FERMT2 Gene

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gene1145 wordssynced 2026-04-02

FERMT2 Gene

Overview

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FERMT2 Gene

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">FERMT2 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>FERMT2</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Fermitin Family Member 2</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Kindlin-2 (MITD2)</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>14q22.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>10979</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000173702</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9BUF5</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>614365</td>
</tr>
<tr>
<td class="label">Domain</td>
<td>Location</td>
</tr>
<tr>
<td class="label">F0 domain</td>
<td>N-terminus</td>
</tr>
<tr>
<td class="label">F1 domain</td>
<td>Central</td>
</tr>
<tr>
<td class="label">F2 domain</td>
<td>Central</td>
</tr>
<tr>
<td class="label">F3 domain</td>
<td>C-terminus</td>
</tr>
<tr>
<td class="label">PH domain</td>
<td>C-terminus</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Rationale</td>
</tr>
<tr>
<td class="label">Integrin modulators</td>
<td>Modulate integrin-kindlin interaction</td>
</tr>
<tr>
<td class="label">Microglial targeting</td>
<td>Enhance Aβ clearance</td>
</tr>
<tr>
<td class="label">BBB protection</td>
<td>Maintain endothelial function</td>
</tr>
<tr>
<td class="label">Anti-inflammatory</td>
<td>Reduce neuroinflammation</td>
</tr>
<tr>
<td class="label">Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Cerebral cortex</td>
<td>High</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Basal ganglia</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Substantia nigra</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Cell Type</td>
<td>Expression</td>
</tr>
<tr>
<td class="label">Neurons</td>
<td>High</td>
</tr>
<tr>
<td class="label">Astrocytes</td>
<td>High</td>
</tr>
<tr>
<td class="label">Microglia</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Endothelial cells</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Oligodendrocytes</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">Integrins (β1, β3, β5)</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">Talin</td>
<td>Cooperative binding</td>
</tr>
<tr>
<td class="label">Vinculin</td>
<td>Focal adhesion</td>
</tr>
<tr>
<td class="label">Paxillin</td>
<td>Focal adhesion</td>
</tr>
<tr>
<td class="label">FAK</td>
<td>Signaling</td>
</tr>
<tr>
<td class="label">ILK</td>
<td>Signaling complex</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">Alzheimer's disease</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">44 edges</a></td>
</tr>
</table>

FERMT2 (Fermitin Family Member 2), also known as Kindlin-2 or MITD2 (Mitogen-Induced Domain-2), encodes a member of the fermitin family of proteins. Kindlin-2 is a critical integrin-activating protein that plays essential roles in cell adhesion, focal adhesion formation, actin cytoskeleton organization, and cell migration. Genome-wide association studies (GWAS) have identified FERMT2 as a risk gene for late-onset Alzheimer's disease (LOAD), making it a protein of significant interest in neurodegeneration research[@lambert2013].

Structure and Function

Protein Structure

Kindlin-2 is a ~80 kDa protein containing several key domains:

Integrin Activation (Inside-Out Signaling)

Kindlin-2 is a key activator of integrin receptors through "inside-out" signaling:

Talin binding: Kindlin-2 cooperates with talin to activate integrins

Integrin clustering: Kindlin-2 promotes integrin clustering and adhesion maturation

Focal adhesion formation: Kindlin-2 localizes to focal adhesions

Actin linkage: Connects integrins to the actin cytoskeleton

Kindlin-2 and talin form a functional complex that fully activates integrins—neither alone is sufficient for maximal activation[@ushio2017].

Subcellular Localization

Kindlin-2 is primarily localized to:

Focal adhesions (cell-matrix adhesion sites)
Cytoplasmic vesicles
Nucleus (in some cell types)
Cell-cell junctions (in epithelial cells)

Normal Physiological Functions

Cell-Matrix Adhesion

Kindlin-2 is essential for:

Integrin activation: Inside-out signaling for integrin function
Focal adhesion formation: Recruitment of adhesion proteins
Adhesion maturation: Transition from nascent to stable adhesions
Cell spreading: Initial attachment and spreading on substrates

Actin Cytoskeleton Organization

Through interactions with various partners:

Actin-binding proteins: Regulates actin polymerization
Vinculin: Links focal adhesions to actin
Alpha-actinin: Cross-links actin filaments

Cell Migration

Kindlin-2 regulates:

Lamellipodia formation
Focal adhesion turnover
Traction force generation
Directional migration[@yu2015]

Role in Neurodegenerative Diseases

Alzheimer's Disease

FERMT2 has emerged as a significant AD risk gene through GWAS[@kelley2018]:

GWAS Evidence:

Multiple independent studies confirm association
Common variants with modest effect size
Expression quantitative trait loci (eQTLs) affect FERMT2 expression

Potential Mechanisms:

Amyloid-β Metabolism:

Kindlin-2 may influence APP processing
Integrin-Aβ interactions affect Aβ clearance
αvβ3/αvβ5 integrins involved in Aβ uptake by microglia

Tau Pathology:

Kindlin-2 may affect tau phosphorylation
Integrin signaling modulates tau kinases
Possible role in tau spread[@liu2019]

Neuroinflammation:

Kindlin-2 in microglia affects inflammatory responses
Integrin-mediated phagocytosis
Cytokine production regulation[@xie2018]

Blood-Brain Barrier:

Kindlin-2 in brain endothelial cells
May affect BBB integrity
Aβ transport across BBB[he2017]

Evidence from Human Studies:

FERMT2 expression altered in AD brain
Genetic variants associated with AD risk
Protein levels correlate with disease severity

Parkinson's Disease

While not a primary GWAS hit, FERMT2 may play roles:

Expressed in dopaminergic neurons
May affect neuronal survival
Altered expression in PD models
Possible interaction with α-synuclein

Multiple Sclerosis

Altered FERMT2 expression in demyelinating lesions
May affect oligodendrocyte function
Integrin signaling in immune cell trafficking

Clinical Significance

Alzheimer's Disease Risk

Genetic association: FERMT2 is a confirmed AD risk locus
Effect size: Modest odds ratio (~1.1-1.2 per risk allele)
Population-specific effects: May vary across ancestries

Cancer

FERMT2 is overexpressed in several cancers:

Breast cancer
Lung cancer
Colorectal cancer
Glioma

This complicates therapeutic targeting.

Therapeutic Implications

Targeting Strategies

Challenges

Peripheral vs. CNS targeting: Must cross the BBB
Integrin redundancy: Multiple kindlins and integrins
Cancer risk: Overexpression in tumors

Expression Pattern

Brain Regions

FERMT2 is expressed in multiple brain regions:

Cell Type Specificity

Key Interactions

Animal Models

Knockout Mice

Fermt2-/-: Embryonic lethal (developmental defects)
Conditional knockouts: Brain-specific deletion viable
Phenotype: Altered integrin signaling, adhesion defects

Transgenic Models

AD models: Crossed with APP/PS1 mice
Overexpression: Neuronal FERMT2 overexpression
Humanized: Express AD-associated variants

Research Methods

Genetic Studies

GWAS meta-analysis
Whole-exome sequencing
eQTL mapping

Molecular Biology

siRNA/shRNA knockdown
CRISPR-Cas9 editing
Co-immunoprecipitation

Imaging

Immunofluorescence for focal adhesions
Live-cell imaging for adhesion dynamics
Super-resolution microscopy

References

[Lambert et al., GWAS meta-analysis AD (2013)](https://pubmed.ncbi.nlm.nih.gov/24162737/)

[Jansen et al., GWAS AD (2019)](https://pubmed.ncbi.nlm.nih.gov/30617256/)

[Wightman et al., GWAS with polygenic scores (2021)](https://pubmed.ncbi.nlm.nih.gov/34799693/)

[Kelley et al., FERMT2 in AD (2018)](https://pubmed.ncbi.nlm.nih.gov/29701046/)

[Ushio et al., Kindlin-2 integrin function (2017)](https://pubmed.ncbi.nlm.nih.gov/28637949/)

[Pluskota et al., Kindlin-2 in platelets (2018)](https://pubmed.ncbi.nlm.nih.gov/29506969/)

[Rognoni et al., Kindlin-2 in mechanotransduction (2016)](https://pubmed.ncbi.nlm.nih.gov/27297034/)

[Ma et al., Kindlin-2 and integrin (2019)](https://pubmed.ncbi.nlm.nih.gov/31048715/)

[Yu et al., Kindlin-2 in migration (2015)](https://pubmed.ncbi.nlm.nih.gov/26284482/)

[Zhang et al., Kindlin-2 in cancer (2019)](https://pubmed.ncbi.nlm.nih.gov/31278473/)

[Zhao et al., FERMT2 and integrin in AD (2020)](https://pubmed.ncbi.nlm.nih.gov/32948747/)

[Xie et al., Kindlin-2 and Aβ clearance (2018)](https://pubmed.ncbi.nlm.nih.gov/29582557/)

[He et al., Kindlin-2 and BBB (2017)](https://pubmed.ncbi.nlm.nih.gov/28584667/)

[Liu et al., Kindlin-2 and tau (2019)](https://pubmed.ncbi.nlm.nih.gov/31478237/)

[Song et al., FERMT2 in AD brain (2018)](https://pubmed.ncbi.nlm.nih.gov/29549874/)

[Antwi et al., Kindlin-2 in memory (2018)](https://pubmed.ncbi.nlm.nih.gov/29438987/)

[Fan et al., Integrin signaling and Aβ (2019)](https://pubmed.ncbi.nlm.nih.gov/31745023/)

[Gao et al., Kindlin-2 in astrocytes (2020)](https://pubmed.ncbi.nlm.nih.gov/32248829/)

[Zhang et al., Targeting FERMT2 (2021)](https://pubmed.ncbi.nlm.nih.gov/33820717/)

[Mort et al., Kindlin-2 in cell-matrix (2018)](https://pubmed.ncbi.nlm.nih.gov/29698814/)

Last updated: 2026-03-25

Pathway Diagram

The following diagram shows the key molecular relationships involving FERMT2 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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FERMT2 Gene

FERMT2 Gene

Overview

FERMT2 Gene

Overview

Structure and Function

Protein Structure

Integrin Activation (Inside-Out Signaling)

Subcellular Localization

Normal Physiological Functions

Cell-Matrix Adhesion

Actin Cytoskeleton Organization

Cell Migration

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Multiple Sclerosis

Clinical Significance

Alzheimer's Disease Risk

Cancer

Therapeutic Implications

Targeting Strategies

Challenges

Expression Pattern

Brain Regions

Cell Type Specificity

Key Interactions

Animal Models

Knockout Mice

Transgenic Models

Research Methods

Genetic Studies

Molecular Biology

Imaging

See Also

References

Pathway Diagram