TOMM22

Chr 22

translocase of outer mitochondrial membrane 22

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

NCBI Gene: 56993ENSG00000100216UniProt: Q9NS69

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]

51
ClinVar variants
20
Pathogenic / LP
0.61
pLI score
0
Active trials
Clinical Summary— TOMM22
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.61) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 24 VUS of 51 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.93Z-score
OE missense 0.71 (0.57–0.88)
57 obs / 80.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.14 (0.05–0.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.57–0.88)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.09
0≤1.21.6
LoF obs/exp: 1 / 7.2Missense obs/exp: 57 / 80.4Syn Z: -0.42

ClinVar Variant Classifications

51 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic2
VUS24
Conflicting1
18
Pathogenic
2
Likely Pathogenic
24
VUS
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
2
0
2
VUS
0
20
4
0
24
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Conflicting
—1
Total02024045

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of sixteen novel candidate genes for late onset Parkinson's disease.
Gialluisi A et al.·Mol Neurodegener
2021
Recent advances in novel mutation genes of Parkinson's disease.
Yang J et al.·J Neurol
2023Review
SARS-CoV-2 infection alters mitochondrial and cytoskeletal function in human respiratory epithelial cells mediated by expression of spike protein.
Yeung-Luk BH et al.·mBio
2023
A mitophagy-related gene signature associated with prognosis and immune microenvironment in colorectal cancer.
Zhang C et al.·Sci Rep
2022
The TOMM machinery is a molecular switch in PINK1 and PARK2/PARKIN-dependent mitochondrial clearance.
Bertolin G et al.·Autophagy
2013
A Novel Gene Signature to Predict Survival Time and Incident Ventricular Arrhythmias in Patients with Dilated Cardiomyopathy.
Ge C et al.·Dis Markers
2020Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Targeting TOMM40 and TOMM22 to Rescue Statin-Impaired Mitochondrial Function, Dynamics, and Mitophagy in Skeletal Myotubes.
Yang NV et al.·Int J Mol Sci
2025🔓 Open Access
Machine learning and single-cell analysis identify the mitophagy-associated gene TOMM22 as a potential diagnostic biomarker for intervertebral disc degeneration.
Wu Y et al.·Heliyon
2024🔓 Open Access
Mitochondrial Translocase TOMM22 Is Overexpressed in Pancreatic Cancer and Promotes Aggressive Growth by Modulating Mitochondrial Protein Import and Function.
Haastrup MO et al.·Mol Cancer Res
2024
Depletion of TMEM65 leads to oxidative stress, apoptosis, induction of mitochondrial unfolded protein response, and upregulation of mitochondrial protein import receptor TOMM22.
Urushima Y et al.·Biochem Biophys Rep
2020🔓 Open Access
Mitochondrial accumulation of amyloid β (Aβ) peptides requires TOMM22 as a main Aβ receptor in yeast.
Hu W et al.·J Biol Chem
2018
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools