IthaID: 1028

Context nucleotide sequence:
GTGAAGGCTCATGGCAAGAAAGTGC [T>C] CGGTGCCTTTAGTGATGGCCTGGCT (Strand: -)

Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVPGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

Also known as:

Comments: Unstable variant associated with severe hemolytic anemia in early childhood. It also exhibits slightly increased oxygen affinity. Although P50 values are uninformative, hemolysate exhibits a biphasic behavior at very low saturation values on the Hill plot, consistent with a high oxygen-affinity Hb exhibiting reduced cooperativity, and present in relatively small quantity [PMID: 2272836]. The insertion of a prolyl in the place of the leucyl residue at the β68 position (E12) in the middle of the Ε-helix disrupts the helix, thus affecting the tertiary structure of the β subunits. This position is next to the β67 (E11) valyl residue, which has an important hydrophobic contact with the heme moiety near the distal histine β63 (E7), thus the β68 Leu>Pro substitution may disturb the heme pocket.

We follow the HGVS sequence variant nomenclature and IUPAC standards.

Heterozygous records (preview in IthaPhen)

1. Ohba Y, Miyaji T, Matsuoka M, Sugiyama K, Suzuki T, Sugiura T, Hemoglobin Mizuho or beta 68 (E 12) leucine leads to proline, a new unstable variant associated with severe hemolytic anemia., Hemoglobin, 1(5), 467-77, 1977 PubMed
2. Labotka RJ, Vida LN, Honig GR, Hb Mizuho [beta 68(E12)Leu----Pro]. Second occurrence identified in a Caucasian child with hemolytic anemia and dense erythrocyte inclusions., Hemoglobin, 14(2), 129-36, 1990 PubMed
3. Keeling MM, Bertolone SJ, Baysal E, Gu YC, Cepreganova B, Wilson JB, Huisman TH, Hb Mizuho or alpha 2 beta (2)68(E12)Leu----Pro in a Caucasian boy with high levels of Hb F; identification by sequencing of amplified DNA., Hemoglobin, 15(6), 477-85, 1991 PubMed