TOMM20

Chr 1

translocase of outer mitochondrial membrane 20

Also known as: MAS20, MOM19, TOM20

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.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.94
Clinical SummaryTOMM20
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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.027
Z-score 1.70
OE 0.41 (0.200.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.58Z-score
OE missense 0.49 (0.380.64)
37 obs / 75.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.200.94)
00.351.4
Missense OE0.49 (0.380.64)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 4 / 9.7Missense obs/exp: 37 / 75.5Syn Z: 0.17
DN
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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TOMM20 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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