IthaID: 1230



Names and Sequences

Functionality: Globin gene causative mutation
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

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.

Location

Chromosome: 11
Locus: NG_000007.3
Locus Location: 71948
Size: 1 bp
Located at: β
Specific Location: Exon 3

Phenotype

Hemoglobinopathy Group: Structural Haemoglobinopathy
Hemoglobinopathy Subgroup: β-chain variant
Allele Phenotype:N/A
Stability: Unstable
Oxygen Affinity: N/A
Associated Phenotypes: N/A

Other details

Type of Mutation: Point-Mutation(Substitution)
Effect on Gene/Protein Function: Missense codons (Protein Structure)
Ethnic Origin: Sudanese
Inheritance: Recessive
DNA Sequence Determined: Yes
Detection Methods: Direct DNA sequencing

Sequence Viewer

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Publications / Origin

  1. Clegg JB, Weatherall DJ, Boon WH, Mustafa D, Two new haemoglobin variants involving proline substitutions., Nature, 222(5191), 379-80, 1969 PubMed
  2. 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 PubMed
  3. Thom CS, Dickson CF, Gell DA, Weiss MJ, Hemoglobin variants: biochemical properties and clinical correlates., Cold Spring Harb Perspect Med, 3(3), a011858, 2013 PubMed
Created on 2010-06-16 16:13:17, Last reviewed on 2019-06-20 10:37:07 (Show full history)

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