IthaID: 810

Context nucleotide sequence:
AGACACCATGGTGCATCTGACTCCT [G>A] AGGAGAAGTCTGCCGTTACTGCCCT (Strand: -)

Protein sequence:
MVHLTPKEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

Also known as:

Comments: The substitution of Glutamic Acid (Glu) with Lysine (Lys) at the sixth position of the beta-globin chain induces an electrostatic interaction between positively charged β6-Lys groups and negatively charged adjacent molecules, leading to the decreased solubility of HbC in red cells. Due to this, crystal formation occurs, leading to increased blood viscosity and decreased red blood cell life span. Hemoglobin C trait (HbAC) is clinically silent. Hemoglobin C disease (HbCC) is also a mild disorder, and, while most people do not have any symptoms, others may experience mild hemolytic anemia, splenomegaly, and jaundice. Co-inheritance with HbS (HbCS) may cause severe complications, including vaso-occlusion crisis.

We follow the HGVS sequence variant nomenclature and IUPAC standards.

Heterozygous records (preview in IthaPhen)

1. ITANO HA, NEEL JV, A new inherited abnormality of human hemoglobin., Proc. Natl. Acad. Sci. U.S.A. , 36(11), 613-7, 1950 PubMed
2. NEEL JV, KAPLAN E, ZUELZER WW, Further studies on hemoglobin C. I. A description of three additional families segregating for hemoglobin C and sickle cell hemoglobin., Blood , 8(8), 724-34, 1953 PubMed
3. RANNEY HM, LARSON DL, McCORMACK GH, Some clinical, biochemical and genetic observations on hemoglobin C., J. Clin. Invest. , 32(12), 1277-84, 1953 PubMed
4. HUNT JA, INGRAM VM, A terminal peptide sequence of human haemoglobin?, Nature , 184(0), 640-1, 1959 PubMed
5. SMITH EW, KREVANS JR, Clinical manifestations of hemoglobin C disorders., Bull Johns Hopkins Hosp , 104(1), 17-43, 1959 PubMed
6. BAGLIONI C, INGRAM VM, Four adult haemoglobin types in one person., Nature , 189(0), 465-7, 1961 PubMed
7. Fabry ME, Kaul DK, Raventos C, Baez S, Rieder R, Nagel RL, Some aspects of the pathophysiology of homozygous Hb CC erythrocytes., J. Clin. Invest. , 67(5), 1284-91, 1981 PubMed
8. Boehm CD, Dowling CE, Antonarakis SE, Honig GR, Kazazian HH, Evidence supporting a single origin of the beta(C)-globin gene in blacks., Am. J. Hum. Genet. , 37(4), 771-7, 1985 PubMed
9. Fischel-Ghodsian N, Hirsch PC, Bohlman MC, Rapid detection of the hemoglobin C mutation by allele-specific polymerase chain reaction., Am. J. Hum. Genet. , 47(6), 1023-4, 1990 PubMed
10. Trabuchet G, Elion J, Dunda O, Lapouméroulie C, Ducrocq R, Nadifi S, Zohoun I, Chaventre A, Carnevale P, Nagel RL, Nucleotide sequence evidence of the unicentric origin of the beta C mutation in Africa., Hum. Genet. , 87(5), 597-601, 1991 PubMed
11. Agarwal A, Guindo A, Cissoko Y, Taylor JG, Coulibaly D, Koné A, Kayentao K, Djimde A, Plowe CV, Doumbo O, Wellems TE, Diallo D, Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S., Blood , 96(7), 2358-63, 2000 PubMed
12. Modiano D, Luoni G, Sirima BS, Simporé J, Verra F, Konaté A, Rastrelli E, Olivieri A, Calissano C, Paganotti GM, D'Urbano L, Sanou I, Sawadogo A, Modiano G, Coluzzi M, Haemoglobin C protects against clinical Plasmodium falciparum malaria., Nature , 414(6861), 305-8, 2001 PubMed
13. Rihet P, Flori L, Tall F, Traore AS, Fumoux F, Hemoglobin C is associated with reduced Plasmodium falciparum parasitemia and low risk of mild malaria attack., Hum. Mol. Genet. , 13(1), 1-6, 2004 PubMed
14. Modiano D, Bancone G, Ciminelli BM, Pompei F, Blot I, Simporé J, Modiano G, Haemoglobin S and haemoglobin C: 'quick but costly' versus 'slow but gratis' genetic adaptations to Plasmodium falciparum malaria., Hum. Mol. Genet. , 17(6), 789-99, 2008 PubMed
15. Gouagna LC, Bancone G, Yao F, Yameogo B, Dabiré KR, Costantini C, Simporé J, Ouedraogo JB, Modiano D, Genetic variation in human HBB is associated with Plasmodium falciparum transmission., Nat. Genet. , 42(4), 328-31, 2010 PubMed
16. Cyrklaff M, Sanchez CP, Kilian N, Bisseye C, Simpore J, Frischknecht F, Lanzer M, Hemoglobins S and C interfere with actin remodeling in Plasmodium falciparum-infected erythrocytes., Science , 334(6060), 1283-6, 2011 PubMed