RARS1

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

Basic information

Region (hg38): 5:168486451-168519301

Previous symbols: [ "RARS" ]

Links

ENSG00000113643 ∙ NCBI:5917 ∙ OMIM:107820 ∙ HGNC:9870 ∙ Uniprot:P54136 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypomyelinating leukodystrophy 9 (Moderate), mode of inheritance: AR
• hypomyelinating leukodystrophy 9 (Supportive), mode of inheritance: AR
• hypomyelinating leukodystrophy 9 (Limited), mode of inheritance: Unknown
• hypomyelinating leukodystrophy 9 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, hypomyelinating 9	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	24777941

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RARS1 gene.

• not provided (10 variants)
• Hypomyelinating leukodystrophy 9 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RARS1 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	35	8	44
missense	1	3	95	3	4	106
nonsense	3	2				5
start loss	3	1				4
frameshift	3	2				5
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)		2	1			3
splice region			8	12	2	22
non coding			3	63	74	140
Total	10	11	103	101	86

Highest pathogenic variant AF is 0.0000329

Variants in RARS1

This is a list of pathogenic ClinVar variants found in the RARS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-168486454-C-A		not specified	Benign (Jan 24, 2016)
5-168486454-C-T		not specified	Likely benign (Aug 15, 2016)
5-168486494-G-A			Uncertain significance (Oct 27, 2022)
5-168486499-A-G		Hypomyelinating leukodystrophy 9	Pathogenic (Sep 01, 2022)
5-168486500-T-A			Pathogenic (Jan 17, 2019)
5-168486500-T-C		Hypomyelinating leukodystrophy 9 • Inborn genetic diseases	Pathogenic/Likely pathogenic (May 14, 2024)
5-168486501-G-T			Pathogenic (Apr 12, 2022)
5-168486503-A-G		Hypomyelinating leukodystrophy 9	Pathogenic (May 08, 2023)
5-168486504-C-T			Likely benign (Oct 24, 2022)
5-168486505-G-A		not specified • Hypomyelinating leukodystrophy 9	Benign (Feb 01, 2024)
5-168486505-G-C		Inborn genetic diseases	Uncertain significance (Jun 12, 2023)
5-168486507-A-C			Likely benign (Aug 24, 2023)
5-168486507-A-G		not specified	Likely benign (Jun 25, 2016)
5-168486508-C-T			Benign (Jan 06, 2024)
5-168486509-T-A		Hypomyelinating leukodystrophy 9	Uncertain significance (Sep 26, 2019)
5-168486510-G-C			Likely benign (Feb 02, 2023)
5-168486513-G-T			Likely benign (Oct 13, 2023)
5-168486515-C-T			Uncertain significance (Apr 15, 2022)
5-168486517-G-C			Uncertain significance (Oct 26, 2023)
5-168486518-A-T			Uncertain significance (Oct 24, 2022)
5-168486521-G-T			Uncertain significance (Sep 26, 2022)
5-168486522-C-T			Likely benign (Nov 03, 2021)
5-168486527-C-T			Uncertain significance (Jun 09, 2023)
5-168486534-G-C		Hypomyelinating leukodystrophy 9	Conflicting classifications of pathogenicity (Dec 24, 2021)
5-168486539-A-G		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RARS1	protein_coding	protein_coding	ENST00000231572	15	32855

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.27e-8	0.997	125671	0	77	125748	0.000306

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.544	319	348	0.918	0.0000175	4343
Missense in Polyphen		138	154.64	0.8924		1891
Synonymous	0.192	116	119	0.978	0.00000547	1210
Loss of Function	2.64	18	34.8	0.517	0.00000188	437

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000849	0.000842
Ashkenazi Jewish	0.00	0.00
East Asian	0.000437	0.000435
Finnish	0.000370	0.000370
European (Non-Finnish)	0.000316	0.000299
Middle Eastern	0.000437	0.000435
South Asian	0.000202	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Forms part of a macromolecular complex that catalyzes the attachment of specific amino acids to cognate tRNAs during protein synthesis (PubMed:25288775). Modulates the secretion of AIMP1 and may be involved in generation of the inflammatory cytokine EMAP2 from AIMP1 (PubMed:17443684). {ECO:0000269|PubMed:17443684, ECO:0000269|PubMed:25288775}.
• Disease: DISEASE: Leukodystrophy, hypomyelinating, 9 (HLD9) [MIM:616140]: An autosomal recessive neurodegenerative disorder characterized by delayed psychomotor development, severe spasticity, nystagmus, and ataxia associated with diffuse hypomyelination apparent on brain MRI. {ECO:0000269|PubMed:24777941}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Amino Acid metabolism;tRNA Aminoacylation;Translation;Metabolism of proteins;Metabolism of amino acids and derivatives;Metabolism;tRNA charging;Selenoamino acid metabolism;Arginine Proline metabolism;SeMet incorporation into proteins;Cytosolic tRNA aminoacylation (Consensus)

Recessive Scores

• pRec: 0.412

Intolerance Scores

• loftool: 0.872
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.64

Haploinsufficiency Scores

• pHI: 0.523
• hipred: Y
• hipred_score: 0.652
• ghis: 0.611

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.993

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rars
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands 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)

Gene ontology

• Biological process: tRNA aminoacylation for protein translation;arginyl-tRNA aminoacylation
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;membrane;aminoacyl-tRNA synthetase multienzyme complex;extracellular exosome
• Molecular function: tRNA binding;arginine-tRNA ligase activity;protein binding;ATP binding;arginine binding;cadherin binding