MTARC2

Chr 1

mitochondrial amidoxime reducing component 2

Also known as: MARC2, MOSC2

NCBI Gene: 54996ENSG00000117791UniProt: Q969Z3

The protein encoded by this gene is an enzyme found in the outer mitochondrial membrane that reduces N-hydroxylated substrates. The encoded protein uses molybdenum as a cofactor and cytochrome b5 type B and NADH cytochrome b5 reductase as accessory proteins. One type of substrate used is N-hydroxylated nucleotide base analogues, which can be toxic to a cell. Other substrates include N(omega)-hydroxy-L-arginine (NOHA) and amidoxime prodrugs, which are activated by the encoded enzyme. Multiple transcript variants encoding the different isoforms have been found for this gene. [provided by RefSeq, Sep 2016]

84
ClinVar variants
29
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MTARC2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
29 Pathogenic / Likely Pathogenic· 50 VUS of 84 total submissions

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.
0.99LOEUF
pLI 0.000
Z-score 1.59
OE 0.55 (0.32–0.99)
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.
0.43Z-score
OE missense 0.91 (0.79–1.04)
150 obs / 165.6 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.0.55 (0.32–0.99)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.79–1.04)
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.1.01
0≤1.21.6
LoF obs/exp: 8 / 14.5Missense obs/exp: 150 / 165.6Syn Z: -0.07

ClinVar Variant Classifications

84 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic1
VUS50
Likely Benign5
28
Pathogenic
1
Likely Pathogenic
50
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
28
0
28
Likely Pathogenic
0
0
1
0
1
VUS
0
45
5
0
50
Likely Benign
0
5
0
0
5
Benign
0
0
0
0
0
Total05034084

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

View in ClinVar →

Protein Context — Lollipop Plot

MTARC2 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
mARC1 in MASLD: Modulation of lipid accumulation in human hepatocytes and adipocytes.
Jones AK et al.·Hepatol Commun
2024
The mammalian molybdenum enzymes of mARC.
Ott G et al.·J Biol Inorg Chem
2015Review
Divergent role of Mitochondrial Amidoxime Reducing Component 1 (MARC1) in human and mouse.
Smagris E et al.·PLoS Genet
2024Functional
Integrating proteomic and transcriptomic high-throughput surveys for search of new biomarkers of colon tumors.
Mikula M et al.·Funct Integr Genomics
2011
The Chlamydomonas reinhardtii molybdenum cofactor enzyme crARC has a Zn-dependent activity and protein partners similar to those of its human homologue.
Chamizo-Ampudia A et al.·Eukaryot Cell
2011
MTARC1 Inactivation Remodels Lipid Droplets to Protect Against Metabolic Fatty Liver Disease.
Tie M et al.·Liver Int
2026Functional
The pivotal role of the mitochondrial amidoxime reducing component 2 in protecting human cells against apoptotic effects of the base analog N6-hydroxylaminopurine.
Plitzko B et al.·J Biol Chem
2015
A novel mitochondrial amidoxime reducing component 2 is a favorable indicator of cancer and suppresses the progression of hepatocellular carcinoma by regulating the expression of p27.
Wu D et al.·Oncogene
2020
The involvement of mitochondrial amidoxime reducing components 1 and 2 and mitochondrial cytochrome b5 in N-reductive metabolism in human cells.
Plitzko B et al.·J Biol Chem
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools