GARS1
glycyl-tRNA synthetase 1, the group of Aminoacyl tRNA synthetases, Class II
Basic information
Region (hg38): 7:30580533-30634033
Previous symbols: [ "CMT2D", "GARS" ]
Links
Phenotypes
GenCC
Source:
- neuronopathy, distal hereditary motor, type 5A (Definitive), mode of inheritance: AD
- Charcot-Marie-Tooth disease type 2D (Supportive), mode of inheritance: AD
- neuronopathy, distal hereditary motor, type 5A (Supportive), mode of inheritance: AD
- spinal muscular atrophy, infantile, James type (Moderate), mode of inheritance: AD
- neuronopathy, distal hereditary motor, type 5A (Definitive), mode of inheritance: AD
- neuronopathy, distal hereditary motor, type 5A (Strong), mode of inheritance: AD
- Charcot-Marie-Tooth disease type 2D (Strong), mode of inheritance: AD
- Charcot-Marie-Tooth disease type 2D (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Charcot-Marie-Tooth disease, axonal, type 2D; Neuronopathy, distal hereditary motor, autosomal dominant 5; Spinal muscular atrophy, infantile, James type | 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 | 8541851; 8872480; 10732809; 9879677; 12690580; 16769947; 19329989; 20169446; 20301420; 20301462; 22462675; 23279345; 32181591 |
ClinVar
This is a list of variants' phenotypes submitted to
- Charcot-Marie-Tooth_disease_type_2 (613 variants)
- not_provided (198 variants)
- not_specified (183 variants)
- Charcot-Marie-Tooth_disease_type_2D (74 variants)
- Charcot-Marie-Tooth_disease (61 variants)
- Neuronopathy,_distal_hereditary_motor,_type_5A (56 variants)
- Distal_spinal_muscular_atrophy (45 variants)
- GARS1-related_disorder (16 variants)
- Neuronopathy,_distal_hereditary_motor,_type_5 (6 variants)
- Spinal_muscular_atrophy,_infantile,_James_type (6 variants)
- See_cases (3 variants)
- GARS-associated_growth_retardation_and_developmental_delay (2 variants)
- GARS-Associated_Axonal_Neuropathy (2 variants)
- Neuronopathy,_distal_hereditary_motor,_autosomal_dominant (1 variants)
- GARS1-related_neuropathies (1 variants)
- Parkinsonian_disorder (1 variants)
- Hereditary_motor_neuron_disease (1 variants)
- Inborn_genetic_diseases (1 variants)
- Tip-toe_gait (1 variants)
- Charcot-Marie-Tooth_disease_type_5 (1 variants)
- Pes_cavus (1 variants)
- Charcot-Marie-Tooth_disease,_type_I (1 variants)
- Motor_neuron_disease (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GARS1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002047.4. 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 | 149 | 158 | ||||
| missense | 12 | 25 | 354 | 44 | 440 | |
| nonsense | 10 | 11 | ||||
| start loss | 3 | 3 | ||||
| frameshift | 13 | 15 | ||||
| splice donor/acceptor (+/-2bp) | 10 | |||||
| Total | 14 | 29 | 392 | 193 | 9 |
Highest pathogenic variant AF is 0.0000509215
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GARS1 | protein_coding | protein_coding | ENST00000389266 | 17 | 39353 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.306 | 0.694 | 124782 | 0 | 16 | 124798 | 0.0000641 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.20 | 334 | 402 | 0.832 | 0.0000216 | 4828 |
| Missense in Polyphen | 91 | 156.06 | 0.5831 | 1884 | ||
| Synonymous | -0.186 | 151 | 148 | 1.02 | 0.00000783 | 1417 |
| Loss of Function | 4.46 | 9 | 39.1 | 0.230 | 0.00000232 | 444 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000116 | 0.000116 |
| Ashkenazi Jewish | 0.0000993 | 0.0000993 |
| East Asian | 0.000167 | 0.000167 |
| Finnish | 0.0000464 | 0.0000464 |
| European (Non-Finnish) | 0.0000618 | 0.0000618 |
| Middle Eastern | 0.000167 | 0.000167 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Catalyzes the ligation of glycine to the 3'-end of its cognate tRNA. Also produces diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs. {ECO:0000269|PubMed:17544401, ECO:0000269|PubMed:19710017, ECO:0000269|PubMed:28675565}.;
- Disease
- DISEASE: Neuronopathy, distal hereditary motor, 5A (HMN5A) [MIM:600794]: A disorder characterized by distal muscular atrophy mainly affecting the upper extremities, in contrast to other distal motor neuronopathies. These constitute a heterogeneous group of neuromuscular diseases caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. {ECO:0000269|PubMed:12690580, ECO:0000269|PubMed:17035524, ECO:0000269|PubMed:23279345, ECO:0000269|PubMed:24627108, ECO:0000269|PubMed:26503042}. Note=The disease is caused by mutations affecting the gene represented in this entry. Contrary to the wild-type protein, HMN5A variant Pro-183 strongly interacts with NRP1. This interaction may compete out VEGFA binding and inhibits VEGFA-NRP1 signling which is essential for motor neuron survival, as suggested by experiments done in a mouse model. {ECO:0000269|PubMed:26503042}.;
- Pathway
- Aminoacyl-tRNA biosynthesis - Homo sapiens (human);3-Phosphoglycerate dehydrogenase deficiency;Non Ketotic Hyperglycinemia;Glycine and Serine Metabolism;Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Dihydropyrimidine Dehydrogenase Deficiency (DHPD);tRNA Aminoacylation;Translation;Metabolism of proteins;Glycine Serine metabolism;tRNA charging;Cytosolic tRNA aminoacylation;Mitochondrial tRNA aminoacylation
(Consensus)
Recessive Scores
- pRec
- 0.0942
Intolerance Scores
- loftool
- 0.290
- rvis_EVS
- -0.71
- rvis_percentile_EVS
- 14.57
Haploinsufficiency Scores
- pHI
- 0.327
- hipred
- Y
- hipred_score
- 0.650
- ghis
- 0.537
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gars
- 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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; muscle phenotype;
Zebrafish Information Network
- Gene name
- gars
- Affected structure
- CaP motoneuron
- Phenotype tag
- abnormal
- Phenotype quality
- decreased length
Gene ontology
- Biological process
- tRNA aminoacylation for protein translation;glycyl-tRNA aminoacylation;diadenosine tetraphosphate biosynthetic process;mitochondrial glycyl-tRNA aminoacylation
- Cellular component
- cytoplasm;mitochondrion;mitochondrial matrix;cytosol;secretory granule;axon;extracellular exosome
- Molecular function
- bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity;glycine-tRNA ligase activity;protein binding;ATP binding;identical protein binding;protein dimerization activity