YARS2

tyrosyl-tRNA synthetase 2, the group of Aminoacyl tRNA synthetases, Class I

Basic information

Region (hg38): 12:32727490-32755897

Links

ENSG00000139131

∙ NCBI:51067 ∙ OMIM:610957 ∙ HGNC:24249 ∙ Uniprot:Q9Y2Z4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

myopathy, lactic acidosis, and sideroblastic anemia 2 (Definitive), mode of inheritance: AR
myopathy, lactic acidosis, and sideroblastic anemia 2 (Strong), mode of inheritance: AR
myopathy, lactic acidosis, and sideroblastic anemia (Supportive), mode of inheritance: AR
myopathy, lactic acidosis, and sideroblastic anemia 2 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopathy, lactic acidosis, and sideroblastic anemia 2	AR	Cardiovascular; Hematologic	Individuals may develop transfusion-dependent sideroblastic anemia in infancy; Surveillance for cardiovascular manifestations may allow early medical interventions	Cardiovascular; Hematologic; Musculoskeletal	20598274; 22504945; 24344687; 24430573

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the YARS2 gene.

not_provided (240 variants)
Inborn_genetic_diseases (64 variants)
Myopathy,_lactic_acidosis,_and_sideroblastic_anemia_2 (38 variants)
Hereditary_Sideroblastic_Anemia_with_Myopathy_and_Lactic_Acidosis (14 variants)
YARS2-related_disorder (14 variants)
not_specified (13 variants)
Myopathy,_lactic_acidosis,_and_sideroblastic_anemia (6 variants)
Mitochondrial_disease (2 variants)
Lethal_Encephalopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the YARS2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001040436.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	86 clinvar		87
missense	4 clinvar	10 clinvar	126 clinvar	8 clinvar		148
nonsense	4 clinvar	2 clinvar	1 clinvar			7
start loss						0
frameshift	10 clinvar	3 clinvar	1 clinvar			14
splice donor/acceptor (+/-2bp)			1 clinvar	1 clinvar		2
Total	18	15	130	95	0

Highest pathogenic variant AF is 0.000174081

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
YARS2	protein_coding	protein_coding	ENST00000324868	5	28413

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.00e-11	0.155	125327	1	420	125748	0.00168

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.264	247	259	0.954	0.0000130	3074
Missense in Polyphen		62	72.149	0.85934		874
Synonymous	-0.966	121	108	1.12	0.00000552	1013
Loss of Function	0.629	18	21.1	0.852	0.00000126	205

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0144	0.0144
Ashkenazi Jewish	0.00	0.00
East Asian	0.000333	0.000326
Finnish	0.00296	0.00296
European (Non-Finnish)	0.000618	0.000615
Middle Eastern	0.000333	0.000326
South Asian	0.000261	0.000261
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr- AMP and then transferred to the acceptor end of tRNA(Tyr). {ECO:0000269|PubMed:15779907, ECO:0000269|PubMed:17997975}.;
Disease: DISEASE: Myopathy with lactic acidosis and sideroblastic anemia 2 (MLASA2) [MIM:613561]: A rare oxidative phosphorylation disorder specific to skeletal muscle and bone marrow. Affected individuals manifest sideroblastic anemia, progressive lethargy, muscle weakness, and exercise intolerance associated with persistent lactic acidemia. {ECO:0000269|PubMed:20598274, ECO:0000269|PubMed:22504945}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);tRNA Aminoacylation;Translation;Metabolism of proteins;Tyrosine metabolism;tRNA charging;Mitochondrial tRNA aminoacylation (Consensus)

Recessive Scores

pRec: 0.285

Intolerance Scores

loftool: 0.846
rvis_EVS: -0.47
rvis_percentile_EVS: 23.43

Haploinsufficiency Scores

pHI: 0.109
hipred: N
hipred_score: 0.317
ghis: 0.587

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.992

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Yars2
Phenotype

Gene ontology

Biological process: translation;tRNA aminoacylation for protein translation;tRNA aminoacylation;mitochondrial tyrosyl-tRNA aminoacylation
Cellular component: mitochondrion;mitochondrial matrix;cytosol;nuclear body
Molecular function: tRNA binding;RNA binding;tyrosine-tRNA ligase activity;protein binding;ATP binding;protein homodimerization activity;tyrosine binding