The PSORS1 locus in the major histocompatibility complex region on chromosome 6p21.3 contains a major predisposing factor for psoriasis for which several candidate genes have been tested. The analyses are complicated by strong linkage disequilibrium in the region and the complex genetic background of psoriasis. In the search for an alternative to HLA-C we have identified a novel gene, PSORS1C3, and characterized it with regard to psoriasis. PSORS1C3 is located approximately 7 kb centromeric to POU5F1. A putative protein of 58 amino acids was predicted and expression was detected in both normal and psoriasis skin. Sequencing of the coding region revealed a total of 11 single nucleotide polymorphisms. When comparing the frequencies of PSORS1C3 variants in a case-control material in the Swedish population, three single nucleotide polymorphisms displayed significant association with psoriasis. This association appeared to be HLA-Cw*0602-dependent due to linkage disequilibrium, thus HLA-C remains the strongest associating factor in the region.