FERMT2

Summary

FERMT2 (FERM domain containing kindlin 2, HGNC:15767) is a protein-coding gene on chromosome 14q22.1, encoding Fermitin family homolog 2 (Q96AC1). Scaffolding protein that enhances integrin activation mediated by TLN1 and/or TLN2, but activates integrins only weakly by itself. It is a selective cancer dependency (DepMap: 49.9% of cell lines).

Enables several functions, including phosphatidylinositol-3,4,5-trisphosphate binding activity; protein serine/threonine kinase binding activity; and type I transforming growth factor beta receptor binding activity. Involved in several processes, including cell surface receptor signaling pathway; positive regulation of cellular component biogenesis; and positive regulation of intracellular signal transduction. Acts upstream of or within cell adhesion and protein localization to cell junction. Located in several cellular components, including adherens junction; cytoplasmic side of plasma membrane; and focal adhesion. Biomarker of acute myeloid leukemia.

Source: NCBI Gene 10979 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 88 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 49.9% of screened cell lines
• MANE Select transcript: NM_006832

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15767
Approved symbol	FERMT2
Name	FERM domain containing kindlin 2
Location	14q22.1
Locus type	gene with protein product
Status	Approved
Aliases	mig-2, KIND2, UNC112B
Ensembl gene	ENSG00000073712
Ensembl biotype	protein_coding
OMIM	607746
Entrez	10979

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 29 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000341590, ENST00000343279, ENST00000395631, ENST00000399304, ENST00000553373, ENST00000553663, ENST00000553768, ENST00000554152, ENST00000554288, ENST00000554712, ENST00000555546, ENST00000555692, ENST00000557255, ENST00000557562, ENST00000635305, ENST00000875230, ENST00000875231, ENST00000875232, ENST00000875233, ENST00000875234, ENST00000875235, ENST00000875236, ENST00000875237, ENST00000921868, ENST00000921869, ENST00000921870, ENST00000921871, ENST00000970379, ENST00000970380, ENST00000970381, ENST00000970382, ENST00000970383, ENST00000970384

RefSeq mRNA: 3 — MANE Select: NM_006832 NM_001134999, NM_001135000, NM_006832

CCDS: CCDS45107, CCDS45108, CCDS9713

Canonical transcript exons

ENST00000341590 — 15 exons

Exon	Start	End
ENSE00000657505	52874177	52874226
ENSE00000657507	52875223	52875357
ENSE00000657510	52881036	52881138
ENSE00000657511	52881244	52881469
ENSE00000657513	52893293	52893427
ENSE00001364235	52950921	52951050
ENSE00001387156	52950412	52950577
ENSE00001606398	52878582	52878689
ENSE00003486213	52919123	52919356
ENSE00003498032	52864401	52864622
ENSE00003499444	52860341	52860465
ENSE00003543974	52872799	52872923
ENSE00003631794	52864747	52864853
ENSE00003672645	52859573	52859714
ENSE00003850988	52857273	52858550

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.7630 / max 265.9175, expressed in 1528 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143273	16.6900	1498
143274	2.1451	1114
143275	0.3882	195
143269	0.3318	155
143276	0.2041	69
143270	0.0037	1

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	99.74	gold quality
cauda epididymis	UBERON:0004360	99.42	gold quality
metanephric glomerulus	UBERON:0004736	99.21	gold quality
renal glomerulus	UBERON:0000074	99.20	gold quality
blood vessel layer	UBERON:0004797	99.18	gold quality
saphenous vein	UBERON:0007318	99.15	gold quality
cartilage tissue	UBERON:0002418	99.04	gold quality
parietal pleura	UBERON:0002400	99.01	gold quality
pleura	UBERON:0000977	98.88	gold quality
seminal vesicle	UBERON:0000998	98.86	gold quality
visceral pleura	UBERON:0002401	98.76	gold quality
tibia	UBERON:0000979	98.70	gold quality
secondary oocyte	CL:0000655	98.57	gold quality
vena cava	UBERON:0004087	98.56	gold quality
smooth muscle tissue	UBERON:0001135	98.51	gold quality
popliteal artery	UBERON:0002250	98.48	gold quality
tibial artery	UBERON:0007610	98.48	gold quality
urethra	UBERON:0000057	98.41	gold quality
aorta	UBERON:0000947	98.37	gold quality
myometrium	UBERON:0001296	98.37	gold quality
superficial temporal artery	UBERON:0001614	98.35	gold quality
synovial joint	UBERON:0002217	98.34	gold quality
placenta	UBERON:0001987	98.25	gold quality
descending thoracic aorta	UBERON:0002345	98.24	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.24	gold quality
thoracic aorta	UBERON:0001515	98.22	gold quality
ascending aorta	UBERON:0001496	98.19	gold quality
lower esophagus	UBERON:0013473	98.19	gold quality
right coronary artery	UBERON:0001625	97.98	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.98	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	442.58
E-ANND-3	yes	17.75
E-HCAD-11	yes	7.38
E-CURD-112	yes	5.79

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZNF236

miRNA regulators (miRDB)

139 targeting FERMT2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4673	100.00	66.64	1490
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AJ-3P	99.96	73.38	5345

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 49.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Mig-2 expression is transcriptionally elevated in leiomyomas and could be involved in its hormone-mediated growth of leiomyomas of the uterus. (PMID:14745725)
• Results identify kindlin-2 as a novel regulator of integrin beta3 activation; it functions as a coactivator. (PMID:18458155)
• Loss-of-function mutations in KIND1 result in marked variability in kindlin-1 immunolabeling in Kindler syndrome skin, which is mirrored by similar changes in kindlin-2 and migfilin immunoreactivity. (PMID:18528435)
• cellular functions and possible clinical relevance of kindlin-2 [REVIEW] (PMID:19854292)
• our study suggests that heightened expression of Kindlin-2 might contribute to tumor progression in MM. (PMID:20127858)
• Tyrosine phosphorylation of integrin beta3 regulates kindlin-2 binding and integrin activation. (PMID:20702409)
• physiological role for kindlin-2 in skin fibroblasts under normal steady-state conditions and during tissue regeneration (PMID:20861856)
• Kindlin-2 regulates podocyte adhesion and fibronectin deposition through interactions with phosphoinositides and integrinb1 and b3. (PMID:21325030)
• The phenotype of kindlin-1-deficient cells can be modulated by regulating kindlin-2 gene expression and vice versa. (PMID:21356350)
• Kindlin-2 is expressed in a small subset of high-grade invasive bladder cancers and may have a role in tumor progression (PMID:21624607)
• secondary structures predicted from amino-acid sequence alignment of kindlin PH domains indicated that our crystallized kindlin-2 PH domain has an additional C-terminal helix (alpha-2) which is highly conserved in all three kindlin-family proteins (PMID:21636915)
• Functional characterization of human Kindlin-2 core promoter identifies a key role of SP1 in Kindlin-2 transcriptional regulation. (PMID:21922223)
• Results define a specific PIP3 recognition mode for the kindlin PH domain and shed light upon a mechanism as to how the PH domain mediates membrane engagement of kindlin-2 to promote integrin activation. (PMID:22030399)
• Kindlin-2 was up-regulated both at RNA (P = .027) and protein levels (P = .014) in gastric cancer tissues and may play an important role in the development and prognosis of gastric cancer. (PMID:22056622)
• a membrane-binding function of the ubiquitin-like domain of kindlin-2, which is likely common for all kindlins, promotes localization to the plasma membrane and controls integrin activation (PMID:22078565)
• Low expression of kindlin-2 correlated with a favorable prognosis for acute myeloid leukemia. (PMID:22391155)
• Kindlin-2 and talin head do not interact with one another but can bind simultaneously to the integrin beta(3) tail without enhancing or inhibiting the interaction of the other binding partner. (PMID:22648415)
• Kindlin 2 forms a tripartite complex with beta-catenin and TCF4. (PMID:22699938)
• the novel focal adhesion gene kindlin-2 may play an important role in promoting the invasion of gastric cancer cells mediated by tumor-associated macrophages through regulating interleukin expression. (PMID:23151599)
• Kindlin-1 and Kindlin-2 have opposite roles in lung cancers (PMID:23209705)
• Kindlin-2 regulates breast cancer progression by inducing genome instability. (PMID:23211537)
• A novel regulatory loop has been described between GLI1 and Kindlin-2 that determines cancer cell viability. (PMID:23337877)
• Kindlin 2 plays a novel role in epigenetic repression of miR-200 family, a mechanism that promotes breast cancer invasion. (PMID:23483548)
• Kindlin-2 was highly expressed in the peritumoral stroma of pancreatic ductal adenocarcinomas. Stromal kindlin-2 expression was related to nodal metastasis (P = 0.03). (PMID:23508013)
• Kindlin-2 mediates activation of TGF-beta/Smad signaling and renal fibrosis. (PMID:23723426)
• Kindlin-2 might promote the invasion of gastric cancer cells through enhancing proliferation and adhesion by the phosphorylation of integrin beta1 and beta3. (PMID:23857544)
• the first evidence that interaction between the integrin beta1 cytoplasmic tail and kindlin-2, a member of a family of adapters implicated in human disease pathogenesis, is mainly governed by the beta1 C-terminal carboxylate moiety (PMID:24599960)
• Data indicate that Kindlin-2 mRNA levels in adult is highly expressed in mesoderm-derived organs. (PMID:24907935)
• A major ILK binding site in the kindlin-2 FERM domain for regulating cell adhesion has been mapped. (PMID:25160619)
• High kindlin-2 expression is associated with esophageal squamous cell carcinoma. (PMID:25605255)
• our findings suggested that Kindlin-2 was highly expressed in hepatocellular carcinoma tissues and was closely related to clinical progression. Kindlin-2 protein could be a potential biomarker for predicting poor prognosis of HCC patients after surgery. (PMID:25618552)
• findings suggest that Src, Kindlin-2 and Migfilin together constitute a positive feedback loop that controls Src activity and regulates integrin-mediated cellular func (PMID:26037143)
• data indicate that kindlin-2 promotes the invasiveness of prostate cancer cells largely through NF-kappaB-dependent upregulation of MMP-9 and MMP-2 (PMID:26551397)
• The F0 domain of K2 binds actin. (PMID:27044892)
• the rs17125944 polymorphism in FERMT2 gene might not be association with late-onset Alzheimer’s disease in northern Han Chinese population (PMID:27244899)
• Kindlin-2 is up-regulated in glioma cells and acts as an oncogene. It is an independent risk factor for poor prognosis. The Kindlin-2/YB-1/beta-catenin complex promotes EGFR transcription and contributes to glioma progression. Kindlin-2 is a potential diagnostic and prognostic marker in glioma, and inhibition of Kindlin-2 may be a novel strategy for glioma treatment. (PMID:27713156)
• We show a direct relationship between kindlin-1 abundance and UV-B induced apoptosis in keratinocytes, whereas kindlin-2 overexpression has no compensatory effect. (PMID:27798104)
• Study found that FERMT2 (a beta3-integrin co-activator) was significantly associated with a variation in cerebrospinal fluid Abeta peptide levels in 2886 Alzheimer’s disease cases.Under-expression of FERMT2 increases Abeta peptide production by raising levels of mature APP at the cell surface and facilitating its recycling (PMID:27933404)
• Long noncoding RNA-ATB functions as a molecular sponge for miR-200b and Kindlin-2. (PMID:28640252)
• Data suggest that the extreme C terminus of kindlin-2 is essential for interaction with and activation of integrin alphaIIBbeta3; these studies were conducted in macrophage cell line and erythroleukemia cell line. (PMID:28652408)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fermt2	ENSDARG00000020242
mus_musculus	Fermt2	ENSMUSG00000037712
rattus_norvegicus	Fermt2	ENSRNOG00000009102
drosophila_melanogaster	Fit1	FBGN0035498
drosophila_melanogaster	Fit2	FBGN0036688
caenorhabditis_elegans		WBGENE00006836

Paralogs (2): FERMT1 (ENSG00000101311), FERMT3 (ENSG00000149781)

Protein

Protein identifiers

Fermitin family homolog 2 — Q96AC1 (reviewed: Q96AC1)

Alternative names: Kindlin-2, Mitogen-inducible gene 2 protein, Pleckstrin homology domain-containing family C member 1

All UniProt accessions (8): Q96AC1, A0A0U1RRM8, G3V281, G3V379, G3V3J0, G3V5R2, H0YJ34, H0YJB6

UniProt curated annotations — full annotation on UniProt →

Function. Scaffolding protein that enhances integrin activation mediated by TLN1 and/or TLN2, but activates integrins only weakly by itself. Binds to membranes enriched in phosphoinositides. Enhances integrin-mediated cell adhesion onto the extracellular matrix and cell spreading; this requires both its ability to interact with integrins and with phospholipid membranes. Required for the assembly of focal adhesions. Participates in the connection between extracellular matrix adhesion sites and the actin cytoskeleton and also in the orchestration of actin assembly and cell shape modulation. Recruits FBLIM1 to focal adhesions. Plays a role in the TGFB1 and integrin signaling pathways. Stabilizes active CTNNB1 and plays a role in the regulation of transcription mediated by CTNNB1 and TCF7L2/TCF4 and in Wnt signaling.

Subunit / interactions. Interacts with ILK. Interacts with FBLIM1. Interacts with ITGB1 and ITGB3. Interacts with active, unphosphorylated CTNNB1. Identified in a complex with CTNNB1 and TCF7L2/TCF4. Interacts with ITGB1; the interaction is inhibited in presence of ITGB1BP1.

Subcellular location. Cytoplasm. Cell cortex. Cytoskeleton. Stress fiber. Cell junction. Focal adhesion. Membrane. Cell projection. Lamellipodium membrane. Nucleus. Myofibril. Sarcomere. I band. Cell surface.

Tissue specificity. Ubiquitous. Found in numerous tumor tissues.

Domain organisation. The FERM domain is not correctly detected by PROSITE or Pfam techniques because it contains the insertion of a PH domain. The PH domain binds phospholipids. Binds preferentially phosphatidylinositol-3,4,5-trisphosphate, and has lower affinity for phosphatidylinositol-4,5-bisphosphate. The N-terminal region displays a ubiquitin-type fold and mediates interaction with membranes containing negatively charged phosphatidylinositol phosphate via a surface enriched in positively charged residues.

Induction. By serum in lung fetal fibroblast cultured cells.

Miscellaneous. May be due to an exon inclusion and an intron retention.

Similarity. Belongs to the kindlin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96AC1-1	1	yes
Q96AC1-2	2
Q96AC1-3	3

RefSeq proteins (3): NP_001128471, NP_001128472, NP_006823* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR019748	FERM_central	Domain
IPR019749	Band_41_domain	Domain
IPR035963	FERM_2	Homologous_superfamily
IPR037837	PH_Kindlin/fermitin	Domain
IPR037843	Kindlin/fermitin	Family
IPR040790	Kindlin_2_N	Domain

Pfam: PF00373, PF18124

UniProt features (47 total): strand 13, mutagenesis site 7, helix 7, modified residue 5, turn 5, splice variant 3, domain 2, region of interest 2, chain 1, sequence conflict 1, binding site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
6XTJ	X-RAY DIFFRACTION	1.6
4F7H	X-RAY DIFFRACTION	1.9
2LGX	SOLUTION NMR
2LKO	SOLUTION NMR
2MSU	SOLUTION NMR
6U4N	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96AC1-F1	80.79	0.50

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 383

Post-translational modifications (5): 666, 159, 181, 339, 351

Mutagenesis-validated functional residues (7):

Position	Phenotype
40	abolishes lipid-binding via the n-terminus; when associated with 74-a–a-81.
74–81	abolishes lipid-binding via the n-terminus; when associated with a-40.
383	reduces phosphatidylinositol phosphate binding. reduces integrin activation; when associated with a-385.
385	reduces integrin activation; when associated with a-383.
390	abolishes phosphatidylinositol phosphate binding.
393	reduces phosphatidylinositol phosphate binding.
614–615	impairs itgb3 binding. abolishes enhancement of talin-mediated integrin activation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-446353	Cell-extracellular matrix interactions
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle

MSigDB gene sets: 487 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, TSENG_IRS1_TARGETS_UP, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_WOUND_HEALING, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CIRCULATORY_SYSTEM_PROCESS, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN

GO Biological Process (29): cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), transforming growth factor beta receptor signaling pathway (GO:0007179), integrin-mediated signaling pathway (GO:0007229), regulation of cell shape (GO:0008360), positive regulation of epithelial to mesenchymal transition (GO:0010718), Wnt signaling pathway (GO:0016055), regulation of cell morphogenesis (GO:0022604), positive regulation of cell migration (GO:0030335), integrin activation (GO:0033622), positive regulation of integrin activation (GO:0033625), adherens junction maintenance (GO:0034334), substrate adhesion-dependent cell spreading (GO:0034446), positive regulation of Rho protein signal transduction (GO:0035025), negative regulation of vascular permeability (GO:0043116), negative regulation of fat cell differentiation (GO:0045599), positive regulation of osteoblast differentiation (GO:0045669), focal adhesion assembly (GO:0048041), positive regulation of stress fiber assembly (GO:0051496), positive regulation of focal adhesion assembly (GO:0051894), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), limb development (GO:0060173), positive regulation of ERK1 and ERK2 cascade (GO:0070374), protein localization to membrane (GO:0072657), positive regulation of substrate adhesion-dependent cell spreading (GO:1900026), positive regulation of protein localization to nucleus (GO:1900182), protein localization to cell junction (GO:1902414), positive regulation of mesenchymal stem cell proliferation (GO:1902462), positive regulation of wound healing, spreading of epidermal cells (GO:1903691)

GO Molecular Function (11): actin binding (GO:0003779), integrin binding (GO:0005178), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), protein kinase binding (GO:0019901), type I transforming growth factor beta receptor binding (GO:0034713), protein serine/threonine kinase activator activity (GO:0043539), SMAD binding (GO:0046332), actin filament binding (GO:0051015), protein serine/threonine kinase binding (GO:0120283), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (18): stress fiber (GO:0001725), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), adherens junction (GO:0005912), focal adhesion (GO:0005925), cell cortex (GO:0005938), cytoplasmic side of plasma membrane (GO:0009898), cell surface (GO:0009986), cell junction (GO:0030054), lamellipodium membrane (GO:0031258), I band (GO:0031674), cytoskeleton (GO:0005856), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RHO GTPase cycle	2
Cell junction organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
cell-substrate adhesion	2
cell surface receptor signaling pathway	2
positive regulation of cell differentiation	2
protein-containing complex binding	2
binding	2
cytoplasm	2
cell periphery	2
cellular process	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
regulation of cell morphogenesis	1
regulation of biological quality	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
positive regulation of multicellular organismal process	1
cell morphogenesis	1
regulation of anatomical structure morphogenesis	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
protein-containing complex assembly	1
positive regulation of protein-containing complex assembly	1
integrin activation	1
regulation of integrin activation	1
adherens junction organization	1
cell-cell junction maintenance	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
regulation of vascular permeability	1
fat cell differentiation	1
negative regulation of cell differentiation	1
regulation of fat cell differentiation	1
osteoblast differentiation	1
regulation of osteoblast differentiation	1
cell-substrate junction assembly	1
cell-matrix adhesion	1
positive regulation of actin filament bundle assembly	1
stress fiber assembly	1

Protein interactions and networks

STRING

1404 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FERMT2	FBLIM1	Q8WUP2	994
FERMT2	ILK	P57043	989
FERMT2	FLNA	P21333	840
FERMT2	PARVA	Q9NVD7	810
FERMT2	PXN	P49023	795
FERMT2	CASS4	Q9NQ75	771
FERMT2	LIMS1	P48059	770
FERMT2	ZCWPW1	Q9H0M4	764
FERMT2	VCL	P18206	763
FERMT2	FLNB	O75369	739
FERMT2	ITGB3	P05106	735
FERMT2	PLEK2	Q9NYT0	723
FERMT2	NME8	Q8N427	720
FERMT2	TLN2	Q9Y4G6	706
FERMT2	TLN1	Q9Y490	702

IntAct

113 interactions, top by confidence:

A	B	Type	Score
CTNNB1	GSK3B	psi-mi:“MI:0914”(association)	0.950
CTNNB1	TCF4	psi-mi:“MI:0914”(association)	0.940
TCF4	CTNNB1	psi-mi:“MI:0914”(association)	0.940
WDR20	USP12	psi-mi:“MI:0914”(association)	0.800
POLR3E	POLR3A	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FERMT2	CTNNB1	psi-mi:“MI:0915”(physical association)	0.680
CTNNB1	FERMT2	psi-mi:“MI:0915”(physical association)	0.680
FERMT2	CTNNB1	psi-mi:“MI:0407”(direct interaction)	0.680
CTNNB1	FERMT2	psi-mi:“MI:0403”(colocalization)	0.680
WDR20	PHLPP1	psi-mi:“MI:0914”(association)	0.670
AP3M1	AP3B1	psi-mi:“MI:0914”(association)	0.640
WDR20	YWHAH	psi-mi:“MI:0914”(association)	0.640
ARL4C	RGS12	psi-mi:“MI:0914”(association)	0.640
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
FERMT2	TCF4	psi-mi:“MI:0914”(association)	0.560
TCF4	FERMT2	psi-mi:“MI:0915”(physical association)	0.560
BBS12	FERMT2	psi-mi:“MI:0915”(physical association)	0.530
GREM2	ZZEF1	psi-mi:“MI:0914”(association)	0.530
F9	UBR5	psi-mi:“MI:0914”(association)	0.530

BioGRID (230): FERMT2 (Affinity Capture-MS), ADRBK1 (Co-fractionation), FERMT2 (Co-fractionation), FERMT2 (Co-fractionation), ILK (Co-fractionation), MAPK1 (Co-fractionation), MAPK3 (Co-fractionation), NAA50 (Co-fractionation), PFKM (Co-fractionation), PICALM (Co-fractionation), FERMT2 (Proximity Label-MS), FERMT2 (Proximity Label-MS), FERMT2 (Proximity Label-MS), FERMT2 (Proximity Label-MS), FERMT2 (Proximity Label-MS)

ESM2 similar proteins: A0A0R4IES7, A0JN62, A2AAE1, A2RV80, A4IFQ0, A6QQW8, F1Q8X5, O35382, P48553, P70398, Q08BT5, Q13769, Q2LD37, Q5F361, Q5R903, Q5RAQ5, Q5REX9, Q62824, Q68FX7, Q6DFZ1, Q6IC98, Q6NRC7, Q6P6Y1, Q6SP92, Q6ZWH5, Q7SXV1, Q7TSG1, Q7Z7G8, Q80TY5, Q8BHY8, Q8BKT7, Q8BQZ4, Q8CB44, Q8CIB5, Q8K3W0, Q8N960, Q8WN69, Q8WN70, Q91W96, Q92538

Diamond homologs: F1Q8X5, P59113, Q18685, Q32LP0, Q5R8M5, Q86UX7, Q8CIB5, Q8K1B8, Q96AC1, Q9BQL6, Q9VZI3, A0A3G2LGI8, P0CE94, P0CE95, P26039, P54939, Q71LX4, Q9Y490, Q9Y4G6

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
SRC	“up-regulates activity”	FERMT2	phosphorylation
FERMT2	“up-regulates activity”	SRC	binding
FERMT2	“up-regulates activity”	FBLIM1	binding
CyclinB/CDK1	“down-regulates quantity by destabilization”	FERMT2	phosphorylation
CUL9	“down-regulates quantity by destabilization”	FERMT2	ubiquitination
SMURF1	“down-regulates quantity by destabilization”	FERMT2	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 132 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of dendritic spine morphogenesis	5	37.0×	2e-04
canonical Wnt signaling pathway	7	8.9×	5e-03
neuron migration	8	8.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

88 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2899 predictions. Top by Δscore:

Variant	Effect	Δscore
14:52858547:TGAC:T	acceptor_gain	1.0000
14:52858549:ACCTG:A	acceptor_loss	1.0000
14:52858551:C:CC	acceptor_gain	1.0000
14:52858551:CT:C	acceptor_loss	1.0000
14:52858557:C:CT	acceptor_gain	1.0000
14:52859567:GTTTA:G	donor_loss	1.0000
14:52859568:TTTA:T	donor_loss	1.0000
14:52859569:TTAC:T	donor_loss	1.0000
14:52859570:TA:T	donor_loss	1.0000
14:52859571:A:AC	donor_gain	1.0000
14:52859572:C:CC	donor_gain	1.0000
14:52859584:C:A	donor_gain	1.0000
14:52859596:T:A	donor_gain	1.0000
14:52859710:GGAAC:G	acceptor_gain	1.0000
14:52859711:GAAC:G	acceptor_gain	1.0000
14:52859711:GAACC:G	acceptor_gain	1.0000
14:52859712:AAC:A	acceptor_gain	1.0000
14:52859712:AACCT:A	acceptor_gain	1.0000
14:52859713:AC:A	acceptor_gain	1.0000
14:52859713:ACC:A	acceptor_gain	1.0000
14:52859714:CC:C	acceptor_gain	1.0000
14:52859714:CCTAT:C	acceptor_gain	1.0000
14:52859715:C:A	acceptor_gain	1.0000
14:52859715:C:CA	acceptor_loss	1.0000
14:52859715:C:CC	acceptor_gain	1.0000
14:52859716:T:A	acceptor_gain	1.0000
14:52859717:A:AC	acceptor_gain	1.0000
14:52859717:A:C	acceptor_gain	1.0000
14:52859721:CATT:C	acceptor_gain	1.0000
14:52859722:A:C	acceptor_gain	1.0000

AlphaMissense

4534 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:52858396:A:G	L675P	1.000
14:52858468:C:T	G651D	1.000
14:52858469:C:G	G651R	1.000
14:52859585:C:A	W619C	1.000
14:52859585:C:G	W619C	1.000
14:52859587:A:G	W619R	1.000
14:52859587:A:T	W619R	1.000
14:52859592:A:T	V617D	1.000
14:52859597:C:A	W615C	1.000
14:52859597:C:G	W615C	1.000
14:52859599:A:G	W615R	1.000
14:52859599:A:T	W615R	1.000
14:52864582:G:T	A474D	1.000
14:52864604:A:G	W467R	1.000
14:52864604:A:T	W467R	1.000
14:52864799:A:G	L443P	1.000
14:52875263:A:G	L353P	1.000
14:52875272:A:G	L350P	1.000
14:52875272:A:T	L350H	1.000
14:52878586:A:G	L320P	1.000
14:52878675:T:A	R290S	1.000
14:52878675:T:G	R290S	1.000
14:52878676:C:G	R290T	1.000
14:52881137:A:G	W252R	1.000
14:52881137:A:T	W252R	1.000
14:52919133:A:C	C127W	1.000
14:52919134:C:T	C127Y	1.000
14:52919301:C:A	W71C	1.000
14:52919301:C:G	W71C	1.000
14:52919303:A:G	W71R	1.000

dbSNP variants (sampled 300 via entrez): RS1000027489 (14:52952328 T>C,G), RS1000050095 (14:52895003 T>C), RS1000133968 (14:52858096 A>G), RS1000148769 (14:52949809 C>G,T), RS1000184276 (14:52949482 A>G), RS1000191870 (14:52860993 T>C), RS1000195306 (14:52909063 C>G), RS1000242352 (14:52943998 A>C), RS1000243054 (14:52903072 T>C), RS1000247767 (14:52909294 A>T), RS1000284247 (14:52891465 C>A), RS1000338974 (14:52952338 C>A), RS1000388386 (14:52897253 C>A,T), RS1000418892 (14:52861228 G>A,T), RS1000446938 (14:52931279 G>A,T)

Disease associations

OMIM: gene MIM:607746 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001942_15	Prostate cancer	2.000000e-14
GCST002245_17	Alzheimer’s disease (late onset)	8.000000e-09
GCST003264_264	Post bronchodilator FEV1/FVC ratio	5.000000e-06
GCST003467_10	Glaucoma (primary angle closure)	3.000000e-11
GCST003467_11	Glaucoma (primary angle closure)	5.000000e-09
GCST004279_3	Systolic blood pressure	4.000000e-10
GCST005580_123	Intraocular pressure	1.000000e-13
GCST006394_96	Intraocular pressure	2.000000e-15
GCST006412_87	Intraocular pressure	7.000000e-13
GCST007045_41	PR interval	2.000000e-08
GCST007094_208	Diastolic blood pressure	1.000000e-08
GCST007096_1	Pulse pressure	2.000000e-06
GCST007099_146	Systolic blood pressure	6.000000e-11
GCST009725_20	Intraocular pressure	5.000000e-16
GCST010321_150	PR interval	2.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0006335	systolic blood pressure
EFO:0004695	intraocular pressure measurement
EFO:0004462	PR interval
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465266 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

76 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation	3
bisphenol A	decreases expression, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Formaldehyde	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects expression, increases reaction	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pirinixic acid	affects binding, decreases expression, increases activity	1
methylselenic acid	increases expression	1
nobiletin	decreases reaction, increases expression	1
sodium arsenate	decreases reaction, increases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
periodate-oxidized adenosine	affects expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
monomethylarsonous acid	increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5378333	Binding	Binding affinity to His6-tagged KIND2 (unknown origin) expressed in Escherichia coli BL21(DE3) by MST assay	Discovery of Inhibitory Fragments That Selectively Target Spire2-FMN2 Interaction. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1S3	Abcam HeLa FERMT2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.