EPRS1

glutamyl-prolyl-tRNA synthetase 1, the group of Aminoacyl tRNA synthetases, Class I|Aminoacyl tRNA synthetases, Class II

Basic information

Region (hg38): 1:219968600-220046530

Previous symbols: [ "QPRS", "QARS", "EPRS" ]

Links

ENSG00000136628

∙ NCBI:2058 ∙ OMIM:138295 ∙ HGNC:3418 ∙ Uniprot:P07814 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

leukodystrophy, hypomyelinating, 15 (Strong), mode of inheritance: AR
leukodystrophy, hypomyelinating, 15 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, hypomyelinating, 15	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Neurologic; Ophthalmologic	29576217

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPRS1 gene.

not_provided (303 variants)
Inborn_genetic_diseases (157 variants)
Leukodystrophy,_hypomyelinating,_15 (29 variants)
EPRS1-related_disorder (29 variants)
not_specified (2 variants)
Global_developmental_delay (1 variants)
Intellectual_disability (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPRS1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004446.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				74 clinvar	8 clinvar	82
missense	5 clinvar	2 clinvar	236 clinvar	19 clinvar	7 clinvar	269
nonsense	7 clinvar	1 clinvar				8
start loss						0
frameshift	3 clinvar					3
splice donor/acceptor (+/-2bp)		1 clinvar	1 clinvar			2
Total	15	4	237	93	15

Highest pathogenic variant AF is 0.00000805535

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPRS1	protein_coding	protein_coding	ENST00000366923	32	78058

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.04e-9	1.00	125664	0	84	125748	0.000334

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.60	669	796	0.841	0.0000402	9951
Missense in Polyphen		207	293.17	0.70607		3441
Synonymous	-1.54	301	269	1.12	0.0000136	2785
Loss of Function	5.28	31	82.9	0.374	0.00000420	1037

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000743	0.000741
Ashkenazi Jewish	0.000202	0.000198
East Asian	0.000440	0.000435
Finnish	0.000234	0.000231
European (Non-Finnish)	0.000275	0.000273
Middle Eastern	0.000440	0.000435
South Asian	0.000574	0.000523
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Multifunctional protein which is primarily part of the aminoacyl-tRNA synthetase multienzyme complex, also know as multisynthetase complex, that catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA (PubMed:1756734, PubMed:24100331, PubMed:23263184). The phosphorylation of EPRS, induced by interferon-gamma, dissociates the protein from the aminoacyl-tRNA synthetase multienzyme complex and recruits it to the GAIT complex that binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin), suppressing their translation. Interferon-gamma can therefore redirect, in specific cells, the EPRS function from protein synthesis to translation inhibition (PubMed:15479637, PubMed:23071094). Also functions as an effector of the mTORC1 signaling pathway by promoting, through SLC27A1, the uptake of long-chain fatty acid by adipocytes. Thereby, it also plays a role in fat metabolism and more indirectly influences lifespan (PubMed:28178239). {ECO:0000269|PubMed:15479637, ECO:0000269|PubMed:1756734, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23263184, ECO:0000269|PubMed:24100331, ECO:0000269|PubMed:28178239}.;
Disease: DISEASE: Leukodystrophy, hypomyelinating, 15 (HLD15) [MIM:617951]: An autosomal recessive disorder characterized by hypomyelinating leukodystrophy with thinning of the corpus callosum. Clinical features include motor and cognitive impairment appearing in the first or second decade of life, dystonia, ataxia, spasticity, and dysphagia. Most patients develop severe optic atrophy, and some have hearing loss. {ECO:0000269|PubMed:29576217}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;
Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);Porphyrin and chlorophyll metabolism - Homo sapiens (human);Hyperornithinemia with gyrate atrophy (HOGA);Creatine deficiency, guanidinoacetate methyltransferase deficiency;L-arginine:glycine amidinotransferase deficiency;Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome];Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency);Prolinemia Type II;Prolidase Deficiency (PD);Arginine and Proline Metabolism;Hyperprolinemia Type I;Hyperprolinemia Type II;Ornithine Aminotransferase Deficiency (OAT Deficiency);Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency);Parkinsons Disease Pathway;Amino Acid metabolism;tRNA modification in the nucleus and cytosol;tRNA processing;tRNA Aminoacylation;Translation;Glutamate Glutamine metabolism;Metabolism of proteins;Metabolism of amino acids and derivatives;Metabolism of RNA;TCR;Metabolism;tRNA charging;Selenoamino acid metabolism;Arginine Proline metabolism;SeMet incorporation into proteins;Cytosolic tRNA aminoacylation (Consensus)

Recessive Scores

pRec: 0.529

Intolerance Scores

loftool: 0.778
rvis_EVS: -0.12
rvis_percentile_EVS: 44.11

Haploinsufficiency Scores

pHI: 0.826
hipred: Y
hipred_score: 0.644
ghis: 0.595

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.985

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Eprs
Phenotype: cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype;

Gene ontology

Biological process: tRNA aminoacylation for protein translation;glutamyl-tRNA aminoacylation;prolyl-tRNA aminoacylation;negative regulation of translation;cellular response to insulin stimulus;long-chain fatty acid import;protein-containing complex assembly;cellular response to interferon-gamma
Cellular component: cytoplasm;cytosol;plasma membrane;membrane;aminoacyl-tRNA synthetase multienzyme complex;GAIT complex;ribonucleoprotein complex
Molecular function: glutamate-tRNA ligase activity;proline-tRNA ligase activity;protein binding;ATP binding;zinc ion binding;RNA stem-loop binding;identical protein binding;protein homodimerization activity;GTPase binding