FER

Summary

FER (FER tyrosine kinase, HGNC:3655) is a protein-coding gene on chromosome 5q21.3, encoding Tyrosine-protein kinase Fer (P16591). Tyrosine-protein kinase that acts downstream of cell surface receptors for growth factors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, lamellipodia formation, cell adhesion, cell migration and chemotaxis.

The protein encoded by this gene is a member of the FPS/FES family of non-transmembrane receptor tyrosine kinases. It regulates cell-cell adhesion and mediates signaling from the cell surface to the cytoskeleton via growth factor receptors. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome X.

Source: NCBI Gene 2241 — RefSeq curated summary.

At a glance

• GWAS associations: 33
• Clinical variants (ClinVar): 122 total
• Druggable target: yes — 56 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005246

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3655
Approved symbol	FER
Name	FER tyrosine kinase
Location	5q21.3
Locus type	gene with protein product
Status	Approved
Aliases	TYK3, PPP1R74
Ensembl gene	ENSG00000151422
Ensembl biotype	protein_coding
OMIM	176942
Entrez	2241

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 16 protein_coding, 5 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000281092, ENST00000438717, ENST00000502752, ENST00000504143, ENST00000505323, ENST00000509035, ENST00000513676, ENST00000513777, ENST00000618353, ENST00000880768, ENST00000880770, ENST00000880771, ENST00000880772, ENST00000880773, ENST00000880774, ENST00000940348, ENST00000940349, ENST00000958835, ENST00000958836, ENST00000958837, ENST00000958838, ENST00000958839

RefSeq mRNA: 4 — MANE Select: NM_005246 NM_001308028, NM_001308031, NM_001308038, NM_005246

CCDS: CCDS4098, CCDS78044

Canonical transcript exons

ENST00000281092 — 20 exons

Exon	Start	End
ENSE00001386589	108768093	108768238
ENSE00001387528	108747897	108748000
ENSE00001821887	109187433	109196841
ENSE00003488256	108897659	108897848
ENSE00003502768	108871365	108871502
ENSE00003504895	108835708	108835807
ENSE00003518658	109180747	109180901
ENSE00003540684	108872093	108872212
ENSE00003556061	108946130	108946222
ENSE00003578730	109100396	109100519
ENSE00003586830	108832770	108832943
ENSE00003587538	109037422	109037478
ENSE00003591936	108798124	108798389
ENSE00003597474	108959225	108959347
ENSE00003622370	109047104	109047198
ENSE00003623850	108883396	108883518
ENSE00003676665	108954729	108954932
ENSE00003685855	109044680	109044795
ENSE00003693653	109186200	109186322
ENSE00003735373	108867767	108867950

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 97.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.4935 / max 493.5377, expressed in 1731 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57908	8.3011	1603
57905	2.3797	642
57904	1.1955	519
57913	0.5439	219
57909	0.3398	152
57907	0.2713	139
57906	0.1805	61
57914	0.1634	86
57912	0.1182	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.03	gold quality
secondary oocyte	CL:0000655	94.84	gold quality
oocyte	CL:0000023	94.22	gold quality
tendon	UBERON:0000043	93.72	gold quality
buccal mucosa cell	CL:0002336	93.42	gold quality
sural nerve	UBERON:0015488	92.67	gold quality
sperm	CL:0000019	91.50	gold quality
tendon of biceps brachii	UBERON:0008188	91.14	gold quality
male germ cell	CL:0000015	89.88	gold quality
corpus callosum	UBERON:0002336	89.87	gold quality
colonic epithelium	UBERON:0000397	89.53	gold quality
medial globus pallidus	UBERON:0002477	88.92	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.53	gold quality
adrenal tissue	UBERON:0018303	86.73	gold quality
globus pallidus	UBERON:0001875	86.67	gold quality
left testis	UBERON:0004533	86.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.32	gold quality
right testis	UBERON:0004534	86.31	gold quality
testis	UBERON:0000473	86.12	gold quality
skin of hip	UBERON:0001554	85.48	gold quality
ventricular zone	UBERON:0003053	85.09	gold quality
cortical plate	UBERON:0005343	84.38	gold quality
mammary duct	UBERON:0001765	83.40	gold quality
trigeminal ganglion	UBERON:0001675	83.25	gold quality
cartilage tissue	UBERON:0002418	83.20	gold quality
parietal pleura	UBERON:0002400	82.91	gold quality
upper leg skin	UBERON:0004262	82.82	gold quality
ganglionic eminence	UBERON:0004023	82.47	gold quality
peripheral nervous system	UBERON:0000010	82.43	gold quality
tibial nerve	UBERON:0001323	82.43	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCFL

miRNA regulators (miRDB)

293 targeting FER, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883

Literature-anchored findings (GeneRIF, showing 33)

• Closing in on the biological functions of Fps/Fes and Fer. A review. (PMID:11994747)
• Fps/Fes and Fer are expressed in human and mouse platelets, and are activated following stimulation with collagen and collagen-related peptide (CRP), suggesting a role in GPVI receptor signaling (PMID:12871378)
• Fer is a regulator of cell-cycle progression in malignant cells and a potential target for cancer intervention. (PMID:16732323)
• FerT coexist in the acroplaxome with phosphorylated cortactin, a regulator of F-actin dynamics[Fer testis ] (PMID:18985748)
• Fer tyrosine kinase level correlates with the development of prostate cancer and aggressiveness of prostate cancer cell lines (PMID:19147545)
• Results suggest that Fer may allow a bypass of focal adhesion kinase-related cell anchorage dependency for intracellular signal transduction in hepatocytes. (PMID:19339212)
• Overexpression of Fer enhanced lamellipodia formation and cell migration in a manner dependent on PLD activity and the PA-FX interaction. (PMID:19738202)
• FER plays a role in the invasion and metastasis of hepatocellular carcinoma cells. (PMID:19835603)
• tyrosine phosphorylation of RhoGDIalpha by Fer as a mechanism to regulate binding of RhoGDIalpha to Rac (PMID:21122136)
• Overexpression of FER from a cDNA confers quinacrine resistance to several different types of cancer cell lines. (PMID:21518868)
• The A allele of SNP rs10447248 in the FER locus was nominally associated with lower MMW (P = 0.016) but was not associated with LMW (P > 0.05) adiponectin levels (PMID:21700879)
• Transcription of the ferT gene in CC cells was found to be driven by an intronic promoter residing in intron 10 of the fer gene and to be regulated by the Brother of the Regulator of Imprinted Sites (BORIS) transcription factor. (PMID:22223638)
• Fer, a non-receptor-type tyrosine kinase, plays a critical role in synthesis of the laminin-binding glycans on alpha-DG. (PMID:22238358)
• Fer expression correlates with renal cell carcinoma cell proliferation both in vitro and in vivo, and with tumor progression and survival (PMID:23445469)
• data show that Fer kinase is elevated in non-small cell lung cancer tumors and is important for cellular invasion and metastasis (PMID:23699534)
• FER kinase promotes breast cancer metastasis by regulating alpha6- and beta1-integrin-dependent cell adhesion and anoikis resistance. (PMID:23873028)
• Fer contributes to aberrant androgen receptor signaling via pSTAT3 cross-talk during castrate-resistant prostate cancer progression. (PMID:23906537)
• Detection of PJA2-FER fusion mRNA is correlated with poor postoperative survival periods in non-small cell lung cancer. (PMID:23931849)
• FER encodes a cytosolic non-receptor tyrosine kinase that influences neutrophil chemotaxis and endothelial permeability. (PMID:25533491)
• Fer serves as a crucial mediator and amplifier of Src-induced tumor progression. (PMID:25867068)
• Many human tumor types and cancer cell lines express the MAN2A1-FER fusion, which increases proliferation and invasiveness of cancer cell lines and has liver oncogenic activity in mice. (PMID:28245430)
• The FER rs4957796 TT genotype remained a significant covariate for the 90-day mortality risk in the multivariate analysis (hazard ratio, 4.62; 95% CI, 1.58-13.50; p = 0.0050). In conclusion, FER rs4957796 might act as a prognostic variable for survival in patients with severe ARDS due to pneumonia. (PMID:28851893)
• Data show that FER tyrosine kinase (Fer/FerT) activity was disrupted by E260, which selectively evokes metabolic stress in cancer cells by imposing mitochondrial dysfunction and deformation. (PMID:29038547)
• FER mediated HGF-independent regulation of HGFR/MET activates RAC1-PAK1 pathway to potentiate metastasis in ovarian cancer. (PMID:29099290)
• We propose a model for the regulation of Fer based on an intramolecular interaction and the curvature-dependent membrane binding mediated by its intrinsically disordered region. (PMID:29208465)
• FER enhances IGF-1R expression, phosphorylation, and signaling to promote cooperative growth and adhesion signaling that may facilitate cancer progression. (PMID:29540831)
• FER overexpression improves survival through STAT activation enhancing innate immunity and accelerating bacterial clearance in the lung. (PMID:29907877)
• Targeting of both FER and MET may be an effective strategy for therapeutic intervention in ovarian cancer. (PMID:29920310)
• This study supports the critical role of FER and FES tyrosine kinase fusions in the pathogenesis of follicular T-cell lymphoma and provides additional evidence that these can drive follicular T-cell lymphoma in the absence of RHOA mutations. (PMID:31746983)
• Phosphorylation of PKCdelta by FER tips the balance from EGFR degradation to recycling. (PMID:33411917)
• Fer and FerT Govern Mitochondrial Susceptibility to Metformin and Hypoxic Stress in Colon and Lung Carcinoma Cells. (PMID:33430475)
• Loss of Fer Jeopardizes Metabolic Plasticity and Mitochondrial Homeostasis in Lung and Breast Carcinoma Cells. (PMID:33806191)
• FER-mediated phosphorylation and PIK3R2 recruitment on IRS4 promotes AKT activation and tumorigenesis in ovarian cancer cells. (PMID:35550247)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fer	ENSDARG00000012196
mus_musculus	Fer	ENSMUSG00000000127
rattus_norvegicus	Fer	ENSRNOG00000015898

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), JAK2 (ENSG00000096968), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), CSK (ENSG00000103653), TYK2 (ENSG00000105397), JAK3 (ENSG00000105639), FRK (ENSG00000111816), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), JAK1 (ENSG00000162434), SYK (ENSG00000165025), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)

Protein

Protein identifiers

Tyrosine-protein kinase Fer — P16591 (reviewed: P16591)

Alternative names: Feline encephalitis virus-related kinase FER, Fujinami poultry sarcoma/Feline sarcoma-related protein Fer, Proto-oncogene c-Fer, Tyrosine kinase 3, p94-Fer

All UniProt accessions (4): D6RAF9, P16591, W0S0X4, W0S4B9

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine-protein kinase that acts downstream of cell surface receptors for growth factors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, lamellipodia formation, cell adhesion, cell migration and chemotaxis. Acts downstream of EGFR, KIT, PDGFRA and PDGFRB. Acts downstream of EGFR to promote activation of NF-kappa-B and cell proliferation. May play a role in the regulation of the mitotic cell cycle. Plays a role in the insulin receptor signaling pathway and in activation of phosphatidylinositol 3-kinase. Acts downstream of the activated FCER1 receptor and plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Plays a role in the regulation of mast cell degranulation. Plays a role in leukocyte recruitment and diapedesis in response to bacterial lipopolysaccharide (LPS). Plays a role in synapse organization, trafficking of synaptic vesicles, the generation of excitatory postsynaptic currents and neuron-neuron synaptic transmission. Plays a role in neuronal cell death after brain damage. Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1, PECAM1 and PTPN11. May phosphorylate JUP and PTPN1. Can phosphorylate STAT3, but the biological relevance of this depends on cell type and stimulus.

Subunit / interactions. Homotrimer. Interacts with ARHGDIA, IRS1, JAK1, NRP1, PIK3R1, PLEC and TMF1. Interacts with PPP1CA and regulates its phosphorylation at ‘Thr-320’. Interacts with CTNND1, EGFR, FLT3, PECAM1, PDGFR and STAT3. Interacts (via SH2 domain) with CTTN. Interacts with HSP90; this stabilizes phosphorylated FER and protects FER against proteasomal degradation. Component of a complex that contains at least FER, CTTN and PTK2/FAK1.

Subcellular location. Cytoplasm. Cytoskeleton. Cell membrane. Cell projection. Cell junction. Membrane. Nucleus. Cell cortex.

Tissue specificity. Isoform 1 is detected in normal colon and in fibroblasts (at protein level). Isoform 3 is detected in normal testis, in colon carcinoma-derived metastases in lung, liver and ovary, and in colon carcinoma and hepato carcinoma cell lines (at protein level). Isoform 3 is not detected in normal colon or in normal fibroblasts (at protein level). Widely expressed.

Post-translational modifications. Autophosphorylated. Polyubiquitinated; this leads to proteasomal degradation.

Activity regulation. Activated by phosphatidic acid binding. Activated by hydrogen peroxide (in vitro). Activated by reactive oxygen species (ROS).

Domain organisation. The coiled coil domains mediate homooligomerization and are required for location at microtubules. The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes.

Miscellaneous. Produced by alternative promoter usage.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. Fes/fps subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P16591-1	1, p94	yes
P16591-2	2
P16591-3	3, FerT, p47

RefSeq proteins (3): NP_001294957, NP_001294960, NP_005237* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000980	SH2	Domain
IPR001060	FCH_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR016250	Tyr-prot_kinase_Fes/Fps	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR031160	F_BAR_dom	Domain
IPR035849	Fes/Fps/Fer_SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR037452	Fer_F-BAR	Domain
IPR050198	Non-receptor_tyrosine_kinases	Family

Pfam: PF00017, PF00611, PF07714

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (47 total): sequence conflict 9, sequence variant 8, strand 7, modified residue 4, domain 3, splice variant 3, helix 3, mutagenesis site 2, coiled-coil region 2, binding site 2, chain 1, region of interest 1, turn 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6KC4	X-RAY DIFFRACTION	1.37
2KK6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16591-F1	88.29	0.70

Functional residue map

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

Catalytic / active sites (1): 684 (proton acceptor)

Ligand- & substrate-binding residues (2): 569–577; 591

Post-translational modifications (4): 402, 434, 615, 714

Mutagenesis-validated functional residues (2):

Position	Phenotype
483	abolishes kinase activity. abolishes location at microtubules.
591	abolishes kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1433557	Signaling by SCF-KIT

MSigDB gene sets: 336 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_REGULATION_OF_MAST_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_SERTOLI_CELL_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_REGULATION_OF_FIBROBLAST_MIGRATION

GO Biological Process (44): microtubule cytoskeleton organization (GO:0000226), regulation of protein phosphorylation (GO:0001932), protein phosphorylation (GO:0006468), chemotaxis (GO:0006935), cell adhesion (GO:0007155), tyrosine phosphorylation of STAT protein (GO:0007260), germ cell development (GO:0007281), positive regulation of cell population proliferation (GO:0008284), insulin receptor signaling pathway (GO:0008286), regulation of lamellipodium assembly (GO:0010591), regulation of fibroblast migration (GO:0010762), peptidyl-tyrosine phosphorylation (GO:0018108), cytokine-mediated signaling pathway (GO:0019221), actin cytoskeleton organization (GO:0030036), positive regulation of cell migration (GO:0030335), positive regulation of actin filament polymerization (GO:0030838), response to lipopolysaccharide (GO:0032496), negative regulation of mast cell activation involved in immune response (GO:0033007), adherens junction assembly (GO:0034333), substrate adhesion-dependent cell spreading (GO:0034446), cellular response to reactive oxygen species (GO:0034614), extracellular matrix-cell signaling (GO:0035426), intracellular signal transduction (GO:0035556), cellular response to macrophage colony-stimulating factor stimulus (GO:0036006), response to platelet-derived growth factor (GO:0036119), Fc-epsilon receptor signaling pathway (GO:0038095), Kit signaling pathway (GO:0038109), regulation of epidermal growth factor receptor signaling pathway (GO:0042058), cell-cell adhesion mediated by cadherin (GO:0044331), protein autophosphorylation (GO:0046777), platelet-derived growth factor receptor signaling pathway (GO:0048008), diapedesis (GO:0050904), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), Sertoli cell development (GO:0060009), interleukin-6-mediated signaling pathway (GO:0070102), seminiferous tubule development (GO:0072520), adherens junction disassembly (GO:0120179), signal transduction (GO:0007165), male gonad development (GO:0008584)

GO Molecular Function (11): protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), epidermal growth factor receptor binding (GO:0005154), ATP binding (GO:0005524), protein phosphatase 1 binding (GO:0008157), lipid binding (GO:0008289), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (17): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), adherens junction (GO:0005912), cell cortex (GO:0005938), cytoplasmic side of plasma membrane (GO:0009898), protein-containing complex (GO:0032991), cell projection (GO:0042995), actin cytoskeleton (GO:0015629), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), lamellipodium (GO:0030027), cell junction (GO:0030054), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoskeleton organization	2
protein phosphorylation	2
regulation of cell migration	2
binding	2
cytoplasm	2
cell periphery	2
cytoskeleton	2
microtubule-based process	1
regulation of protein modification process	1
regulation of phosphorylation	1
phosphorylation	1
protein modification process	1
response to chemical	1
taxis	1
cellular process	1
cell surface receptor signaling pathway via JAK-STAT	1
peptidyl-tyrosine phosphorylation	1
developmental process involved in reproduction	1
gamete generation	1
cellular process involved in reproduction in multicellular organism	1
cell development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
lamellipodium assembly	1
regulation of plasma membrane bounded cell projection assembly	1
regulation of lamellipodium organization	1
fibroblast migration	1
peptidyl-tyrosine modification	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
actin filament-based process	1
cell migration	1
positive regulation of cell motility	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1

Protein interactions and networks

STRING

1000 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FER	FLT3LG	P49771	730
FER	IL2RA	P01589	559
FER	CTNND1	O60716	542
FER	CCDC88C	Q9P219	453
FER	PLEC	Q15149	442
FER	NRG1	P98202	432
FER	ERBB3	P21860	429
FER	AKT1	P31749	417
FER	NTF3	P20783	408
FER	KITLG	P21583	373
FER	THPO	P40225	356
FER	ZBTB37	Q5TC79	333
FER	CD34	P28906	320
FER	FAM204A	Q9H8W3	317
FER	FLT3	P36888	280

IntAct

49 interactions, top by confidence:

A	B	Type	Score
CDH2	PTPN1	psi-mi:“MI:0914”(association)	0.840
FER	CDC37	psi-mi:“MI:0915”(physical association)	0.710
FKBP5	IKBKB	psi-mi:“MI:0914”(association)	0.640
FYB1	NCK2	psi-mi:“MI:0914”(association)	0.620
HSP90AB1	FER	psi-mi:“MI:0915”(physical association)	0.560
ARC	FER	psi-mi:“MI:0914”(association)	0.530
	FER	psi-mi:“MI:0915”(physical association)	0.500
KCTD4	FER	psi-mi:“MI:0915”(physical association)	0.490
Bcat	FER	psi-mi:“MI:0407”(direct interaction)	0.440
PTPN1	FER	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
FER	NSF	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
FER	ERBB2	psi-mi:“MI:0407”(direct interaction)	0.440
FER	ERBB3	psi-mi:“MI:0407”(direct interaction)	0.440
FER	ABI1	psi-mi:“MI:0407”(direct interaction)	0.440
Ctnnb1	FER	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
FER	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
FER	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
PIK3R3	FER	psi-mi:“MI:0915”(physical association)	0.370
PPP1R7	FER	psi-mi:“MI:0915”(physical association)	0.370
CRK	FER	psi-mi:“MI:0915”(physical association)	0.370
PIK3R1	FER	psi-mi:“MI:0915”(physical association)	0.370
LIMA1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
	PLK4	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
	GAK	psi-mi:“MI:0914”(association)	0.350
	SGK1	psi-mi:“MI:0914”(association)	0.350

BioGRID (76): FER (Affinity Capture-RNA), TMF1 (Two-hybrid), KCTD4 (Two-hybrid), PIK3R1 (Two-hybrid), PIK3R3 (Two-hybrid), PPP1R7 (Two-hybrid), CRK (Two-hybrid), FER (Affinity Capture-MS), FER (Reconstituted Complex), FER (Affinity Capture-MS), CTNNB1 (Biochemical Activity), FER (Reconstituted Complex), CTTN (Affinity Capture-Western), CTTN (Co-fractionation), DNM1 (Co-fractionation)

ESM2 similar proteins: A7MBI0, D3ZYR1, O13154, O43586, O55148, O60749, O60861, P09760, P16591, P70451, P97531, P97814, Q0JRZ9, Q15642, Q2HWF0, Q3KR97, Q3UQN2, Q4V920, Q5R411, Q5R807, Q5RCJ1, Q5T0N5, Q5U3Q6, Q60780, Q61644, Q6DCZ7, Q6GNV5, Q6GUF4, Q8CJ53, Q8I190, Q8I1A6, Q8I1C0, Q8I1I3, Q8K012, Q8T390, Q91VH2, Q99JB8, Q99M15, Q99N27, Q9BY11

Diamond homologs: A0A0K3AV08, A7J1T0, A7J1T2, A7MBB4, A8X775, D3ZG83, G5EE56, H2KZW3, O01700, O19064, O22558, O43283, O54967, O60674, P00529, P00533, P00534, P00535, P03949, P04412, P06239, P06240, P08069, P08922, P08941, P09760, P09769, P11273, P11362, P13388, P14234, P14616, P14617, P16092, P16591, P18461, P21802, P21803, P21804, P22607

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
FER	up-regulates	AR	phosphorylation
FER	“up-regulates activity”	PECAM1	phosphorylation
FER	“up-regulates activity”	PRKCD	phosphorylation
HSP90AA1	“down-regulates activity”	FER	phosphorylation
FER	“down-regulates activity”	ARHGDIA	phosphorylation
FER	“up-regulates activity”	PTK2	phosphorylation
FER	“up-regulates activity”	STAT3	phosphorylation
FER	“up-regulates activity”	JUP	phosphorylation
FER	“down-regulates activity”	JUP	phosphorylation
FER	“down-regulates activity”	CTNNB1	phosphorylation
FER	“up-regulates activity”	FER	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
RAC2 GTPase cycle	5	20.5×	8e-04
PIP3 activates AKT signaling	6	12.9×	8e-04
RAC1 GTPase cycle	6	11.8×	9e-04
Signaling by Receptor Tyrosine Kinases	5	8.3×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
cell migration	6	10.2×	3e-03
negative regulation of apoptotic process	8	7.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	5
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

5876 predictions. Top by Δscore:

Variant	Effect	Δscore
5:108756468:GGC:G	donor_gain	1.0000
5:108756469:GC:G	donor_gain	1.0000
5:108756470:C:CG	donor_gain	1.0000
5:108756470:C:G	donor_gain	1.0000
5:108798385:CCAAG:C	donor_loss	1.0000
5:108798387:AAGGT:A	donor_loss	1.0000
5:108798389:GGTA:G	donor_loss	1.0000
5:108798390:G:C	donor_loss	1.0000
5:108798391:T:A	donor_loss	1.0000
5:108832767:A:AG	acceptor_gain	1.0000
5:108832768:A:AG	acceptor_gain	1.0000
5:108832769:G:GA	acceptor_gain	1.0000
5:108832769:GTCTT:G	acceptor_gain	1.0000
5:108832940:CAAG:C	donor_loss	1.0000
5:108832941:AAG:A	donor_loss	1.0000
5:108832945:T:G	donor_loss	1.0000
5:108834884:GGGTT:G	donor_gain	1.0000
5:108835702:T:TA	acceptor_gain	1.0000
5:108835704:ACAGG:A	acceptor_gain	1.0000
5:108835706:A:AG	acceptor_gain	1.0000
5:108835706:AG:A	acceptor_gain	1.0000
5:108835707:G:GA	acceptor_gain	1.0000
5:108835707:GG:G	acceptor_gain	1.0000
5:108835707:GGT:G	acceptor_gain	1.0000
5:108835707:GGTT:G	acceptor_gain	1.0000
5:108835707:GGTTA:G	acceptor_gain	1.0000
5:108835805:AAGG:A	donor_loss	1.0000
5:108835806:AG:A	donor_gain	1.0000
5:108835806:AGGT:A	donor_loss	1.0000
5:108835807:GG:G	donor_gain	1.0000

AlphaMissense

5469 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:108954777:T:A	W460R	1.000
5:108954777:T:C	W460R	1.000
5:108954780:T:G	Y461D	1.000
5:108954799:G:C	R467T	1.000
5:108954800:A:C	R467S	1.000
5:108954800:A:T	R467S	1.000
5:108954837:T:C	F480L	1.000
5:108954838:T:C	F480S	1.000
5:108954839:T:A	F480L	1.000
5:108954839:T:G	F480L	1.000
5:108954844:T:A	V482E	1.000
5:108954846:C:G	R483G	1.000
5:108954847:G:C	R483P	1.000
5:108954877:T:A	V493D	1.000
5:108954880:T:A	L494H	1.000
5:108954880:T:C	L494P	1.000
5:108954880:T:G	L494R	1.000
5:108954882:T:C	S495P	1.000
5:108954883:C:T	S495F	1.000
5:108954909:C:G	H504D	1.000
5:108954910:A:G	H504R	1.000
5:108954911:T:A	H504Q	1.000
5:108954911:T:G	H504Q	1.000
5:108954912:T:C	F505L	1.000
5:108954913:T:C	F505S	1.000
5:108954914:T:A	F505L	1.000
5:108954914:T:G	F505L	1.000
5:108954919:T:A	I507K	1.000
5:108954919:T:G	I507R	1.000
5:108959235:G:C	R515P	1.000

dbSNP variants (sampled 300 via entrez): RS1000001532 (5:109124907 G>A,T), RS1000008741 (5:108906511 C>A,T), RS1000011571 (5:108925969 C>G,T), RS1000015184 (5:108964599 C>G,T), RS1000015972 (5:109019340 C>G,T), RS1000045024 (5:109074016 C>G), RS1000050888 (5:109111819 C>G), RS1000051759 (5:108843887 A>G), RS1000054642 (5:108950508 A>G), RS1000056879 (5:108825080 C>G,T), RS1000057249 (5:109019124 C>G), RS1000076118 (5:109024379 T>G), RS1000077052 (5:108849763 A>G), RS1000081037 (5:109001290 C>T), RS1000082479 (5:109032737 A>C,G)

Disease associations

OMIM: gene MIM:176942 | disease phenotypes: MIM:126800

GenCC curated gene-disease

Mondo (1): Duane retraction syndrome (MONDO:0007473)

Orphanet (1): Duane retraction syndrome (Orphanet:233)

HPO phenotypes

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

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST000817_115	Height	3.000000e-08
GCST001122_4	Adiponectin levels	5.000000e-08
GCST002647_124	Height	3.000000e-13
GCST002725_1	Sepsis from pneumonia (survival)	6.000000e-08
GCST003831_1	Asthma	1.000000e-06
GCST003832_20	Asthma (childhood onset)	7.000000e-06
GCST003832_4	Asthma (childhood onset)	3.000000e-06
GCST004063_44	Waist circumference adjusted for body mass index	3.000000e-10
GCST004063_51	Waist circumference adjusted for body mass index	4.000000e-07
GCST004138_9	Early-onset Parkinson’s disease	4.000000e-133
GCST004251_3	Paneth cell defects in Crohn’s disease	7.000000e-07
GCST004500_129	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	2.000000e-07
GCST004501_41	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	1.000000e-08
GCST004501_42	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	3.000000e-06
GCST004503_11	Waist circumference adjusted for BMI in smokers	2.000000e-06
GCST005170_53	Intraocular pressure	1.000000e-13
GCST005580_47	Intraocular pressure	1.000000e-12
GCST005580_77	Intraocular pressure	1.000000e-11
GCST006394_1	Intraocular pressure	8.000000e-10
GCST006412_49	Intraocular pressure	2.000000e-11
GCST007096_36	Pulse pressure	2.000000e-11
GCST007099_198	Systolic blood pressure	6.000000e-07
GCST007267_203	Systolic blood pressure	1.000000e-08
GCST007269_236	Pulse pressure	3.000000e-16
GCST009725_59	Intraocular pressure	4.000000e-09
GCST010320_42	PR interval	4.000000e-08
GCST012227_177	Hip circumference adjusted for BMI	2.000000e-10
GCST012227_179	Hip circumference adjusted for BMI	1.000000e-11
GCST012227_180	Hip circumference adjusted for BMI	2.000000e-08
GCST90002407_461	White blood cell count	1.000000e-09

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004502	adiponectin measurement
EFO:0000714	survival time
EFO:0006834	septic shock
EFO:0007789	BMI-adjusted waist circumference
EFO:0007963	abnormal paneth cell measurement
EFO:0004318	smoking behavior
EFO:0004695	intraocular pressure measurement
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0004462	PR interval
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004370	Duane Retraction Syndrome	C10.292.562.700.375.500; C11.270.235; C11.590.436.400.500; C16.320.290.235

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3982 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

56 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 200,926 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1738797	ALECTINIB	4	6,731
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3286830	LORLATINIB	4	3,598
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL3545308	ROCILETINIB	3	1,729
CHEMBL483158	ALISERTIB	3	2,305
CHEMBL491473	CEDIRANIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1230609	FORETINIB	2
CHEMBL1231124	AZD-1480	2
CHEMBL1721885	SU-014813	2
CHEMBL1738757	REBASTINIB	2
CHEMBL1922094	APITOLISIB	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL1967878	CENISERTIB	2

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Fer family

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
DS21360717	Inhibition	9.31	pIC50
compound 8e [PMID: 24432909]	Inhibition	8.7	pIC50
Ro3280	Inhibition	7.28	pKd
compound 25b [PMID: 22564207]	Inhibition	7.07	pIC50

Binding affinities (BindingDB)

10 measured of 10 human assays (10 total across all organisms); most potent 10 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
IBRUTINIB	IC50	0.8 nM	US-9278100: Inhibitors of bruton’s tyrosine kinase for the treatment of solid tumors
N-[4-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexyl]prop-2-enamide	IC50	1.1 nM	US-9278100: Inhibitors of bruton’s tyrosine kinase for the treatment of solid tumors
Staurosporine	KD	1.7 nM
PKC-412	KD	190 nM
4-[[7-[2,6-bis(fluoranyl)phenyl]-9-chloranyl-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	KD	300 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

270 potent at pChembl≥5 of 273 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.69	IC50	0.203	nM	STAUROSPORINE
9.49	IC50	0.32	nM	CHEMBL5597957
9.46	IC50	0.35	nM	CHEMBL5598347
9.46	IC50	0.35	nM	STAUROSPORINE
9.44	IC50	0.365	nM	STAUROSPORINE
9.38	IC50	0.42	nM	CHEMBL5598005
9.31	IC50	0.49	nM	CHEMBL4461851
9.31	IC50	0.49	nM	CHEMBL5596211
8.89	IC50	1.3	nM	CHEMBL5188373
8.89	IC50	1.3	nM	BRIGATINIB
8.85	Kd	1.4	nM	TAE-684
8.80	Ki	1.585	nM	CHEMBL461876
8.74	IC50	1.8	nM	STAUROSPORINE
8.70	IC50	2	nM	CHEMBL3128069
8.70	IC50	2	nM	CHEMBL4473365
8.59	IC50	2.6	nM	CHEMBL4457164
8.57	IC50	2.7	nM	CHEMBL4456804
8.51	IC50	3.1	nM	CHEMBL5596100
8.51	IC50	3.1	nM	CHEMBL6165880
8.50	Ki	3.162	nM	CHEMBL1974328
8.50	Ki	3.162	nM	CHEMBL1980995
8.50	Ki	3.162	nM	CHEMBL1983111
8.48	IC50	3.3	nM	LORLATINIB
8.48	Ki	3.3	nM	LORLATINIB
8.48	IC50	3.3	nM	CHEMBL5712062
8.40	IC50	4	nM	CHEMBL5598480
8.33	IC50	4.7	nM	CHEMBL4524587
8.33	IC50	4.7	nM	CHEMBL5589677
8.30	Ki	5.012	nM	ENTRECTINIB
8.20	Ki	6.31	nM	CHEMBL1977148
8.10	Kd	7.978	nM	CHEMBL5653589
8.04	IC50	9.1	nM	CHEMBL5596289
8.03	Kd	9.3	nM	CHEMBL464552
8.00	IC50	10	nM	CHEMBL4557212
8.00	Ki	10	nM	CHEMBL458997
8.00	Ki	10	nM	CHEMBL243088
7.90	Kd	12.55	nM	CHEMBL3752910
7.90	Ki	12.59	nM	CHEMBL1989708
7.90	Ki	12.59	nM	R-406
7.89	IC50	13	nM	CHEMBL466397
7.85	IC50	14	nM	CHEMBL4455220
7.72	ED50	18.89	nM	CHEMBL5653589
7.70	Ki	19.95	nM	CHEMBL1987034
7.70	Ki	19.95	nM	CHEMBL2002165
7.70	Ki	19.95	nM	CHEMBL1974254
7.62	Kd	24	nM	STAUROSPORINE
7.60	IC50	25	nM	CHEMBL4548027
7.60	Ki	25.12	nM	CHEMBL1993941
7.60	Ki	25.12	nM	CHEMBL1989708
7.60	Ki	25.12	nM	CHEMBL2007064

PubChem BioAssay actives

120 with measured affinity, of 1126 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715349: Inhibition of human FER using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0002	uM
7-[[(1R,2S)-2-aminocyclohexyl]amino]-5-[3-[(2R,6S)-2,6-dimethylmorpholin-4-yl]anilino]-4-oxo-3H-pyrido[3,4-d]pyridazine-8-carbonitrile	2120514: Inhibition of N-terminal His-tagged recombinant human FER using FL-Peptide22 as substrate incubated for 90 mins in presence of ATP	ic50	0.0003	uM
7-[[(1R,2S)-2-aminocyclohexyl]amino]-5-(3-morpholin-4-ylanilino)-4-oxo-3H-pyrido[3,4-d]pyridazine-8-carbonitrile	2120514: Inhibition of N-terminal His-tagged recombinant human FER using FL-Peptide22 as substrate incubated for 90 mins in presence of ATP	ic50	0.0003	uM
7-[[(1R,2S)-2-aminocyclohexyl]amino]-5-[3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)anilino]-4-oxo-3H-pyrido[3,4-d]pyridazine-8-carbonitrile	2120514: Inhibition of N-terminal His-tagged recombinant human FER using FL-Peptide22 as substrate incubated for 90 mins in presence of ATP	ic50	0.0004	uM
7-[[(1R,2S)-2-aminocyclohexyl]amino]-5-(3-methylanilino)-4-oxo-3H-pyrido[3,4-d]pyridazine-8-carbonitrile	1509344: Inhibition of recombinant N-terminal His-tagged human FER (SH2 domain to C-terminal) expressed in Escherichia coli assessed as decrease in FL-Peptide22 substrate phosphorylation incubated for 90 mins	ic50	0.0005	uM
7-[(2-aminocyclohexyl)amino]-5-(3-methylanilino)-4-oxo-3H-pyrido[3,4-d]pyridazine-8-carbonitrile	2120514: Inhibition of N-terminal His-tagged recombinant human FER using FL-Peptide22 as substrate incubated for 90 mins in presence of ATP	ic50	0.0005	uM
5-bromo-4-N-(5-dimethylphosphoryl-2,3-dihydro-1,4-benzodioxin-6-yl)-2-N-[2-methoxy-4-[4-[3-(methoxymethyl)azetidin-1-yl]piperidin-1-yl]-5-methylphenyl]pyrimidine-2,4-diamine	1862876: Inhibition of FER (unknown origin)	ic50	0.0013	uM
Brigatinib	2182794: Inhibition of human FER using poly (Glu, Tyr)4:1 as substrate in presence of [gamma33P]-ATP by HotSpot assay	ic50	0.0013	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625010: Binding constant for FER kinase domain	kd	0.0014	uM
N-[5-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	1584371: Inhibition of recombinant GST/His-tagged human FER catalytic domain expressed in baculovirus expression system by Z-LYTE assay	ic50	0.0020	uM
(2R)-2-[5-[6-amino-5-[(1R)-1-[5-fluoro-2-(triazol-2-yl)phenyl]ethoxy]-3-pyridinyl]-4-methyl-1,3-thiazol-2-yl]propane-1,2-diol	1074706: Inhibition of FER (unknown origin) using Km levels of ATP	ic50	0.0020	uM
6-[[(1R,2S)-2-aminocyclohexyl]amino]-5-cyano-2-(3-methylanilino)pyridine-3-carboxamide	1509344: Inhibition of recombinant N-terminal His-tagged human FER (SH2 domain to C-terminal) expressed in Escherichia coli assessed as decrease in FL-Peptide22 substrate phosphorylation incubated for 90 mins	ic50	0.0026	uM
7-[[(1R,2S)-2-aminocyclohexyl]amino]-8-bromo-5-(3-methylanilino)-3H-pyrido[3,4-d]pyridazin-4-one	1509344: Inhibition of recombinant N-terminal His-tagged human FER (SH2 domain to C-terminal) expressed in Escherichia coli assessed as decrease in FL-Peptide22 substrate phosphorylation incubated for 90 mins	ic50	0.0027	uM
7-[[(1R,2S)-2-aminocyclohexyl]amino]-8-fluoro-5-(3-morpholin-4-ylanilino)-3H-pyrido[3,4-d]pyridazin-4-one	2120514: Inhibition of N-terminal His-tagged recombinant human FER using FL-Peptide22 as substrate incubated for 90 mins in presence of ATP	ic50	0.0031	uM
(16R)-19-amino-13-fluoro-4,8,16-trimethyl-9-oxo-17-oxa-4,5,8,20-tetrazatetracyclo[16.3.1.02,6.010,15]docosa-1(22),2,5,11,13,18,20-heptaene-3-carbonitrile	2187698: Inhibition of His-tagged recombinant FER (541 to 822 residues) (unknown origin) expressed in baculovirus expression system	ic50	0.0033	uM
Lorlatinib	1153111: Inhibition of FER (unknown origin) by TR-FRET-based Z’-LYTE assay	ic50	0.0033	uM
7-[(2-aminocyclohexyl)amino]-8-fluoro-5-(3-methylanilino)-3H-pyrido[3,4-d]pyridazin-4-one	2120514: Inhibition of N-terminal His-tagged recombinant human FER using FL-Peptide22 as substrate incubated for 90 mins in presence of ATP	ic50	0.0040	uM
7-[(2-aminocyclohexyl)amino]-8-chloro-5-(3-methylanilino)-3H-pyrido[3,4-d]pyridazin-4-one	1509344: Inhibition of recombinant N-terminal His-tagged human FER (SH2 domain to C-terminal) expressed in Escherichia coli assessed as decrease in FL-Peptide22 substrate phosphorylation incubated for 90 mins	ic50	0.0047	uM
7-[(2-aminocyclohexyl)amino]-5-(3-ethoxyanilino)-8-fluoro-3H-pyrido[3,4-d]pyridazin-4-one	2120514: Inhibition of N-terminal His-tagged recombinant human FER using FL-Peptide22 as substrate incubated for 90 mins in presence of ATP	ic50	0.0047	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148382: Binding affinity to human FER incubated for 45 mins by Kinobead based pull down assay	kd	0.0080	uM
7-[(2-aminocyclohexyl)amino]-8-fluoro-5-[3-(4-methylpiperazin-1-yl)anilino]-3H-pyrido[3,4-d]pyridazin-4-one	2120514: Inhibition of N-terminal His-tagged recombinant human FER using FL-Peptide22 as substrate incubated for 90 mins in presence of ATP	ic50	0.0091	uM
2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide	625010: Binding constant for FER kinase domain	kd	0.0093	uM
7-[[(1R,2S)-2-aminocyclohexyl]amino]-5-(3-methylanilino)-3H-pyrido[3,4-d]pyridazin-4-one	1509344: Inhibition of recombinant N-terminal His-tagged human FER (SH2 domain to C-terminal) expressed in Escherichia coli assessed as decrease in FL-Peptide22 substrate phosphorylation incubated for 90 mins	ic50	0.0100	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148382: Binding affinity to human FER incubated for 45 mins by Kinobead based pull down assay	kd	0.0126	uM
N-(2,6-difluorophenyl)-5-[3-[2-[5-ethyl-2-methoxy-4-[4-(4-methylsulfonylpiperazin-1-yl)piperidin-1-yl]anilino]pyrimidin-4-yl]imidazo[1,2-a]pyridin-2-yl]-2-methoxybenzamide	2167072: Inhibition of N-terminal His6 tagged recombinant human Fer (541 to end residues) expressed in baculovirus infected Sf21 cells by filter binding assay	ic50	0.0130	uM
7-[(2-aminocyclohexyl)amino]-5-(3-methylanilino)-3H-pyrido[3,4-d]pyridazin-4-one	1509344: Inhibition of recombinant N-terminal His-tagged human FER (SH2 domain to C-terminal) expressed in Escherichia coli assessed as decrease in FL-Peptide22 substrate phosphorylation incubated for 90 mins	ic50	0.0140	uM
6-[[(1R,2S)-2-aminocyclohexyl]amino]-5-chloro-2-(3-methylanilino)pyridine-3-carboxamide	1509344: Inhibition of recombinant N-terminal His-tagged human FER (SH2 domain to C-terminal) expressed in Escherichia coli assessed as decrease in FL-Peptide22 substrate phosphorylation incubated for 90 mins	ic50	0.0250	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526227: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged FER (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0270	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507943: Binding affinity to FER	kd	0.0280	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526227: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged FER (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0300	uM
6-[(2-aminocyclohexyl)amino]-8-(3-methylanilino)-2H-2,7-naphthyridin-1-one	1509344: Inhibition of recombinant N-terminal His-tagged human FER (SH2 domain to C-terminal) expressed in Escherichia coli assessed as decrease in FL-Peptide22 substrate phosphorylation incubated for 90 mins	ic50	0.0310	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	435160: Binding constant for FER kinase domain	kd	0.0340	uM
3-(6,7-dimethoxyquinazolin-4-yl)oxy-N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-4-methylbenzamide	2180127: Inhibition of FER (unknown origin) ACT labeling site by KiNativ Profiling analysis	ic50	0.0361	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	625010: Binding constant for FER kinase domain	kd	0.0370	uM
7-[(2-aminocyclohexyl)amino]-8-fluoro-5-[(1-methylpyrazol-4-yl)amino]-3H-pyrido[3,4-d]pyridazin-4-one	2120514: Inhibition of N-terminal His-tagged recombinant human FER using FL-Peptide22 as substrate incubated for 90 mins in presence of ATP	ic50	0.0400	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1425002: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0470	uM
6-[[(1R,2S)-2-aminocyclohexyl]amino]-7-fluoro-4-(1-methylpyrazol-4-yl)-1,2-dihydropyrrolo[3,4-c]pyridin-3-one	1330033: Inhibition of human recombinant FER cytoplasmic domain (541 to 822 residues) expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0510	uM
6-[[(1R,2R)-2-aminocyclohexyl]amino]-5-cyano-2-(3-methylanilino)pyridine-3-carboxamide	1509344: Inhibition of recombinant N-terminal His-tagged human FER (SH2 domain to C-terminal) expressed in Escherichia coli assessed as decrease in FL-Peptide22 substrate phosphorylation incubated for 90 mins	ic50	0.0570	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625010: Binding constant for FER kinase domain	kd	0.0730	uM
N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-[(6-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]benzamide	2180127: Inhibition of FER (unknown origin) ACT labeling site by KiNativ Profiling analysis	ic50	0.0748	uM
N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)benzamide	2180127: Inhibition of FER (unknown origin) ACT labeling site by KiNativ Profiling analysis	ic50	0.0823	uM
3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-2-carboxamide	1425002: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0850	uM
(1S,2S,3R,4R)-3-[[5-chloro-2-[[(7S)-4-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide	676089: Inhibition of human Fer	ic50	0.0850	uM
N-[2-[4-[[4-(cyclobutylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]-11-azatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-11-yl]-2-oxoethyl]acetamide	1425002: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1030	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine	1425002: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1050	uM
N-[4-(6,7-dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-4-ethoxy-1-(4-fluoro-2-methylphenyl)pyrazole-3-carboxamide	2146580: Binding affinity to FER in human Hs-578T cells	kd	0.1070	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625010: Binding constant for FER kinase domain	kd	0.1200	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625010: Binding constant for FER kinase domain	kd	0.1300	uM
Gilteritinib	1425002: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1880	uM
6-[(2-aminocyclohexyl)amino]-8-(3-methylanilino)-3,4-dihydro-2H-2,7-naphthyridin-1-one	1509344: Inhibition of recombinant N-terminal His-tagged human FER (SH2 domain to C-terminal) expressed in Escherichia coli assessed as decrease in FL-Peptide22 substrate phosphorylation incubated for 90 mins	ic50	0.2100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	7
Benzo(a)pyrene	decreases expression, increases expression, affects expression, affects methylation	4
bisphenol A	affects cotreatment, increases methylation, increases expression	2
trichostatin A	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dimethylarsinous acid	decreases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Aspirin	decreases expression	1
Caffeine	decreases phosphorylation	1

ChEMBL screening assays

348 unique, capped per target: 347 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1035882	Binding	Binding affinity to human FER at 10 uM relative to control	Assessment of chemical coverage of kinome space and its implications for kinase drug discovery. — J Med Chem
CHEMBL1963815	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FER	PubChem BioAssay data set

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1S2	Abcam HeLa FER KO	Cancer cell line	Female
CVCL_SN41	HAP1 FER (-) 1	Cancer cell line	Male
CVCL_SN42	HAP1 FER (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03059420	Not specified	RECRUITING	Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies