QARS1 (glutaminyl-tRNA synthetase 1)

Gene

• Entrez ID: 5859
• Gene name: Glutaminyl-tRNA synthetase 1
• Gene symbol: QARS1
• Synonyms (NCBI Gene): GLNRS, MSCCA, PRO2195, QARS
• Chromosome: 3
• Chromosome location: 3p21.31
• Summary: Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first prot

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs62621067	G>T	Conflicting-interpretations-of-pathogenicity, likely-benign	Non coding transcript variant, coding sequence variant, missense variant
rs144563810	G>A	Conflicting-interpretations-of-pathogenicity	Missense variant, non coding transcript variant, coding sequence variant
rs370934093	G>A	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs587777331	C>A	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs587777333	A>G	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1024765171	G>A,T	Likely-pathogenic, uncertain-significance	Intron variant
rs1241706645	C>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1398173228	T>C	Likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs1553751717	G>-	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1559966797	GT>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004819	Function	Glutamine-tRNA ligase activity	IBA
GO:0004819	Function	Glutamine-tRNA ligase activity	IDA	26869582
GO:0004819	Function	Glutamine-tRNA ligase activity	IEA
GO:0004819	Function	Glutamine-tRNA ligase activity	TAS	8078941
GO:0004860	Function	Protein kinase inhibitor activity	IMP	11096076
GO:0005515	Function	Protein binding	IPI	15231748, 21988832, 24656866, 25416956, 25910212, 31515488, 32296183, 32814053
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IDA	10791971, 24656866
GO:0005737	Component	Cytoplasm	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IDA	19289464
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006412	Process	Translation	IEA
GO:0006418	Process	TRNA aminoacylation for protein translation	IEA
GO:0006418	Process	TRNA aminoacylation for protein translation	TAS
GO:0006425	Process	Glutaminyl-tRNA aminoacylation	IBA
GO:0006425	Process	Glutaminyl-tRNA aminoacylation	IDA	24656866, 26869582
GO:0006425	Process	Glutaminyl-tRNA aminoacylation	IEA
GO:0007420	Process	Brain development	IMP	24656866
GO:0016874	Function	Ligase activity	IEA
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IBA
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IDA	19131329
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IEA
GO:0019901	Function	Protein kinase binding	IPI	11096076
GO:0032873	Process	Negative regulation of stress-activated MAPK cascade	IDA	11096076
GO:0032991	Component	Protein-containing complex	IMP	11096076
GO:0043039	Process	TRNA aminoacylation	IEA
GO:0045892	Process	Negative regulation of DNA-templated transcription	IDA	11096076
GO:2001234	Process	Negative regulation of apoptotic signaling pathway	IDA	11096076

Other IDs

• MIM: 603727
• HGNC: 9751
• e!Ensembl: ENSG00000172053

Protein

• UniProt ID: P47897
• Protein name: Glutamine--tRNA ligase (EC 6.1.1.18) (Glutaminyl-tRNA synthetase) (GlnRS)
• Protein function: Glutamine--tRNA ligase (PubMed:26869582). Plays a critical role in brain development (PubMed:24656866).
• PDB: 4R3Z, 4YE6, 4YE8, 4YE9
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF04558	tRNA_synt_1c_R1	5 → 162		Family
  PF04557	tRNA_synt_1c_R2	165 → 254		Family
  PF00749	tRNA-synt_1c	263 → 563	tRNA synthetases class I (E and Q), catalytic domain	Domain
  PF03950	tRNA-synt_1c_C	565 → 752	tRNA synthetases class I (E and Q), anti-codon binding domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in fetal cerebral cortex, particularly in the ventricular zone, inner subventricular zone, outer subventricular zone, and cortical plate. {ECO:0000269|PubMed:24656866}.
• Sequence:

  MAALDSLSLFTSLGLSEQKARETLKNSALSAQLREAATQAQQTLGSTIDKATGILLYGLA
  SRLRDTRRLSFLVSYIASKKIHTEPQLSAALEYVRSHPLDPIDTVDFERECGVGVIVTPE
  QIEEAVEAAINRHRPQLLVERYHFNMGLLMGEARAVLKWADGKMIKNEVDMQVLHLLGPK
  LEADLEKKFKVAKARLEETDRRTAKDVVENGETADQTLSLMEQLRGEALKFHKPGENYKT
  PGYVVTPHTMNLLKQHLEITGGQVRTRFPPEPNGILHIGHAKAINFNFGYAKANNGICFL
  RFDDTNPEKEEAKFFTAICDMVAWLGYTPYKVTYASDYFDQLYAWAVELIRRGLAYVCHQ
  RGEELKGHNTLPSPWRDRPMEESLLLFEAMRKGKFSEGEATLRMKLVMEDGKMDPVAYRV
  KYTPHHRTGDKWCIYPTYDYTHCLCDSIEHITHSLCTKEFQARRSSYFWLCNALDVYCPV
  QWEYGRLNLHYAVVSKRKILQLVATGAVRDWDDPRLFTLTALRRRGFPPEAINNFCARVG
  VTVAQTTMEPHLLEACVRDVLNDTAPRAMAVLESLRVIITNFPAAKSLDIQVPNFPADET
  KGFHQVPFAPIVFIERTDFKEEPEPGFKRLAWGQPVGLRHTGYVIELQHVVKGPSGCVES
  LEVTCRRADAGEKPKAFIHWVSQPLMCEVRLYERLFQHKNPEDPTEVPGGFLSDLNLASL
  HVVDAALVDCSVALAKPFDKFQFERLGYFSVDPDSHQGKLVFNRTVTLKEDPGKV

• Sequence length: 775

Pathways

KEGG:

Aminoacyl-tRNA biosynthesis
Metabolic pathways

Reactome:

Cytosolic tRNA aminoacylation
Mitochondrial tRNA aminoacylation

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome	Likely pathogenic; Pathogenic	rs1232739970, rs1262558494, rs746293241, rs2107099019, rs2042438780, rs772343264, rs747938605, rs2107101318, rs587777331, rs587777333, rs587777334, rs2107112006, rs2107100555, rs2107111037, rs1331307146, rs957599864, rs372844870, rs1238347256, rs2107102230, rs2107095933, rs1217013234, rs2042451819, rs1230015326, rs2107108875, rs2042511461, rs2107111718, rs1157267701, rs2042417862, rs2471852020, rs2471852703, rs2471867217, rs2471863066, rs2471856206, rs79363335, rs2471844538, rs2471867142, rs1187534568, rs1559967310, rs937998415, rs746028168, rs2471859404, rs1064795119, rs755674457, rs1241706645, rs1553751717, rs1559966797, rs767667312, rs1024765171, rs141184565, rs1186557939, rs2042472129, rs751537797, rs2042500119, rs2042518770, rs2042510074, rs776344968	RCV001379874 RCV001376894 RCV001380568 RCV001381438 RCV001381217 RCV001389844 RCV002579441 RCV001783657 RCV000114972 RCV000114974 RCV000114975 RCV002625361 RCV002568523 RCV002569142 RCV002642089 RCV002550363 RCV002571354 RCV002563562 RCV002563621 RCV002551190 RCV002569143 RCV002564380 RCV002545644 RCV002545327 RCV002579650 RCV002552303 RCV002545414 RCV002647438 RCV002676620 RCV002706068 RCV002735867 RCV002851205 RCV003003212 RCV003009995 RCV003026456 RCV003583258 RCV003583263 RCV003583855 RCV003746711 RCV003746430 RCV003862589 RCV004586282 RCV002525873 RCV004760598 RCV003746540 RCV005091877 RCV003583174 RCV000685922 RCV000785086 RCV001066418 RCV001070505 RCV001050256 RCV001211409 RCV001230976 RCV001231975 RCV001239582 RCV001265598
Intellectual disability, autosomal dominant 43	Likely pathogenic; Pathogenic	rs587777334	RCV004764850
Ovarian serous cystadenocarcinoma	Likely pathogenic	rs1024765171	RCV005897420
QARS1-related disorder	Pathogenic	rs587777331	RCV003415881
Thymoma	Likely pathogenic	rs1232739970	RCV005912624

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Attention deficit hyperactivity disorder	Uncertain significance	rs1575400316	RCV000851207
Cervical cancer	Uncertain significance	rs1052975324	RCV005922842
Clear cell carcinoma of kidney	Uncertain significance	rs777424712	RCV005901630
Familial cancer of breast	Benign	rs138271247	RCV005896650
Hepatocellular carcinoma	Benign	rs4521268	RCV005896288
Lung cancer	Benign	rs138271247	RCV005896653
Microcephaly	Uncertain significance; Conflicting classifications of pathogenicity	rs778807845, rs752600100	RCV001252759 RCV004798883
Sarcoma	Benign	rs138271247	RCV005896651
See cases	Benign; Likely benign; Conflicting classifications of pathogenicity	rs202012811, rs141983717	RCV001197406 RCV004584386

Associations from Text Mining
Disease Name	Relationship Type	References
Anemia	Associate	29875423
Attention Deficit Disorder with Hyperactivity	Associate	28332277
Brain Diseases	Associate	26869582
Hypoalbuminemia	Associate	29875423
Hypokalemia Familial	Associate	29875423
Lung Diseases	Associate	29875423
Neurologic Manifestations	Associate	26869582