MTARC1

Chr 1

mitochondrial amidoxime reducing component 1

Also known as: MARC1, MOSC1

NCBI Gene: 64757 ENSG00000186205 UniProt: Q5VT66 OMIM: 614126

The protein catalyzes the reduction of N-oxygenated molecules in mitochondria, functioning as a counterpart to cytochrome P450 in metabolic cycles and playing a role in prodrug conversion and nitric oxide regulation. Mutations cause autosomal recessive spastic paraplegia and developmental delay. This gene shows minimal constraint against loss-of-function variants (low pLI score).

OMIM ResearchSummary from RefSeq, UniProt

Enables molybdenum ion binding activity; molybdopterin cofactor binding activity; and oxidoreductase activity, acting on other nitrogenous compounds as donors. Contributes to nitrite reductase (NO-forming) activity. Involved in cellular detoxification of nitrogen compound; nitrate metabolic process; and nitric oxide biosynthetic process. Located in mitochondrion. Part of nitric-oxide synthase complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.27

Clinical Summary— MTARC1

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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

49 VUS of 61 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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?

1.27LOEUF

pLI 0.000

Z-score 0.74

OE 0.80 (0.52–1.27)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.58Z-score

OE missense 0.87 (0.77–1.00)

151 obs / 172.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.80 (0.52–1.27)

0≤0.351.4

Missense OE?0.87 (0.77–1.00)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 13 / 16.2Missense obs/exp: 151 / 172.6Syn Z: 0.82

This gene — mechanism propensity

0.6455th %ile

GOF

0.4381th %ile

LOF

0.3549th %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

61 submitted variants in ClinVar

ClinVar

Classification Summary

VUS49

Likely Benign2

Benign5

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	49	0	0	49
Likely Benign	2	0	0	2
Benign	2	1	2	5
Total	53	1	2	56

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap MTARC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →