YARS1

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

Basic information

Region (hg38): 1:32775237-32818031

Previous symbols: [ "YARS" ]

Links

ENSG00000134684

∙ NCBI:8565 ∙ OMIM:603623 ∙ HGNC:12840 ∙ Uniprot:P54577 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Charcot-Marie-Tooth disease dominant intermediate C (Supportive), mode of inheritance: AD
Charcot-Marie-Tooth disease dominant intermediate C (Strong), mode of inheritance: AD
neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2 (Strong), mode of inheritance: AR
Charcot-Marie-Tooth disease (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurologic, endocrine, and pancreatic disease, infantile-onset 2	AR	Audiologic/Otolaryngologic; Endocrine; Gastrointestinal	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; The condition may include multiple endocrine abnormalities, including early-onset hypoglycemia, and awareness may allow prompt diagnosis and medical management; Individuals have been described with varying degrees of hepatic dysfunction, and awareness may allow management of sequelae	Audiologic/Otolaryngologic; Endocrine; Gastrointestinal; Neurologic	14606043; 16429158; 27633801; 30214071; 30304524; 33490854

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the YARS1 gene.

Charcot-Marie-Tooth_disease_dominant_intermediate_C (459 variants)
Inborn_genetic_diseases (104 variants)
not_provided (97 variants)
not_specified (32 variants)
Neurologic,_endocrine,_and_pancreatic_disease,_multisystem,_infantile-onset_2 (17 variants)
YARS1-related_disorder (12 variants)
Charcot-Marie-Tooth,_Intermediate (3 variants)
Charcot-Marie-Tooth_disease (3 variants)
Neurologic,_endocrine,_and_pancreatic_disease,_multisystem,_infantile-onset (2 variants)
Neurodevelopmental_delay (2 variants)
Corpus_callosum,_agenesis_of (1 variants)
Acute_kidney_injury (1 variants)
Severe_hearing_impairment (1 variants)
Recurrent_infections (1 variants)
Hyperinsulinemic_hypoglycemia (1 variants)
Primary_amenorrhea (1 variants)
Liver_failure (1 variants)
Metachromatic_leukodystrophy (1 variants)
Anemia (1 variants)
Hepatic_steatosis (1 variants)
Retinal_degeneration (1 variants)
recessive_ARS-related_multisystem_disease (1 variants)
Global_developmental_delay (1 variants)
Cholestatic_liver_disease (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the YARS1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003680.4. 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			3 clinvar	103 clinvar	2 clinvar	108
missense	4 clinvar	13 clinvar	258 clinvar	14 clinvar	2 clinvar	291
nonsense		1 clinvar	10 clinvar			11
start loss						0
frameshift	1 clinvar	2 clinvar	16 clinvar			19
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	5	16	295	117	4

Highest pathogenic variant AF is 0.0000334589

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
YARS1	protein_coding	protein_coding	ENST00000373477	13	42915

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00100	0.999	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.14	228	282	0.809	0.0000158	3449
Missense in Polyphen		82	113.76	0.72081		1452
Synonymous	-0.852	124	113	1.10	0.00000674	1037
Loss of Function	3.05	10	27.2	0.368	0.00000137	354

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.000272	0.000272
South Asian	0.000131	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr- AMP and then transferred to the acceptor end of tRNA(Tyr). {ECO:0000250}.;
Disease: DISEASE: Charcot-Marie-Tooth disease, dominant, intermediate type, C (CMTDIC) [MIM:608323]: A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. The dominant intermediate type C is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. {ECO:0000269|PubMed:16429158}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);Phenylalanine and Tyrosine Metabolism;Phenylketonuria;Tyrosinemia Type 3 (TYRO3);Tyrosinemia Type 2 (or Richner-Hanhart syndrome);tRNA Aminoacylation;Translation;Metabolism of proteins;tRNA charging;Cytosolic tRNA aminoacylation (Consensus)

Recessive Scores

pRec: 0.278

Intolerance Scores

loftool: 0.674
rvis_EVS: -0.2
rvis_percentile_EVS: 38.82

Haploinsufficiency Scores

pHI: 0.188
hipred: Y
hipred_score: 0.657
ghis: 0.522

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: Yars
Phenotype: homeostasis/metabolism phenotype; 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); growth/size/body region phenotype; embryo phenotype;

Gene ontology

Biological process: tRNA aminoacylation for protein translation;tyrosyl-tRNA aminoacylation;apoptotic process
Cellular component: extracellular space;cytoplasm;cytosol;nuclear body;aminoacyl-tRNA synthetase multienzyme complex;methionyl glutamyl tRNA synthetase complex
Molecular function: tRNA binding;RNA binding;tyrosine-tRNA ligase activity;interleukin-8 receptor binding;protein binding;ATP binding