IthaID: 1281
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Variant of Uncertain Significance |
|---|---|---|---|
| Common Name: | CD 139 AAT>AAR [Asn>Lys] | HGVS Name: | HBB:c.420T>R |
| Hb Name: | Hb Hinsdale | Protein Info: | β 139(H17) Asn>Lys |
Context nucleotide sequence:
AGAAAGTGGTGGCTGGTGTGGCTAA [A/G/T] GCCCTGGCCCACAAGTATCACTAAG (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVAKALAHKYH
Also known as:
Comments: Reported by protein analysis as an asparagine [AAT] to lysine [AAG or AAA] substitution at positon β139(H17). Oxygen affinity studies show that the variant has low affinity for oxygen (p50 = 34.3 mmHg) and reduced cooperativity. Heat and isopropanol instability tests are negative. The mutation involves a site that lies in the central cavity close to the 2,3-diphosphoglycerate (2,3-DPG) binding site.
We follow the HGVS sequence variant nomenclature and IUPAC standards.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-chain variant |
| Allele Phenotype: | N/A |
| Stability: | N/A |
| Oxygen Affinity: | Decreased Oxygen Affinity |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 71994 |
| Size: | 1 bp |
| Located at: | β |
| Specific Location: | Exon 3 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | N/A |
| Ethnic Origin: | N/A |
| Molecular mechanism: | N/A |
| Inheritance: | Recessive |
| DNA Sequence Determined: | No |
In silico pathogenicity prediction
Publications / Origin
- Moo-Penn WF, Johnson MH, Jue DL, Lonser R, Hb Hinsdale [beta 139 (H17)Asn----Lys]: a variant in the central cavity showing reduced affinity for oxygen and 2,3-diphosphoglycerate., Hemoglobin, 13(5), 455-64, 1989
- Bonaventura C, Arumugam M, Cashon R, Bonaventura J, Moo-Penn WF, Chloride masks effects of opposing positive charges in Hb A and Hb Hinsdale (beta 139 Asn-->Lys) that can modulate cooperativity as well as oxygen affinity., J Mol Biol, 239(4), 561-8, 1994