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9 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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TOMM40L
translocase of outer mitochondrial membrane 40 like
Chromosome 1 · 1q23.3
NCBI Gene: 84134Ensembl: ENSG00000158882.16HGNC: HGNC:25756UniProt: Q969M1
21PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein-containing complexmitochondriontransmembrane protein transporter activityprotein import into mitochondrial matrixneurodegenerative diseaseKleefstra syndrome 1hepatocellular carcinomanephrotic syndrome
✦AI Summary

TOMM40L is a mitochondrial outer membrane translocase implicated in protein import into mitochondria 1. As a channel-forming protein, it likely facilitates the translocation of protein precursors across the mitochondrial outer membrane, similar to its homolog TOMM40. The gene's functional significance extends beyond basic mitochondrial biology into neurodegeneration and cancer pathology. In neurodegenerative disease, TOMM40L shows disease-relevant associations. The APOEɛ4-TOMM40L poly-T length variant (L allele) haplotype significantly increases the risk of mild cognitive impairment conversion to Alzheimer's disease (OR=5.83), with shorter conversion times, possibly mediated by cerebrospinal fluid biomarkers and mitochondrial dysfunction 2. Additionally, increased TOMM40L abundance in preserved cognitive states suggests it reflects mitochondrial oxidative phosphorylation capacity associated with better cognition across Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease dementia 1. Clinically, TOMM40L has emerged as a prognostic biomarker in hepatocellular carcinoma and endometrial cancer. It serves as a core component of mitochondria-related gene signatures predictive of adverse prognosis, poor immunotherapy response, and differential drug sensitivity 345. Notably, TOMM40L shares sequence homology with tobacco mosaic virus coat protein, raising questions about molecular mimicry mechanisms in disease 6. These findings position TOMM40L as both a functional mitochondrial protein and a clinically relevant biomarker for cognitive decline and cancer outcomes.

Sources cited
1
TOMM40L is a key mitochondrial oxidative phosphorylation protein more abundant in preserved cognitive states across multiple dementia types
PMID: 39711511
2
APOEɛ4-TOMM40L L allele haplotype significantly increases risk of MCI conversion to AD with shorter conversion times, associated with mitochondrial dysfunction
PMID: 33016906
3
TOMM40L is a component of a mitochondria-related gene signature predictive of adverse HCC prognosis and poor immunotherapy response
PMID: 40659697
4
TOMM40L is one of eight mitochondria-related genes identified in a prognostic signature for endometrial cancer associated with drug sensitivity and immune therapy response
PMID: 40354443
5
TOMM40L is a key stemness-related gene whose elevated levels correlate with unfavorable HCC prognosis, and knockdown inhibits HCC cell progression and stemness
PMID: 40746880
6
TOMM40L contains homology to tobacco mosaic virus coat protein and exhibits cross-reactivity with anti-TMV antibodies, suggesting molecular mimicry
PMID: 23573274
7
TOMM40L was among the top 5 differentially expressed genes with higher transcript levels in kidney allograft recipients at week 1 post-transplant
PMID: 25946140
8
TOMM40L was a highly upregulated gene in human dental pulp cells exposed to TEGDMA monomer toxicity
PMID: 24438040
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.53Moderate
Kleefstra syndrome 1Open Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.07Suggestive
nephrotic syndromeOpen Targets
0.07Suggestive
benign soft tissue neoplasmOpen Targets
0.03Suggestive
respiratory system diseaseOpen Targets
0.02Suggestive
deep vein thrombosisOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.01Suggestive
Parkinson diseaseOpen Targets
0.01Suggestive
cancerOpen Targets
0.00Suggestive
liver hemangiomaOpen Targets
0.00Suggestive
obesityOpen Targets
0.00Suggestive
meningococcal infectionOpen Targets
0.00Suggestive
metastatic melanomaOpen Targets
0.00Suggestive
ependymomaOpen Targets
0.00Suggestive
asthmaOpen Targets
0.00Suggestive
liver cancerOpen Targets
0.00Suggestive
hepatitis C virus induced hepatocellular carcinomaOpen Targets
0.00Suggestive
hereditary breast carcinomaOpen Targets
0.00Suggestive
Uterine CarcinosarcomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TOMM5Protein interaction100%TOMM6Protein interaction100%MTX1Protein interaction99%VDAC2Protein interaction99%VDAC3Protein interaction99%TOMM20Protein interaction99%
Tissue Expression6 tissues
Liver
100%
Heart
97%
Bone Marrow
41%
Brain
37%
Lung
36%
Ovary
13%
Gene Interaction Network
Click a node to explore
TOMM40LTOMM5TOMM6MTX1VDAC2VDAC3TOMM20
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q969M1
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.63LoF Tolerant
pLIⓘ
0.18Tolerant
Observed/Expected LoF0.42 [0.29–0.63]
RankingsWhere TOMM40L stands among ~20K protein-coding genes
  • #14,047of 20,598
    Most Researched21
  • #4,507of 17,882
    Most Constrained (LOEUF)0.63
Genes detectedTOMM40L
Sources retrieved9 papers
Response time—
📄 Sources
9▼
1
Proteomic signatures of Alzheimer's disease and Lewy body dementias: A comparative analysis.
PMID: 39711511
Alzheimers Dement · 2025
1.00
2
A mitochondrial-related gene signature predicts prognosis and immunotherapy response in hepatocellular carcinoma.
PMID: 40659697
Sci Rep · 2025
0.89
3
Humans have antibodies against a plant virus: evidence from tobacco mosaic virus.
PMID: 23573274
PLoS One · 2013
0.78
4
APOEɛ4-TOMM40L Haplotype Increases the Risk of Mild Cognitive Impairment Conversion to Alzheimer's Disease.
PMID: 33016906
J Alzheimers Dis · 2020
0.67
5
Novel Stemness-Associated Scores: Enhancing Predictions of Hepatocellular Carcinoma Prognosis and Tumor Immune Microenvironment.
PMID: 40746880
Oncol Res · 2025
0.56