IthaID: 418
Names and Sequences
Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
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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 |
Context nucleotide sequence:
CACCGTGCTGACCTCCAAATACCGT [A/C/G/T] AAGCTGGAGCCTCGGTAGCCGTTCC (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYRQ
Also known as:
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.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
Hemoglobinopathy Group: | Thalassaemia and Structural Haemoglobinopathy |
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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 |
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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) |
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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
A/A | Date | Curator(s) | Comments |
---|---|---|---|
1 | 2010-06-16 16:13:15 | The IthaGenes Curation Team | Created |
2 | 2013-10-15 17:00:14 | The IthaGenes Curation Team | Reviewed. |
3 | 2016-11-15 11:55:29 | The IthaGenes Curation Team | Reviewed. |
4 | 2019-05-07 09:25:17 | The IthaGenes Curation Team | Reviewed. Mutation comment added. |
5 | 2022-11-10 14:48:29 | The IthaGenes Curation Team | Reviewed. Link added. |
6 | 2023-05-19 10:21:39 | The IthaGenes Curation Team | Reviewed. Comment updated. |