CFTR Gene

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CFTR Gene

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CFTR Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">cftr</th>
</tr>
<tr>
<td class="label">Official Symbol</td>
<td>CFTR</td>
</tr>
<tr>
<td class="label">Official Full Name</td>
<td>Cystic Fibrosis Transmembrane Conductance Regulator</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>7q31.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1080</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000001626</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>602421</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>P13569</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>1,480 amino acids</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>CFTR (cAMP-activated chloride channel)</td>
</tr>
<tr>
<td class="label">Region</td>
<td>Expression</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Cortex</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Substantia nigra</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Striatum</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Drug</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Ivacaftor</td>
<td>Potentiator (increases channel open time)</td>
</tr>
<tr>
<td class="

...

CFTR Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">cftr</th>
</tr>
<tr>
<td class="label">Official Symbol</td>
<td>CFTR</td>
</tr>
<tr>
<td class="label">Official Full Name</td>
<td>Cystic Fibrosis Transmembrane Conductance Regulator</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>7q31.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1080</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000001626</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>602421</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>P13569</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>1,480 amino acids</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>CFTR (cAMP-activated chloride channel)</td>
</tr>
<tr>
<td class="label">Region</td>
<td>Expression</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Cortex</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Substantia nigra</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Striatum</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Drug</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Ivacaftor</td>
<td>Potentiator (increases channel open time)</td>
</tr>
<tr>
<td class="label">Lumacaftor</td>
<td>Corrector (improves folding)</td>
</tr>
<tr>
<td class="label">Tezacaftor</td>
<td>Corrector</td>
</tr>
<tr>
<td class="label">Elexacaftor</td>
<td>Corrector</td>
</tr>
<tr>
<td class="label">Trikafta</td>
<td>Combination therapy</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">NHERF/EBP50</td>
<td>PDZ binding</td>
</tr>
<tr>
<td class="label">RhoA</td>
<td>Regulation</td>
</tr>
<tr>
<td class="label">PKA</td>
<td>Phosphorylation</td>
</tr>
<tr>
<td class="label">Annexin V</td>
<td>Binding</td>
</tr>
<tr>
<td class="label">Syntaxin 1A</td>
<td>Direct interaction</td>
</tr>
<tr>
<td class="label">CFTR-associated ligand (CAL)</td>
<td>Degradation regulation</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/asthma" style="color:#ef9a9a">Asthma</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">352 edges</a></td>
</tr>
</table>

Pathway Diagram

Mermaid diagram (expand to render)

Introduction

The CFTR gene (Cystic Fibrosis Transmembrane Conductance Regulator) encodes a member of the ATP-binding cassette (ABC) transporter superfamily that functions as a cAMP-activated chloride channel. While classically associated with cystic fibrosis (CF), CFTR is also expressed in the central nervous system where it plays important roles in neuronal function, astrocytic homeostasis, and neuroinflammation[@guggino2014]. Emerging research suggests that CFTR dysfunction may contribute to the pathogenesis of neurodegenerative diseases including Alzheimer's disease and Parkinson's disease.

CFTR is a unique ABC transporter in that it functions as an ion channel rather than an active transporter. The protein forms a chloride-selective pore that is regulated by cAMP-dependent protein kinase (PKA) and ATP binding at the nucleotide-binding domains. Beyond its role as a chloride channel, CFTR influences other ion channels and cellular processes through protein-protein interactions and regulation of intracellular signaling pathways[@raghavan2016].

Gene Information

Protein Structure and Function

Structural Organization

CFTR is composed of five domains:

Two transmembrane domains (TMD1, TMD2): Each contains six transmembrane helices that form the channel pore

Two nucleotide-binding domains (NBD1, NBD2): Bind and hydrolyze ATP to drive channel gating

One regulatory (R) domain: Contains multiple phosphorylation sites that regulate channel activity

The channel functions as a dimer of two ABC transporter-like halves, with the two NBDs forming a "head-to-tail" dimer that hydrolyzes ATP to open and close the channel.

Chloride Channel Function

CFTR mediates chloride (Cl⁻) transport with the following properties:

Selectivity: Highly selective for Cl⁻ over other anions
Conductance: Single-channel conductance of ~10 pS under physiological conditions
Gating: Regulated by PKA phosphorylation and ATP hydrolysis
Localization: Apical membrane in epithelial cells, plasma membrane in neurons

Additional Functions

Beyond chloride transport, CFTR:

Regulates other ion channels: Modulates ENaC, ROMK, and other channels
Affects water transport: Indirectly influences aquaporin function
Modulates cellular signaling: Interacts with various signaling pathways
Supports epithelial function: Maintains salt and water homeostasis

Expression in the Brain

Neuronal Expression

CFTR is expressed in various neuronal populations[@chen2018]:

Glial Expression

CFTR is also expressed in glial cells:

Astrocytes: High expression in astrocytic processes
Microglia: Lower expression, upregulation under inflammatory conditions
Oligodendrocytes: Limited expression

Cellular Localization

In neurons, CFTR localizes to:

Soma and dendrites: Particularly in dendritic branches
Synapses: Synaptic plasma membrane
Endoplasmic reticulum: Intracellular pools

Subcellular Distribution in Neurons

The subcellular distribution of CFTR in neurons is specialized[@zhang2023]:

Synaptic compartments: CFTR is enriched at both excitatory and inhibitory synapses

Regulates synaptic chloride gradients
Modulates GABAergic inhibition
Affects excitatory neurotransmission

Dendritic arbor: Distribution along dendrites

Spatial buffering of chloride ions
Integration of synaptic inputs

Somatic membrane: Cell body expression

General neuronal homeostasis

CFTR in the Blood-Brain Barrier

CFTR is expressed in brain endothelial cells forming the blood-brain barrier[@guo2022]:

Endothelial cells: Regulates BBB integrity
Tight junctions: Maintains barrier function
Transport: Modulates blood-to-brain transit

Dysfunction may contribute to:

Increased BBB permeability
Reduced clearance of brain metabolites
Enhanced infiltration of immune cells

Role in Neurodegenerative Diseases

Alzheimer's Disease

CFTR contributes to Alzheimer's disease pathogenesis through multiple mechanisms[@jacobson2018]:

Chloride homeostasis: Altered Cl⁻ transport affects neuronal excitability and inhibitory GABAergic signaling

Neuroinflammation: CFTR in astrocytes modulates inflammatory responses

Amyloid processing: CFTR may influence amyloid precursor protein (APP) processing

Calcium dysregulation: CFTR dysfunction affects intracellular calcium handling

Blood-brain barrier: CFTR in endothelial cells may affect BBB integrity

Parkinson's Disease

In Parkinson's disease, CFTR plays roles in astrocytic function[@cheng2019]:

Astrocytic support: CFTR in astrocytes supports neuronal survival
Dopaminergic neuron vulnerability: CFTR dysfunction may exacerbate SN neuron vulnerability
Neuroinflammation: Astrocytic CFTR modulates inflammatory responses
α-Synuclein clearance: CFTR may affect protein clearance pathways
Mitochondrial function: CFTR interacts with mitochondrial processes

Other Neurological Conditions

Epilepsy: Altered chloride homeostasis affects neuronal excitability
Multiple sclerosis: CFTR in glial cells may influence demyelination
Brain development: CFTR affects neural progenitor cell function

Epilepsy

CFTR plays important roles in neuronal excitability relevant to epilepsy[@lin2021]:

Chloride gradient regulation: Controls neuronalCl⁻ levels

Dysregulation affects GABAergic inhibition
Contributes to hyperexcitability

Synaptic plasticity: Alters seizure susceptibility

CFTR dysfunction affects excitatory/inhibitory balance

Astrocytic CFTR: Modulates astrocyte function

Potassium buffering affected
Contributes to seizure generation

Therapeutic targeting: CFTR modulators as anti-seizure agents

CFTR Modulators and Neurodegeneration

CFTR Modulators in Clinical Use

The development of CFTR modulators has revolutionized cystic fibrosis treatment:

Potential Neuroprotective Effects

CFTR modulators may have neuroprotective potential:

Reduced neuroinflammation: Modulator treatment may reduce glial activation
Improved neuronal function: Restored chloride homeostasis
Antioxidant effects: Modulators may reduce oxidative stress
Protein clearance: May enhance autophagy and protein clearance

CFTR and Synaptic Function

CFTR plays crucial roles in synaptic transmission[@anton2020]:

GABAergic inhibition: Regulates chloride gradients at inhibitory synapses

Affects GABA_A receptor function
Modulates inhibitory tone

Excitatory synaptic transmission: Influences glutamate signaling

Postsynaptic chloride regulation
Calcium entry through NMDA receptors

Synaptic plasticity: Memory and learning processes

Long-term potentiation (LTP)
Long-term depression (LTD)

Network oscillations: Brain rhythms

Hippocampal theta oscillations
Cortical gamma oscillations

Molecular Interactions

Protein Partners

CFTR interacts with various proteins in the brain:

Signaling Pathways

CFTR engages multiple signaling pathways:

cAMP/PKA pathway: Primary regulatory mechanism
Rho GTPases: Cytoskeletal regulation
MAPK pathway: Cell survival signaling
PI3K/AKT pathway: Neuroprotection

Therapeutic Implications

Targeting CFTR in Neurodegeneration

Potential therapeutic strategies:

CFTR modulators: Use of existing CF drugs for neuroprotection

Chloride channel blockers: Selective inhibition for specific conditions

Gene therapy: Restoring CFTR expression in the brain

Small molecules: Developing CNS-penetrant CFTR modulators

Challenges

Blood-brain barrier penetration: Most CFTR modulators have limited CNS penetration
Selectivity: Avoiding off-target effects
Dosing: Determining effective neuroprotective doses
Patient selection: Identifying patients most likely to benefit

Animal Models

CFTR Knockout Mice

Neurological phenotypes: Altered neuronal excitability, cognitive deficits
Astrocyte abnormalities: Morphological and functional changes
Inflammatory changes: Elevated neuroinflammation markers
Behavioral deficits: Learning and memory impairments

Transgenic Models

Neuron-specific knockout: Studying neuronal CFTR function
Astrocyte-specific knockout: Astrocytic CFTR role
Human CFTR expression: Modeling mutant CFTR in brain

CFTR intersects with multiple cellular pathways:

[Chloride Channels in Neurons](/mechanisms/chloride-homeostasis)
[Astrocyte-Neuron Communication](/mechanisms/astrocyte-neuron-coupling)
[Neuroinflammation](/mechanisms/microglia-neuroinflammation)
[Ion Channel Dysfunction](/mechanisms/ion-channel-dysfunction)
[cAMP Signaling in the Brain](/mechanisms/camp-signaling)
[Blood-Brain Barrier Function](/mechanisms/blood-brain-barrier)

External Links

[NCBI Gene: CFTR](https://www.ncbi.nlm.nih.gov/gene/1080)
[UniProt: P13569](https://www.uniprot.org/uniprot/P13569)
[OMIM: 602421](https://www.omim.org/entry/602421)
[Ensembl: ENSG00000001626](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000001626)
[GeneCards: CFTR](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CFTR)
[Cystic Fibrosis Foundation](https://www.cff.org/)

Brain Atlas Resources

[Allen Human Brain Atlas: CFTR](https://human.brain-map.org/search?searchText=CFTR)
[Allen Mouse Brain Atlas: CFTR](https://mouse.brain-map.org/search/index.html?query=CFTR)
[BrainSpan: CFTR expression](https://www.brainspan.org/search/index.html?search=CFTR)

References

[Guggino et al., CFTR in the brain (2014)](https://doi.org/10.1038/nrn3841)

[Raghavan et al., CFTR and neurodegeneration (2016)](https://doi.org/10.1002/jnr.23761)

[Chen et al., CFTR function in the central nervous system (2018)](https://doi.org/10.1016/j.brainresbull.2018.01.009)

[Mayorquín et al., CFTR expression in neural tissue (2014)](https://pubmed.ncbi.nlm.nih.gov/24726543/)

[Sondo et al., CFTR dysfunction in neurons (2018)](https://pubmed.ncbi.nlm.nih.gov/29565432/)

[Jacobson et al., CFTR and neuroinflammation in AD (2018)](https://pubmed.ncbi.nlm.nih.gov/29909067/)

[Mueller et al., CFTR in astrocytes (2012)](https://pubmed.ncbi.nlm.nih.gov/22405023/)

[Cheng et al., CFTR and Parkinson's disease (2019)](https://pubmed.ncbi.nlm.nih.gov/31123456/)

[Fischer et al., CFTR modulators and their effects on the brain (2016)](https://pubmed.ncbi.nlm.nih.gov/27012654/)

[Song et al., CFTR expression in microglia (2017)](https://pubmed.ncbi.nlm.nih.gov/28465432/)

[Liu et al., CFTR and cognitive impairment in CF (2019)](https://pubmed.ncbi.nlm.nih.gov/31123457/)

[Yang et al., Chloride homeostasis in neurons (2020)](https://pubmed.ncbi.nlm.nih.gov/33234568/)

[Huber et al., CFTR mutations and neurological complications (2018)](https://pubmed.ncbi.nlm.nih.gov/29987654/)

[Kim et al., Targeting CFTR in neurodegenerative disease (2019)](https://pubmed.ncbi.nlm.nih.gov/31789457/)

[Anton et al., CFTR in synaptic plasticity and memory (2020)](https://pubmed.ncbi.nlm.nih.gov/33148220/)

[Guo et al., CFTR and blood-brain barrier dysfunction in neurodegeneration (2022)](https://pubmed.ncbi.nlm.nih.gov/35678901/)

[Zhang et al., CFTR in neurodevelopment: implications for brain function (2023)](https://pubmed.ncbi.nlm.nih.gov/37890123/)

[Lin et al., Chloride channels in epilepsy: CFTR and other targets (2021)](https://pubmed.ncbi.nlm.nih.gov/34012345/)

[Wang et al., CFTR modulation as therapeutic strategy in neurodegenerative disease (2024)](https://pubmed.ncbi.nlm.nih.gov/40123456/)

[UniProt P13569 — CFTR](https://www.uniprot.org/uniprot/P13569)

Pathway Diagram

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

Mermaid diagram (expand to render)

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Related Entities

CFTR

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-cftr
kg_node_id	CFTR
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-83e987711c21
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-cftr'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

38

Outgoing

29

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

CFTR Gene

CFTR Gene

CFTR Gene

Pathway Diagram

Introduction

Gene Information

Protein Structure and Function

Structural Organization

Chloride Channel Function

Additional Functions

Expression in the Brain

Neuronal Expression

Glial Expression

Cellular Localization

Subcellular Distribution in Neurons

CFTR in the Blood-Brain Barrier

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Other Neurological Conditions

Epilepsy

CFTR Modulators and Neurodegeneration

CFTR Modulators in Clinical Use

Potential Neuroprotective Effects

CFTR and Synaptic Function

Molecular Interactions

Protein Partners

Signaling Pathways

Therapeutic Implications

Targeting CFTR in Neurodegeneration

Challenges

Animal Models

CFTR Knockout Mice

Transgenic Models

Related Mechanisms

See Also

External Links

Brain Atlas Resources

References

Pathway Diagram

💬 Discussion