PET100

Chr 19AR

PET100 cytochrome c oxidase chaperone

Also known as: C19orf79, MC4DN12

NCBI Gene: 100131801 ENSG00000229833 UniProt: P0DJ07 OMIM: 614770

PET100 encodes a small protein essential for the maturation and assembly of mitochondrial complex IV (cytochrome c oxidase), which is part of the respiratory electron transport chain. Mutations cause mitochondrial complex IV deficiency with autosomal recessive inheritance, resulting in a mitochondrial respiratory chain disorder. The gene is not highly constrained against loss-of-function variants, consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Mitochondrial complex IV, or cytochrome c oxidase, is a large transmembrane protein complex that is part of the respiratory electron transport chain of mitochondria. The small protein encoded by this gene plays a role in the biogenesis of mitochondrial complex IV. This protein localizes to the inner mitochondrial membrane and is exposed to the intermembrane space. Mutations in this gene are associated with mitochondrial complex IV deficiency. This gene has a pseudogene on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.821 OMIM phenotype

Clinical Summary— PET100

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Gene-Disease Validity (ClinGen)

Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

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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

12 unique Pathogenic / Likely Pathogenic· 37 VUS of 124 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PET100

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.82LOEUF

pLI 0.000

Z-score -0.06

OE 1.03 (0.53–1.82)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.24Z-score

OE missense 0.90 (0.69–1.17)

38 obs / 42.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.03 (0.53–1.82)

0≤0.351.4

Missense OE?0.90 (0.69–1.17)

0≤0.61.4

Synonymous OE?0.54

0≤1.21.6

LoF obs/exp: 5 / 4.9Missense obs/exp: 38 / 42.4Syn Z: 1.37

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongPET100-related mitochondrial complex IV deficiencyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.75top 25%

GOF

0.76top 25%

LOF

0.2483th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

124 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic7

VUS37

Likely Benign54

Benign12

Conflicting5

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	2	1	0	5
Likely Pathogenic	5	2	0	0	7
VUS	3	30	4	0	37
Likely Benign	0	6	36	12	54
Benign	0	1	10	1	12
Conflicting	—				5
Total	10	41	51	13	120

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap PET100 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →