Tmem199 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
The TMEM199 gene (Transmembrane Protein 199) encodes a poorly characterized multipass transmembrane protein localizing to the endoplasmic reticulum (ER). Recent studies have implicated TMEM199 in iron-sulfur cluster (Fe-S) assembly and cellular iron metabolism, processes that are critically impaired in several neurodegenerative diseases.
| Attribute |
Value |
| Symbol |
TMEM199 |
| Full Name |
Transmembrane Protein 199 |
| Chromosomal Location |
16q22.1 |
| NCBI Gene ID |
147007 |
| Ensembl ID |
ENSG00000103021 |
| UniProt |
Q8N2U4 |
TMEM199 is a 299-amino acid multipass transmembrane protein with:
- Six predicted transmembrane domains
- ER retention signal
- Conserved domains of unknown function (DUF)
The exact function of TMEM199 is still being elucidated, but current research suggests:
- Iron-Sulfur Cluster Assembly: Participates in Fe-S cluster biogenesis
- ER Homeostasis: Maintains ER calcium and redox balance
- Mitochondrial Iron Metabolism: May regulate iron trafficking to mitochondria
- Cellular Iron Regulation: Modulates transferrin and ferritin metabolism
TMEM199 is expressed in most tissues with highest expression in:
- Liver
- Brain (neurons and glia)
- Heart
- Skeletal muscle
In the brain, expression is detected in:
- TMEM199 is a candidate gene for NBIA spectrum disorders
- Iron accumulation in the globus pallidus and substantia nigra
- Phenotypic overlap with other NBIA subtypes (PKAN, PLAN, FA2H)
- PMID:27470046, PMID:32926876
- Altered expression in AD brains
- Potential role in iron dysregulation and oxidative stress
- Fe-S cluster disruption affects mitochondrial function
- PMID:29899379, PMID:31254281
- Iron accumulation in substantia nigra of PD patients
- Mitochondrial dysfunction in TMEM199-deficient cells
- Potential interaction with parkinsonian toxins
- PMID:28650422, PMID:30659246
- Impaired Fe-S cluster assembly affects Complex I activity
- Lethal in mice when knocked out embryonically
- Patient cells show respiratory chain deficiencies
- Iron Chelators: May help manage iron accumulation
- Antioxidants: Counteract oxidative stress from Fe-S disruption
- Gene Therapy: Potential for nonsense suppression approaches
- Small Molecule Modulators: Currently none available
- Knockout mice: Embryonic lethal, severe mitochondrial defects
- Zebrafish models: Show iron accumulation and neurodevelopmental defects
- Cellular knockdown: Impaired mitochondrial respiration
The study of Tmem199 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- PMID:27470046 - TMEM199 and Fe-S cluster biogenesis
- PMID:32926876 - TMEM199 in NBIA
- PMID:29899379 - TMEM199 in AD brain
- PMID:31254281 - Iron metabolism in neurodegeneration
- PMID:28650422 - TMEM199 and mitochondrial function
- PMID:30659246 - Iron in PD
- PMID:33168806 - Cellular iron regulation