MARS1

Chr 12ARAD

methionyl-tRNA synthetase 1

Also known as: CMT2U, ILFS2, ILLD, MARS, METRS, MRS, MTRNS, SPG70

NCBI Gene: 4141ENSG00000166986UniProt: P56192

This gene encodes a member of the class I family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. The encoded protein is a component of the multi-tRNA synthetase complex and catalyzes the ligation of methionine to tRNA molecules. [provided by RefSeq, Jan 2011]

Primary Disease Associations & Inheritance

?Trichothiodystrophy 9, nonphotosensitiveMIM #619692
AR
Charcot-Marie-Tooth disease, axonal, type 2UMIM #616280
AD
Interstitial lung and liver diseaseMIM #615486
AR
Spastic paraplegia 70, autosomal recessiveMIM #620323
AR
585
ClinVar variants
3
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— MARS1
🧬
Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease · ADLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
3 Pathogenic / Likely Pathogenic· 343 VUS of 585 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.78LOEUF
pLI 0.000
Z-score 2.91
OE 0.58 (0.44–0.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.14Z-score
OE missense 0.86 (0.79–0.93)
437 obs / 509.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.58 (0.44–0.78)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.79–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 33 / 56.6Missense obs/exp: 437 / 509.3Syn Z: 0.14

ClinVar Variant Classifications

585 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic2
VUS343
Likely Benign227
Benign2
Conflicting10
1
Pathogenic
2
Likely Pathogenic
343
VUS
227
Likely Benign
2
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
0
0
1
Likely Pathogenic
0
1
1
0
2
VUS
32
263
45
3
343
Likely Benign
0
3
109
115
227
Benign
0
0
1
1
2
Conflicting
—10
Total32268156119585

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MARS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Trichothiodystrophy 9, nonphotosensitive

MIM #619692

Molecular basis of disorder known

Autosomal recessive

Charcot-Marie-Tooth disease, axonal, type 2U

MIM #616280

Molecular basis of disorder known

Autosomal dominant

Interstitial lung and liver disease

MIM #615486

Molecular basis of disorder known

Autosomal recessive

Spastic paraplegia 70, autosomal recessive

MIM #620323

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — MARS1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Classification of patients with sepsis according to blood genomic endotype: a prospective cohort study.
Scicluna BP et al.·Lancet Respir Med
2017Cohort
Uncovering heterogeneity in sepsis: a comparative analysis of subphenotypes.
van Amstel RBE et al.·Intensive Care Med
2023
Host and Microbe Blood Metagenomics Reveals Key Pathways Characterizing Critical Illness Phenotypes.
Neyton LPA et al.·Am J Respir Crit Care Med
2024
Expanding the genotypes and phenotypes for 19 rare diseases by exome sequencing performed in pediatric intensive care unit.
Liu J et al.·Hum Mutat
2021
Homocysitaconate controls inflammation through reshaping methionine metabolism and N-homocysteinylation.
Lin M et al.·Cell Metab
2025
N-Homocysteinylation of HMGB1/2 Promotes Corpus Cavernosum Endothelial Senescence in Erectile Dysfunction.
Hu P et al.·Int J Biol Sci
2025
Deep phenotyping of MARS1 (interstitial lung and liver disease) and LARS1 (infantile liver failure syndrome 1) recessive multisystemic disease using Human Phenotype Ontology annotation: Overlap and differences. Case report and review of literature.
La Fay C et al.·Eur J Med Genet
2021Review
Comprehensive Genomic Analysis of Cemento-Ossifying Fibroma.
Gomez RS et al.·Mod Pathol
2024
Four pedigrees with aminoacyl-tRNA synthetase abnormalities.
Okamoto N et al.·Neurol Sci
2022
New staining method using methionyl-tRNA synthetase 1 antibody for brushing cytology of bile duct cancer.
Jang SI et al.·Gastrointest Endosc
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
AnemiaGeneticsErythropoiesis

Genomic of CONgenital Sideroblastic Anemias

RECRUITING
NCT07459816Phase NACentre Hospitalier Universitaire, AmiensStarted 2025-10-28
blood redrawal

External Resources

Links to major genomics databases and tools