LARS2

leucyl-tRNA synthetase 2, mitochondrial, the group of Aminoacyl tRNA synthetases, Class I

Basic information

Region (hg38): 3:45388561-45554726

Links

ENSG00000011376 ∙ NCBI:23395 ∙ OMIM:604544 ∙ HGNC:17095 ∙ Uniprot:Q15031 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Perrault syndrome 4 (Strong), mode of inheritance: AR
• hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome (Limited), mode of inheritance: AR
• Perrault syndrome (Supportive), mode of inheritance: AR
• hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome (Strong), mode of inheritance: AR
• Perrault syndrome 4 (Strong), mode of inheritance: AR
• Perrault syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Perrault syndrome 4	AR	Audiologic/Otolaryngologic; Biochemical; Endocrine; Gastrointestinal; Hematologic; Neurologic; Obstetric	Genetic knowledge may allow fertility preservation such as by storing eggs in woman with premature ovarian failure	Audiologic/Otolaryngologic; Endocrine; Genitourinary; Hematologic; Obstetric; Pulmonary	23541342; 26537577; 32442335

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LARS2 gene.

• not provided (13 variants)
• Perrault syndrome 4 (4 variants)
• Nonsyndromic genetic hearing loss (2 variants)
• Perrault syndrome (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LARS2 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	99	10	110
missense	3	13	145	7	3	171
nonsense	6	6	1			13
start loss						0
frameshift	8	1				9
inframe indel						0
splice donor/acceptor (+/-2bp)		4				4
splice region			4	19	1	24
non coding			1	87	44	132
Total	17	24	148	193	57

Highest pathogenic variant AF is 0.0000460

Variants in LARS2

This is a list of pathogenic ClinVar variants found in the LARS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-45388659-G-A			Benign (Jun 29, 2018)
3-45388665-C-G		not specified	Likely benign (May 15, 2017)
3-45388686-C-A		not specified	Likely benign (Nov 03, 2017)
3-45388690-C-G		not specified	Likely benign (Apr 07, 2017)
3-45388753-C-G			Benign (Jun 29, 2018)
3-45391483-C-A			Likely benign (Aug 28, 2020)
3-45391634-G-A		not specified	Benign (Feb 02, 2016)
3-45391775-C-G			Likely benign (Jun 29, 2018)
3-45394190-T-C			Likely benign (Jul 15, 2018)
3-45394357-A-T			Benign (Jun 26, 2018)
3-45394420-C-T		not specified	Likely benign (Jan 24, 2018)
3-45394475-T-C		not specified • LARS2-related disorder	Benign (Jan 22, 2024)
3-45394493-CTT-C		Perrault syndrome 4	Pathogenic (-)
3-45394512-A-G			Uncertain significance (Sep 06, 2023)
3-45394542-G-A			Uncertain significance (Feb 01, 2022)
3-45394551-T-C			Uncertain significance (Jun 08, 2022)
3-45394555-C-T			Likely benign (May 27, 2023)
3-45394556-G-A			Uncertain significance (Jul 12, 2022)
3-45394566-GA-G			Pathogenic (Jan 01, 2024)
3-45394578-G-A			Uncertain significance (Dec 15, 2020)
3-45394588-A-T			Uncertain significance (Sep 28, 2022)
3-45394596-CAA-C			Pathogenic (Sep 30, 2022)
3-45394598-A-G			Uncertain significance (Jan 19, 2024)
3-45394601-G-A		Inborn genetic diseases	Uncertain significance (Mar 13, 2023)
3-45394610-T-C		not specified	Benign (Jan 31, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LARS2	protein_coding	protein_coding	ENST00000415258	20	160916

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.93e-17	0.952	125645	0	103	125748	0.000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.33	427	512	0.834	0.0000275	5914
Missense in Polyphen		135	209.55	0.64424		2460
Synonymous	0.485	185	194	0.956	0.0000110	1729
Loss of Function	2.40	34	52.8	0.644	0.00000255	587

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000653	0.000652
Ashkenazi Jewish	0.00	0.00
East Asian	0.00104	0.00103
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000406	0.000396
Middle Eastern	0.00104	0.00103
South Asian	0.000633	0.000621
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Hydrops, lactic acidosis, and sideroblastic anemia (HLASA) [MIM:617021]: A lethal, multisystem metabolic disorder characterized by severe lactic acidosis, hydrops, and sideroblastic anemia. Additional features include impaired cardiac function, disordered coagulation, pulmonary hypertension, and progressive renal disease. {ECO:0000269|PubMed:26537577}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);Amino Acid metabolism;tRNA Aminoacylation;Translation;Metabolism of proteins;tRNA charging;Valine, leucine and isoleucine degradation;Mitochondrial tRNA aminoacylation (Consensus)

Recessive Scores

• pRec: 0.233

Intolerance Scores

• loftool: 0.567
• rvis_EVS: -0.75
• rvis_percentile_EVS: 13.74

Haploinsufficiency Scores

• pHI: 0.526
• hipred: N
• hipred_score: 0.414
• ghis: 0.584

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lars2

Gene ontology

• Biological process: tRNA aminoacylation for protein translation;leucyl-tRNA aminoacylation;mitochondrial translation;aminoacyl-tRNA metabolism involved in translational fidelity
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: aminoacyl-tRNA editing activity;leucine-tRNA ligase activity;ATP binding