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

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
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

  1. Clegg JB, Weatherall DJ, Milner PF, Haemoglobin Constant Spring--a chain termination mutant?, Nature, 234(5328), 337-40, 1971
Created on 2010-06-16 16:13:15, Last reviewed on 2023-05-19 10:21:39 (Show full history)

Disclaimer: The information on this website is provided as an information resource only and must not to be used as a substitute for professional diagnosis and treatment. The ITHANET Portal and IthaGenes are not responsible or liable for any advice, course of treatment, diagnosis or any other information, services or products that an individual obtains through this website.