MTARC2

Chr 1

mitochondrial amidoxime reducing component 2

Also known as: MARC2, MOSC2

NCBI Gene: 54996 ENSG00000117791 UniProt: Q969Z3 OMIM: 614127

The MTARC2 protein is an outer mitochondrial membrane enzyme that reduces N-hydroxylated substrates using molybdenum as a cofactor, including toxic nucleotide base analogues and amidoxime prodrugs. This gene has very low constraint against loss-of-function variants (LOEUF 0.994), indicating that complete loss of protein function is generally tolerated. Currently, no established Mendelian disease phenotypes have been definitively linked to MTARC2 mutations in clinical practice.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.99

Clinical Summary— MTARC2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

45 VUS of 52 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.99LOEUF

pLI 0.000

Z-score 1.59

OE 0.55 (0.32–0.99)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.43Z-score

OE missense 0.91 (0.79–1.04)

150 obs / 165.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.55 (0.32–0.99)

0≤0.351.4

Missense OE?0.91 (0.79–1.04)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 8 / 14.5Missense obs/exp: 150 / 165.6Syn Z: -0.07

This gene — mechanism propensity

0.6358th %ile

GOF

0.4875th %ile

LOF

0.3647th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

52 submitted variants in ClinVar

ClinVar

Classification Summary

VUS45

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	45	45
Likely Benign	5	5
Benign	0	0
Total	50	50

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap MTARC2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →