NARS1

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

Basic information

Region (hg38): 18:57600656-57622213

Previous symbols: [ "NARS" ]

Links

ENSG00000134440 ∙ NCBI:4677 ∙ OMIM:108410 ∙ HGNC:7643 ∙ Uniprot:O43776 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (Strong), mode of inheritance: AD
• neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (Strong), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (Moderate), mode of inheritance: AD
• neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities	AD/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	Craniofacial; Musculoskeletal; Neurologic	32738225; 32788587

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NARS1 gene.

• Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (1 variants)
• not provided (1 variants)
• Developmental disorder (1 variants)
• Neurodevelopmental disorder (1 variants)
• Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NARS1 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				13	1	14
missense		8	105	5		118
nonsense	1	1	2			4
start loss						0
frameshift			5			5
inframe indel						0
splice donor/acceptor (+/-2bp)		1	5			6
splice region			2			2
non coding					1	1
Total	1	10	117	18	2

Variants in NARS1

This is a list of pathogenic ClinVar variants found in the NARS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-57601634-C-T			Benign (Sep 05, 2019)
18-57601659-G-A		not specified	Uncertain significance (Jan 03, 2024)
18-57601666-G-A		Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities	Likely pathogenic (Jun 25, 2021)
18-57601683-T-C		not specified	Uncertain significance (Oct 12, 2022)
18-57601687-A-G			Likely benign (Jan 01, 2025)
18-57601693-C-T		not specified	Uncertain significance (Apr 09, 2021)
18-57601698-C-T		not specified	Uncertain significance (Sep 01, 2023)
18-57601699-G-A		Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities • Neurodevelopmental disorder • Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities • Developmental disorder	Pathogenic (Dec 06, 2024)
18-57601702-T-C			Uncertain significance (Nov 16, 2022)
18-57601724-C-T			Likely benign (Aug 01, 2022)
18-57601725-G-A		not specified	Uncertain significance (Oct 01, 2024)
18-57601730-G-T		not specified	Uncertain significance (Aug 28, 2024)
18-57601731-A-G			Uncertain significance (Oct 06, 2023)
18-57601734-C-T		Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities	Uncertain significance (Jul 17, 2023)
18-57601735-G-A		Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities	Pathogenic/Likely pathogenic (May 26, 2023)
18-57601738-C-G		NARS1-related disorder	Uncertain significance (Sep 14, 2022)
18-57601744-C-T		Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities	Uncertain significance (Dec 29, 2023)
18-57601761-T-C			Uncertain significance (Jul 08, 2024)
18-57601773-C-A			Uncertain significance (Jun 13, 2023)
18-57601774-C-T		Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities	Uncertain significance (May 10, 2021)
18-57601775-G-A			Likely benign (Jun 01, 2022)
18-57601777-A-G			Uncertain significance (Jan 13, 2023)
18-57602361-C-T			Likely benign (Jan 01, 2024)
18-57602375-A-G			Uncertain significance (Feb 10, 2023)
18-57602378-GA-G			Uncertain significance (Aug 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NARS1	protein_coding	protein_coding	ENST00000256854	14	21558

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.95e-9	0.996	125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.828	268	309	0.868	0.0000172	3578
Missense in Polyphen		70	102.07	0.68584		1138
Synonymous	-0.339	118	113	1.04	0.00000638	1023
Loss of Function	2.62	20	37.2	0.537	0.00000244	398

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000271	0.000268
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000186	0.000185
European (Non-Finnish)	0.000243	0.000237
Middle Eastern	0.0000544	0.0000544
South Asian	0.000361	0.000359
Other	0.000328	0.000326

dbNSFP

Source: dbNSFP

• Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);Hypoacetylaspartia;Aspartate Metabolism;Canavan Disease;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;Photodynamic therapy-induced unfolded protein response;tRNA Aminoacylation;Alanine Aspartate Asparagine metabolism;Translation;Metabolism of proteins;tRNA charging;Cytosolic tRNA aminoacylation (Consensus)

Recessive Scores

• pRec: 0.150

Intolerance Scores

• loftool: 0.493
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.56

Haploinsufficiency Scores

• pHI: 0.448
• hipred: Y
• hipred_score: 0.648
• ghis: 0.577

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nars

Gene ontology

• Biological process: tRNA aminoacylation for protein translation;asparaginyl-tRNA aminoacylation
• Cellular component: cytoplasm;cytosol;extracellular exosome
• Molecular function: nucleic acid binding;asparagine-tRNA ligase activity;ATP binding