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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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AARS1
alanyl-tRNA synthetase 1
Chromosome 16 Β· 16q22.1
NCBI Gene: 16Ensembl: ENSG00000090861.17HGNC: HGNC:20UniProt: A0A6Q8PH44
154PubMed Papers
24Diseases
0Drugs
84Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
extracellular exosomeaminoacyl-tRNA deacylase activitypositive regulation of hippo signalingpeptide lactyltransferase (ATP-dependent) activityCharcot-Marie-Tooth disease axonal type 2Ndevelopmental and epileptic encephalopathy, 29Autosomal dominant Charcot-Marie-Tooth disease type 2Nundetermined early-onset epileptic encephalopathy
✦AI Summary

AARS1 (alanyl-tRNA synthetase 1) is a dual-function enzyme with primary roles in protein synthesis and metabolic sensing. Canonically, AARS1 catalyzes aminoacylation of tRNA(Ala) through a two-step reaction: alanine activation by ATP to form Ala-AMP, followed by transfer to tRNA(Ala) 1. The enzyme also possesses editing activity to remove incorrectly charged tRNAs 1. Beyond translation, AARS1 functions as a critical lactate sensor and lactyltransferase 2. Under high lactate conditions, AARS1 catalyzes protein lactylation by activating lactate to form lactate-AMP and transferring the lactyl moiety to lysine residues in target proteins including p53, TEAD1, and YAP1 34. AARS1-mediated p53 lactylation impairs DNA binding and transcriptional activation, thereby inhibiting p53 activity and promoting tumorigenesis 4. In the Hippo pathway, AARS1 lactylation of YAP1 and TEAD1 activates the complex to promote cell proliferation 3. Recent studies reveal AARS1 lactylates histone H3K18 and STAT1 to regulate ferroptosis in diabetic nephropathy 5 and sepsis-induced acute lung injury 6. Mutations in AARS1 are associated with Charcot-Marie-Tooth disease and developmental epileptic encephalopathy, linking the enzyme to neurological disorders.

Sources cited
1
AARS1 catalyzes aminoacylation of tRNA(Ala) and possesses editing activity
PMID: 27622773
2
AARS1 mediates lysine lactylation of p53, impairing its DNA binding and transcriptional activation in tumors
PMID: 38653238
3
AARS1 lactylates YAP1 and TEAD1 to promote Hippo pathway signaling in gastric cancer
PMID: 38512451
4
AARS1 is an intracellular lactate sensor that catalyzes ATP-dependent lysine lactylation
PMID: 39322678
5
AARS1-mediated H3K18 and STAT1 lactylation regulates ferroptosis in diabetic nephropathy
PMID: 40987895
6
AARS1 enhances LPCAT2 lactylation to promote ferroptosis in sepsis-induced acute lung injury
PMID: 41057687
Disease Associationsβ“˜24
Charcot-Marie-Tooth disease axonal type 2NOpen Targets
0.75Strong
developmental and epileptic encephalopathy, 29Open Targets
0.74Strong
Autosomal dominant Charcot-Marie-Tooth disease type 2NOpen Targets
0.68Moderate
undetermined early-onset epileptic encephalopathyOpen Targets
0.63Moderate
trichothiodystrophy 8, nonphotosensitiveOpen Targets
0.57Moderate
Charcot-Marie-Tooth disease type 2Open Targets
0.56Moderate
genetic developmental and epileptic encephalopathyOpen Targets
0.54Moderate
genetic disorderOpen Targets
0.51Moderate
leukoencephalopathy, hereditary diffuse, with spheroids 2Open Targets
0.50Moderate
Charcot-Marie-Tooth diseaseOpen Targets
0.42Moderate
trichothiodystrophyOpen Targets
0.37Weak
peripheral neuropathyOpen Targets
0.27Weak
Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented gliaOpen Targets
0.26Weak
hyperlipidemiaOpen Targets
0.20Weak
metabolic diseaseOpen Targets
0.18Weak
osteoarthritis, kneeOpen Targets
0.16Weak
osteoarthritisOpen Targets
0.15Weak
Charcot-Marie-Tooth disease type 1Open Targets
0.14Weak
clubfootOpen Targets
0.12Weak
Progressive distal muscular atrophyOpen Targets
0.12Weak
Charcot-Marie-Tooth disease, axonal, type 2NUniProt
Developmental and epileptic encephalopathy 29UniProt
Leukoencephalopathy, hereditary diffuse, with spheroids 2UniProt
Trichothiodystrophy 8, non-photosensitiveUniProt
Pathogenic Variants84
NM_001605.3(AARS1):c.986G>A (p.Arg329His)Pathogenic
Charcot-Marie-Tooth disease axonal type 2N|Charcot-Marie-Tooth disease|Charcot-Marie-Tooth disease type 2|not provided|AARS1-related disorder|Hereditary neuropathy or pain disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 329
NM_001605.3(AARS1):c.997C>T (p.Arg333Ter)Pathogenic
not provided|Charcot-Marie-Tooth disease type 2
β˜…β˜…β˜†β˜†2025β†’ Residue 333
NM_001605.3(AARS1):c.37C>T (p.Arg13Ter)Pathogenic
Charcot-Marie-Tooth disease type 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 13
NM_001605.3(AARS1):c.817-1G>ALikely pathogenic
Charcot-Marie-Tooth disease type 2|Inborn genetic diseases|Developmental and epileptic encephalopathy, 29
β˜…β˜…β˜†β˜†2025
NM_001605.3(AARS1):c.985C>T (p.Arg329Cys)Likely pathogenic
not provided|Charcot-Marie-Tooth disease type 2
β˜…β˜…β˜†β˜†2025β†’ Residue 329
NM_001605.3(AARS1):c.2177+1G>APathogenic
Charcot-Marie-Tooth disease type 2|not provided|Colon adenocarcinoma
β˜…β˜…β˜†β˜†2024
NM_001605.3(AARS1):c.736C>T (p.Arg246Ter)Pathogenic
Charcot-Marie-Tooth disease type 2|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 246
NM_001605.3(AARS1):c.327_331del (p.Tyr109_Lys111delinsTer)Pathogenic
not provided|Charcot-Marie-Tooth disease type 2
β˜…β˜…β˜†β˜†2024β†’ Residue 109
NM_001605.3(AARS1):c.966T>G (p.Tyr322Ter)Pathogenic
Inborn genetic diseases|Charcot-Marie-Tooth disease type 2|Charcot-Marie-Tooth disease axonal type 2N
β˜…β˜…β˜†β˜†2023β†’ Residue 322
NM_001605.3(AARS1):c.988C>T (p.Arg330Ter)Pathogenic
Developmental and epileptic encephalopathy, 29|Charcot-Marie-Tooth disease type 2
β˜…β˜…β˜†β˜†2023β†’ Residue 330
NM_001605.3(AARS1):c.304G>C (p.Gly102Arg)Likely pathogenic
Charcot-Marie-Tooth disease type 2|Charcot-Marie-Tooth disease|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 102
NM_001605.3(AARS1):c.312G>A (p.Trp104Ter)Pathogenic
Charcot-Marie-Tooth disease type 2|Charcot-Marie-Tooth disease axonal type 2N
β˜…β˜…β˜†β˜†2023β†’ Residue 104
NM_001605.3(AARS1):c.277dup (p.Tyr93fs)Likely pathogenic
Charcot-Marie-Tooth disease axonal type 2N
β˜…β˜†β˜†β˜†2026β†’ Residue 93
NM_001605.3(AARS1):c.822_829del (p.Gly275fs)Pathogenic
Charcot-Marie-Tooth disease type 2
β˜…β˜†β˜†β˜†2026β†’ Residue 275
NM_001605.3(AARS1):c.2625_2628dup (p.Leu877fs)Pathogenic
Charcot-Marie-Tooth disease type 2
β˜…β˜†β˜†β˜†2026β†’ Residue 877
NM_001605.3(AARS1):c.1490dup (p.Tyr497Ter)Pathogenic
Charcot-Marie-Tooth disease type 2
β˜…β˜†β˜†β˜†2025β†’ Residue 497
NM_001605.3(AARS1):c.11_15del (p.Thr4fs)Pathogenic
Charcot-Marie-Tooth disease type 2
β˜…β˜†β˜†β˜†2025β†’ Residue 4
NM_001605.3(AARS1):c.1038_1039del (p.Ala347fs)Pathogenic
Charcot-Marie-Tooth disease type 2
β˜…β˜†β˜†β˜†2025β†’ Residue 347
NM_001605.3(AARS1):c.720_721del (p.Gly241fs)Pathogenic
Charcot-Marie-Tooth disease type 2
β˜…β˜†β˜†β˜†2025β†’ Residue 241
NM_001605.3(AARS1):c.672-565_760delinsCATAGTTGTCATLikely pathogenic
Charcot-Marie-Tooth disease type 2
β˜…β˜†β˜†β˜†2025
View on ClinVar β†—
Related Genes
KARS1Protein interaction100%MARS1Protein interaction100%DARS1Protein interaction100%QARS1Protein interaction100%AIMP1Protein interaction100%EEF1E1Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Liver
54%
Heart
38%
Lung
33%
Ovary
27%
Bone Marrow
11%
Gene Interaction Network
Click a node to explore
AARS1KARS1MARS1DARS1QARS1AIMP1EEF1E1
PROTEIN STRUCTURE
Preparing viewer…
PDB4XEM Β· 1.28 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.77LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.63 [0.52–0.77]
RankingsWhere AARS1 stands among ~20K protein-coding genes
  • #2,927of 20,598
    Most Researched154 Β· top quartile
  • #889of 5,498
    Most Pathogenic Variants84 Β· top quartile
  • #6,259of 17,882
    Most Constrained (LOEUF)0.77
Genes detectedAARS1
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Alanyl-tRNA synthetase, AARS1, is a lactate sensor and lactyltransferase that lactylates p53 and contributes to tumorigenesis.
PMID: 38653238
Cell Β· 2024
1.00
2
AARS1 and AARS2 sense L-lactate to regulate cGAS as global lysine lactyltransferases.
PMID: 39322678
Nature Β· 2024
0.90
3
The alanyl-tRNA synthetase AARS1 moonlights as a lactyltransferase to promote YAP signaling in gastric cancer.
PMID: 38512451
J Clin Invest Β· 2024
0.80
4
Emerging roles of lysine lactyltransferases and lactylation.
PMID: 40185947
Nat Cell Biol Β· 2025
0.70
5
AARS1 and AARS2: From Protein Synthesis to Lactylation-Driven Oncogenesis.
PMID: 41008630
Biomolecules Β· 2025
0.60