GNE myopathy is an autosomal recessive distal myopathy caused by pathogenic variants in <i>GNE</i> gene, which encodes a protein having two enzymatic activities, UDP-GlcNAc 2-epimerase and ManNAc kinase on sialic acid biosynthesis. We have identified a variant, c.620A>T (p.D207V), with which majority of the homozygotes are healthy, while compound heterozygotes develop myopathy. Notwithstanding, the identified three affected homozygotes had no additional variation in the <i>GNE</i> gene nor in genes in sialic acid biosynthetic pathway, while their sialylation was mildly, but certainly decreased. We hypothesized this discrepancy can be explainable by partial failure of GNE oligomerization. The constructed full-length GNE structure by Alphafold2 indicated that Asp207 locates midway between each domain and near subunit interface, but not in catalytic site. The mutant was predicted to cause no severe changes in a whole structure, though the change of polarity of the mutated residue and failure of oligomerization are hypothesized to affect intramolecular and inter-subunit ManNAc transfer between domains. Since this pathogenic variant is in non-catalytic site and did not cause drastic structural changes, ManNAc production has possibility to be pharmacologically recovered by small molecules. Here, we performed <i>in silico</i> prediction-based screening to identify the drugs that activate GNE. First, we targeted a deep narrow cavity found in the back of the allosteric site, to find small molecules that interfere with negative feedback inhibition. We then performed docking simulation of 8042 known compounds in Drugbank database to the cavity, and selected well-fitted 8 compounds. We measured the effect of the compounds on ManNAc production. However, no compounds could activate it nor repress inhibitory effect of CMP-NeuAc. In this presentation, we will discuss brand-new approach to find activators for endogenous mutated GNE protein using structural information.