IthaID: 3758
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 126 GAC>AAC [Asp>Asn] | HGVS Name: | HBA2:c.379G>A |
| Hb Name: | Hb Tarrant | Protein Info: | α2 126(H9) Asp>Asn |
Context nucleotide sequence:
CACCCCTGCGGTGCACGCCTCCCTG [G/A] ACAAGTTCCTGGCTTCTGTGAGCAC (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLNKFLASVSTVLTSKYR
Also known as:
Comments: Asparagine at α126 (or position 9 of the H-helix) is essential for the formation of a salt bond with the carboxy-terminal arginyl residue of the other α chain when the hemoglobin is deoxygenated. Its substitution for aspartic acid destabilizes the deoxy conformation. High oxygen affinity Hb variant, ranging from ~25% (heterozygotes) to ~50% (homozygote) of total Hb. Erythrocytosis with a blood P50 value of ~15.1 mm Hg (heterozygotes) down to ~9 mm Hg (homozygote) [PMID: 7019159]. The heterozygotes have mild erythrocytosis which is considerably more severe in the homozygote. Hb Tarrant was initially detected in a few Mexican families by protein analysis (HBA2 or HBA1 gene) and was later found by molecular analysis in HBA2 in another Mexican family, as well as a Chinese family.
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: | Increased Oxygen Affinity |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 16 |
|---|---|
| Locus: | NG_000006.1 |
| Locus Location: | 34413 |
| Size: | 1 bp |
| Located at: | α2 |
| Specific Location: | Exon 3 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | Chinese, Mexican |
| Molecular mechanism: | N/A |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Moo-Penn WF, Jue DL, Johnson MH, Wilson SM, Therrell B, Schmidt RM, Hemoglobin Tarrant: alpha126(H9) Asp leads to Asn. A new hemoglobin variant in the alpha1beta1 contact region showing high oxygen affinity and reduced cooperativity., Biochim. Biophys. Acta , 490(2), 443-51, 1977
- Ibarra B, Vaca G, Cantú JM, Wilson JB, Lam H, Stallings M, Gravely ME, Huisman TH, Heterozygosity and homozygosity for the high oxygen affinity hemoglobin Tarrant or alpha 126 (H9) Asp replaced by Asn in two Mexican families., Hemoglobin , 5(4), 337-48, 1981
- Perea FJ, Zamudio G, Meillon LA, Ibarra B, The Hb Tarrant [alpha126(H9)Asp-->Asn]] mutation is localized in the alpha2-globin gene., Hemoglobin, 23(3), 295-7, 1999
- 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
- Ip KaLingRosalina,So JasonChi-Chiu,Law Man-Fai,Wong RaymondSM,Tam HoChi,Ng MargaretHL, Hb Tarrant [α126(H9)Asp→Asn; HBA2: c.379G > A (or HBA1)] in a Chinese Family as a Cause of Familial Erythrocytosis., Hemoglobin, 4(4), 260-3, 2017