Genomic organization of the HSET locus and the possible association of HLA-linked genes with immotile cilia syndrome (ICS)

The kinesin-related protein (HSET) gene belongs to the kinesin superfamily, the members of which are involved in cellular transport processes. The HSE T gene product was previously characterized by partial cDNA sequencing. The gene is located on the short arm of human Chromosome 6 (6p21.3), at the ce ntromeric end of the major histocompatibility complex. Here, we report the genomic structure of the complete HSET gene together with its flanking loci . Sequence analysis of the 40 kilobase (kb) cosmid clone containing the HSE T gene also revealed the presence of several new genes not related to the k inesin superfamily. These include a 60S ribosomal protein L35A-like pseudog ene (rPL35A-like) on the telomeric side and a polycomblike gene (PHF1), a c opper tolerance-like gene (CUTA1) and the 5' part of the synaptic ras-GTPas e-activating protein (SynGAP) gene centromeric of HSET. In addition, a comp lete 60S ribosomal protein L12-like (rPL12L) gene in intron 3 of the HSET g ene was identified which appears to have an open reading frame. The possibl e involvement of the HSET gene and a P-tubulin gene (TUBB) in the pathogene sis of immotile cilia syndrome (ICS) was studied by screening two unrelated ICS families with microtubular defects and suspected HLA linkage for mutat ions within the HSET gene and the TUBB gene. Four single base substitutions were detected in the HSET gene and none in thp gene. On the basis of these data, a role of the HSET and TUBB products in the pathogenesis of ICS in t he two families is unlikely.