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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FMNL2
formin like 2
Chromosome 2 · 2q23.3
NCBI Gene: 114793Ensembl: ENSG00000157827.21HGNC: HGNC:18267UniProt: A0ABJ7H3E2
85PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cadherin bindingcell migrationactin filament bindingcortical actin cytoskeleton organizationopen-angle glaucomaglaucomafrozen shoulderkeratoconjunctivitis
✦AI Summary

FMNL2 (formin-like 2) is a diaphanous-related formin protein located on chromosome 2.3 that regulates cytoskeletal dynamics and cell morphology 1. As a formin homology protein containing FDD, FH1, and FH2 domains 1, FMNL2 nucleates and polymerizes actin filaments at the plasma membrane, with its N-terminal myristoylation targeting it to filopodia tips and C-terminal phosphorylation by PKCα regulating dynamic filopodia formation 2. FMNL2 also participates in cell-cell junction assembly, focal adhesion formation, and subcellular trafficking 3, and surprisingly localizes to exosomes, suggesting a novel role in extracellular vesicle assembly 3. In disease contexts, FMNL2 is highly expressed in metastatic colorectal cancer cells and directly promotes cancer cell invasion and metastasis 4. miR-34a suppresses colorectal cancer progression by targeting FMNL2, indicating its oncogenic role 5. In Alzheimer's disease, FMNL2 expression increases in response to amyloid toxicity and cerebrovascular pathology, promoting astroglia detachment from blood vessels and disrupting gliovascular interactions that normally facilitate amyloid-tau clearance 6. Thus FMNL2 represents a therapeutic target linking cytoskeletal regulation to both cancer metastasis and neurodegeneration.

Sources cited
1
FMNL2 is a formin homology protein with FDD, FH1, and FH2 domains located on chromosome 2q23.3; involved in polarity control, invasion, migration, and metastasis through Rho-related signaling
PMID: 12684686
2
FMNL2 promotes rapid filopodia formation through N-terminal myristoylation-dependent tip localization and PKCα-mediated serine 1072 phosphorylation
PMID: 36979484
3
FMNL2 participates in filopodia assembly, lamellipodia force generation, cell-cell junction assembly, focal adhesion formation, and is present in exosomes
PMID: 38891874
4
FMNL2 is highly expressed in metastatic colorectal cancer cells and knockdown reduces cell invasiveness, supporting its role in cancer invasion and metastasis
PMID: 18971169
5
miR-34a targets FMNL2 to suppress colorectal cancer cell proliferation and invasion, demonstrating FMNL2's oncogenic function
PMID: 26103003
6
FMNL2 expression increases in AD brains with cerebrovascular pathology; amyloid toxicity promotes fmnl2a expression in astroglia causing end-foot detachment and disrupting gliovascular interactions
PMID: 35608697
Disease Associationsⓘ20
open-angle glaucomaOpen Targets
0.52Moderate
glaucomaOpen Targets
0.48Moderate
frozen shoulderOpen Targets
0.31Weak
keratoconjunctivitisOpen Targets
0.31Weak
Keratoconjunctivitis siccaOpen Targets
0.30Weak
Abnormal nasolacrimal system morphologyOpen Targets
0.27Weak
diabetes mellitusOpen Targets
0.27Weak
Crohn's diseaseOpen Targets
0.26Weak
injuryOpen Targets
0.25Weak
preeclampsiaOpen Targets
0.24Weak
neurodegenerative diseaseOpen Targets
0.20Weak
inflammatory bowel diseaseOpen Targets
0.19Weak
ovarian neoplasmOpen Targets
0.17Weak
brain aneurysmOpen Targets
0.12Weak
colorectal carcinomaOpen Targets
0.10Weak
breast cancerOpen Targets
0.09Suggestive
melanomaOpen Targets
0.09Suggestive
Alzheimer diseaseOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.07Suggestive
Absent tibia - polydactylyOpen Targets
0.05Suggestive
Pathogenic Variants1
NM_052905.4(FMNL2):c.407T>C (p.Leu136Pro)Likely pathogenic
Crohn disease
☆☆☆☆2021→ Residue 136
View on ClinVar ↗
Related Genes
RHOCProtein interaction88%PFN1Protein interaction88%CDC42Protein interaction87%FMNL3Shared pathway67%FMNL1Shared pathway63%CDC42BPAShared pathway38%
Tissue Expression6 tissues
Brain
100%
Ovary
75%
Lung
33%
Heart
17%
Liver
7%
Bone Marrow
4%
Gene Interaction Network
Click a node to explore
FMNL2RHOCPFN1CDC42FMNL3FMNL1CDC42BPA
PROTEIN STRUCTURE
Preparing viewer…
PDB4YC7 · 2.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.54Moderately Constrained
pLIⓘ
0.07Tolerant
Observed/Expected LoF0.42 [0.33–0.54]
RankingsWhere FMNL2 stands among ~20K protein-coding genes
  • #5,609of 20,598
    Most Researched85
  • #4,943of 5,498
    Most Pathogenic Variants1
  • #3,436of 17,882
    Most Constrained (LOEUF)0.54 · top quartile
Genes detectedFMNL2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Identification and characterization of human FMNL1, FMNL2 and FMNL3 genes in silico.
PMID: 12684686
Int J Oncol · 2003
1.00
2
FMNL2 regulates gliovascular interactions and is associated with vascular risk factors and cerebrovascular pathology in Alzheimer's disease.
PMID: 35608697
Acta Neuropathol · 2022
0.90
3
Identification and characterization of human FNBP3 gene in silico.
PMID: 12964049
Int J Mol Med · 2003
0.80
4
Identification of an FMNL2 Interactome by Quantitative Mass Spectrometry.
PMID: 38891874
Int J Mol Sci · 2024
0.70
5
Identification and characterization of the human FMN1 gene in silico.
PMID: 15202026
Int J Mol Med · 2004
0.60