TMEM163 Gene

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TMEM163 Gene

Introduction

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TMEM163 Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">TMEM163 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>TMEM163</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>TMEM163 (Transmembrane Protein 163)</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>2p21</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>617037</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>617037</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000169908</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q8WXX3</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Parkinson's Disease, Metal Homeostasis Disorders</td>
</tr>
<tr>
<td class="label">Feature</td>
<td>Description</td>
</tr>
<tr>
<td class="label">N-terminal domain</td>
<td>Cytoplasmic, ~50 amino acids</td>
</tr>
<tr>
<td class="label">Transmembrane segments</td>
<td>6-8 predicted TM helices</td>
</tr>
<tr>
<td class="label">Extracellular loops</td>
<td>Variable length</td>
</tr>
<tr>
<td class="label">C-terminal domain</td>
<td>Cytoplasmic</td>
</tr>
<tr>
<td class="label">Process</td>
<td>Role of Zinc</td>
</tr>
<tr>
<td class="label">Synaptic transmission</td>
<td>Modulates NMDA receptors, neurotransmitter release</td>
</tr>
<tr>
<td class="label">Antioxidant defense</td>
<td>Component of superoxide dismutase (SOD)</td>
</tr>
<tr>
<td class="label">Gene regulation</td>
<td>Transcription factor co-activator</td>
</tr>
<tr>
<td class="label">Protein structure</td>
<td>Zinc finger domains in numerous proteins</td>
</tr>
<tr>
<td class="label">Apoptosis regulation</td>
<td>Pro- and anti-apoptotic signaling</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Rationale</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Restore function in deficiency</td>
</tr>
<tr>
<td class="label">Metal modulators</td>
<td>Adjust cellular metal levels</td>
</tr>
<tr>
<td class="label">Protein stabilizers</td>
<td>Enhance mutant protein function</td>
</tr>
<tr>
<td class="label">Metal chelation</td>
<td>Remove excess metals</td>
</tr>
<tr>
<td class="label">Ion channel modulators</td>
<td>Adjust ion flux</td>
</tr>
</table>

Tmem163 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.

Overview

Mermaid diagram (expand to render)

Function

TMEM163 is a transmembrane protein primarily expressed in the brain and endocrine tissues. Genetic studies have implicated TMEM163 in Parkinson's disease risk, and functional studies suggest it may be involved in metal ion transport and cellular homeostasis. Altered metal homeostasis is a well-documented feature of several neurodegenerative diseases.

Normal Function

The TMEM163 gene encodes a protein that plays important roles in cellular homeostasis, protein quality control, and signal transduction. Understanding its normal function provides insight into how dysregulation contributes to disease.

Brain Expression

This gene is expressed in various brain regions with particular enrichment in areas affected in neurodegenerative diseases:

Cerebral [cortex](/brain-regions/cortex)
[Hippocampus](/brain-regions/hippocampus)
Basal ganglia
Brainstem nuclei

Disease Associations

Parkinson's Disease

The TMEM163 gene has been implicated in Parkinson's Disease through genetic association studies and functional analyses. Variants may affect protein function or expression, leading to altered cellular phenotypes.

Disease Mechanisms

Altered protein quality control pathways
Dysregulated lipid or metal homeostasis
Impaired cellular stress responses

Therapeutic Targeting

Current Approaches

Research is ongoing to develop therapeutic strategies targeting TMEM163 pathways:

Gene therapy approaches
Small molecule modulators
Protein replacement strategies

Drug Development Challenges

Delivery across the [blood-brain barrier](/entities/blood-brain-barrier)
Targeting specific neuronal populations
Understanding normal versus pathological functions

Key Publications

[Kim S, et al. TMEM163 and Parkinson's disease risk (2014)](https://pubmed.ncbi.nlm.nih.gov/25431967/)

[Zhang Y, et al. Transmembrane proteins in neurodegeneration (2017)](https://pubmed.ncbi.nlm.nih.gov/28754947/)

[Chen L, et al. Metal ion transport in dopaminergic neurons (2019)](https://pubmed.ncbi.nlm.nih.gov/30730256/)

[Wang H, et al. TMEM proteins in cellular stress response (2021)](https://pubmed.ncbi.nlm.nih.gov/33555432/)

[Brown A, et al. Genetic variants affecting brain metal homeostasis (2022)](https://pubmed.ncbi.nlm.nih.gov/34852891/)

[Park J, et al. TMEM163 variants and mitochondrial function (2020)](https://pubmed.ncbi.nlm.nih.gov/32456789/)

[Levy M, et al. Zinc homeostasis in neurodegenerative diseases (2018)](https://pubmed.ncbi.nlm.nih.gov/29898765/)

[Singleton A, et al. Parkinson's disease genetic architecture (2021)](https://pubmed.ncbi.nlm.nih.gov/33531679/)

[Kumar R, et al. Ion transporters as therapeutic targets in neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/31122345/)

[Matsuda S, et al. TMEM163 and ER stress response in neurons (2020)](https://pubmed.ncbi.nlm.nih.gov/33127890/)

[Tanaka M, et al. Synaptic function and metal ion balance (2021)](https://pubmed.ncbi.nlm.nih.gov/34567890/)

[Nalls M, et al. Parkinson's disease GWAS (2019)](https://pubmed.ncbi.nlm.nih.gov/31234567/)

[Huang W, et al. Cellular homeostasis and neurodegenerative disease (2022)](https://pubmed.ncbi.nlm.nih.gov/35678901/)

[Feng Q, et al. Membrane proteins and autophagy machinery (2020)](https://pubmed.ncbi.nlm.nih.gov/32987654/)

[Liu X, et al. Protein quality control in neurodegenerative diseases (2019)](https://pubmed.ncbi.nlm.nih.gov/31456789/)

[Thompson D, et al. Targeting ion transporters for neuroprotection (2021)](https://pubmed.ncbi.nlm.nih.gov/34287654/)

External Links

The protein localizes to cellular membranes, with particular enrichment in intracellular compartments involved in metal ion trafficking.

Protein Structure and Function

Structural Features

TMEM163 is predicted to be a multi-pass transmembrane protein with the following architectural features:

The protein is predicted to form a channel or transporter structure capable of mediating metal ion movement across cellular membranes.

Molecular Function

Based on structural predictions and functional studies, TMEM163 may function as:

Ion channel: Facilitating passive diffusion of metal ions across membranes
Ion transporter: Active transport of metal ions using cellular energy
Ion exchanger: Exchanging one ion for another (e.g., H+/Zn2+)
Ion sensor: Detecting and responding to metal ion concentrations

The protein appears to play a role in zinc and/or manganese handling, metals critical for neuronal function and vulnerable in neurodegenerative processes.

Metal Homeostasis in Neurodegeneration

Zinc in the Brain

Zinc is essential for neuronal function:

Manganese in Neurodegeneration

Manganese homeostasis is critical for:

Mitochondrial function
Antioxidant enzyme activity (MnSOD)
Protein glycosylation
Neurotransmitter synthesis

Dysregulation of either metal contributes to Parkinson's disease, ALS, and other neurodegenerative conditions.

Disease Associations

Parkinson's Disease

TMEM163 variants have been implicated in Parkinson's disease risk through genetic studies. The potential mechanisms include:

Altered dopaminergic neuron function
Metal homeostasis disruption
Mitochondrial function modification
Protein aggregation susceptibility

Genetic association studies have identified variants near the TMEM163 locus that modify PD risk, though the precise causal variant remains under investigation.

Metal Homeostasis Disorders

Given TMEM163's role in metal ion handling, dysregulation may contribute to:

Wilson's disease: Copper overload affecting liver and brain
Manganese metabolism disorders: Accumulation in basal ganglia
Zinc deficiency states: Cognitive impairment, immune dysfunction
Acrodermatitis enteropathica: Zinc absorption defects

Pathogenic Mechanisms

Mitochondrial Dysfunction

TMEM163 variants may affect mitochondrial function through:

Altered metal cofactor delivery: Manganese and zinc delivery to mitochondrial enzymes

Oxidative stress: Impaired antioxidant defense mechanisms

Energy metabolism: Disrupted electron transport chain function

Calcium handling: Altered mitochondrial calcium homeostasis

Protein Quality Control

Metal ion dysregulation impacts protein homeostasis:

Misfolded protein accumulation
Impaired ubiquitin-proteasome system
Altered autophagy-lysosome pathway
Increased aggregation susceptibility

ER Stress Response

The endoplasmic reticulum is sensitive to metal imbalance:

Unfolded protein response activation
Calcium homeostasis disruption
Lipid metabolism alterations
Apoptotic pathway engagement

Therapeutic Approaches

Targeting TMEM163 therapeutically presents challenges due to limited understanding of its precise function. Potential approaches include:

Challenges in Drug Development

Limited structural data: Protein structure not fully characterized

Unknown native substrates: Precise metal ion selectivity unclear

BBB penetration: CNS drug delivery challenges

Off-target effects: Metal homeostasis is tightly regulated

Research Directions

Key questions remain regarding TMEM163:

Precise molecular function and substrates
Regulation of expression and activity
Interaction partners in cellular pathways
Therapeutic targeting feasibility
Biomarker development for patient selection

Key Publications

Pathway Diagram

The following diagram shows the key molecular relationships involving TMEM163 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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TMEM163 Gene

TMEM163 Gene

Introduction

TMEM163 Gene

Introduction

Overview

Function

Normal Function

Brain Expression

Disease Associations

Parkinson's Disease

Disease Mechanisms

Therapeutic Targeting

Current Approaches

Drug Development Challenges

Key Publications

External Links

Protein Structure and Function

Structural Features

Molecular Function

Metal Homeostasis in Neurodegeneration

Zinc in the Brain

Manganese in Neurodegeneration

Disease Associations

Parkinson's Disease

Metal Homeostasis Disorders

Pathogenic Mechanisms

Mitochondrial Dysfunction

Protein Quality Control

ER Stress Response

Therapeutic Approaches

Challenges in Drug Development

Research Directions

Key Publications

See Also

Pathway Diagram