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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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MTARC1
mitochondrial amidoxime reducing component 1
Chromosome 1 · 1q41
NCBI Gene: 64757Ensembl: ENSG00000186205.15HGNC: HGNC:26189UniProt: Q5VT66
70PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nitrite reductase (NO-forming) activitynitrite reductase activitynitric oxide biosynthetic processnitrate metabolic processliver diseasecirrhosis of liveralcohol drinkingAbnormality of the liver
✦AI Summary

MTARC1 encodes mitochondrial amidoxime-reducing component 1 (mARC1), a molybdenum-dependent oxidoreductase that catalyzes reduction of N-oxygenated compounds including amidoxime prodrugs and N-hydroxylated substrates 12. The enzyme accepts electrons from NADH via cytochrome b5 reductase and cytochrome b5 to cleave N-OH bonds, enhancing drug bioavailability and potentially regulating endogenous nitric oxide biosynthesis 12. Clinically, MTARC1 has emerged as a key modifier of steatotic liver disease pathogenesis. Protective genetic variants in MTARC1 (particularly p.Ala165Thr) are associated with reduced hepatic steatosis, lower liver enzymes, and altered plasma lipid profiles 34. Conversely, increased MTARC1 mRNA associates with fatty liver disease progression 3. Mechanistically, hepatocyte mARC1 knockdown decreases hepatic lipid accumulation, increases triglyceride secretion, and alters lipid metabolism pathways in both cultured hepatocytes and mouse models 35. The protein also modulates lipid homeostasis in adipocytes 5. Importantly, MTARC1 p.Ala165Thr carriers show 39-50% reduced liver-related mortality without increased cardiovascular risk 4, establishing MTARC1 inhibition as a promising therapeutic target for metabolic dysfunction-associated steatotic liver disease 6.

Sources cited
1
MTARC1 catalyzes N-oxygenated molecule reduction and amidoxime prodrug conversion; involves electron transfer from NADH through cytochrome b5 reductase and cytochrome b5
PMID: 19053771
2
MTARC1 reduces N-oxygenated molecules with electron transfer mechanism; may regulate endogenous nitric oxide levels through NOHA reduction
PMID: 21029045
3
Hepatocyte mARC1 knockdown decreases lipid accumulation and increases triglyceride secretion; MTARC1 variants associated with liver enzymes, liver fat, and plasma lipids; increased mARC1 has adverse effects on metabolic traits
PMID: 37122688
4
MTARC1 p.Ala165Thr associated with 15% reduced NAFLD risk, distinctive lipid phenotype, and 39-50% lower liver-related mortality without cardiovascular harm
PMID: 34258604
5
mARC1 depletion in hepatocytes and adipocytes modulates lipid accumulation and cell death; protective variants decrease mARC1 protein; affects distinct lipid species and inflammatory pathway genes
PMID: 38619429
6
MTARC1 identified as genetic target for steatotic liver disease therapy through gene-based approaches
PMID: 40254880
7
MTARC1 harbors rare protective loss-of-function variants associated with NAFLD, proposed as potential drug target
PMID: 36280732
8
MTARC1 genetic variants demonstrate distinct VLDL-lipidomic signatures reflecting differential impact on hepatocellular lipid homeostasis in MASLD
PMID: 40408305
Disease Associationsⓘ20
liver diseaseOpen Targets
0.53Moderate
cirrhosis of liverOpen Targets
0.51Moderate
alcohol drinkingOpen Targets
0.47Moderate
Abnormality of the liverOpen Targets
0.43Moderate
glomerulonephritisOpen Targets
0.43Moderate
non-alcoholic fatty liver diseaseOpen Targets
0.35Weak
radiculitisOpen Targets
0.35Weak
metabolic syndromeOpen Targets
0.34Weak
physical activityOpen Targets
0.33Weak
nervous system diseaseOpen Targets
0.31Weak
goutOpen Targets
0.25Weak
response to statinOpen Targets
0.14Weak
Abnormality of the skeletal systemOpen Targets
0.08Suggestive
CirrhosisOpen Targets
0.08Suggestive
Abruptio PlacentaeOpen Targets
0.07Suggestive
Hyperlipoproteinemia type 1Open Targets
0.05Suggestive
non-alcoholic steatohepatitisOpen Targets
0.05Suggestive
Platelet-activating factor acetylhydrolase deficiencyOpen Targets
0.04Suggestive
hypoparathyroidism, familial isolated, 2Open Targets
0.04Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MTARC2Shared pathway100%CYB5R3Protein interaction75%TSTShared pathway33%SPRShared pathway33%CYB5BShared pathway25%GSTM3Shared pathway20%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
49%
Brain
36%
Heart
19%
Lung
17%
Ovary
8%
Gene Interaction Network
Click a node to explore
MTARC1MTARC2CYB5R3TSTSPRCYB5BGSTM3
PROTEIN STRUCTURE
Preparing viewer…
PDB7P41 · 1.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.23LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.89 [0.65–1.23]
RankingsWhere MTARC1 stands among ~20K protein-coding genes
  • #6,735of 20,598
    Most Researched70
  • #12,948of 17,882
    Most Constrained (LOEUF)1.23
Genes detectedMTARC1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Multiomics study of nonalcoholic fatty liver disease.
PMID: 36280732
Nat Genet · 2022
1.00
2
Hepatocyte mARC1 promotes fatty liver disease.
PMID: 37122688
JHEP Rep · 2023
0.90
3
Gene-based therapies for steatotic liver disease.
PMID: 40254880
Mol Ther · 2025
0.80
4
mARC1 in MASLD: Modulation of lipid accumulation in human hepatocytes and adipocytes.
PMID: 38619429
Hepatol Commun · 2024
0.70
5
Therapeutic opportunities for the treatment of NASH with genetically validated targets.
PMID: 37207913
J Hepatol · 2023
0.60