TARS2

threonyl-tRNA synthetase 2, mitochondrial, the group of MicroRNA protein coding host genes|Aminoacyl tRNA synthetases, Class II

Basic information

Region (hg38): 1:150487414-150507602

Previous symbols: [ "TARSL1" ]

Links

ENSG00000143374 ∙ NCBI:80222 ∙ OMIM:612805 ∙ HGNC:30740 ∙ Uniprot:Q9BW92 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation defect type 21 (Supportive), mode of inheritance: AR
• combined oxidative phosphorylation defect type 21 (Moderate), mode of inheritance: AR
• combined oxidative phosphorylation defect type 21 (Strong), mode of inheritance: AR
• Leigh syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 21	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	Biochemical; Musculoskeletal; Neurologic	24827421

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TARS2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TARS2 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			1	43	5	49
missense		1	78	6	2	87
nonsense		2	3			5
start loss			1			1
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)			2			2
splice region		1	8	9	1	19
non coding			1	33	40	74
Total	0	3	88	82	47

Variants in TARS2

This is a list of pathogenic ClinVar variants found in the TARS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-150487417-CTGTT-C		not specified	Benign (Aug 01, 2016)
1-150487429-G-A			Likely benign (Jun 23, 2021)
1-150487451-A-T			Uncertain significance (Dec 27, 2021)
1-150487455-C-T			Uncertain significance (Sep 24, 2021)
1-150487458-T-A			Uncertain significance (Aug 31, 2022)
1-150487459-G-C			Likely benign (Jun 09, 2023)
1-150487481-C-T		Inborn genetic diseases	Uncertain significance (May 27, 2022)
1-150487499-G-A		Combined oxidative phosphorylation defect type 21 • Inborn genetic diseases	Uncertain significance (Jun 02, 2023)
1-150487511-C-T			Uncertain significance (Feb 04, 2023)
1-150487651-T-TCTAA			Benign (Feb 04, 2019)
1-150487692-A-G			Benign (Jun 14, 2018)
1-150487872-C-T		not specified • TARS2-related disorder	Benign (Jan 29, 2024)
1-150487882-T-A		Inborn genetic diseases	Uncertain significance (Nov 06, 2023)
1-150487892-A-G			Uncertain significance (Jun 01, 2018)
1-150487932-A-G		not specified	Likely benign (Sep 29, 2017)
1-150487934-A-G			Uncertain significance (Aug 13, 2022)
1-150487950-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 22, 2022)
1-150487962-A-G			Likely benign (Aug 19, 2023)
1-150487968-G-A			Likely benign (Oct 27, 2023)
1-150487977-G-A			Likely benign (Sep 05, 2023)
1-150487981-T-C		Inborn genetic diseases	Uncertain significance (May 31, 2023)
1-150487982-C-G			Likely pathogenic (Apr 20, 2023)
1-150487984-C-G			Uncertain significance (Jul 21, 2022)
1-150488027-C-T			Uncertain significance (Oct 13, 2023)
1-150488044-C-T		Inborn genetic diseases	Uncertain significance (Sep 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TARS2	protein_coding	protein_coding	ENST00000369064	18	20192

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.22e-12	0.979	125688	0	59	125747	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.77	323	426	0.758	0.0000254	4598
Missense in Polyphen		102	168.8	0.60428		1805
Synonymous	0.153	163	166	0.985	0.00000892	1512
Loss of Function	2.39	26	42.9	0.606	0.00000225	442

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000387	0.000387
Ashkenazi Jewish	0.000498	0.000496
East Asian	0.000381	0.000381
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000238	0.000237
Middle Eastern	0.000381	0.000381
South Asian	0.000261	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr). Also edits incorrectly charged tRNA(Thr) via its editing domain. {ECO:0000269|PubMed:26811336}.
• Disease: DISEASE: Combined oxidative phosphorylation deficiency 21 (COXPD21) [MIM:615918]: A mitochondrial disorder characterized by a lethal encephalomyopathy. Shortly after birth, affected individuals manifest axial hypotonia, limb hypertonia, psychomotor delay, and increased serum lactate. Additional features include subsarcolemmal lipofuscin-positive deposits in muscle, cerebral spongiosis, and hepatic steatosis. {ECO:0000269|PubMed:24827421, ECO:0000269|PubMed:26811336}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);tRNA Aminoacylation;Translation;Metabolism of proteins;tRNA charging;Mitochondrial tRNA aminoacylation;Glycine, serine, alanine and threonine metabolism (Consensus)

Recessive Scores

• pRec: 0.0841

Intolerance Scores

• loftool: 0.405
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.82

Haploinsufficiency Scores

• pHI: 0.161
• hipred: Y
• hipred_score: 0.520
• ghis: 0.519

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.918

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tars2

Gene ontology

• Biological process: threonyl-tRNA aminoacylation;mitochondrial threonyl-tRNA aminoacylation;aminoacyl-tRNA metabolism involved in translational fidelity
• Cellular component: cellular_component;cytoplasm;mitochondrial matrix
• Molecular function: aminoacyl-tRNA editing activity;threonine-tRNA ligase activity;ATP binding;protein homodimerization activity