TOMM22

Chr 22

translocase of outer mitochondrial membrane 22

Also known as: 1C9-2, MST065, MSTP065, TOM22

The encoded protein is a central receptor component of the translocase of the outer mitochondrial membrane (TOM) complex that recognizes and translocates cytosolic mitochondrial preproteins across the outer mitochondrial membrane. Mutations cause autosomal recessive mitochondrial complex assembly factor deficiency, presenting as early-onset mitochondrial disease affecting multiple organ systems. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.66), consistent with its essential role in mitochondrial protein import.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.66
Clinical SummaryTOMM22
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.61) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.66LOEUF
pLI 0.608
Z-score 2.14
OE 0.14 (0.050.66)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
0.93Z-score
OE missense 0.71 (0.570.88)
57 obs / 80.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.14 (0.050.66)
00.351.4
Missense OE0.71 (0.570.88)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 1 / 7.2Missense obs/exp: 57 / 80.4Syn Z: -0.42
DN
0.6648th %ile
GOF
0.6346th %ile
LOF
0.4528th %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

TOMM22 · 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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