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
Phenotypes
GenCC
Source:
- neuronopathy, distal hereditary motor, type 9 (Strong), mode of inheritance: AD
- distal hereditary motor neuropathy (Limited), mode of inheritance: AD
- neuronopathy, distal hereditary motor, type 9 (Moderate), mode of inheritance: AD
- distal hereditary motor neuropathy (Definitive), mode of inheritance: AD
- neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities (Limited), mode of inheritance: AR
Clinical Genomic Database
Source:
| 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
- Inborn_genetic_diseases (58 variants)
- not_provided (26 variants)
- Neuronopathy,_distal_hereditary_motor,_type_9 (8 variants)
- WARS1-related_disorder (7 variants)
- Neurodevelopmental_disorder_with_microcephaly_and_speech_delay,_with_or_without_brain_abnormalities (6 variants)
- not_specified (4 variants)
- See_cases (2 variants)
- Schizophrenia (1 variants)
- Developmental_delay (1 variants)
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. These statistics are base on transcript: NM_000004184.4. 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 | 8 | |||||
| missense | 73 | 85 | ||||
| nonsense | 1 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 1 | 4 | 76 | 16 | 0 |
Highest pathogenic variant AF is 0.00024239643
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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