FARSA

Chr 19AR

phenylalanyl-tRNA synthetase subunit alpha

Also known as: CML33, FARSL, FARSLA, FRSA, PheHA, RILDBC2

NCBI Gene: 2193ENSG00000179115UniProt: Q9Y285

Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. This gene encodes a product which is similar to the catalytic subunit of prokaryotic and Saccharomyces cerevisiae phenylalanyl-tRNA synthetases (PheRS). This gene product has been shown to be expressed in a tumor-selective and cell cycle stage- and differentiation-dependent manner, the first member of the tRNA synthetase gene family shown to exhibit this type of regulated expression [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Rajab interstitial lung disease with brain calcifications 2MIM #619013
AR
124
ClinVar variants
24
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— FARSA
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 82 VUS of 124 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 0.014
Z-score 3.54
OE 0.30 (0.18–0.53)
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.
1.22Z-score
OE missense 0.81 (0.73–0.90)
268 obs / 330.3 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.0.30 (0.18–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.73–0.90)
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.1.01
0≤1.21.6
LoF obs/exp: 9 / 29.9Missense obs/exp: 268 / 330.3Syn Z: -0.06

ClinVar Variant Classifications

124 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic3
VUS82
Likely Benign10
Benign7
Conflicting1
21
Pathogenic
3
Likely Pathogenic
82
VUS
10
Likely Benign
7
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
18
0
21
Likely Pathogenic
0
1
2
0
3
VUS
0
74
7
1
82
Likely Benign
0
2
0
8
10
Benign
0
3
2
2
7
Conflicting
—1
Total0832911124

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

View in ClinVar →

Protein Context — Lollipop Plot

FARSA · 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

?Rajab interstitial lung disease with brain calcifications 2

MIM #619013

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Phenylalanyl-tRNA synthetase deficiency caused by biallelic variants in FARSA gene and literature review.
Guo R et al.·BMC Med Genomics
2023Review
Two Novel Biallelic Variants in the FARSA Gene: The First Italian Case and a Literature Review.
Lomuscio S et al.·Genes (Basel)
2024Review
Systemic inflammatory syndrome in children with FARSA deficiency.
Charbit-Henrion F et al.·Clin Genet
2022
Fatal systemic disorder caused by biallelic variants in FARSA.
Kim SY et al.·Orphanet J Rare Dis
2022
FARSA mutations mimic phenylalanyl-tRNA synthetase deficiency caused by FARSB defects.
Krenke K et al.·Clin Genet
2019Case report
FARS1-related disorders caused by bi-allelic mutations in cytosolic phenylalanyl-tRNA synthetase genes: Look beyond the lungs!
Schuch LA et al.·Clin Genet
2021
Compound heterozygosity for loss-of-function FARSB variants in a patient with classic features of recessive aminoacyl-tRNA synthetase-related disease.
Antonellis A et al.·Hum Mutat
2018Case report
Homozygosity for FARSB mutation leads to Phe-tRNA synthetase-related disease of growth restriction, brain calcification, and interstitial lung disease.
Zadjali F et al.·Hum Mutat
2018
Characterization of fusidic acid-resistant Staphylococcus aureus isolates in the community of Casablanca (Morocco).
Elazhari M et al.·Int J Med Microbiol
2012
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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