RARS2

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

Basic information

Region (hg38): 6:87513459-87590028

Previous symbols: [ "RARSL" ]

Links

ENSG00000146282

∙ NCBI:57038 ∙ OMIM:611524 ∙ HGNC:21406 ∙ Uniprot:Q5T160 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

pontocerebellar hypoplasia type 6 (Definitive), mode of inheritance: AR
pontocerebellar hypoplasia type 6 (Strong), mode of inheritance: AR
pontocerebellar hypoplasia type 6 (Strong), mode of inheritance: AR
pontocerebellar hypoplasia type 6 (Strong), mode of inheritance: AR
pontocerebellar hypoplasia type 6 (Supportive), mode of inheritance: AR
complex neurodevelopmental disorder (Limited), mode of inheritance: AD
pontocerebellar hypoplasia type 6 (Strong), mode of inheritance: AR
mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia, type 6	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	Neurologic	17847012; 20635367; 22569581; 25809939

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RARS2 gene.

not provided (51 variants)
Pontocerebellar hypoplasia type 6 (13 variants)
Inborn genetic diseases (2 variants)
Pontoneocerebellar hypoplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RARS2 gene is commonly pathogenic or not. These statistics are base on trasncript: . Only rare variants are included in the table.

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			2 clinvar	180 clinvar	1 clinvar	183
missense	1 clinvar	16 clinvar	120 clinvar	8 clinvar	3 clinvar	148
nonsense	21 clinvar	28 clinvar				49
start loss	4	5				9
frameshift	25 clinvar	52 clinvar	2 clinvar			79
splice donor/acceptor (+/-2bp)	8 clinvar	52 clinvar				60
Total	59	153	124	188	4

Highest pathogenic variant AF is 0.0000262795

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RARS2	protein_coding	protein_coding	ENST00000369536	20	75626

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.74e-14	0.844	125645	0	103	125748	0.000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0650	308	305	1.01	0.0000159	3780
Missense in Polyphen		101	118.72	0.85078		1392
Synonymous	-0.735	115	105	1.09	0.00000562	1068
Loss of Function	1.95	27	40.3	0.669	0.00000204	472

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000941	0.000941
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000653	0.000653
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000502	0.000501
Middle Eastern	0.000653	0.000653
South Asian	0.000359	0.000359
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

Disease: DISEASE: Pontocerebellar hypoplasia 6 (PCH6) [MIM:611523]: A disorder characterized by an abnormally small cerebellum and brainstem, infantile encephalopathy, generalized hypotonia, lethargy and poor feeding. Recurrent apnea, intractable seizures occur early in the course of this condition. {ECO:0000269|PubMed:17847012}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);Hyperornithinemia with gyrate atrophy (HOGA);Creatine deficiency, guanidinoacetate methyltransferase deficiency;L-arginine:glycine amidinotransferase deficiency;Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome];Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency);Prolinemia Type II;Prolidase Deficiency (PD);Arginine and Proline Metabolism;Hyperprolinemia Type I;Hyperprolinemia Type II;Ornithine Aminotransferase Deficiency (OAT Deficiency);Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency);tRNA Aminoacylation;Translation;Metabolism of proteins;tRNA charging;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Mitochondrial tRNA aminoacylation (Consensus)

Recessive Scores

pRec: 0.123

Intolerance Scores

loftool: 0.879
rvis_EVS: -0.13
rvis_percentile_EVS: 43.91

Haploinsufficiency Scores

pHI: 0.504
hipred: N
hipred_score: 0.476
ghis: 0.615

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.964

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Rars2
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype;

Zebrafish Information Network

Gene name: rars2
Affected structure: midbrain hindbrain boundary
Phenotype tag: abnormal
Phenotype quality: dorso-ventrally flattened

Gene ontology

Biological process: tRNA aminoacylation for protein translation;arginyl-tRNA aminoacylation;mitochondrial translation
Cellular component: mitochondrion;mitochondrial matrix
Molecular function: RNA binding;arginine-tRNA ligase activity;ATP binding