QARS1

glutaminyl-tRNA synthetase 1, the group of MicroRNA protein coding host genes|Aminoacyl tRNA synthetases, Class I

Basic information

Region (hg38): 3:49095932-49105130

Previous symbols: [ "QARS" ]

Links

ENSG00000172053 ∙ NCBI:5859 ∙ OMIM:603727 ∙ HGNC:9751 ∙ Uniprot:P47897 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome (Strong), mode of inheritance: AR
• diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome (Supportive), mode of inheritance: AR
• microcephaly-short stature-intellectual disability-facial dysmorphism syndrome (Supportive), mode of inheritance: AR
• diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy	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	Craniofacial; Neurologic	24656866

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the QARS1 gene.

• Diffuse_cerebral_and_cerebellar_atrophy_-_intractable_seizures_-_progressive_microcephaly_syndrome (886 variants)
• not_provided (195 variants)
• Inborn_genetic_diseases (113 variants)
• not_specified (67 variants)
• QARS1-related_disorder (17 variants)
• Microcephaly (2 variants)
• See_cases (2 variants)
• Intellectual_disability,_autosomal_dominant_43 (1 variants)
• Attention_deficit_hyperactivity_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the QARS1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005051.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	201	3	209
missense	1	13	395	13	1	423
nonsense	15	4	1			20
start loss	2					2
frameshift	24	2	2			28
splice donor/acceptor (+/-2bp)		18	1			19
Total	42	37	404	214	4

Highest pathogenic variant AF is 0.00008054483

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
QARS1	protein_coding	protein_coding	ENST00000306125	24	9189

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.70e-13	0.992	125656	0	92	125748	0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.220	438	451	0.971	0.0000267	5022
Missense in Polyphen		203	232.08	0.87469		2638
Synonymous	-1.03	184	167	1.10	0.00000884	1529
Loss of Function	2.64	28	47.6	0.588	0.00000257	533

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00101	0.00101
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000454	0.000448
Middle Eastern	0.00	0.00
South Asian	0.000361	0.000359
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Glutamine--tRNA ligase (PubMed:26869582). Plays a critical role in brain development (PubMed:24656866). {ECO:0000269|PubMed:24656866, ECO:0000269|PubMed:26869582}.
• Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);2-Hydroxyglutric Aciduria (D And L Form);Homocarnosinosis;Hyperinsulinism-Hyperammonemia Syndrome;Succinic semialdehyde dehydrogenase deficiency;4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency;Glutamate Metabolism;tRNA Aminoacylation;Translation;Glutamate Glutamine metabolism;Metabolism of proteins;Metabolism of amino acids and derivatives;Metabolism;tRNA charging;Selenoamino acid metabolism;SeMet incorporation into proteins;Cytosolic tRNA aminoacylation;Mitochondrial tRNA aminoacylation (Consensus)

Recessive Scores

• pRec: 0.189

Intolerance Scores

• loftool: 0.889
• rvis_EVS: -0.64
• rvis_percentile_EVS: 16.68

Haploinsufficiency Scores

• pHI: 0.244
• hipred: Y
• hipred_score: 0.648
• ghis: 0.567

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Qars

Zebrafish Information Network

• Gene name: qars
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: tRNA aminoacylation for protein translation;glutaminyl-tRNA aminoacylation;negative regulation of protein kinase activity;brain development;negative regulation of stress-activated MAPK cascade;negative regulation of transcription, DNA-templated;negative regulation of apoptotic signaling pathway
• Cellular component: cytoplasm;mitochondrial matrix;cytosol;aminoacyl-tRNA synthetase multienzyme complex;protein-containing complex
• Molecular function: glutamine-tRNA ligase activity;protein kinase inhibitor activity;protein binding;ATP binding;protein kinase binding