TMEM127: Transmembrane Protein 127
A tumor suppressor gene associated with pheochromocytoma and paraganglioma
Gene Information Card
| Symbol | TMEM127 |
|---|---|
| Full Name | Transmembrane Protein 127 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q11.2 |
| NCBI Gene ID | 55654 ncbi.nlm.nih.gov/gene/55654 |
| Ensembl ID | ENSG00000163131 |
| UniProt ID | Q5JUK6 |
| OMIM ID | 613403 |
| HGNC ID | 26038 |
| Aliases | FLJ20500, MGC131895 |
Description
TMEM127 encodes a transmembrane protein that functions as a tumor suppressor. It is involved in the regulation of mTORC1 signaling and endosomal trafficking. Germline mutations in TMEM127 predispose to hereditary pheochromocytoma and paraganglioma, often with a later age of onset and lower metastatic risk compared to other susceptibility genes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pheochromocytoma | Loss-of-function mutations lead to dysregulated mTORC1 signaling and tumorigenesis in chromaffin cells | Multiple studies in ClinVar and OMIM |
| Paraganglioma | Similar mechanism as pheochromocytoma, affecting extra-adrenal paraganglia | ClinVar and literature reports |
| Hereditary pheochromocytoma-paraganglioma syndrome | Germline TMEM127 mutations cause autosomal dominant predisposition | OMIM #613403 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal gland | 12.5 | Medium |
| Kidney | 8.3 | Low |
| Brain | 6.7 | Low |
| Heart | 5.1 | Low |
| Liver | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | Embryonic kidney cells |
| HeLa | 10.8 | Cervical cancer cells |
| SH-SY5Y | 9.4 | Neuroblastoma cells |
| HepG2 | 7.1 | Liver cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.410_411delAG | Frameshift | Rare | Loss of function |
| c.208C>T | Nonsense | Rare | Loss of function |
| c.112A>G | Missense | Rare | Uncertain significance |
| c.1A>G | Start loss | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most TMEM127 mutations are loss-of-function, leading to reduced protein expression or impaired mTORC1 regulation.
Gain of Function (GOF)
No gain-of-function mutations have been reported.
Dominant Negative (DN)
Not described; haploinsufficiency is the proposed mechanism.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • endosome (GO:0005768) |
| • integral component of membrane (GO:0016021) | • regulation of TOR signaling (GO:0032006) |
| • metal ion binding (GO:0046872) |
Pathways
• mTOR signaling pathway (Reactome: R-HSA-165159)
• Endosomal trafficking (Reactome: R-HSA-199991)
Protein Summary
TMEM127 is a 248-amino acid transmembrane protein localized to endosomes and the plasma membrane. It negatively regulates mTORC1 signaling by promoting its lysosomal degradation or by modulating endosomal trafficking. Loss of TMEM127 leads to constitutive mTORC1 activation, contributing to tumorigenesis in neuroendocrine tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMEM127 Knockout HEK293 Cell Line | EDJ-KQ15792 | Human | 55654 | Details Get a Quote |
| TMEM127 Knockout A-549 Cell Line | EDJ-KQ48983 | Human | 55654 | Details Get a Quote |
| TMEM127 Knockout HCT 116 Cell Line | EDJ-KQ48984 | Human | 55654 | Details Get a Quote |
| TMEM127 Knockout HeLa Cell Line | EDJ-KQ48985 | Human | 55654 | Details Get a Quote |
