IthaID: 1230
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Benign / Likely Benign |
|---|---|---|---|
| Common Name: | CD 124 CCA>CGA [Pro>Arg] | HGVS Name: | HBB:c.374C>G |
| Hb Name: | Hb Khartoum | Protein Info: | β 124(H2) Pro>Arg |
Context nucleotide sequence:
CATCACTTTGGCAAAGAATTCACCC [A/C/G/T] ACCAGTGCAGGCTGCCTATCAGAAA (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTRPVQAAYQKVVAGVANALAHKYH
Also known as:
Comments: The loss of Pro 124 alters the configuration of the β chain and interferes with α1β1 dimerization, resulting in the accumulation of unstable free globin subunits. However, no intracellular inclusion bodies or free α-chains in hemolysates could be demonstrated. Reported to be slightly less heat stable than a normal control. Hb Khartoum alone does not cause clinical or haematological abnormalities, while co-inheritance with a γ+-thalassaemia mutation presented with severe neonatal hemolytic anemia in a Sudanese family. As Pro 124 (H2) of the β-chain interacts with α-chain residues Glu 30 (B11), Arg 31 (B12) and Leu 34 (B15) in the α1β1 interface, the presence of Arg at the position β124 is expected, yet not shown, to affect the oxygen binding properties of the haemoglobin. Detected by isoelectrofocusing, HPLC, and peptide mapping.
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: | Unstable |
| Oxygen Affinity: | N/A |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 71948 |
| Size: | 1 bp |
| Located at: | β |
| Specific Location: | Exon 3 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | Sudanese |
| Molecular mechanism: | Altered α1β1 interface |
| Inheritance: | Recessive |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Clegg JB, Weatherall DJ, Boon WH, Mustafa D, Two new haemoglobin variants involving proline substitutions., Nature, 222(5191), 379-80, 1969
- Bayoumi RA, Dawodu A, Qureshi MM, Al-Khider A, Fitzgerald P, Riou J, Fisher CA, Fitches A, Old JM, The association of Hb Khartoum [beta124(H2)Pro-->Arg] with gamma+-thalassemia is responsible for hemolytic disease in the newborn of a Sudanese family., Hemoglobin, 23(1), 33-45, 1999
- Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013