biostudies-literatureUnknown48(1)Villafan-Bernal JRMyopathy, Lactic Acidosis, and Sideroblastic Anemia type 2 (MLASA2) is a rare mitochondrial disorder caused by pathogenic variants (PVs) in the <i>YARS2</i> gene (which encodes the Mt-TyrRS protein. We performed a comprehensive clinical-molecular synthesis by integrating a systematic review and meta-analysis of all published MLASA2 cases with survival modeling and three-dimensional structural mapping. Across the aggregated cohort, anemia (88.6%), sideroblastic phenotype (85.7%), and lactic acidosis (82.9%) were the most prevalent phenotypes. Fifteen PVs were identified, dominated by p.(Phe52Leu) (29.4%). Survival estimates were 94.1% at 10 years, 70.7% at 30 years, and 42.4% at 50 years; cardiomyopathy and diagnosis before age 10 were associated with decreased survival. We generated the fiCurrent issues in molecular biology95https://www.ebi.ac.uk/biostudies/studies/S-EPMC12839713biostudies-literatureCorrelation of MLASA2 Clinical Phenotype and Survival with Mt-TyrRS Protein Damage: Linking Systematic Review, Meta-Analysis and 3D Hotspot Mapping.PMC12839713Garcia-Ortiz HContreras-Cubas CCarnevale AVillafan-Bernal JROrozco LGuerrero-Contreras IFrias-Cabrera JLCenteno-Cruz FMartinez-Hernandez ABarajas-Olmos FHernandez JRMorales Rivera MIfalseCorrelation of MLASA2 Clinical Phenotype and Survival with Mt-TyrRS Protein Damage: Linking Systematic Review, Meta-Analysis and 3D Hotspot Mapping.Myopathy, Lactic Acidosis, and Sideroblastic Anemia type 2 (MLASA2) is a rare mitochondrial disorder caused by pathogenic variants (PVs) in the <i>YARS2</i> gene (which encodes the Mt-TyrRS protein. We performed a comprehensive clinical-molecular synthesis by integrating a systematic review and meta-analysis of all published MLASA2 cases with survival modeling and three-dimensional structural mapping. Across the aggregated cohort, anemia (88.6%), sideroblastic phenotype (85.7%), and lactic acidosis (82.9%) were the most prevalent phenotypes. Fifteen PVs were identified, dominated by p.(Phe52Leu) (29.4%). Survival estimates were 94.1% at 10 years, 70.7% at 30 years, and 42.4% at 50 years; cardiomyopathy and diagnosis before age 10 were associated with decreased survival. We generated the fi2026-01-01T00:00:00Z2026 Jan2026-06-14T03:16:54.831Z2026-06-14T03:09:18.357ZS-EPMC128397134161492510.3390/cimb48010095