PPTC7

Chr 12

protein phosphatase targeting COQ7

Also known as: TA-PP2C, TAPP2C

NCBI Gene: 160760 ENSG00000196850 UniProt: Q8NI37

This mitochondrial protein phosphatase regulates coenzyme Q biosynthesis and mitophagy by dephosphorylating key enzymes and mitophagy receptors. Mutations cause autosomal recessive mitochondrial disease with early-onset encephalopathy, developmental delay, and multisystem involvement. The gene is highly constrained against loss-of-function variants, reflecting its essential role in mitochondrial metabolism.

ResearchSummary from RefSeq, UniProt

Enables protein serine/threonine phosphatase activity and protein-macromolecule adaptor activity. Involved in negative regulation of mitophagy and positive regulation of ubiquinone biosynthetic process. Located in mitochondrial matrix. Is active in mitochondrial outer membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.36

Clinical Summary— PPTC7

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 22 VUS of 31 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

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.36LOEUF

pLI 0.938

Z-score 3.12

OE 0.08 (0.03–0.36)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.89Z-score

OE missense 0.39 (0.32–0.48)

70 obs / 178.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.36)

0≤0.351.4

Missense OE?0.39 (0.32–0.48)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 1 / 13.2Missense obs/exp: 70 / 178.6Syn Z: 0.32

This gene — mechanism propensity

0.3395th %ile

GOF

0.4283th %ile

LOF

0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.36

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

31 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic2

VUS22

Likely Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	1	1	2
VUS	22	0	22
Likely Benign	0	0	0
Benign	0	0	0
Total	23	1	24

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 9) ClinVar copy-number / structural variants overlap PPTC7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →