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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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FARSA
phenylalanyl-tRNA synthetase subunit alpha
Chromosome 19 Β· 19p13.13
NCBI Gene: 2193Ensembl: ENSG00000179115.12HGNC: HGNC:3592UniProt: Q6IBR2
187PubMed Papers
21Diseases
0Drugs
4Pathogenic Variants
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein heterotetramerizationprotein bindingRNA bindingphenylalanyl-tRNA aminoacylationRajab interstitial lung disease with brain calcifications 2Rajab interstitial lung disease with brain calcifications 1type 2 diabetes mellitusdiabetes mellitus
✦AI Summary

FARSA encodes the alpha subunit of cytoplasmic phenylalanyl-tRNA synthetase (FARS1), which forms a heterotetramer with two FARSB beta subunits to catalyze phenylalanine-tRNA aminoacylation essential for protein biosynthesis 1. The enzyme transfers phenylalanine to tRNAPhe through magnesium-dependent ATP hydrolysis, with key residues like R475 involved in phenylalanine activation and transfer 2. Biallelic pathogenic variants in FARSA cause a multisystemic disorder characterized by interstitial lung disease, brain abnormalities with calcifications, liver dysfunction, growth restriction, and facial dysmorphism 13. Patients may also present with inflammatory profiles, autoimmunity, and systemic inflammatory syndrome 4. Disease-causing variants either disrupt heterotetramer formation or reduce enzymatic activity, with some variants showing complete loss of catalytic function 2. FARSA exhibits non-canonical functions beyond aminoacylation, including cell cycle regulation through PI3K-AKT and FOXO1-RAG1 pathways 5, and competition with Notch signaling via its N-terminal domain 6. The protein can be functionally inhibited by C9orf72-associated repeat RNA, leading to reduced phenylalanine incorporation in proteins 7. Clinically, FARSA deficiency represents a severe, often fatal condition requiring supportive care and potential JAK inhibition for inflammatory complications 4.

Sources cited
1
FARSA encodes alpha subunit of cytoplasmic phenylalanyl-tRNA synthetase forming heterotetramer with FARSB subunits, and biallelic variants cause multisystemic disorder
PMID: 37833669
2
Clinical features include interstitial lung disease, brain abnormalities, liver dysfunction, and growth restriction
PMID: 39766840
3
Key residues R475 involved in phenylalanine activation, variants can disrupt tetramer formation or reduce enzymatic activity
PMID: 35918773
4
Patients may present with systemic inflammatory syndrome and autoimmunity, treatable with JAK inhibition
PMID: 35132614
5
Non-canonical function in cell cycle regulation through PI3K-AKT and FOXO1-RAG1 pathways
PMID: 36675119
6
N-terminal domain competes with Notch signaling
PMID: 35486661
7
Functional inhibition by C9orf72 repeat RNA reduces phenylalanine incorporation in proteins
PMID: 37717009
Disease Associationsβ“˜21
Rajab interstitial lung disease with brain calcifications 2Open Targets
0.57Moderate
Rajab interstitial lung disease with brain calcifications 1Open Targets
0.37Weak
type 2 diabetes mellitusOpen Targets
0.14Weak
diabetes mellitusOpen Targets
0.11Weak
Mantle cell lymphomaOpen Targets
0.07Suggestive
colorectal carcinomaOpen Targets
0.07Suggestive
hyperinsulinism due to INSR deficiencyOpen Targets
0.04Suggestive
hyperinsulinism due to glucokinase deficiencyOpen Targets
0.04Suggestive
coronary artery disease, autosomal dominant 2Open Targets
0.04Suggestive
ossification of the posterior longitudinal ligament of the spineOpen Targets
0.03Suggestive
autosomal recessive hypophosphatemic ricketsOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.03Suggestive
exercise-induced hyperinsulinismOpen Targets
0.03Suggestive
Estrogen resistance syndromeOpen Targets
0.03Suggestive
infectionOpen Targets
0.02Suggestive
diffuse large B-cell lymphomaOpen Targets
0.02Suggestive
amyotrophic lateral sclerosisOpen Targets
0.01Suggestive
frontotemporal dementiaOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
interstitial lung diseaseOpen Targets
0.01Suggestive
Rajab interstitial lung disease with brain calcifications 2UniProt
Pathogenic Variants4
NM_004461.3(FARSA):c.1040C>T (p.Pro347Leu)Likely pathogenic
Rajab interstitial lung disease with brain calcifications 2
β˜…β˜†β˜†β˜†2022β†’ Residue 347
NM_004461.3(FARSA):c.766T>C (p.Phe256Leu)Pathogenic
Rajab interstitial lung disease with brain calcifications 2
β˜…β˜†β˜†β˜†2022β†’ Residue 256
NM_004461.3(FARSA):c.812G>A (p.Arg271His)Pathogenic
Rajab interstitial lung disease with brain calcifications 2
β˜…β˜†β˜†β˜†2022β†’ Residue 271
NM_004461.3(FARSA):c.1230C>A (p.Asn410Lys)Pathogenic
Rajab interstitial lung disease with brain calcifications 2
β˜†β˜†β˜†β˜†2020β†’ Residue 410
View on ClinVar β†—
Related Genes
EPRS1Protein interaction100%YARS1Protein interaction97%IARS1Protein interaction97%LRRC47Protein interaction94%QARS1Protein interaction89%VARS1Protein interaction84%
Tissue Expression6 tissues
Brain
100%
Liver
73%
Heart
63%
Bone Marrow
48%
Lung
46%
Ovary
46%
Gene Interaction Network
Click a node to explore
FARSAEPRS1YARS1IARS1LRRC47QARS1VARS1
PROTEIN STRUCTURE
Preparing viewer…
PDB3L4G Β· 3.30 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.78LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.59 [0.45–0.78]
RankingsWhere FARSA stands among ~20K protein-coding genes
  • #2,291of 20,598
    Most Researched187 Β· top quartile
  • #3,701of 5,498
    Most Pathogenic Variants4
  • #6,430of 17,882
    Most Constrained (LOEUF)0.78
Genes detectedFARSA
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Phenylalanyl-tRNA synthetase deficiency caused by biallelic variants in FARSA gene and literature review.
PMID: 37833669
BMC Med Genomics Β· 2023
1.00
2
Two Novel Biallelic Variants in the
PMID: 39766840
Genes (Basel) Β· 2024
0.90
3
Phenylalanine-tRNA aminoacylation is compromised by ALS/FTD-associated C9orf72 C4G2 repeat RNA.
PMID: 37717009
Nat Commun Β· 2023
0.80
4
Systemic inflammatory syndrome in children with FARSA deficiency.
PMID: 35132614
Clin Genet Β· 2022
0.70
5
FARSB Facilitates Hepatocellular Carcinoma Progression by Activating the mTORC1 Signaling Pathway.
PMID: 38069034
Int J Mol Sci Β· 2023
0.68