IARS1

isoleucyl-tRNA synthetase 1, the group of Aminoacyl tRNA synthetases, Class I|Small nucleolar RNA protein coding host genes|MicroRNA protein coding host genes

Basic information

Region (hg38): 9:92210207-92293854

Previous symbols: [ "IARS" ]

Links

ENSG00000196305 ∙ NCBI:3376 ∙ OMIM:600709 ∙ HGNC:5330 ∙ Uniprot:P41252 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy (Supportive), mode of inheritance: AR
• growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy	AR	Biochemical	Patients have been shown to have zinc deficiency (possibly related to chronic liver disease), and medical management (with zinc supplementation) has been shown to be beneficial	Biochemical; Gastrointestinal; Musculoskeletal; Neurologic	27426735

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IARS1 gene.

• not provided (11 variants)
• Growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IARS1 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				61	7	68
missense			150	12	7	169
nonsense	6					6
start loss						0
frameshift	7	4				11
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2	1			3
splice region			6	17	5	28
non coding				33	9	42
Total	13	6	152	106	23

Highest pathogenic variant AF is 0.0000329

Variants in IARS1

This is a list of pathogenic ClinVar variants found in the IARS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-92210821-T-C		not specified	Uncertain significance (Oct 04, 2022)
9-92210869-C-T		IARS1-related disorder	Benign (Jan 25, 2024)
9-92210876-G-A			Likely benign (Jan 01, 2024)
9-92210883-G-A			Likely benign (Jan 15, 2024)
9-92210893-G-T		not specified	Uncertain significance (Nov 12, 2020)
9-92210896-T-C			Likely benign (Mar 28, 2022)
9-92210905-A-G			Likely benign (Nov 15, 2022)
9-92222502-G-A			Likely benign (Jul 17, 2023)
9-92222512-C-T			Likely benign (Dec 11, 2023)
9-92222524-C-T			Likely benign (Dec 18, 2023)
9-92222533-C-G		Growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy	Uncertain significance (May 21, 2018)
9-92222538-T-C		Intellectual disability	Uncertain significance (Mar 10, 2020)
9-92222541-G-C		not specified	Uncertain significance (Jan 29, 2024)
9-92222545-C-T			Likely benign (Aug 03, 2022)
9-92222558-C-T		not specified	Uncertain significance (Dec 17, 2023)
9-92222559-T-G			Likely benign (Jul 29, 2018)
9-92222564-C-T		not specified	Uncertain significance (Feb 22, 2021)
9-92222568-G-A			Uncertain significance (Aug 06, 2022)
9-92222593-C-T			Likely benign (Mar 29, 2018)
9-92222614-T-C			Benign (Jan 24, 2024)
9-92222648-G-A		not specified	Uncertain significance (Aug 22, 2022)
9-92222655-C-T			Uncertain significance (Jun 14, 2022)
9-92222663-A-G		Growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy • not specified	Uncertain significance (Nov 14, 2022)
9-92222675-G-A			Uncertain significance (Jul 20, 2022)
9-92222681-G-C		IARS1-related disorder	Likely benign (May 08, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IARS1	protein_coding	protein_coding	ENST00000375643	33	83550

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.73e-21	0.999	125594	0	154	125748	0.000613

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.13	594	677	0.877	0.0000351	8281
Missense in Polyphen		211	258.48	0.8163		3121
Synonymous	-0.831	258	242	1.07	0.0000126	2395
Loss of Function	3.24	46	76.6	0.601	0.00000410	898

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00108	0.00108
Ashkenazi Jewish	0.00	0.00
East Asian	0.000876	0.000870
Finnish	0.000370	0.000370
European (Non-Finnish)	0.000644	0.000642
Middle Eastern	0.000876	0.000870
South Asian	0.000693	0.000686
Other	0.000979	0.000978

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:0000269|PubMed:8052601}.
• Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);Amino Acid metabolism;tRNA Aminoacylation;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: 0.192

Intolerance Scores

• loftool: 0.972
• rvis_EVS: -1.07
• rvis_percentile_EVS: 7.34

Haploinsufficiency Scores

• pHI: 0.718
• hipred: Y
• hipred_score: 0.747
• ghis: 0.598

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: Iars

Zebrafish Information Network

• Gene name: iars
• Affected structure: trunk vasculature
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: osteoblast differentiation;tRNA aminoacylation for protein translation;isoleucyl-tRNA aminoacylation;aminoacyl-tRNA metabolism involved in translational fidelity
• Cellular component: cytoplasm;cytosol;membrane;aminoacyl-tRNA synthetase multienzyme complex;extracellular exosome
• Molecular function: tRNA binding;aminoacyl-tRNA editing activity;isoleucine-tRNA ligase activity;protein binding;ATP binding;GTPase binding