Type II human complement C2 deficiency. Allele-specific amino acid substitutions (Ser super(189) arrow right Phe; Gly super(444) arrow right Arg) cause impaired C2 secretion

Type II complement protein C2 deficiency is characterized by a selective block in C2 secretion. The Type II C2 null allele (C2Q0) is linked to two major histocompatibility haplotypes (MHC) that differ from the MHC of the more common Type I C2 deficiency. To determine the molecular basis of Type II deficiency the two Type II C2Q0 genes were isolated and transfected separately into L-cells. Subsequent molecular biology, biosynthetic, and immunofluorescence studies demonstrated that C2 secretion is impaired in Type II C2 deficiency because of different missense mutations at highly conserved residues in each of the C2Q0 alleles. One is in exon 5 (nucleotide C super(566) arrow right T; Ser super(189) arrow right Phe) of the C2Q0 gene linked to the MHC haplotype A11,B35,DRw1,BFS,C4A0B1. The other is in exon 11 (G super(1930) arrow right A; Gly super(444) arrow right Arg) of the C2Q0 gene linked to the MHC haplotype A2,B5,Drw4,BFS,C4A3B1. Each mutant C2 gene product is retained early in the secretory pathway. These mutations provide models for elucidating the C2 secretory pathway.