TOMM20

Chr 1

translocase of outer mitochondrial membrane 20

Also known as: MAS20, MOM19, TOM20

NCBI Gene: 9804ENSG00000173726UniProt: Q15388

Enables mitochondrion targeting sequence binding activity; protein-transporting ATPase activity; and unfolded protein binding activity. Involved in protein targeting to mitochondrion. Located in mitochondria-associated endoplasmic reticulum membrane contact site and mitochondrial outer membrane. Is active in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

73
ClinVar variants
46
Pathogenic / LP
0.03
pLI score
1
Active trials
Clinical Summary— TOMM20
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
46 Pathogenic / Likely Pathogenic· 18 VUS of 73 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.94LOEUF
pLI 0.027
Z-score 1.70
OE 0.41 (0.20–0.94)
Tolerant

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.
1.58Z-score
OE missense 0.49 (0.38–0.64)
37 obs / 75.5 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.0.41 (0.20–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.49 (0.38–0.64)
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.0.96
0≤1.21.6
LoF obs/exp: 4 / 9.7Missense obs/exp: 37 / 75.5Syn Z: 0.17

ClinVar Variant Classifications

73 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic2
VUS18
Benign1
44
Pathogenic
2
Likely Pathogenic
18
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
44
0
44
Likely Pathogenic
0
0
2
0
2
VUS
0
10
8
0
18
Likely Benign
0
0
0
0
0
Benign
0
0
1
0
1
Total01055065

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

View in ClinVar →

Protein Context — Lollipop Plot

TOMM20 · 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
Artesunate Sensitizes human hepatocellular carcinoma to sorafenib via exacerbating AFAP1L2-SRC-FUNDC1 axis-dependent mitophagy.
Ma Z et al.·Autophagy
2024
Autophagy deficiency abolishes liver mitochondrial DNA segregation.
Tostes K et al.·Autophagy
2022
Alternative mitochondrial quality control mediated by extracellular release.
Choong CJ et al.·Autophagy
2021
Tethering ATG16L1 or LC3 induces targeted autophagic degradation of protein aggregates and mitochondria.
Mei L et al.·Autophagy
2023
Mitophagy initiates retrograde mitochondrial-nuclear signaling to guide retinal pigment cell heterogeneity.
Datta S et al.·Autophagy
2023
The NLRX1-SLC39A7 complex orchestrates mitochondrial dynamics and mitophagy to rejuvenate intervertebral disc by modulating mitochondrial Zn(2+) trafficking.
Song Y et al.·Autophagy
2024
CARM1 drives mitophagy and autophagy flux during fasting-induced skeletal muscle atrophy.
Stouth DW et al.·Autophagy
2024
Inhibition of PINK1 senses ROS signaling to facilitate neuroblastoma cell pyroptosis.
Zhu Y et al.·Autophagy
2025
KDM4A-induced tumor senescence enhances the efficacy of immunotherapy by inhibiting AGT-PHB1 axis-mediated mitophagy in colorectal cancer.
Cai T et al.·Autophagy
2025
Sustained oral spermidine supplementation rescues functional and structural defects in COL6-deficient myopathic mice.
Gambarotto L et al.·Autophagy
2023Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Proximity Labeling Reveals RNA-Binding Proteins Associating with the Human Mitochondrial Import Receptor TOMM20.
Akram S et al.·J Proteome Res
2026🔓 Open Access
GATA-1-driven TOMM20-mediated mitophagy regulates PDLSCs osteogenesis and enhances periodontal bone regeneration.
Cai Q et al.·Biochem Biophys Res Commun
2026
A mitochondrial outer membrane protein TOMM20 maintains protein stability of androgen receptor and regulates AR transcriptional activity in prostate cancer cells.
Yin L et al.·Oncogene
2025
TOMM20 as a driver of cancer aggressiveness via oxidative phosphorylation, maintenance of a reduced state, and resistance to apoptosis.
Islam R et al.·Mol Oncol
2025🔓 Open Access
TMCO1 regulates energy metabolism and mitochondrial function of hepatocellular carcinoma cells through TOMM20, affecting the growth of subcutaneous graft tumors and infiltration of CAFs.
Wang G et al.·Biochem Cell Biol
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
AcromegalyGigantismFamilial Isolated Pituitary Adenoma

Genetics of Endocrine Tumours - Familial Isolated Pituitary Adenoma - FIPA

RECRUITING
NCT00461188Barts & The London NHS TrustStarted 2007-03-01

External Resources

Links to major genomics databases and tools