TMEM65: Transmembrane Protein 65 – A Key Regulator of Mitochondrial Function and Cardiac Conduction
Comprehensive genomic and proteomic overview of TMEM65, including expression, mutations, and disease associations.
Gene Information Card
| Symbol | TMEM65 |
|---|---|
| Full Name | Transmembrane Protein 65 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.13 |
| NCBI Gene ID | 157378 ncbi.nlm.nih.gov/gene/157378 |
| Ensembl ID | ENSG00000164733 |
| UniProt ID | Q6P1J6 |
| OMIM ID | 616178 |
| HGNC ID | 26272 |
| Aliases | MGC14836, FLJ32709 |
Description
TMEM65 encodes a transmembrane protein localized to the inner mitochondrial membrane. It is involved in mitochondrial function, particularly in maintaining mitochondrial membrane potential and respiratory chain activity. The protein is also implicated in cardiac conduction, with mutations linked to arrhythmias and mitochondrial disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cardiac conduction defect | Loss-of-function mutations in TMEM65 disrupt mitochondrial membrane potential, impairing cardiac electrical activity. | ClinVar, OMIM |
| Mitochondrial complex I deficiency | TMEM65 deficiency reduces complex I assembly and activity, leading to mitochondrial dysfunction. | UniProt, NCBI Gene |
| Arrhythmia | TMEM65 variants are associated with prolonged QT interval and sudden cardiac death. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Skeletal muscle | 8.3 | Medium |
| Liver | 4.1 | Low |
| Brain | 3.7 | Low |
| Kidney | 2.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes | 15.2 | High expression in cardiac cells |
| HepG2 | 5.8 | Moderate expression |
| SH-SY5Y | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.389C>T (p.Pro130Leu) | Missense | Rare | Likely pathogenic; associated with cardiac conduction defect |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; reported in mitochondrial disease |
| c.742G>A (p.Gly248Arg) | Missense | Rare | Uncertain significance; affects protein stability |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., start loss, missense affecting stability) impair mitochondrial membrane potential and complex I activity, leading to cardiac and mitochondrial phenotypes.
Gain of Function (GOF)
No gain-of-function mutations reported for TMEM65.
Dominant Negative (DN)
No dominant-negative mutations reported for TMEM65.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005743 – mitochondrial inner membrane | • GO:0005739 – mitochondrion |
| • GO:0016021 – integral component of membrane | • GO:0006120 – mitochondrial electron transport |
| • NADH to ubiquinone | • GO:0055114 – oxidation-reduction process |
Pathways
• Mitochondrial complex I assembly (Reactome: R-HSA-6799198)
• Respiratory electron transport (Reactome: R-HSA-611105)
Protein Summary
TMEM65 is a 293-amino-acid transmembrane protein localized to the inner mitochondrial membrane. It plays a critical role in maintaining mitochondrial membrane potential and supporting complex I activity of the respiratory chain. The protein is highly expressed in heart and skeletal muscle, consistent with its role in cardiac conduction and energy metabolism. Mutations in TMEM65 are associated with cardiac arrhythmias and mitochondrial complex I deficiency.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMEM65 Knockout HEK293 Cell Line | EDJ-KQ15772 | Human | 157378 | Details Get a Quote |
| TMEM65 Knockout A-549 Cell Line | EDJ-KQ48956 | Human | 157378 | Details Get a Quote |
| TMEM65 Knockout HCT 116 Cell Line | EDJ-KQ48957 | Human | 157378 | Details Get a Quote |
| TMEM65 Knockout HeLa Cell Line | EDJ-KQ48958 | Human | 157378 | Details Get a Quote |
| TMEM65 Knockout HCT116-LUC Cell Line | EDC08309 | Human | 157378 | Details Get a Quote |
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