TIMM22

Chr 17AR

translocase of inner mitochondrial membrane 22

Also known as: COXPD43, TEX4, TIM22

NCBI Gene: 29928ENSG00000177370UniProt: Q9Y584

Multipass transmembrane proteins are brought into mitochondria and inserted into the mitochondrial inner membrane by way of the TIM22 complex. This complex has six subunits and is a twin-pore translocase. The protein encoded by this gene is a subunit of TIM22 and represents the voltage-activated and signal-gated channel. [provided by RefSeq, Jul 2016]

Primary Disease Associations & Inheritance

?Combined oxidative phosphorylation deficiency 43MIM #618851
AR
0
Active trials
68
Pathogenic / LP
133
ClinVar variants
3
Pubs (1 yr)
-0.2
Missense Z
1.64
LOEUF
Clinical Summary— TIMM22
🧬
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.
📋
ClinVar Variants
68 Pathogenic / Likely Pathogenic· 57 VUS of 133 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.64LOEUF
pLI 0.000
Z-score 0.25
OE 0.90 (0.51–1.64)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.22Z-score
OE missense 1.06 (0.91–1.23)
125 obs / 118.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.90 (0.51–1.64)
0≤0.351.4
Missense OE1.06 (0.91–1.23)
0≤0.61.4
Synonymous OE1.09
0≤1.21.6
LoF obs/exp: 7 / 7.8Missense obs/exp: 125 / 118.3Syn Z: -0.47
DN
DN
0.76top 25%
GOF
0.5856th %ile
LOF
0.3745th %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

133 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic59
Likely Pathogenic9
VUS57
Likely Benign5
Benign1
Conflicting2
59
Pathogenic
9
Likely Pathogenic
57
VUS
5
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
59
0
59
Likely Pathogenic
0
0
9
0
9
VUS
0
27
30
0
57
Likely Benign
0
1
2
2
5
Benign
0
0
1
0
1
Conflicting
—2
Total0281012133

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

TIMM22 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TIMM22-related combined oxidative phosphorylation deficiency

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantstop gained NMD escaping

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients