MARS1

methionyl-tRNA synthetase 1, the group of MicroRNA protein coding host genes|Aminoacyl tRNA synthetases, Class I

Basic information

Region (hg38): 12:57475444-57517569

Previous symbols: [ "MARS" ]

Links

ENSG00000166986 ∙ NCBI:4141 ∙ OMIM:156560 ∙ HGNC:6898 ∙ Uniprot:P56192 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Charcot-Marie-Tooth disease axonal type 2U (Supportive), mode of inheritance: AD
• autosomal recessive spastic paraplegia type 70 (Supportive), mode of inheritance: AR
• severe early-onset pulmonary alveolar proteinosis due to MARS deficiency (Supportive), mode of inheritance: AR
• trichothiodystrophy 9, nonphotosensitive (Limited), mode of inheritance: AR
• severe early-onset pulmonary alveolar proteinosis due to MARS deficiency (Strong), mode of inheritance: AR
• Charcot-Marie-Tooth disease axonal type 2U (Strong), mode of inheritance: AD
• trichothiodystrophy 9, nonphotosensitive (Limited), mode of inheritance: Unknown
• spastic paraplegia 70, autosomal recessive (Limited), mode of inheritance: Unknown
• Charcot-Marie-Tooth disease (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Interstitial lung and liver disease	AR	Hematologic	While the condition may involve multiple issues related to medical care, the described individual had transfusion-dependent anemia, and awareness may allow prompt recognition and treatment	Biochemical; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic; Pulmonary	23729695; 24103465; 24354524; 24482476; 25913036; 33909043; 34585293

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MARS1 gene.

• Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency;Charcot-Marie-Tooth disease axonal type 2U (352 variants)
• Inborn genetic diseases (131 variants)
• Charcot-Marie-Tooth disease axonal type 2U;Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency (127 variants)
• not provided (96 variants)
• Charcot-Marie-Tooth disease (61 variants)
• not specified (45 variants)
• Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency (12 variants)
• Charcot-Marie-Tooth disease axonal type 2U (8 variants)
• MARS1-related condition (5 variants)
• Spastic paraplegia 70, autosomal recessive (3 variants)
• Trichothiodystrophy 9, nonphotosensitive (3 variants)
• See cases (2 variants)
• MARS-Related Disorder (2 variants)
• - (1 variants)
• Hereditary spastic paraplegia (1 variants)
• Distal spinal muscular atrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MARS1 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			3	109	4	116
missense		1	251	9		261
nonsense	1		13			14
start loss			1			1
frameshift	2		15			17
inframe indel			3			3
splice donor/acceptor (+/-2bp)			9			9
splice region			21	24	3	48
non coding			8	74	9	91
Total	3	1	303	192	13

Highest pathogenic variant AF is 0.0000131

Variants in MARS1

This is a list of pathogenic ClinVar variants found in the MARS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-57476106-C-T		not specified	Uncertain significance (Feb 16, 2023)
12-57476351-C-G		not specified	Likely benign (Jan 02, 2024)
12-57476372-A-C		Coronary artery spasm 3, susceptibility to	Uncertain significance (Jan 01, 2010)
12-57476450-T-C		not specified	Uncertain significance (Sep 14, 2023)
12-57476616-C-A		not specified	Uncertain significance (Jun 01, 2023)
12-57476621-T-A		not specified	Uncertain significance (Jan 31, 2023)
12-57476638-G-A		not specified	Uncertain significance (Aug 12, 2021)
12-57476893-G-C		not specified	Uncertain significance (May 31, 2023)
12-57477182-C-T		not specified	Uncertain significance (Aug 04, 2023)
12-57477262-C-T		not specified	Uncertain significance (Aug 22, 2023)
12-57477470-G-T		not specified	Uncertain significance (Dec 21, 2023)
12-57477481-G-A		not specified	Uncertain significance (Oct 27, 2023)
12-57477623-G-A		not specified	Uncertain significance (May 31, 2023)
12-57478562-G-A		not specified	Likely benign (Nov 15, 2021)
12-57478590-C-T		not specified	Uncertain significance (Jul 27, 2022)
12-57478665-G-A			Uncertain significance (-)
12-57478668-G-T		not specified	Uncertain significance (Jun 26, 2023)
12-57478754-G-A		not specified	Uncertain significance (Jul 06, 2021)
12-57479200-A-C			Benign (Jul 16, 2018)
12-57487850-CA-C			Benign (May 05, 2020)
12-57487850-CAA-C			Benign (Oct 27, 2020)
12-57487850-CAAA-C			Likely benign (Feb 13, 2020)
12-57488073-C-T		Hereditary spastic paraplegia	Uncertain significance (Mar 07, 2017)
12-57488092-T-A		Charcot-Marie-Tooth disease axonal type 2U;Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency	Uncertain significance (Jul 24, 2023)
12-57488095-G-C		Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency;Charcot-Marie-Tooth disease axonal type 2U	Uncertain significance (Aug 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MARS1	protein_coding	protein_coding	ENST00000262027	21	42125

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.05e-15	0.997	125617	0	131	125748	0.000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.14	437	509	0.858	0.0000291	5837
Missense in Polyphen		115	171.14	0.67196		1960
Synonymous	0.144	197	200	0.987	0.0000107	1797
Loss of Function	2.91	33	56.6	0.583	0.00000320	577

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00167	0.00167
Ashkenazi Jewish	0.00	0.00
East Asian	0.000490	0.000489
Finnish	0.000140	0.000139
European (Non-Finnish)	0.000554	0.000554
Middle Eastern	0.000490	0.000489
South Asian	0.000425	0.000425
Other	0.000163	0.000163

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:11714285}.
• Disease: DISEASE: Interstitial lung and liver disease (ILLD) [MIM:615486]: An autosomal recessive, life-threatening disorder characterized by respiratory insufficiency and progressive liver disease with onset in infancy or early childhood. Clinical features include failure to thrive, hypotonia, intermittent lactic acidosis, aminoaciduria, hypothyroidism, interstitial lung disease, pulmonary alveolar proteinosis, anemia, and liver canalicular cholestasis, steatosis, and iron deposition. {ECO:0000269|PubMed:24103465, ECO:0000269|PubMed:25913036}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease 2U (CMT2U) [MIM:616280]: An axonal 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. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2U is a slowly progressive, autosomal dominant form characterized by late-adult onset. {ECO:0000269|PubMed:23729695, ECO:0000269|PubMed:24354524}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Selenocompound metabolism - Homo sapiens (human);Aminoacyl-tRNA biosynthesis - Homo sapiens (human);S-Adenosylhomocysteine (SAH) Hydrolase Deficiency;Methionine Metabolism;Methionine Adenosyltransferase Deficiency;Glycine N-methyltransferase Deficiency;Hypermethioninemia;Methylenetetrahydrofolate Reductase Deficiency (MTHFRD);Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cblG complementation type;Selenoamino Acid Metabolism;Cystathionine Beta-Synthase Deficiency;tRNA Aminoacylation;Translation;Metabolism of proteins;Metabolism of amino acids and derivatives;Metabolism;tRNA charging;Methionine Cysteine metabolism;Selenoamino acid metabolism;SeMet incorporation into proteins;Cytosolic tRNA aminoacylation (Consensus)

Recessive Scores

• pRec: 0.502

Intolerance Scores

• loftool: 0.963
• rvis_EVS: -0.97
• rvis_percentile_EVS: 8.95

Haploinsufficiency Scores

• pHI: 0.658
• hipred: Y
• hipred_score: 0.594
• ghis: 0.547

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.993

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mars

Zebrafish Information Network

• Gene name: mars
• Affected structure: pharyngeal arch 1
• Phenotype tag: abnormal
• Phenotype quality: hypoplastic

Gene ontology

• Biological process: tRNA aminoacylation for protein translation;methionyl-tRNA aminoacylation;cellular response to starvation;rRNA transcription;cellular response to insulin stimulus;cellular response to platelet-derived growth factor stimulus;cellular response to epidermal growth factor stimulus;positive regulation of transcription of nucleolar large rRNA by RNA polymerase I
• Cellular component: nucleolus;cytoplasm;cytosol;membrane;aminoacyl-tRNA synthetase multienzyme complex;extracellular exosome
• Molecular function: tRNA binding;methionine-tRNA ligase activity;ATP binding