WARS1

tryptophanyl-tRNA synthetase 1, the group of Aminoacyl tRNA synthetases, Class I

Basic information

Region (hg38): 14:100333790-100376805

Previous symbols: [ "IFI53", "WARS" ]

Links

ENSG00000140105 ∙ NCBI:7453 ∙ OMIM:191050 ∙ HGNC:12729 ∙ Uniprot:P23381 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuronopathy, distal hereditary motor, type 9 (Strong), mode of inheritance: AD
• distal hereditary motor neuropathy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuronopathy, distal hereditary motor, type IX	AD	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	Neurologic	28369220; 31069783; 31321409

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WARS1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WARS1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6	1	7
missense		1	40	6		47
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	1	3
non coding				1	12	13
Total	0	1	42	13	13

Variants in WARS1

This is a list of pathogenic ClinVar variants found in the WARS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-100334893-C-A		WARS1-related disorder	Likely benign (Oct 28, 2019)
14-100334938-C-A		Inborn genetic diseases	Uncertain significance (Feb 27, 2024)
14-100334943-T-G			Uncertain significance (Nov 01, 2022)
14-100334945-C-T		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)
14-100334949-G-A		Neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities	Uncertain significance (-)
14-100334985-C-T			Uncertain significance (Mar 28, 2023)
14-100334988-T-C		Inborn genetic diseases	Uncertain significance (Jun 18, 2024)
14-100334994-C-T		Inborn genetic diseases	Likely benign (Apr 25, 2023)
14-100335036-C-T		Neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities	Pathogenic (Apr 19, 2023)
14-100335086-T-C			Benign (May 16, 2021)
14-100335164-G-C			Benign (May 17, 2021)
14-100335207-A-G			Benign (May 22, 2021)
14-100337027-A-G		Neuronopathy, distal hereditary motor, type 9	Benign (Dec 05, 2021)
14-100337068-G-C		Neuronopathy, distal hereditary motor, type 9	Uncertain significance (-)
14-100337081-T-C		Inborn genetic diseases	Likely benign (Jan 23, 2023)
14-100337085-C-T		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
14-100337086-G-A		WARS1-related disorder	Benign/Likely benign (Jul 01, 2023)
14-100337161-C-A		Inborn genetic diseases	Uncertain significance (May 25, 2022)
14-100337318-C-A			Benign (May 16, 2021)
14-100337345-T-C			Benign (May 16, 2021)
14-100337405-C-G			Benign (May 17, 2021)
14-100342389-A-G			Likely benign (Feb 01, 2023)
14-100342448-G-A		Inborn genetic diseases	Uncertain significance (Jan 09, 2024)
14-100342449-G-T		Inborn genetic diseases	Uncertain significance (Jul 12, 2023)
14-100342453-C-G		Inborn genetic diseases	Uncertain significance (Jul 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WARS1	protein_coding	protein_coding	ENST00000355338	10	43018

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.303	0.697	125738	0	8	125746	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.99	188	282	0.666	0.0000161	3170
Missense in Polyphen		27	101.91	0.26493		1197
Synonymous	1.01	101	115	0.880	0.00000767	868
Loss of Function	3.28	5	21.4	0.234	0.00000107	251

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000619	0.0000619
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.00000880	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 1, isoform 2 and T1-TrpRS have aminoacylation activity while T2-TrpRS lacks it. Isoform 2, T1-TrpRS and T2-TrpRS possess angiostatic activity whereas isoform 1 lacks it. T2-TrpRS inhibits fluid shear stress-activated responses of endothelial cells. Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression. {ECO:0000269|PubMed:11773625, ECO:0000269|PubMed:11773626, ECO:0000269|PubMed:1373391, ECO:0000269|PubMed:14630953, ECO:0000269|PubMed:28369220}.
• Disease: DISEASE: Neuronopathy, distal hereditary motor, 9 (HMN9) [MIM:617721]: An autosomal dominant neurologic disorder characterized by juvenile onset of slowly progressive distal muscle weakness and atrophy affecting both the lower and upper limbs. {ECO:0000269|PubMed:28369220}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);Tryptophan Metabolism;Photodynamic therapy-induced unfolded protein response;Amino Acid metabolism;Tryptophan metabolism;tRNA Aminoacylation;Translation;Metabolism of proteins;tRNA charging;Tryptophan degradation;Cytosolic tRNA aminoacylation (Consensus)

Recessive Scores

• pRec: 0.420

Intolerance Scores

• loftool: 0.425
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.6

Haploinsufficiency Scores

• pHI: 0.195
• hipred: Y
• hipred_score: 0.662
• ghis: 0.550

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.933

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wars
• Phenotype: vision/eye phenotype; hematopoietic system phenotype; 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); homeostasis/metabolism phenotype

Gene ontology

• Biological process: angiogenesis;negative regulation of protein phosphorylation;translation;tRNA aminoacylation for protein translation;tryptophanyl-tRNA aminoacylation;negative regulation of protein kinase activity;negative regulation of cell population proliferation;positive regulation of gene expression;regulation of protein ADP-ribosylation;positive regulation of protein complex assembly;regulation of angiogenesis
• Cellular component: nucleus;cytoplasm;cytosol;protein-containing complex;extracellular exosome
• Molecular function: tryptophan-tRNA ligase activity;protein binding;ATP binding;kinase inhibitor activity;protein kinase binding;protein domain specific binding;protein homodimerization activity