. Separation and characterization of the alpha and beta chains by chromatography, and the determination of two new variants, hb Chesapeak and hb J (Bangkok)., Journal of molecular biology, 19(1), 91-108, 1966
- Charache S, Weatherall DJ, Clegg JB, Polycythemia associated with a hemoglobinopathy., J. Clin. Invest. , 45(6), 813-22, 1966
- Greer J, Three-dimensional structure of abnormal human haemoglobins Chesapeake and J Capetown., J. Mol. Biol. , 62(1), 241-9, 1971
- Gibson QH, Nagel RL, Allosteric transition and ligand binding in hemoglobin Chesapeake., J. Biol. Chem. , 249(22), 7255-9, 1974
- Imai K, Hemoglobin Chesapeake (92 alpha, arginine--leucine). Precise measurements and analyses of oxygen equilibrium., J. Biol. Chem. , 249(23), 7607-12, 1974
- Jones CM, Charache S, Hathaway PJ, The effect of hemoglobin F-Chesapeake (alpha 2 92 Arg. leads to Leu gamma 2) on fetal oxygen affinity and erythropoiesis., Pediatr. Res. , 13(7), 851-3, 1979
- Harano T, Harano K, Shibata S, Ueda S, Mori H, Imai K, Hb Chesapeake [alpha 92 (FG 4) Arg replaced by Leu] and Hb J Cape Town [alpha 92 (FG 4) Arg leads to Gln] first discovered in Japanese., Hemoglobin , 7(5), 461-5, 1983
- Granel B, Serratrice J, Badens C, Lena-Russo D, Disdier P, Weiller PJ, A new case of hemoglobin Chesapeake., Haematologica , 86(1), 105, 2001