Ask about this productRelated genes to: YARS2 antibody
- Gene:
- YARS2 NIH gene
- Name:
- tyrosyl-tRNA synthetase 2
- Previous symbol:
- -
- Synonyms:
- FLJ13995, CGI-04, mt-TyrRS
- Chromosome:
- 12p11.21
- Locus Type:
- gene with protein product
- Date approved:
- 2005-06-28
- Date modifiied:
- 2015-12-04
Related products to: YARS2 antibody
Related articles to: YARS2 antibody
- MLASA syndrome is a rare mitochondrial disorder that presents in three distinct genetic forms: MLASA1, MLASA2, and MLASA3; MLASA1 is the most common form. The clinical features include mitochondrial myopathy, lactic acidosis, and sideroblastic anemia. Although presence of other features is not uncommon, its association with long QT (LQT) syndrome has not been described before. In addition, while MLASA syndrome has been reported from several countries worldwide, we present the first patient with MLASA1 syndrome from the Kingdom of Saudi Arabia in this case report. The 10-year-old girl with history of poor health since infancy and recurrent hospital admissions for infections and blood transfusions was referred to our hospital for allogeneic bone marrow transplantation. Early in her childhood, she was diagnosed with symptomatic LQT syndrome and, at a later age, with sideroblastic anemia. Whole-exome sequencing (WES) revealed homozygous mutations in the gene and heterozygous mutations in the gene. The WES test of the parents was negative, and there was no family history suggestive of a similar diagnosis. Therefore, our patient has most probably developed the syndrome as a result of a sporadic mutation; however, the possibility of sex cell germline mosaicism cannot be excluded. Heterozygous gene mutation is associated with the development of type 1 LQT syndrome. Detection of the MLASA syndrome and proper intervention at an early age are crucial for successful management. Associated LQT syndrome should always be anticipated. Despite the presence of a fully tissue-matched sibling, the parents of our patient declined the option of allogeneic bone marrow transplantation due to potential severe cardiac and liver complications. - Source: PubMed
Publication date: 2026/01/19
Abbas Adil AbdelhamedMonagel Dania AdelAlthubaiti Sami Jowaiber - Leber hereditary optic neuropathy (LHON) is a paradigm for mitochondrial retinopathy. Here, we investigate the mechanism underlying the interaction between nuclear modifier and mtDNA mutation(s) that manifests optic neuropathy in vivo to develop an effective therapeutic approach for this disease using mouse models bearing LHON-linked Yars2 or COI mutation alone and double mutations. Yars2 alters mitochondrial translation and assembly and activities of complex I, III, and IV, while COI reduces complex IV activity. However, a single Yars2 or COI mutation causes mild declines in ATP production and yields relatively mild degeneration of retinal ganglion cells (RGCs). Notably, the synergy between COI and Yars2 mutations aggravates mitochondrial dysfunction and oxidative stress. Interestingly, COI mainly promotes apoptosis, and Yars2 contributes to ferroptosis. The combination of two mutations accelerates the degeneration of RGCs and photoreceptors. Strikingly, AAV-mediated Yars2 expression in the mouse retina carrying both Yars2 and COI mutations corrects the defective translation and ferroptosis arising from the Yars2 mutation and remarkably improves mitochondrial function and causes morphologic and functional recovery of RGCs and photoreceptors. These findings provide mechanistic insights into the pathophysiology of LHON arising from nuclear modifiers and mtDNA mutation(s) and potential therapeutic strategies for LHON and other mitochondrial diseases. - Source: PubMed
Publication date: 2026/02/08
Li HuiyingAi ChengJin XiaofenWang JingYu JunGao YinlongWallace Douglas CGuan Min-Xin - Myopathy, Lactic Acidosis, and Sideroblastic Anemia type 2 (MLASA2) is a rare mitochondrial disorder caused by pathogenic variants (PVs) in the 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 first 3D structural map of all reported Mt-TyrRS PVs, identifying nine spatial hotspots across catalytic, anticodon-binding, and tRNA-binding domains. An integrated framework combining structural density, clinical severity, in silico predictions, and ΔΔG destabilization classified three clusters as High-risk, three as Medium-risk, and three as Low-risk. Among them, cluster 3, a large catalytic hotspot encompassing 44 residues and including nearly half of all MLASA2 cases, showed the strongest pathogenic convergence. This clinical-structural integration provides new insights for a better comprehension of MLASA2, enhancing variant interpretation and improving diagnostic and prognostic precision. - Source: PubMed
Publication date: 2026/01/16
Villafan-Bernal José RafaelMartínez-Hernández AngélicaGarcía-Ortiz HumbertoContreras-Cubas CeciliaGuerrero-Contreras IsraelFrías-Cabrera José LuisCenteno-Cruz FedericoMorales Rivera Monserrat IvonneHernández Jhonatan RosasCarnevale AlessandraBarajas-Olmos FranciscoOrozco Lorena - - Source: PubMed
Publication date: 2026/01/23
Franco GiovanniBruno Lucia PiaAlviano Antonio MariaVankann LuciaBrümmendorf TimGuerra FabiolaVendemini FrancescaFaverio PaolaL'Imperio VincenzoCazzaniga GiovanniLuppi FabrizioBiondi AndreaBalduzzi AdrianaBeier FabianSaettini Francesco - MLASA2 is a rare mitochondrial disorder with limited geographic representation in published medical literature. Here, we report the first confirmed case of MLASA2 in a Latin American 16-year-old male harboring a homozygous pathogenic variant p.(Asp311Glu) in the gene. The patient presented with sideroblastic anemia and short stature, accompanied by other skeletal dysplasia features not previously associated with MLASA2, including epiphyseal dysplasia, rib edge widening, and poorly defined vertebral structures, but without lactic acidosis. Notably, the patient did not present exercise intolerance but recently exhibited reduced muscle strength. The p.(Asp311Glu) variant, located in the anticodon-binding domain of the mitochondrial tyrosyl-tRNA synthetase (Mt-TyrRS), was consistently predicted to be pathogenic by multiple in silico tools. Molecular modeling revealed that this variant destabilizes the 'KMSKS' motif, potentially compromising tRNA recognition fidelity and aminoacylation efficiency. Analysis of runs of homozygosity (ROH) revealed significantly elevated consanguinity (ROH: 31.93%), consistent with a consanguineous mating between biological parents. This case expands the geographic distribution of MLASA2, documents previously unreported phenotypes, suggests a novel pathogenic mechanism, and demonstrates the utility of genomic approaches for diagnosing rare mitochondrial disorders in the absence of complete clinical information and family history. - Source: PubMed
Publication date: 2025/12/14
Villafán-Bernal José RafaelRosas-Hernández JhonatanGarcía-Ortiz HumbertoMartínez-Hernández AngélicaContreras-Cubas CeciliaGuerrero-Contreras IsraelLee HaneSeo Go HunCarnevale AlessandraBarajas-Olmos FranciscoOrozco Lorena