TOMM22

Chr 22

translocase of outer mitochondrial membrane 22

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

NCBI Gene: 56993 ENSG00000100216 UniProt: Q9NS69 OMIM: 607046

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is an integral membrane protein of the mitochondrial outer membrane. The encoded protein interacts with TOMM20 and TOMM40, and forms a complex with several other proteins to import cytosolic preproteins into the mitochondrion. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.66

Clinical Summary— TOMM22

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.61) — some intolerance to loss-of-function variants.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.66LOEUF

pLI 0.608

Z-score 2.14

OE 0.14 (0.05–0.66)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

0.93Z-score

OE missense 0.71 (0.57–0.88)

57 obs / 80.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.14 (0.05–0.66)

0≤0.351.4

Missense OE?0.71 (0.57–0.88)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 1 / 7.2Missense obs/exp: 57 / 80.4Syn Z: -0.42

This gene — mechanism propensity

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.