PARS2

Chr 1AR

prolyl-tRNA synthetase 2, mitochondrial

This protein is a mitochondrial aminoacyl-tRNA synthetase that catalyzes the attachment of proline to its corresponding tRNA molecule, essential for mitochondrial protein synthesis. Mutations cause developmental and epileptic encephalopathy 75, which follows an autosomal recessive inheritance pattern. The condition involves early-onset seizures and developmental impairment affecting the central nervous system.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.881 OMIM phenotype
Clinical SummaryPARS2
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

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
0.88LOEUF
pLI 0.004
Z-score 1.88
OE 0.45 (0.240.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.29Z-score
OE missense 0.95 (0.861.05)
266 obs / 279.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.45 (0.240.88)
00.351.4
Missense OE0.95 (0.861.05)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 6 / 13.4Missense obs/exp: 266 / 279.5Syn Z: 0.78
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePARS2-related developmental and epileptic encephalopathy with or without cardiomyopathyOTHERAR

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

DN
0.75top 25%
GOF
0.4973th %ile
LOF
0.2775th %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

PARS2 · 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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