Cytokine receptor genes: structure, chromosomal location, and involvement in human disease

Haemopoietic cytokines regulate haemopoietic cell function via specific cell surface receptors. These receptors are members of a large superfamily of transmembrane proteins and are characterised by a 200 amino acid extracellular sequence encoding the ligand binding domain. Several of the genes for members of this superfamily have now been characterised at the molecular level revealing a highly conserved organisation and a number of these genes have been localised cytogenetically. The recent finding that genes for the IL-3 and GM-CSF receptor alpha chain subunits colocalise to a small region of the pseudoautosomal region and the observation that the LIF receptor locus is present in a cluster of receptor genes on chromosome 5 suggest the possibility that subsets of cytokine receptor genes may be organised into clusters. This possibility is discussed and the potential significance of cytokine receptor gene clusters is assessed. Several of the receptor genes are known to be involved in inherited disorders and there is evidence to suggest lesions in cytokine receptor genes could have a role in leukaemia. We review the gene organisation, localisation and involvement in disease for the known cytokine receptor loci. This large family of receptors is expanding with the steady discovery of new members--all of which have the potential to be involved in human disorders.