CARS2

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

Basic information

Region (hg38): 13:110641411-110713603

Links

ENSG00000134905 ∙ NCBI:79587 ∙ OMIM:612800 ∙ HGNC:25695 ∙ Uniprot:Q9HA77 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation defect type 27 (Supportive), mode of inheritance: AR
• combined oxidative phosphorylation defect type 27 (Moderate), mode of inheritance: AR
• combined oxidative phosphorylation defect type 27 (Strong), mode of inheritance: AR
• mitochondrial disease (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 27	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	Biochemical; Neurologic	25361775; 25787132

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CARS2 gene.

• Combined oxidative phosphorylation defect type 27 (617 variants)
• not provided (121 variants)
• Inborn genetic diseases (46 variants)
• not specified (40 variants)
• See cases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CARS2 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			5	133	4	142
missense			282	4	7	293
nonsense		1	8			9
start loss			4			4
frameshift	1		14			15
inframe indel			6			6
splice donor/acceptor (+/-2bp)			8		1	9
splice region			25	30	1	56
non coding			3	106	50	159
Total	1	1	330	243	62

Variants in CARS2

This is a list of pathogenic ClinVar variants found in the CARS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-110641483-C-G			Benign (Jun 28, 2018)
13-110641500-G-A			Benign (Jun 26, 2018)
13-110641537-T-G		Combined oxidative phosphorylation defect type 27	Uncertain significance (Aug 03, 2022)
13-110641539-A-C		Combined oxidative phosphorylation defect type 27	Uncertain significance (Jul 01, 2020)
13-110641540-G-C		Combined oxidative phosphorylation defect type 27	Uncertain significance (Nov 25, 2021)
13-110641539-A-ACC		Combined oxidative phosphorylation defect type 27	Uncertain significance (Nov 25, 2021)
13-110641543-C-T		not specified • Combined oxidative phosphorylation defect type 27	Likely benign (Jan 21, 2024)
13-110641544-G-A		Combined oxidative phosphorylation defect type 27	Uncertain significance (May 07, 2022)
13-110641547-G-C		Combined oxidative phosphorylation defect type 27	Uncertain significance (Feb 05, 2022)
13-110641547-G-GT		Combined oxidative phosphorylation defect type 27	Uncertain significance (Jan 16, 2018)
13-110641548-A-AT		Combined oxidative phosphorylation defect type 27 • CARS2-related disorder	Conflicting classifications of pathogenicity (Jan 29, 2024)
13-110641551-T-C		Combined oxidative phosphorylation defect type 27 • CARS2-related disorder	Benign (Jan 25, 2024)
13-110641554-G-A		Combined oxidative phosphorylation defect type 27	Uncertain significance (May 20, 2022)
13-110641556-T-C		Combined oxidative phosphorylation defect type 27	Uncertain significance (Oct 04, 2022)
13-110641565-C-G		Combined oxidative phosphorylation defect type 27	Uncertain significance (Sep 01, 2021)
13-110641566-T-C		Combined oxidative phosphorylation defect type 27	Uncertain significance (Feb 04, 2019)
13-110641568-T-G		not specified • Combined oxidative phosphorylation defect type 27	Benign (Feb 01, 2024)
13-110641570-A-G		Combined oxidative phosphorylation defect type 27	Likely benign (Apr 01, 2023)
13-110641573-C-T		Combined oxidative phosphorylation defect type 27	Likely benign (Oct 22, 2023)
13-110641574-A-G		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)
13-110641578-G-T		Combined oxidative phosphorylation defect type 27	Uncertain significance (May 22, 2022)
13-110641582-C-T		Inborn genetic diseases	Uncertain significance (Jul 18, 2016)
13-110641583-C-T		Combined oxidative phosphorylation defect type 27	Uncertain significance (Jul 09, 2021)
13-110641584-A-C		Combined oxidative phosphorylation defect type 27	Uncertain significance (Jan 01, 2021)
13-110641585-C-T		Combined oxidative phosphorylation defect type 27	Likely benign (Jan 22, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CARS2	protein_coding	protein_coding	ENST00000257347	15	72192

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.59e-8	0.983	125214	6	528	125748	0.00213

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.249	318	331	0.961	0.0000199	3625
Missense in Polyphen		112	114.69	0.97657		1308
Synonymous	-0.732	151	140	1.08	0.00000957	1118
Loss of Function	2.23	16	28.9	0.553	0.00000130	339

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0326	0.0295
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000152	0.000149
Middle Eastern	0.000109	0.000109
South Asian	0.000376	0.000359
Other	0.000755	0.000652

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Combined oxidative phosphorylation deficiency 27 (COXPD27) [MIM:616672]: An autosomal recessive mitochondrial disorder characterized by multiple mitochondrial respiratory- chain-complex deficiencies causing neurological regression, progressive cognitive decline, complex movement disorder, epileptic encephalopathy, progressive spastic tetraparesis, and progressive impairment of vision and hearing. {ECO:0000269|PubMed:25361775, ECO:0000269|PubMed:25787132}. 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;tRNA charging;Methionine and cysteine metabolism;Mitochondrial tRNA aminoacylation (Consensus)

Recessive Scores

• pRec: 0.208

Intolerance Scores

• loftool: 0.716
• rvis_EVS: 0.09
• rvis_percentile_EVS: 60.68

Haploinsufficiency Scores

• pHI: 0.0914
• hipred: N
• hipred_score: 0.492
• ghis: 0.461

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.201

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cars2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: cars2
• Affected structure: gonadotrophin-releasing hormone neuronal migration to the hypothalamus
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: cysteinyl-tRNA aminoacylation
• Cellular component: cytoplasm;mitochondrial matrix
• Molecular function: cysteine-tRNA ligase activity;ATP binding;metal ion binding