TMEM33 (Transmembrane Protein 33): Structure, Function, and Clinical Relevance
A comprehensive overview of the TMEM33 gene, including its genomic context, protein characteristics, expression patterns, associated diseases, and mutational landscape.
Gene Information Card
| Symbol | TMEM33 |
|---|---|
| Full Name | Transmembrane Protein 33 |
| Gene Type | Protein coding |
| Chromosomal Location | 4p13 |
| NCBI Gene ID | 55161 ncbi.nlm.nih.gov/gene/55161 |
| Ensembl ID | ENSG00000138668 |
| UniProt ID | Q9BQJ4 |
| OMIM ID | 615850 |
| HGNC ID | 28777 |
| Aliases | FLJ13305, DKFZp686L2420 |
Description
TMEM33 encodes a transmembrane protein that localizes to the endoplasmic reticulum (ER) and is involved in ER stress response, calcium homeostasis, and regulation of the unfolded protein response (UPR). It is widely expressed across tissues and has been implicated in various cellular processes, including lipid metabolism and immune signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | TMEM33 overexpression promotes tumor growth and metastasis via activation of the PI3K/AKT pathway. | PMID: 31578321 |
| Colorectal cancer | TMEM33 knockdown reduces cell proliferation and induces apoptosis, suggesting an oncogenic role. | PMID: 31265123 |
| Breast cancer | TMEM33 is upregulated in breast cancer tissues and correlates with poor prognosis; it may regulate ER stress-mediated apoptosis. | PMID: 30565921 |
| Viral infection (e.g., HCV) | TMEM33 interacts with viral proteins and modulates ER stress, affecting viral replication. | PMID: 29390139 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | Medium |
| Kidney | 10.1 | Medium |
| Heart | 8.5 | Low |
| Brain | 6.2 | Low |
| Lung | 9.8 | Medium |
| Pancreas | 7.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | 15.2 | High expression; used in studies of TMEM33 function in hepatoma. |
| MCF7 (breast cancer) | 11.8 | Moderate expression; associated with ER stress response. |
| A549 (lung cancer) | 9.5 | Low to moderate; role in lung cancer under investigation. |
| HEK293 (embryonic kidney) | 12.0 | Commonly used for overexpression studies. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.341C>T (p.Pro114Leu) | Missense | 0.01% (gnomAD) | Unknown; predicted benign by in silico tools. |
| c.523A>G (p.Thr175Ala) | Missense | 0.02% | Unknown; may affect protein stability. |
| c.789_790insA (frameshift) | Insertion | Rare | Predicted loss-of-function; may lead to truncated protein. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations are rare and may impair ER stress regulation, potentially leading to increased cellular stress and apoptosis.
Gain of Function (GOF)
Gain-of-function mutations have not been clearly identified; overexpression of wild-type TMEM33 is associated with oncogenic effects.
Dominant Negative (DN)
No dominant-negative mutations have been reported to date.
View complete mutation data：
Gene Ontology (GO)
| • endoplasmic reticulum membrane | • integral component of membrane |
| • unfolded protein response | • calcium ion homeostasis |
| • response to endoplasmic reticulum stress | • regulation of cell proliferation |
Pathways
• Unfolded Protein Response (UPR)
• Endoplasmic Reticulum Stress Pathway
• PI3K-AKT signaling pathway (in cancer context)
Protein Summary
TMEM33 is a 33 kDa transmembrane protein with multiple hydrophobic domains, localized primarily to the ER membrane. It plays a role in maintaining ER homeostasis by modulating the UPR and calcium flux. Structurally, it contains conserved transmembrane segments and a cytoplasmic C-terminal domain. Its expression is ubiquitous, with higher levels in metabolically active tissues. Functionally, TMEM33 is involved in protein quality control, lipid metabolism, and immune signaling. Aberrant expression has been linked to cancer progression and viral infections.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMEM33 Knockout HEK293 Cell Line | EDJ-KQ15759 | Human | 55161 | Details Get a Quote |
| TMEM33 Knockout HCT 116 Cell Line | EDJ-KQ48926 | Human | 55161 | Details Get a Quote |
| TMEM33 Knockout HeLa Cell Line | EDJ-KQ48927 | Human | 55161 | Details Get a Quote |
| TMEM33 Knockout A-549 Cell Line | EDJ-KQ46699 | Human | 55161 | Details Get a Quote |
