TARS1

protein-coding

threonyl-tRNA synthetase 1, the group of Aminoacyl tRNA synthetases, Class II

Gene 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 proteins that appeared in evolution. Threonyl-tRNA synthetase belongs to the class-II aminoacyl-tRNA synthetase family [provided by RefSeq, Jul 2008]

Previous symbols:

TARS

MANE transcript

NM_152295.5

Inheritance

ClinVar variants

P:5U:136B:14

Top phenotype

Trichothiodystrophy 7, nonphotosensitive

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr5:33,440,696-33,468,091

External References & Databases

Ensembl (ENSG00000113407)

Transcript & Mutation Effects

hg38 • Region Span ~27.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

trichothiodystrophySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018053

Submitter: Orphanet

trichothiodystrophy 7, nonphotosensitiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032806

Submitter: PanelApp Australia

trichothiodystrophy 7, nonphotosensitiveMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032806

Submitter: G2P

Clinical Genomic Database (CGD)

Trichothiodystrophy 7, nonphotosensitiveAR

Manifestation: Allergy/Immunology/Infectious; Dermatologic; Musculoskeletal; Neurologic

Intervention: Allergy/Immunology/Infectious

Rationale: The condition has been described as involve recurrent respiratory infections, and awareness may allow prompt diagnosis and management of infections

Refs: 31374204

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TARS1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 115

TARS1-related disorderTotal: 17

not providedTotal: 12

Trichothiodystrophy 7, nonphotosensitiveTotal: 5

TrichothiodystrophyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152295.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	4 clinvar	1 clinvar	7
missense	2 clinvar		120 clinvar	3 clinvar	6 clinvar	131
nonsense	1 clinvar					1
start loss			1 clinvar			1
frameshift		2 clinvar	1 clinvar			3
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	3	2	136	7	7	155

Highest pathogenic variant AF is 0.000016331782

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152295.5	RefSeq	NP_689508.3	19	MANE Select
ENST00000265112.8	Ensembl	ENSP00000265112.3	19	MANE Select
NM_001258437.1	RefSeq	NP_001245366.1	19	Standard
NM_001258438.2	RefSeq	NP_001245367.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Aminoacyl-tRNA biosynthesis - Homo sapiens (human)
tRNA Aminoacylation
Translation
Metabolism of proteins
Glycine Serine metabolism

Biological Process

translation
tRNA aminoacylation for protein translation
threonyl-tRNA aminoacylation

Molecular Function

tRNA binding
threonine-tRNA ligase activity
protein binding
ATP binding
protein homodimerization activity

Cellular Component

cytoplasm
cytosol
actin cytoskeleton
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000455217
Coding exons: 20
Length: 28843
Individuals with no LoFs: 125678
Homozygous LoFs: 0
Heterozygous LoFs: 70
Defined: 125748
p: 0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.15	354	420	0.842	0.0000224	5006
Missense (PolyPhen)		118	159.62	0.73927		1855
Synonymous	-0.316	148	143	1.03	0.00000756	1360
Loss of Function	2.67	27	46.7	0.578	0.00000251	540

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00046	0.00043	rare
Latino/Admixed American	0.00050	0.00049	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00076	0.00076	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.00017	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.144

Intolerance Scores

LoFtool: 0.546
RVIS EVS: 0.6
RVIS percentile EVS: 82.87

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.957

Gene Damage Prediction

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