TOMM40: Translocase of Outer Mitochondrial Membrane 40
A key regulator of mitochondrial protein import and a genetic risk factor for Alzheimer's disease
Gene Information Card
| Symbol | TOMM40 |
|---|---|
| Full Name | Translocase of Outer Mitochondrial Membrane 40 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 10452 ncbi.nlm.nih.gov/gene/10452 |
| Ensembl ID | ENSG00000130204 |
| UniProt ID | O96008 |
| OMIM ID | 608061 |
| HGNC ID | 15748 |
| Aliases | TOM40, PER-EC1, D19S1177E, MGC:12580 |
Description
TOMM40 encodes the central channel-forming subunit of the translocase of the outer mitochondrial membrane (TOM) complex. This protein is essential for the import of nuclear-encoded mitochondrial precursor proteins into the mitochondria. The TOM complex is the main entry gate for most mitochondrial proteins. TOMM40 is located adjacent to the APOE gene on chromosome 19, and polymorphisms in TOMM40 have been associated with altered risk and age of onset of late-onset Alzheimer's disease, likely through effects on mitochondrial function and APOE expression regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer's disease, late-onset | Polymorphisms (e.g., rs10524523) in the TOMM40 poly-T repeat region influence APOE expression and mitochondrial protein import efficiency, contributing to mitochondrial dysfunction and neurodegeneration. | ClinVar, NCBI Gene, OMIM |
| Mitochondrial import deficiency | Loss-of-function mutations impair TOM complex assembly, reducing mitochondrial protein import and causing cellular energy deficits. | UniProt, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cortex) | 28.5 | High |
| Liver | 22.1 | High |
| Heart | 18.7 | Medium |
| Skeletal muscle | 15.3 | Medium |
| Kidney | 14.9 | Medium |
| Pancreas | 10.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 32.4 | Neuronal model, high expression |
| HepG2 (hepatocellular carcinoma) | 25.1 | Liver model, high expression |
| HeLa (cervical carcinoma) | 20.3 | Moderate expression |
| HEK293 (embryonic kidney) | 18.9 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs10524523 (poly-T repeat) | Variable length polymorphism | Common in population | Associated with altered APOE expression and Alzheimer's disease risk |
| c.1A>G (p.Met1Val) | Missense | Rare | Potential loss of start codon, reduced protein expression |
Mutation functional classification
Loss of Function (LOF)
Rare missense or truncating mutations that impair TOM complex assembly or channel function, leading to reduced mitochondrial protein import.
Gain of Function (GOF)
Not described for TOMM40.
Dominant Negative (DN)
Not described for TOMM40.
View complete mutation data：
Gene Ontology (GO)
| • Mitochondrial outer membrane translocase complex | • Protein transmembrane transporter activity |
| • Mitochondrial protein import | • Protein targeting to mitochondrion |
| • Outer mitochondrial membrane |
Pathways
• Mitochondrial protein import (KEGG: hsa03060)
• TOM complex assembly
Protein Summary
TOMM40 (TOM40) is a 40 kDa protein that forms the central pore of the TOM complex in the outer mitochondrial membrane. It functions as a beta-barrel channel that allows the passage of nuclear-encoded mitochondrial precursor proteins. The protein is essential for mitochondrial biogenesis and cellular energy metabolism. Its proximity to the APOE gene on chromosome 19 has made it a focus of Alzheimer's disease genetics.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TOMM40L Knockout HEK293 Cell Line | EDJ-KQ9992 | Human | 84134 | Details Get a Quote |
| TOMM40L Knockout A-549 Cell Line | EDJ-KQ36941 | Human | 84134 | Details Get a Quote |
| TOMM40L Knockout HCT 116 Cell Line | EDJ-KQ36942 | Human | 84134 | Details Get a Quote |
| TOMM40L Knockout HeLa Cell Line | EDJ-KQ36943 | Human | 84134 | Details Get a Quote |
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