LARS1

Chr 5AR

leucyl-tRNA synthetase 1

Also known as: HSPC192, ILFS1, LARS, LEURS, LEUS, LFIS, LRS, PIG44

NCBI Gene: 51520ENSG00000133706UniProt: Q9P2J5

This gene encodes a cytosolic leucine-tRNA synthetase, a member of the class I aminoacyl-tRNA synthetase family. The encoded enzyme catalyzes the ATP-dependent ligation of L-leucine to tRNA(Leu). It is found in the cytoplasm as part of a multisynthetase complex and interacts with the arginine tRNA synthetase through its C-terminal domain. A mutation in this gene was found in affected individuals with infantile liver failure syndrome 1. Alternatively spliced transcript variants of this gene have been observed. [provided by RefSeq, Dec 2015]

Primary Disease Associations & Inheritance

?Infantile liver failure syndrome 1MIM #615438
AR
367
ClinVar variants
16
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— LARS1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 134 VUS of 367 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.53LOEUF
pLI 0.000
Z-score 4.83
OE 0.38 (0.28–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.48Z-score
OE missense 0.83 (0.77–0.90)
514 obs / 617.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.38 (0.28–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.77–0.90)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 27 / 70.8Missense obs/exp: 514 / 617.9Syn Z: 0.53

ClinVar Variant Classifications

367 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic7
VUS134
Likely Benign132
Benign77
Conflicting8
9
Pathogenic
7
Likely Pathogenic
134
VUS
132
Likely Benign
77
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
6
0
9
Likely Pathogenic
3
2
2
0
7
VUS
1
125
7
1
134
Likely Benign
0
2
87
43
132
Benign
0
1
76
0
77
Conflicting
—8
Total613117844367

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

View in ClinVar →

Protein Context — Lollipop Plot

LARS1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Infantile liver failure syndrome 1

MIM #615438

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination.
Yin Y et al.·Adv Sci (Weinh)
2024
Restoration of N-glycosylation via leucine-activated leucyl-tRNA synthetase 1 overcomes chemoresistance in intrahepatic cholangiocarcinoma.
Liu H et al.·J Hepatol
2026
MRI in LARS1 deficiency-Spectrum, patterns, and correlation with acute neurological deterioration.
Hammann N et al.·J Inherit Metab Dis
2024
Deep phenotyping of MARS1 (interstitial lung and liver disease) and LARS1 (infantile liver failure syndrome 1) recessive multisystemic disease using Human Phenotype Ontology annotation: Overlap and differences. Case report and review of literature.
La Fay C et al.·Eur J Med Genet
2021Review
Early onset and liver failure indicating poor prognosis of infant liver failure syndrome type 1.
Li SY et al.·Orphanet J Rare Dis
2024
Phenotype and Long-Term Outcome in Recurrent Paediatric Acute Liver Failure: Systematic Review and Individual Participant Data Analysis.
Sutton H et al.·Liver Int
2025Review
Biallelic variants in LARS1 induce steatosis in developing zebrafish liver via enhanced autophagy.
Inoue M et al.·Orphanet J Rare Dis
2024Functional
Lactylation in diabetes mellitus and its complications: mechanisms of action and therapeutic potential - recent advances.
Zhou M et al.·Front Endocrinol (Lausanne)
2025Review
Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants in LARS1.
Lenz D et al.·Genet Med
2020
Study of Acute Liver Failure in Children Using Next Generation Sequencing Technology.
Hegarty R et al.·J Pediatr
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Identification of amino acid metabolism-related gene Leucyl-tRNA synthetase 1 (LARS1) as a potential prognostic and therapeutic target in hepatocellular carcinoma.
Shi Q et al.·Front Oncol
2025🔓 Open Access
LARS1 knockdown suppresses the biological activities of thyroid cancer cells by stimulating autophagy.
Jin C et al.·Tissue Cell
2025
LARS1 lactylation inhibits autophagy by activating mTORC1 to promote podocytes injury in diabetic kidney disease.
Fan Z et al.·Cell Signal
2025
LARS1 Promotes Tubular Epithelial Cells Epithelial Mesenchymal Transition in Chronic Kidney Disease by Inhibiting Lipophagy.
Guo R et al.·Inflammation
2025🔓 Open Access
Rg3 inhibits hypoxia-induced tumor exosomes from boosting pancreatic cancer vasculogenic mimicry through the HIF-1α/LARS1/mTOR axis.
Zhao T et al.·Phytomedicine
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools