DNA sequencing using the SOLiD technique identified a C to A transversion at position 1187 of the Chst4 transcript. Two transcripts of the Chst4 gene are displayed on Ensembl. The mutated nucleotide causes a glutamine to lysine substitution at amino acid 365 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

The Chst4 gene encodes a 388 amino acid protein that is a single pass type II membrane protein localized to the Golgi, and is known as carbohydrate sulfotransferase 4 (CHST4). CHST4 catalyzes the transfer of sulfate to position 6 of non-reducing N-acetylglucosamine (GlcNAc) residues within mucin-associated glycans that ultimately serve as L-selectin ligands. L-selectin ligands are present in high endothelial cells (HEVs) and play a central role in lymphocyte homing at sites of inflammation. CHST4 participates in the biosynthesis of L-selectin ligand sialyl 6-sulfo Lewis X on L-selectin counter receptors CD43, GlyCAM-1 and MAdCAM-1, and is also involved in the biosynthesis of L-selectin ligand recognized by MECA-79 antibody. CHST4 plays a central role in lymphocyte trafficking during chronic inflammation, and has a catalytic preference for core 2-branched mucin-type O-glycans. Its substrate specificity may be influenced by its subcellular location (Uniprot Q9R1I1). Mice homozygous for disruptions in this gene do not accumulate lymphocytes in peripheral lymph nodes to as great an extent as normal. The animals are phenotypically normal otherwise.

 

The Q365K change is predicted to be benign by the PolyPhen program.