TOMM20

Chr 1

translocase of outer mitochondrial membrane 20

ENSG00000173726 UniProt: Q15388 OMIM: 601848

TOMM20 encodes a central receptor component of the translocase of the outer mitochondrial membrane (TOM) complex that recognizes and translocates cytosolically synthesized mitochondrial preproteins across the outer mitochondrial membrane. Mutations cause autosomal recessive mitochondrial complex V deficiency with early-onset encephalomyopathy, cardiomyopathy, and growth retardation. The gene shows tolerance to loss-of-function variants (pLI 0.03, LOEUF 0.94), suggesting that complete loss of function may be required for disease manifestation.

OMIM ResearchSummary from RefSeq, UniProt

Central receptor component of the translocase of the outer membrane of mitochondria (TOM) complex essential for the recognition and translocation of cytosolically synthesized mitochondrial preproteins (PubMed:40080546). Together with TOMM22 functions as the transit peptide receptor at the surface of the mitochondrion outer membrane and facilitates the movement of preproteins into the TOM40 translocation pore (PubMed:18331822). The TOM complex associates with the ion channel VDAC2 and PINK1 kinase at depolarized mitochondria, this interaction stabilizes PINK1 at the outer mitochondrial membrane and triggers downstream mitophagy by the recruitment of the E3 ubiquitin ligase PRKN (PubMed:40080546). Required for the translocation across the mitochondrial outer membrane of cytochrome P450 monooxygenases (By similarity)

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.94

Clinical Summary— TOMM20

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Population Constraint (gnomAD)

Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

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

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Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.94LOEUF

pLI 0.027

Z-score 1.70

OE 0.41 (0.20–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.58Z-score

OE missense 0.49 (0.38–0.64)

37 obs / 75.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.41 (0.20–0.94)

0≤0.351.4

Missense OE?0.49 (0.38–0.64)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 4 / 9.7Missense obs/exp: 37 / 75.5Syn Z: 0.17

This gene — mechanism propensity

0.79top 25%

GOF

0.5367th %ile

LOF

0.2873th %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.