Fig. 4: Examples of proteins having two disease phenotypes with mLOF scores indicating both loss-of-function and alternative mechanisms. | Nature Communications

Fig. 4: Examples of proteins having two disease phenotypes with mLOF scores indicating both loss-of-function and alternative mechanisms.

From: Prevalence of loss-of-function, gain-of-function and dominant-negative mechanisms across genetic disease phenotypes

Fig. 4

Phenotype pairs in top-ranking genes; see main text for a discussion on these and Table 4 for their phenotype definitions. Structures are predicted models from the AlphaFold database. Red and blue spheres represent missense variants associated with the LOF-like and non-LOF-like phenotypes, respectively. Regions below a pLDDT of 70 are shown in purple. a AlphaFold model of SMCHD1 (A6NHR9 [https://alphafold.ebi.ac.uk/files/AF-A6NHR9-F1-model_v1.pdb]) b AlphaFold model of KRAS (P01116 [https://alphafold.ebi.ac.uk/files/AF-P01116-F1-model_v1.pdb]). c AlphaFold model of TP53 (P04637 [https://alphafold.ebi.ac.uk/files/AF-P04637-F1-model_v1.pdb]) superimposed onto the DNA-bound TP63 complex (3USO [https://doi.org/10.2210/pdb3USO/pdb])122. d AlphaFold model of BRAF (P15056 [https://alphafold.ebi.ac.uk/files/AF-P15056-F1-model_v1.pdb]) e AlphaFold model of MTOR (P42345 [https://alphafold.ebi.ac.uk/files/AF-P42345-F1-model_v1.pdb]). f AlphaFold model of AARS1 (P49588 [https://alphafold.ebi.ac.uk/files/AF-P49588-F1-model_v1.pdb]).

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