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 |
Context nucleotide sequence:
GAGCACCGTGCTGACCTCCAAATAC [C/T] GTTAAGCTGGAGCCTCGGTGGCCAT (Strand: +)
Protein sequence:
MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYC
Also known as:
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.
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: | 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
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
- 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
- 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