IthaID: 780
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 141 CTG>TGT [Arg>Cys] | HGVS Name: | HBA2:c.424C>T |
| Hb Name: | Hb Nunobiki | Protein Info: | α2 141(HC3) Arg>Cys |
| Also known as: |
We follow the
HGVS sequence variant nomenclature
and
IUPAC standards.
Context nucleotide sequence:
GAGCACCGTGCTGACCTCCAAATAC [C/T] GTTAAGCTGGAGCCTCGGTGGCCAT (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYC
Comments: Hb Nunobiki displays high oxygen affinity, relatively slow auto-oxidation, and normal stability in heat and isopropanol testing. It was initially detected in a 41-year-old Japanese male with borderline erythrocytosis as an α141 Arg>Cys change in either HBA1 or HBA2 gene by structural analysis. It was later detected by molecular testing in HBA2 in a Belgian woman with no Japanese background, as well as in 7 cases from four Spanish families with minimum levels of erythrocytosis [DOI: 10.4172/2157-7412.1000180]. The replacement of the last amino acid of the outer surface of the α chain C-terminal region terminal -Arginine (basic) with Cysteine (ambivalent), implies the modification of its electrical charge, and thus detection by any kind of electrophoresis system.
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: | 34458 |
| 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: | Japanese, Belgian, Spanish |
| Molecular mechanism: | N/A |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
HPLC
| ID | Hb Variant | Gene | Instrument | Method | Area (%) | Ret Time (min) | Comments | ||
|---|---|---|---|---|---|---|---|---|---|
| 220 | Hb Nunobiki | α2 | D-10 | Dual Kit Program | 5.8 | 1.44 | Heterozygous. Increased oxygen affinity leading to a mild erythrocytosis. | [PDF] | |
| 221 | Hb Nunobiki | α2 | VARIANT | β-thal Short Program | 12.8 | 1.51 | Heterozygous. Increased oxygen affinity leading to a mild erythrocytosis. | [PDF] | |
| 222 | Hb Nunobiki | α2 | VARIANT II | β-thal Short Program | 12.7 | 1.6 | Heterozygous. Increased oxygen affinity leading to a mild erythrocytosis. | [PDF] | |
| 223 | Hb Nunobiki | α2 | VARIANT II | Dual Kit Program | 6 | 1.55 | Heterozygous. Increased oxygen affinity leading to a mild erythrocytosis. | [PDF] |
In silico pathogenicity prediction
Sequence Viewer
Publications / Origin
- Shimasaki S, A new hemoglobin variant, hemoglobin Nunobiki [alpha 141 (HC3) Arg----Cys]. Notable influence of the carboxy-terminal cysteine upon various physico-chemical characteristics of hemoglobin., J. Clin. Invest. , 75(2), 695-701, 1985 PubMed
- Kazanetz EG, Leonova JY, Huisman TH, van der Dijs FP, Smit JW, Hb Nunobiki or alpha 2 141 (HC3)Arg-->Cys beta 2 in a Belgian female results from a CGT-->TGT mutation in the alpha 2-globin gene., Hemoglobin, 20(4), 443-5, 1996 PubMed
- de la Fuente-Gonzalo F, Nieto JM, Villegas A, González FA, Martínez R, Ropero P, Characterization of deletional and non-deletional alpha globin variants in a large cohort from Spain between 2009 and 2014., Ann Hematol, 98(7), 1537-1545, 2019 PubMed