FARS2

Chr 6AR

phenylalanyl-tRNA synthetase 2, mitochondrial

Also known as: COXPD14, FARS1, HSPC320, PheRS, SPG77, mtPheRS

The protein charges mitochondrial tRNA with phenylalanine, which is essential for mitochondrial protein synthesis. Autosomal recessive mutations cause combined oxidative phosphorylation deficiency 14 (Alpers encephalopathy) and spastic paraplegia 77 through impaired mitochondrial translation. The pathogenic mechanism involves defective aminoacylation of mitochondrial tRNA(Phe), leading to respiratory chain dysfunction.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.152 OMIM phenotypes
Clinical SummaryFARS2
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

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
1.15LOEUF
pLI 0.000
Z-score 1.04
OE 0.75 (0.501.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.68Z-score
OE missense 0.88 (0.790.98)
232 obs / 263.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.75 (0.501.15)
00.351.4
Missense OE0.88 (0.790.98)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 15 / 20.0Missense obs/exp: 232 / 263.1Syn Z: -0.50
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFARS2-related neurometabolic disorderLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6258th %ile
GOF
0.4283th %ile
LOF
0.3843th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FARS2 · 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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