CARS1

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

Basic information

Region (hg38): 11:3000922-3057613

Previous symbols: [ "CARS" ]

Links

ENSG00000110619 ∙ NCBI:833 ∙ OMIM:123859 ∙ HGNC:1493 ∙ Uniprot:P49589 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly, developmental delay, and brittle hair syndrome	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	Dermatologic; Endocrine; Gastrointestinal; Neurologic	30824121

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CARS1 gene.

• Microcephaly, developmental delay, and brittle hair syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CARS1 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				12	5	17
missense		2	67	7	3	79
nonsense						0
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding				1		1
Total	1	2	67	20	8

Variants in CARS1

This is a list of pathogenic ClinVar variants found in the CARS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-3001129-A-C		not specified	Uncertain significance (Jun 29, 2023)
11-3001161-G-A		not specified	Uncertain significance (Sep 16, 2021)
11-3001208-T-C		not specified	Uncertain significance (Dec 27, 2022)
11-3001989-T-C		not specified	Uncertain significance (Nov 01, 2022)
11-3001996-C-T		not specified	Uncertain significance (Apr 12, 2022)
11-3002020-T-TG		Microcephaly, developmental delay, and brittle hair syndrome	Pathogenic (Aug 12, 2021)
11-3002560-C-T		not specified	Uncertain significance (Jan 16, 2024)
11-3002577-C-T			Likely benign (Mar 01, 2023)
11-3005379-T-C		not specified	Uncertain significance (Jan 10, 2023)
11-3006882-C-T		not specified	Uncertain significance (Jun 03, 2022)
11-3006936-C-T		not specified	Uncertain significance (Sep 29, 2022)
11-3006944-T-C		not specified	Uncertain significance (Jan 08, 2024)
11-3012221-A-G		not specified	Uncertain significance (May 06, 2024)
11-3012259-C-A		not specified	Uncertain significance (May 30, 2023)
11-3012266-G-T		not specified	Uncertain significance (Dec 20, 2023)
11-3015797-G-A		CARS1-related disorder	Likely benign (Sep 22, 2023)
11-3015805-G-A			Likely benign (Jun 28, 2017)
11-3015809-G-A		not specified	Uncertain significance (Jan 02, 2024)
11-3015812-A-T		Microcephaly, developmental delay, and brittle hair syndrome • not specified	Uncertain significance (Jul 22, 2024)
11-3015837-C-T		not specified	Likely benign (Jul 12, 2022)
11-3017132-C-T		not specified	Uncertain significance (Jul 11, 2023)
11-3017133-G-C		not specified	Uncertain significance (Sep 22, 2023)
11-3017133-G-T			Benign (Jul 15, 2018)
11-3017136-G-A			Benign (Jul 26, 2018)
11-3017171-C-T		not specified	Likely benign (Jan 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CARS1	protein_coding	protein_coding	ENST00000380525	23	56692

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000403	1.00	125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.20	411	485	0.847	0.0000287	5472
Missense in Polyphen		125	168.76	0.74071		1909
Synonymous	0.303	190	195	0.972	0.0000128	1522
Loss of Function	4.31	15	46.8	0.321	0.00000216	573

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000313	0.000304
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000274	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.000274	0.000272
South Asian	0.000183	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Note=A chromosomal aberration involving CARS is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;11)(p23;p15) with ALK.
• Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);Beta-mercaptolactate-cysteine disulfiduria;Cysteine Metabolism;Cystinosis, ocular nonnephropathic;tRNA Aminoacylation;Translation;Metabolism of proteins;Glycine Serine metabolism;tRNA charging;Methionine Cysteine metabolism;Cytosolic tRNA aminoacylation (Consensus)

Recessive Scores

• pRec: 0.233

Intolerance Scores

• loftool: 0.794
• rvis_EVS: -0.39
• rvis_percentile_EVS: 27.03

Haploinsufficiency Scores

• pHI: 0.174
• hipred: N
• hipred_score: 0.414
• ghis: 0.548

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: Cars

Zebrafish Information Network

• Gene name: cars
• Affected structure: skeletal muscle
• Phenotype tag: abnormal
• Phenotype quality: degenerate

Gene ontology

• Biological process: tRNA aminoacylation for protein translation;cysteinyl-tRNA aminoacylation
• Cellular component: cytoplasm;cytosol
• Molecular function: tRNA binding;cysteine-tRNA ligase activity;protein binding;ATP binding;protein homodimerization activity;metal ion binding