Soybean (Glycine max) is a globally important oilseed and protein crop. The world’s most damaging pathogen of soybean is soybean cyst nematode (SCN; Heterodera glycines), which routinely causes over $1 billion USD in yield losses in the US each year. Pathogen management relies on the commonly deployed QTL, Resistance to Heterodera glycines 1 (Rhg1). Rhg1 is a multi-gene locus that displays copy number variation: <3 copies in rhg1-a and >4 in rhg1-b. One of the Rhg1 genes encodes an alpha-SNAP (alpha Soluble NSF Attachment Protein) that has an unusual set of C-terminal amino acids that disrupt its ability to interact with NSF (N-ethylmaleimide Sensitive Factor), leading to degeneration and collapse of SCN feeding sites. This thesis further characterizes Rhg1 in cultivated and wild soybeans (G. max and G. soja) and molecular interactions of Rhg1-encoded alpha-SNAPs. In the work of chapter 2, we discovered that all resistant-type G. max have a chromosome 7 QTL that contains a polymorphic NSF, termed RAN07 (Rhg1-Associated NSF on Chromosome 7). Experiments in vitro demonstrated that RAN07 exhibits a higher affinity than "wild-type" NSF for interaction with resistance-type alpha-SNAPs. Subsequent in planta studies demonstrated that RAN07 is required for the viability of soybeans carrying resistance-conferring Rhg1 haplotypes. Additionally, soybean varieties with rhg1-a often carry a QTL on chromosome 11, which we found is associated with an intron retention allele that reduces the overall abundance of “wild-type” alpha-SNAP. In the work of chapter 3 we characterized rhg1-a in G. max, focusing on the discovery that rhg1-a haplotypes contain a retrotransposon in the first intron of the Rhg1 alpha-SNAP. In chapter 4, we discovered a unique haplotype of Rhg1 termed rhg1-cs in a small subgroup of G. soja, that seems to predate the split of rhg1-a and rhg1-b in G. max. Characterization of rhg1-cs revealed a low copy number and a distinct Rhg1-encoded alpha-SNAP. Interestingly, the rhg1-cs G. soja accessions chosen for further study carry resistance to problematic HG type 2.5.7 SCN populations, due to additional uncharacterized resistance mechanisms. Finally, we discovered a novel -SNAP encoded on chromosome 11 of one of the rhg1-cs G. soja varieties.