LARS1

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

Basic information

Region (hg38): 5:146110566-146182696

Previous symbols: [ "LARS" ]

Links

ENSG00000133706 ∙ NCBI:51520 ∙ OMIM:151350 ∙ HGNC:6512 ∙ Uniprot:Q9P2J5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• infantile liver failure syndrome 1 (Supportive), mode of inheritance: AR
• infantile liver failure syndrome 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Infantile liver failure syndrome 1	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	Gastrointestinal; Hematologic; Neurologic; Renal	22607940

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LARS1 gene.

• not provided (4 variants)
• not specified (3 variants)
• Infantile liver failure syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LARS1 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	44	11	56
missense	1	4	101	11	5	122
nonsense	3	3	1			7
start loss						0
frameshift	3	3	1			7
inframe indel			2			2
splice donor/acceptor (+/-2bp)		2				2
splice region			6	12	8	26
non coding			1	73	95	169
Total	7	12	107	128	111

Highest pathogenic variant AF is 0.0000329

Variants in LARS1

This is a list of pathogenic ClinVar variants found in the LARS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-146113959-A-C			Likely benign (Jul 27, 2018)
5-146114133-G-A		not specified	Likely benign (Jan 22, 2018)
5-146114137-A-G			Uncertain significance (Jun 01, 2023)
5-146114174-T-C		LARS1-related disorder	Likely benign (Dec 28, 2023)
5-146114194-T-C		not specified	Uncertain significance (Mar 28, 2024)
5-146114212-G-A		not specified	Uncertain significance (Aug 02, 2022)
5-146114228-C-T		not specified	Likely benign (Jun 25, 2015)
5-146114252-G-A			Uncertain significance (Jan 06, 2022)
5-146114257-C-T		not specified	Uncertain significance (Apr 07, 2022)
5-146114258-G-A			Uncertain significance (Sep 10, 2021)
5-146114260-C-T		Infantile liver failure syndrome 1	Uncertain significance (May 20, 2023)
5-146114301-T-C		not specified	Benign/Likely benign (Oct 01, 2023)
5-146114314-A-G		not specified	Likely benign (Apr 14, 2016)
5-146114505-G-A			Benign (Jul 15, 2018)
5-146114521-G-C			Benign (Jun 14, 2018)
5-146120214-C-G			Benign (Jul 15, 2018)
5-146120289-G-C			Likely benign (Jul 09, 2018)
5-146120369-AC-A		Infantile liver failure syndrome 1	Likely pathogenic (Sep 22, 2024)
5-146120382-C-G		not specified	Uncertain significance (May 15, 2024)
5-146120382-C-T			Uncertain significance (Jul 28, 2022)
5-146120383-G-A		Infantile liver failure syndrome 1 • Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins • LARS1-related disorder	Pathogenic/Likely pathogenic (Nov 04, 2022)
5-146120385-T-C		not specified	Uncertain significance (Apr 13, 2022)
5-146120401-G-A		not specified	Uncertain significance (Dec 09, 2023)
5-146120407-T-C		not specified	Uncertain significance (Jan 02, 2024)
5-146120408-T-C		not specified	Uncertain significance (May 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LARS1	protein_coding	protein_coding	ENST00000394434	32	69623

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.21e-9	1.00	125671	0	77	125748	0.000306

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.48	514	618	0.832	0.0000311	7763
Missense in Polyphen		91	151.22	0.60176		1830
Synonymous	0.531	200	210	0.953	0.0000106	2100
Loss of Function	4.83	27	70.8	0.381	0.00000343	895

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000922	0.000920
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000442	0.000435
Finnish	0.0000928	0.0000924
European (Non-Finnish)	0.000292	0.000290
Middle Eastern	0.000442	0.000435
South Asian	0.000171	0.000163
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the specific attachment of an amino acid to its cognate tRNA in a two step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. Exhibits a post-transfer editing activity to hydrolyze mischarged tRNAs. {ECO:0000269|PubMed:19426743}.
• Disease: DISEASE: Infantile liver failure syndrome 1 (ILFS1) [MIM:615438]: A life-threatening disorder of hepatic function that manifests with acute liver failure in the first few months of life. Clinical features include anemia, renal tubulopathy, developmental delay, seizures, failure to thrive, and liver steatosis and fibrosis. {ECO:0000269|PubMed:22607940}. 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;Metabolism of amino acids and derivatives;Metabolism;tRNA charging;Selenoamino acid metabolism;SeMet incorporation into proteins;Cytosolic tRNA aminoacylation (Consensus)

Intolerance Scores

• loftool: 0.846
• rvis_EVS: -0.44
• rvis_percentile_EVS: 24.68

Haploinsufficiency Scores

• pHI: 0.760
• hipred: Y
• hipred_score: 0.637
• ghis: 0.616

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lars
• 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)

Gene ontology

• Biological process: tRNA aminoacylation for protein translation;glutaminyl-tRNA aminoacylation;leucyl-tRNA aminoacylation;protein targeting to lysosome;regulation of cell size;negative regulation of autophagy;cellular response to amino acid starvation;positive regulation of GTPase activity;cellular response to amino acid stimulus;cellular response to leucine;aminoacyl-tRNA metabolism involved in translational fidelity;positive regulation of TORC1 signaling;cellular response to leucine starvation
• Cellular component: cytoplasm;lysosome;endoplasmic reticulum;cytosol;endomembrane system;nuclear body;aminoacyl-tRNA synthetase multienzyme complex
• Molecular function: aminoacyl-tRNA editing activity;glutamine-tRNA ligase activity;leucine-tRNA ligase activity;GTPase activator activity;protein binding;ATP binding