CARS2

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

Basic information

Region (hg38): 13:110641412-110713603

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 (Moderate), mode of inheritance: AR
combined oxidative phosphorylation defect type 27 (Supportive), mode of inheritance: AR
combined oxidative phosphorylation defect type 27 (Strong), mode of inheritance: AR
mitochondrial disease (Moderate), mode of inheritance: AR
combined oxidative phosphorylation defect type 27 (Strong), 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 (680 variants)
not_provided (111 variants)
Inborn_genetic_diseases (97 variants)
not_specified (39 variants)
CARS2-related_disorder (23 variants)
See_cases (2 variants)
Maturity-onset_diabetes_of_the_young_type_2 (1 variants)
Microcephaly (1 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. These statistics are base on transcript: NM_000024537.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	177 clinvar	1 clinvar	180
missense		2 clinvar	297 clinvar	16 clinvar	4 clinvar	319
nonsense		2 clinvar	9 clinvar			11
start loss		1	4			5
frameshift	1 clinvar	4 clinvar	15 clinvar	1 clinvar		21
splice donor/acceptor (+/-2bp)			8 clinvar		1 clinvar	9
Total	1	9	335	194	6

Highest pathogenic variant AF is 0.0000231391

Loading clinvar variants...

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