TOMM7

Chr 7AR

translocase of outer mitochondrial membrane 7

Also known as: GMPGS, TOM7

The protein is a component of the translocase of the outer mitochondrial membrane (TOM) complex that is essential for importing cytosolically synthesized proteins into mitochondria and regulates the assembly and stability of the translocase complex. Mutations cause Garg-Mishra progeroid syndrome, an autosomal recessive disorder. The gene shows tolerance to loss-of-function variants (pLI 0.01, LOEUF 1.76), suggesting that complete loss of function may be required for disease manifestation.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 1.761 OMIM phenotype
Clinical SummaryTOMM7
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.76LOEUF
pLI 0.010
Z-score 0.34
OE 0.81 (0.361.76)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.15Z-score
OE missense 1.08 (0.811.46)
31 obs / 28.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.81 (0.361.76)
00.351.4
Missense OE1.08 (0.811.46)
00.61.4
Synonymous OE1.79
01.21.6
LoF obs/exp: 3 / 3.7Missense obs/exp: 31 / 28.7Syn Z: -1.96
DN
0.76top 25%
GOF
0.6540th %ile
LOF
0.3356th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

TOMM7 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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