IthaID: 418
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 142 (TAA>CAA) >172aa | HGVS Name: | HBA2:c.427T>C |
| Hb Name: | Hb Constant Spring | Protein Info: | α2 142, Stop>Gln; modified C-terminal sequence: (142)Gln-Ala-Gly-Ala-Ser-Val-Ala-Val-Pro-Pro-Ala- Arg-Trp-Ala-Ser-Gln-Arg-Ala-Leu-Leu-Pro- Ser-Leu-His-Arg-Pro-Phe-Leu-Val-Phe-(172)Glu-COOH |
| Also known as: |
We follow the
HGVS sequence variant nomenclature
and
IUPAC standards.
Context nucleotide sequence:
CACCGTGCTGACCTCCAAATACCGT [A/C/G/T] AAGCTGGAGCCTCGGTAGCCGTTCC (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYRQ
Comments: Antitermination mutation (TAA>CAA) that permits ribosomes to read 31 codons into the 3'UTR. Loss of mRNA stability as a result of interfering with the pyrimidine-rich element (PRE) in the 3'UTR that provides the binding site for the α-globin poly(C)-binding protein (αCP). The heterozygote of Hb CS is mostly clinically and hematologically normal. The homozygote shows a clinical picture as thalassemia intermedia with mild anemia, jaundice and hepatosplenomegaly. Co-inheritance with an α0 allele leads to Hb H-CS disease which has a more severe phenotype (e.g. thalassemia intermedia and splenomegaly) than deletional Hb H disease.
Phenotype
| Hemoglobinopathy Group: | Thalassaemia and Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | α-thalassaemia, α-chain variant |
| Allele Phenotype: | α⁺ |
| Stability: | Unstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | Haemolytic anaemia [HP:0001878] |
Location
| Chromosome: | 16 |
|---|---|
| Locus: | NG_000006.1 |
| Locus Location: | 34461 |
| Size: | 1 bp |
| Located at: | α2 |
| Specific Location: | Exon 3 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | N/A |
| Ethnic Origin: | Southeast Asian |
| Molecular mechanism: | Elongated globin |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Frequencies
Publications / Origin
- Clegg JB, Weatherall DJ, Milner PF, Haemoglobin Constant Spring--a chain termination mutant?, Nature, 234(5328), 337-40, 1971