RHOA, a member of the Rho family of small GTPases, harbors recurrent mutations in diverse cancers, but how these mutations cause their cellular effects remains poorly understood. To investigate their cellular consequences, we expressed oncogenic RHOA variants (R5Q, G17V, C16R, and A161P) in Saccharomyces cerevisiae, substituting for the essential yeast homologue RHO1. While the E40Q variant failed to complement RHO1 deletion, other mutants supported viability and enabled phenotypic characterization. All four variants conferred myriocin resistance, suggesting activation of the membrane stress response pathway, but induced no major changes in growth or caspofungin sensitivity. Using high-dimensional image analysis, we quantified 501 morphological parameters and applied principal component analysis and linear discriminant analysis to determine distinct phenotypic profiles. Gain-of-function (C16R and A161P) and loss-of-function (R5Q and G17V) mutants formed separate morphological clusters, indicating functional divergence. Our yeast model enabled systematic dissection of the functions of RHOA mutants and highlighted the utility of morphology-based approaches to characterize context-dependent mechanisms of oncogenesis.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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