The rhg1 gene or genes lie at a co-dominant locus, necessary for resistance to all Hg types of the soybean (Glycine max (L.) Merr.) cyst nematode (Heterodera glycines). Genomic research identified nucleotide changes within a candidate gene encoding a receptor like kinase (RLK) that were capable of altering resistance to Hg types 0 (race 3). Reverse genetic approaches have failed to show this gene acts alone to confer resistance and a functional paralog has been found on linkage group A1. Evidence for activity from stable soybean transgenics is awaited. By precise genetic mapping with massive RIL and NIL populations a quantitative trait nucleotide (QTN) in the RLK at rhg1 was inferred that alters A47 to V47 in the context of H297 rather than N297. The allele differences change the structure, interacting partners and activity of the RHG1 protein. The two amino acid changes between the alleles result in 53 proteins (judged by 2 D gels), 112 metabolites (by FTICRMS) and 8 metabolites (by GCMS) to increase in abundance in roots during SCN infection in the resistant allele. A method for protein expression in E.coli was developed that allowed refolding to the normal structure as measured by circular dichroism. The refolded protein was effective in identifying interacting partners, among protein (cyclophilin) and small molecules. A molecular basis for recessive and co-dominant resistance that involves interactions among paralagous disease resistance genes that are also involved in plant development was inferred. Further analysis of the interactome during the root cells responses to SCN will lead to discoveries in cell sensing and will be used to improve methods for developing new nematode resistant soybean cultivars that do not suffer from the yield drag and low seed germination rates of existing cultivars. Ruben et al. Molec Genet & Genom 276: 320-330.