EPRS1

Chr 1AR

glutamyl-prolyl-tRNA synthetase 1

Also known as: EARS, EPRS, GLUPRORS, HLD15, PARS, PIG32, QARS, QPRS

NCBI Gene: 2058ENSG00000136628UniProt: P07814OMIM: 138295

The protein encoded by EPRS1 is a multifunctional aminoacyl-tRNA synthetase that catalyzes the aminoacylation of glutamic acid and proline tRNA species in the cytoplasm. Mutations cause hypomyelinating leukodystrophy 15 through autosomal recessive inheritance. The pathogenic mechanism likely involves disrupted protein synthesis due to impaired tRNA charging with these essential amino acids.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.511 OMIM phenotype
Clinical Summary— EPRS1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 unique Pathogenic / Likely Pathogenic· 174 VUS of 300 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.000
Z-score 5.28
OE 0.37 (0.28–0.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.60Z-score
OE missense 0.84 (0.79–0.90)
669 obs / 795.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.28–0.51)
0≤0.351.4
Missense OE0.84 (0.79–0.90)
0≤0.61.4
Synonymous OE1.12
0≤1.21.6
LoF obs/exp: 31 / 82.9Missense obs/exp: 669 / 795.6Syn Z: -1.54
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongEPRS1-related hypomyelinating leukodystrophyLOFAR

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

DN
0.6161th %ile
GOF
0.6345th %ile
LOF
0.4037th %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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic1
VUS174
Likely Benign71
Benign3
Conflicting1
13
Pathogenic
1
Likely Pathogenic
174
VUS
71
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
6
0
13
Likely Pathogenic
0
1
0
0
1
VUS
1
163
10
0
174
Likely Benign
0
8
27
36
71
Benign
0
0
3
0
3
Conflicting
—1
Total81724636263

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

View in ClinVar →

Protein Context — Lollipop Plot

EPRS1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients