title: Mutations that diminish expression of Kell surface protein and lead to the Kmod RBC phenotype.
abstract: BACKGROUND
  Kmod is an inherited rare RBC phenotype characterized by weak but detectable expression of high-incidence Kell antigens.
  
  
  METHODS
  The 19 exons and the intron-exon regions of the KEL gene from four unrelated Kmod individuals were sequenced and compared to wild-type KEL. To study the mechanisms by which the mutations result in depression of Kell antigens, mutant and wild-type Kell proteins were expressed in 293T cells and the amounts of protein present on the cell surface were determined.
  
  
  RESULTS
  The following point mutations were identified: Kmod-1, homozygous 1208G>A, S363N; Kmod-2, heterozygous, 1208G>A, S363N and 2150 A>G, Y677C; Kmod-3 (previously classified as KEL:-13), heterozygous 1106T>C, L329P and 1716G>A, W532Stop; Kmod-4, heterozygous, 2227G>A, G703R and a silent 1839C>T mutation. In transfected 293T cells, fewer G703R and L329P mutant Kell proteins were transported to the cell surface compared with wild-type Kell protein, and there was no detectable Y677C mutant Kell protein. Previously, it was shown that that S363N Kell protein was not detected on the cell surface.
  
  
  CONCLUSIONS
  Different point mutations, causing amino acid substitutions and presumably altering protein conformation, inhibit transport of the mutant Kell proteins to the cell surface. The different mutations leading to the Kmod phenotype explain why anti-Ku made by persons with the Kmod phenotype are not mutually compatible.
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10021, USA. slee@nybc.org
authors.forename: Soohee
authors.initials: S
authors.lastname: Lee
authors.forename: David C W
authors.initials: DC
authors.lastname: Russo
authors.forename: Marion E
authors.initials: ME
authors.lastname: Reid
authors.forename: Colvin M
authors.initials: CM
authors.lastname: Redman
mesh_terms: D019943:Amino Acid Substitution; D000954:Antigens, Surface / Q000235:genetics* / Q000378:metabolism*; D001692:Biological Transport; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism / Q000502:physiology*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D010641:Phenotype; D017354:Point Mutation; D014162:Transfection
chemical_list: D000954:Antigens, Surface; D001798:Blood Proteins; C041106:kell-active proteins