OMA1

Chr 1

OMA1 zinc metallopeptidase

Also known as: 2010001O09Rik, MPRP-1, MPRP1, YKR087C, ZMPOMA1, peptidase

NCBI Gene: 115209 ENSG00000162600 UniProt: Q96E52

OMA1 encodes a mitochondrial metalloprotease that regulates mitochondrial quality control by cleaving target proteins including OPA1, DELE1, and UQCC3 in response to mitochondrial stress. Mutations cause autosomal recessive primary mitochondrial myopathy with early-onset progressive external ophthalmoplegia, ptosis, and exercise intolerance. The gene shows minimal constraint against loss-of-function variants (LOEUF 1.13), suggesting that complete loss of function may be tolerated in the heterozygous state.

ResearchSummary from RefSeq, UniProt

Enables metalloendopeptidase activity. Involved in several processes, including HRI-mediated signaling; proteolysis; and regulation of mitochondrion organization. Located in mitochondrial inner membrane. Is active in mitochondrial intermembrane space. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.13

Clinical Summary— OMA1

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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

24 total variants — no pathogenic classifications of 24 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.13LOEUF

pLI 0.000

Z-score 1.04

OE 0.78 (0.55–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.49Z-score

OE missense 0.92 (0.82–1.02)

248 obs / 270.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.55–1.13)

0≤0.351.4

Missense OE?0.92 (0.82–1.02)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 20 / 25.7Missense obs/exp: 248 / 270.9Syn Z: 0.71

This gene — mechanism propensity

0.7229th %ile

GOF

0.5758th %ile

LOF

0.3648th %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

24 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Benign4

Benign7

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	0	0	0	0
Likely Benign	4	0	0	4
Benign	4	1	2	7
Total	8	1	2	11

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap OMA1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →