DARS1

aspartyl-tRNA synthetase 1, the group of Aminoacyl tRNA synthetases, Class II

Basic information

Region (hg38): 2:135905881-135986100

Previous symbols: [ "DARS" ]

Links

ENSG00000115866 ∙ NCBI:1615 ∙ OMIM:603084 ∙ HGNC:2678 ∙ Uniprot:P14868 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypomyelination with brain stem and spinal cord involvement and leg spasticity (Definitive), mode of inheritance: AR
• hypomyelination with brain stem and spinal cord involvement and leg spasticity (Supportive), mode of inheritance: AR
• hypomyelination with brain stem and spinal cord involvement and leg spasticity (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypomyelination with brainstem and spinal cord involvement and leg spasticity	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	23643384

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DARS1 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DARS1 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	27		28
missense	1	3	61	2	1	68
nonsense			5			5
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			2	1		3
splice region			5	13	3	21
non coding			2	27	16	45
Total	1	3	72	57	17

Highest pathogenic variant AF is 0.0000197

Variants in DARS1

This is a list of pathogenic ClinVar variants found in the DARS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-135907329-C-T		Hypomyelination with brain stem and spinal cord involvement and leg spasticity • Inborn genetic diseases	Uncertain significance (Nov 09, 2023)
2-135907330-G-A			Uncertain significance (Jan 20, 2020)
2-135907332-T-G		Inborn genetic diseases	Uncertain significance (Mar 03, 2021)
2-135907336-G-C			Uncertain significance (Apr 10, 2022)
2-135907341-C-T		Hypomyelination with brain stem and spinal cord involvement and leg spasticity	Likely pathogenic (May 03, 2020)
2-135907342-G-A			Uncertain significance (Aug 24, 2022)
2-135907342-G-C		Hypomyelination with brain stem and spinal cord involvement and leg spasticity	Pathogenic (May 02, 2013)
2-135907362-C-T			Uncertain significance (Jul 18, 2022)
2-135907363-G-A		Hypomyelination with brain stem and spinal cord involvement and leg spasticity	Conflicting classifications of pathogenicity (Oct 17, 2022)
2-135907381-G-C		Inborn genetic diseases	Uncertain significance (Nov 29, 2023)
2-135907390-T-G		Inborn genetic diseases	Uncertain significance (Dec 14, 2021)
2-135907396-C-T			Uncertain significance (Jan 15, 2022)
2-135907405-A-G		not specified	Benign (Jan 24, 2024)
2-135911120-A-C			Likely benign (Sep 06, 2022)
2-135911121-G-A		not specified	Benign (Jan 21, 2024)
2-135911162-G-A			Conflicting classifications of pathogenicity (Nov 01, 2023)
2-135911173-G-A			Likely benign (Sep 26, 2022)
2-135911174-C-T		Hypomyelination with brain stem and spinal cord involvement and leg spasticity	Pathogenic (May 02, 2013)
2-135911179-G-C		DARS1-related disorder	Likely benign (Jun 13, 2019)
2-135911217-A-G			Likely benign (Dec 02, 2021)
2-135911217-A-T			Likely benign (Dec 30, 2022)
2-135911368-T-C		not specified	Benign (Jan 15, 2024)
2-135911368-TTTAAG-T			Likely benign (Mar 18, 2022)
2-135911370-T-C			Likely benign (Oct 17, 2022)
2-135911399-GCT-G			Uncertain significance (Oct 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DARS1	protein_coding	protein_coding	ENST00000264161	16	79424

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000854	0.999	125718	0	28	125746	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.747	235	270	0.872	0.0000136	3291
Missense in Polyphen		88	109.9	0.80072		1328
Synonymous	0.107	87	88.3	0.986	0.00000444	906
Loss of Function	2.96	14	32.1	0.436	0.00000170	388

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000248	0.000245
Ashkenazi Jewish	0.00	0.00
East Asian	0.000164	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000163	0.000158
Middle Eastern	0.000164	0.000163
South Asian	0.0000330	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. {ECO:0000250|UniProtKB:P15178}.
• Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);Hypoacetylaspartia;Aspartate Metabolism;Canavan Disease;Alanine and aspartate metabolism;tRNA Aminoacylation;Alanine Aspartate Asparagine metabolism;Translation;Metabolism of proteins;Metabolism of amino acids and derivatives;Metabolism;tRNA charging;Selenoamino acid metabolism;SeMet incorporation into proteins;Cytosolic tRNA aminoacylation (Consensus)

Recessive Scores

• pRec: 0.196

Intolerance Scores

• loftool: 0.456
• rvis_EVS: 0.26
• rvis_percentile_EVS: 70.44

Haploinsufficiency Scores

• pHI: 0.634
• hipred: Y
• hipred_score: 0.706
• ghis: 0.588

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dars
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: translation;tRNA aminoacylation for protein translation;aspartyl-tRNA aminoacylation;protein-containing complex assembly
• Cellular component: cytoplasm;cytosol;membrane;aminoacyl-tRNA synthetase multienzyme complex;synapse;extracellular exosome
• Molecular function: RNA binding;aminoacylase activity;aspartate-tRNA ligase activity;protein binding;ATP binding