Fig. 1.

Unstudied, high-frequency variants of ALDH2 have been extracted from the ExAC database (A). Sequence analysis from human samples showing examples of the Latino ALDH2*4 (P92T) and ALDH2*6 (V304M) variants. (B) All mutations identified in the Exome Aggregation Consortium (ExAC) database are shown on a linearized map of the ALDH2 protein structure. (C) Previously uncharacterized mutations in ALDH2 were identified using the ExAC database. Those variants with allele frequency percentages greater than 0.1% in a given ethnic population are shown in Table S1, along with the previously studied mutant E504K. Mutation numbering refers to the amino acid sequence of the mature protein with the 17-amino acid mitochondrial targeting sequence. Color code assignments are used consistently in the reporting of this work. Ethnicity assignments were made based off of available information in the ExAC database and might not represent all affected populations. (D) The mutated residues are shown with their respective color codes on the crystal structure (PDB: 1O05) of the ALDH2 monomer (top) and tetramer (bottom, inset).