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25 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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FERMT2
FERM domain containing kindlin 2
Chromosome 14 · 14q22.1
NCBI Gene: 10979Ensembl: ENSG00000073712.16HGNC: HGNC:15767UniProt: Q96AC1
155PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytoplasmprotein localization to cell junctionactin bindingpositive regulation of substrate adhesion-dependent cell spreadingopen-angle glaucomaprostate carcinomaneurodegenerative diseaseglaucoma
✦AI Summary

FERMT2 (Kindlin 2) is a scaffolding protein that functions as a critical regulator of integrin activation and cell-matrix adhesion. As an integrin co-activator, FERMT2 enhances integrin-mediated signaling by cooperating with talin proteins and binding to phosphoinositide-enriched membrane regions, facilitating focal adhesion assembly and actin cytoskeleton organization 1. Beyond adhesion, FERMT2 participates in TGFβ signaling pathways and stabilizes β-catenin, influencing Wnt-mediated transcription 2. Clinically, FERMT2 has emerged as a significant disease risk factor across multiple conditions. Genome-wide association studies identified FERMT2 as an Alzheimer's disease (AD) susceptibility gene 3, with functional studies demonstrating that FERMT2 reduction decreases extracellular amyloid-β and phosphorylated tau in human neurons 4. FERMT2 also associates with primary angle-closure glaucoma risk 5. In gastric cancer, FERMT2 drives peritoneal metastasis through anoikis resistance and extracellular matrix remodeling via TGFβ-RI/FN1 signaling, establishing a feedback loop that promotes tumor-stroma crosstalk 26. Similarly, in oral squamous cell carcinoma, FERMT2 upregulation in cancer-associated fibroblasts enhances epithelial-mesenchymal transition and macrophage polarization 7. These findings position FERMT2 as a multi-functional therapeutic target across neurodegenerative and malignant diseases.

Sources cited
1
FERMT2 identified as a genetic risk factor for late-onset Alzheimer's disease through genome-wide association studies
PMID: 24951455
2
FERMT2 knockdown reduces extracellular amyloid-β levels and phosphorylated tau in human induced pluripotent stem cell-derived neurons
PMID: 30371777
3
FERMT2 associated with primary angle-closure glaucoma susceptibility through GWAS studies
PMID: 28505344
4
FERMT2 promotes anoikis resistance and peritoneal metastasis in gastric cancer through SOX2 stabilization and fibronectin deposition via TGFβ signaling
PMID: 40024947
5
FERMT2 in cancer-associated fibroblasts maintains myofibroblastic phenotype and drives tumor-stroma crosstalk through TGFβ1/FERMT2/COL6A1 feedback loop in gastric cancer peritoneal dissemination
PMID: 41079932
6
FERMT2 upregulation in oral cancer-associated fibroblasts enhances epithelial-mesenchymal transition and M2 macrophage polarization through modulation of extracellular matrix proteins
PMID: 37357349
7
FERMT2 is highly expressed in placental trophoblast cells and mediates integrin-dependent trophoblast adhesion and invasion
PMID: 30382829
8
FERMT2 forms complexes with TGFBR1 and PYCR1 that regulate TGF-β signaling and collagen synthesis in cancer-associated fibroblasts
PMID: 38910148
Disease Associationsⓘ20
open-angle glaucomaOpen Targets
0.51Moderate
prostate carcinomaOpen Targets
0.50Moderate
neurodegenerative diseaseOpen Targets
0.50Moderate
glaucomaOpen Targets
0.49Moderate
Alzheimer diseaseOpen Targets
0.46Moderate
prostate cancerOpen Targets
0.41Moderate
atrial fibrillationOpen Targets
0.39Weak
Abnormality of the skeletal systemOpen Targets
0.33Weak
hypertensionOpen Targets
0.33Weak
primary angle closure glaucomaOpen Targets
0.32Weak
small intestine carcinomaOpen Targets
0.32Weak
small intestine neuroendocrine tumorOpen Targets
0.32Weak
dementiaOpen Targets
0.30Weak
small intestine cancerOpen Targets
0.30Weak
COVID-19Open Targets
0.29Weak
brain aneurysmOpen Targets
0.25Weak
urinary bladder carcinomaOpen Targets
0.24Weak
liver diseaseOpen Targets
0.23Weak
musculoskeletal system diseaseOpen Targets
0.23Weak
late-onset Alzheimers diseaseOpen Targets
0.23Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TLN2Protein interaction100%TLN1Protein interaction100%CTNNB1Protein interaction100%FLNCProtein interaction99%ITGB1Protein interaction97%PARVAProtein interaction95%
Tissue Expression6 tissues
Heart
100%
Liver
68%
Ovary
58%
Lung
57%
Brain
41%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
FERMT2TLN2TLN1CTNNB1FLNCITGB1PARVA
PROTEIN STRUCTURE
Preparing viewer…
PDB6XTJ · 1.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.30Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.18 [0.11–0.30]
RankingsWhere FERMT2 stands among ~20K protein-coding genes
  • #2,912of 20,598
    Most Researched155 · top quartile
  • #1,183of 17,882
    Most Constrained (LOEUF)0.30 · top 10%
Genes detectedFERMT2
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Alzheimer's disease risk genes and mechanisms of disease pathogenesis.
PMID: 24951455
Biol Psychiatry · 2015
1.00
2
Engineered extracellular vesicles for targeted reprogramming of cancer-associated fibroblasts to potentiate therapy of pancreatic cancer.
PMID: 38910148
Signal Transduct Target Ther · 2024
0.90
3
Genetics of glaucoma.
PMID: 28505344
Hum Mol Genet · 2017
0.80
4
FERMT2 drives anoikis resistance and peritoneal metastasis by enhancing extracellular matrix deposition in gastric cancer.
PMID: 40024947
Gastric Cancer · 2025
0.70
5
FERMT2 rs17125944 polymorphism with Alzheimer's disease risk: a replication and meta-analysis.
PMID: 27244899
Oncotarget · 2016
0.64