YARS2

Chr 12AR

tyrosyl-tRNA synthetase 2

Also known as: CGI-04, MLASA2, MT-TYRRS, TYRRS

NCBI Gene: 51067ENSG00000139131UniProt: Q9Y2Z4

The protein encoded by this gene is a mitochondrial aminoacyl-tRNA synthetase that catalyzes the attachment of tyrosine to tRNA(Tyr), essential for mitochondrial protein synthesis. Mutations cause myopathy with lactic acidosis and sideroblastic anemia type 2 (MLASA2), inherited in an autosomal recessive pattern. The pathogenic mechanism involves impaired mitochondrial translation due to defective tyrosyl-tRNA synthetase function.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Myopathy, lactic acidosis, and sideroblastic anemia 2MIM #613561
AR
UniProtMyopathy with lactic acidosis and sideroblastic anemia 2
1
Active trials
7
Pubs (1 yr)
85
P/LP submissions
16%
P/LP missense
1.26
LOEUF
LOF
Mechanism· G2P
Clinical Summary— YARS2
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
73 unique Pathogenic / Likely Pathogenic· 168 VUS of 412 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.26LOEUF
pLI 0.000
Z-score 0.63
OE 0.85 (0.59–1.26)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.26Z-score
OE missense 0.95 (0.86–1.06)
247 obs / 259.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.85 (0.59–1.26)
0≤0.351.4
Missense OE0.95 (0.86–1.06)
0≤0.61.4
Synonymous OE1.12
0≤1.21.6
LoF obs/exp: 18 / 21.1Missense obs/exp: 247 / 259.0Syn Z: -0.97
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveYARS2-related myopathy, lactic acidosis, and sideroblastic anemiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6259th %ile
GOF
0.5072th %ile
LOF
0.4233th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

412 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic57
Likely Pathogenic16
VUS168
Likely Benign135
Benign11
Conflicting19
57
Pathogenic
16
Likely Pathogenic
168
VUS
135
Likely Benign
11
Benign
19
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
4
40
0
57
Likely Pathogenic
3
8
5
0
16
VUS
2
136
29
1
168
Likely Benign
0
3
36
96
135
Benign
0
0
10
1
11
Conflicting
—19
Total1815112098406

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

YARS2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 3 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and genetic analysis of essential hypertension with mitochondrial tRNA(Met) 4435A>G and YARS2 mutation.
Guo M et al.·Zhejiang Da Xue Xue Bao Yi Xue Ban
2024Case report
Clinical Features, Molecular Heterogeneity, and Prognostic Implications in YARS2-Related Mitochondrial Myopathy.
Sommerville EW et al.·JAMA Neurol
2017
An animal model for mitochondrial tyrosyl-tRNA synthetase deficiency reveals links between oxidative phosphorylation and retinal function.
Jin X et al.·J Biol Chem
2021Functional
Decompensation of cardiorespiratory function and emergence of anemia during pregnancy in a case of mitochondrial myopathy, lactic acidosis, and sideroblastic anemia 2 with compound heterozygous YARS2 pathogenic variants.
Rudaks LI et al.·Am J Med Genet A
2022Case report
A kinetic model for compound heterozygous pathogenic variants in Tyrosyl-tRNA synthetase gene YARS2-Associated neonatal phenotype.
Christian T et al.·J Biol Chem
2025Functional
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients