YARS1

Chr 1ADAR

tyrosyl-tRNA synthetase 1

Also known as: CMTDIC, IMNEPD2, TYRRS, YARS, YRS, YTS

The protein catalyzes the aminoacylation of tRNA with tyrosine and also functions as a cytokine when cleaved into N-terminal and C-terminal fragments. Mutations cause autosomal dominant Charcot-Marie-Tooth disease intermediate type C and autosomal recessive infantile-onset multisystem neurologic, endocrine, and pancreatic disease. The pathogenic mechanism likely involves disruption of protein synthesis through impaired tRNA charging and potential loss of cytokine signaling functions.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismAD/ARLOEUF 0.622 OMIM phenotypes
Clinical SummaryYARS1
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Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.62LOEUF
pLI 0.001
Z-score 3.05
OE 0.37 (0.230.62)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.14Z-score
OE missense 0.81 (0.730.90)
228 obs / 281.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.230.62)
00.351.4
Missense OE0.81 (0.730.90)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 10 / 27.2Missense obs/exp: 228 / 281.7Syn Z: -0.85
DN
0.6161th %ile
GOF
0.6151th %ile
LOF
0.3550th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

YARS1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗