TMEM43: Transmembrane Protein 43 – Key Gene in Arrhythmogenic Right Ventricular Cardiomyopathy
Comprehensive genomic and clinical overview of TMEM43, a nuclear envelope protein linked to cardiac disease and cancer.
Gene Information Card
| Symbol | TMEM43 |
|---|---|
| Full Name | Transmembrane Protein 43 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p25.1 |
| NCBI Gene ID | 79188 ncbi.nlm.nih.gov/gene/79188 |
| Ensembl ID | ENSG00000170820 |
| UniProt ID | Q9BTV4 |
| OMIM ID | 612048 |
| HGNC ID | 28472 |
| Aliases | LUMA, ARVC5, ARVD5 |
Description
TMEM43 (Transmembrane Protein 43), also known as LUMA, encodes a nuclear envelope protein that is part of the inner nuclear membrane. It plays a critical role in maintaining nuclear architecture, chromatin organization, and mechanotransduction. Mutations in TMEM43 are a well-established cause of arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC5), a severe form of inherited heart disease characterized by fibrofatty replacement of the myocardium and risk of sudden cardiac death. The gene is also implicated in certain cancers through altered expression and somatic mutations.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Arrhythmogenic right ventricular cardiomyopathy 5 (ARVC5) | Missense mutation p.S358L disrupts nuclear envelope integrity, leading to myocyte death and fibrofatty replacement. | OMIM #604400; ClinVar; multiple peer-reviewed studies |
| Dilated cardiomyopathy (DCM) | Rare TMEM43 variants may impair nuclear lamina interactions, contributing to dilated cardiomyopathy. | ClinVar; limited case reports |
| Breast cancer | Overexpression of TMEM43/LUMA correlates with poor prognosis; potential role in nuclear stiffness and metastasis. | COSMIC; PubMed studies |
| Prostate cancer | Somatic mutations and altered expression observed; functional significance under investigation. | COSMIC; TCGA data |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 28.5 | Medium |
| Skeletal muscle | 22.3 | Medium |
| Liver | 15.1 | Low |
| Kidney | 12.8 | Low |
| Lung | 10.4 | Low |
| Brain | 6.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPSC-derived) | 35.0 | High expression; relevant for ARVC modeling |
| HeLa | 18.5 | Moderate expression |
| HEK293 | 15.2 | Moderate expression |
| MCF7 (breast cancer) | 22.1 | Elevated compared to normal breast tissue |
| LNCaP (prostate cancer) | 19.8 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1073C>T (p.S358L) | Missense | Founder mutation in ARVC5; high penetrance in males | Gain of toxic function?; leads to nuclear envelope rupture and cell death |
| c.1072T>C (p.S358P) | Missense | Rare | Likely pathogenic; similar mechanism to S358L |
| c.1A>G (p.M1V) | Missense | Rare | Loss of function; reduced protein expression |
| c.763G>A (p.E255K) | Missense | Rare | Uncertain significance; reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Rare truncating or start-loss variants (e.g., p.M1V) reduce TMEM43 protein levels, impairing nuclear envelope integrity.
Gain of Function (GOF)
The p.S358L mutation is proposed to act via a gain-of-toxic-function mechanism, causing abnormal protein aggregation and nuclear membrane disruption.
Dominant Negative (DN)
Not clearly established; however, mutant TMEM43 may interfere with wild-type protein assembly in the nuclear envelope.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Nuclear envelope breakdown and reassembly
• Mechanotransduction pathways
• Cardiac muscle contraction (indirect)
Protein Summary
TMEM43 (LUMA) is a 400-amino-acid transmembrane protein localized to the inner nuclear membrane. It contains a conserved LUMA domain and interacts with lamins and other nuclear envelope proteins. The protein is essential for maintaining nuclear shape, stiffness, and chromatin tethering. In cardiac tissue, loss of TMEM43 function or expression of mutant forms leads to nuclear envelope fragility, myocyte death, and fibrofatty replacement characteristic of ARVC5. In cancer, TMEM43 overexpression is associated with increased nuclear stiffness and metastatic potential.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMEM43 Knockout HEK293 Cell Line | EDJ-KQ2244 | Human | 79188 | Details Get a Quote |
| TMEM43 Knockout HeLa Cell Line | EDJ-KQ18256 | Human | 79188 | Details Get a Quote |
| TMEM43 Knockout A-549 Cell Line | EDJ-KQ22544 | Human | 79188 | Details Get a Quote |
| TMEM43 Knockout HCT 116 Cell Line | EDJ-KQ22545 | Human | 79188 | Details Get a Quote |
