TIMM22

Chr 17AR

translocase of inner mitochondrial membrane 22

Also known as: COXPD43, TEX4, TIM22

The protein is an essential core component of the TIM22 complex that forms a voltage-activated channel mediating import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. Mutations cause combined oxidative phosphorylation deficiency 43, inherited in an autosomal recessive pattern. This gene appears to be tolerant to loss-of-function variants in the general population based on constraint metrics.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.641 OMIM phenotype
Clinical SummaryTIMM22
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — 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
1.64LOEUF
pLI 0.000
Z-score 0.25
OE 0.90 (0.511.64)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.22Z-score
OE missense 1.06 (0.911.23)
125 obs / 118.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.90 (0.511.64)
00.351.4
Missense OE1.06 (0.911.23)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 7 / 7.8Missense obs/exp: 125 / 118.3Syn Z: -0.47
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedTIMM22-related combined oxidative phosphorylation deficiencyOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.76top 25%
GOF
0.5856th %ile
LOF
0.3745th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TIMM22 · 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.

Search ClinicalTrials.gov →