IthaID: 473
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Variant of Uncertain Significance |
|---|---|---|---|
| Common Name: | CD 19 GCG>GAG [Ala>Glu] | HGVS Name: | HBA2:c.59C>A |
| Hb Name: | Hb J-Tashikuergan | Protein Info: | α2 19(AB1) Ala>Glu |
Context nucleotide sequence:
AAGGCCGCCTGGGGTAAGGTCGGCG [C/A] GCACGCTGGCGAGTATGGTGCGGAG (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGEHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR
Also known as:
Comments: Initially reported in three unrelated fmilies of the Tajike ethnic group and identified by peptide mapping and amino acid analysis as a Ala > Glu change in the 19th position of the α-chain [PMID: 6548207]. This same amino acid change was reported in the Silk Road region of NW China [PMID: 2265836]. Detected by Sanger sequencing in the HBA2 gene and found to co-elute with HbA1c [PMID: 33315479]. Residue α19 (AB) is in the external and non-helical segment of the α-chain and is not involved in either haem or interchain contacts. The Ala>Glu change at this residue is therefore not expected to be associated with haemoglobin instability or to affect haem binding or oxygen dissociation.
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: | N/A |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 16 |
|---|---|
| Locus: | NG_000006.1 |
| Locus Location: | 33834 |
| Size: | 1 bp |
| Located at: | α2 |
| Specific Location: | Exon 1 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | Tajiks, Chinese |
| Molecular mechanism: | N/A |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Li HJ, Liu DX, Liu ZG, Li P, Li L, Chen J, Hou SZ, A new fast-moving hemoglobin variant, Hb J-Tashikuergan alpha 19(AB1) Ala----Glu., Hemoglobin , 8(4), 391-5, 1984
- Li HJ, Zhao XN, Qin F, Li HW, Li L, He XJ, Chang XS, Li ZM, Liang KX, Xing FL, Abnormal hemoglobins in the Silk Road region of China., Hum. Genet. , 86(2), 231-5, 1990
- Henderson SJ, Timbs AT, McCarthy J, Gallienne AE, Proven M, Rugless MJ, Lopez H, Eglinton J, Dziedzic D, Beardsall M, Khalil MS, Old JM, Ten Years of Routine α- and β-Globin Gene Sequencing in UK Hemoglobinopathy Referrals Reveals 60 Novel Mutations., Hemoglobin , 40(2), 75-84, 2016
- Xu J, Zhong Z, Deng Y, Unexpected HbA results in the presence of three rare hemoglobin variants., Scand J Clin Lab Invest, 81(1), 59-64, 2021