FRK

Summary

FRK (fyn related Src family tyrosine kinase, HGNC:3955) is a protein-coding gene on chromosome 6q22.1, encoding Tyrosine-protein kinase FRK (P42685). Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation.

The protein encoded by this gene belongs to the TYR family of protein kinases. This tyrosine kinase is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth.

Source: NCBI Gene 2444 — RefSeq curated summary.

At a glance

• GWAS associations: 41
• Clinical variants (ClinVar): 60 total
• Druggable target: yes — 71 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002031

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3955
Approved symbol	FRK
Name	fyn related Src family tyrosine kinase
Location	6q22.1
Locus type	gene with protein product
Status	Approved
Aliases	RAK, GTK
Ensembl gene	ENSG00000111816
Ensembl biotype	protein_coding
OMIM	606573
Entrez	2444

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000606080, ENST00000891226, ENST00000891227, ENST00000891228

RefSeq mRNA: 1 — MANE Select: NM_002031 NM_002031

CCDS: CCDS5103

Canonical transcript exons

ENST00000606080 — 8 exons

Exon	Start	End
ENSE00000762579	116003877	116003998
ENSE00000762581	115968576	115968739
ENSE00000762582	115967551	115967719
ENSE00000762585	115956452	115956610
ENSE00000762586	115944244	115944425
ENSE00000762607	115943020	115943185
ENSE00001447601	116059968	116060891
ENSE00003696238	115931149	115942625

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 92.78.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6303 / max 64.2603, expressed in 425 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75236	0.7555	317
75234	0.6532	250
75235	0.2215	130

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	92.78	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.60	gold quality
colonic mucosa	UBERON:0000317	90.28	gold quality
esophagus squamous epithelium	UBERON:0006920	88.37	gold quality
epithelium of nasopharynx	UBERON:0001951	88.13	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.75	gold quality
bronchial epithelial cell	CL:0002328	85.48	gold quality
buccal mucosa cell	CL:0002336	84.64	gold quality
palpebral conjunctiva	UBERON:0001812	83.13	gold quality
epithelium of esophagus	UBERON:0001976	82.09	gold quality
parotid gland	UBERON:0001831	81.87	gold quality
sperm	CL:0000019	80.81	gold quality
corpus epididymis	UBERON:0004359	80.72	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	80.61	gold quality
heart right ventricle	UBERON:0002080	80.01	gold quality
duodenum	UBERON:0002114	78.96	gold quality
caput epididymis	UBERON:0004358	78.83	gold quality
oral cavity	UBERON:0000167	78.80	gold quality
epithelium of bronchus	UBERON:0002031	78.59	gold quality
squamous epithelium	UBERON:0006914	78.50	gold quality
male germ cell	CL:0000015	78.24	silver quality
seminal vesicle	UBERON:0000998	78.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.06	silver quality
gingival epithelium	UBERON:0001949	78.01	gold quality
bronchus	UBERON:0002185	77.94	gold quality
visceral pleura	UBERON:0002401	77.32	gold quality
ileal mucosa	UBERON:0000331	77.12	silver quality
tendon of biceps brachii	UBERON:0008188	76.32	silver quality
gingiva	UBERON:0001828	76.30	gold quality
islet of Langerhans	UBERON:0000006	76.08	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-6	yes	3523.97
E-MTAB-6678	yes	1845.49
E-GEOD-130473	yes	962.52
E-CURD-97	yes	497.81
E-MTAB-7008	yes	239.84
E-ANND-3	yes	6.15
E-MTAB-9067	no	1442.30
E-MTAB-7249	no	425.12
E-MTAB-7381	no	305.63
E-ENAD-20	no	146.09
E-GEOD-70580	no	84.72

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
TERT	Repression

Upstream regulators (CollecTRI, top): CTNNB1

miRNA regulators (miRDB)

97 targeting FRK, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AZ-3P	99.82	70.56	3549

Literature-anchored findings (GeneRIF, showing 26)

• Breast cancer cell line proliferation blocked by the Src-related Rak tyrosine kinase (PMID:12569567)
• The tyrosine kinases Brk/PTK6/Sik, Srm, Frk/Rak/Gtk/Iyk/Bsk, and Src42A/Dsrc41 have a low degree of sequence homology to other known kinases. The exon structure of these kinases, called the Brk family, is highly conserved and distinct. (PMID:12725532)
• Three common Japanese polymorphisms of the Fyn kinase gene studied in 127 healthy controls and 182 sporadic Alzheimer’s disease failed to demonstrate any significant difference. (PMID:15082191)
• Rak functions as a tumor suppressor by regulating PTEN protein stability and function in breast and bone neoplasms. (PMID:19345329)
• Study searched for mutations in the FRK gene, a recently identified tumor suppressor gene, for the first time in NSCLC. Somatic FRK mutations were found at a very low frequency in NSCLCs. (PMID:21074287)
• Genetic variation near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration. (PMID:21665990)
• these results clearly indicate that FRK may play a protective role against the progression of glioma by suppressing cell migration and invasion (PMID:22790444)
• The expression levels of FRK were significantly correlated with invasiveness in both Hep3B and HepG2 tumor cell lines. (PMID:23267173)
• Data indicaate that the Rak/Frk SH2 and SH3 domains collaborate to increase the Rak-EGFR interaction. (PMID:23318459)
• exome sequencing identified recurrent somatic FRK mutations that induce constitutive kinase activity, STAT3 activation, and cell proliferation sensitive to Src inhibitors (PMID:24735922)
• our results demonstrate a combined mechanism for the anti-proliferative effects of FRK by inhibiting cyclin D1 nucleus accumulation and pRb phosphorylation in glioma cells. (PMID:24792491)
• FRK over-expression promoted beta-catenin translocation to the plasma membrane, where it formed complex with N-cadherin. (PMID:24969324)
• antagomir-1290 significantly inhibited the proliferation, clonogenicity, invasion, and migration of CD133(+) cells by targeting fyn-related Src family tyrosine kinase. (PMID:25783528)
• Loss of FRK protein may be implicated into the tumorigenesis and cell motility/invasiveness of human cervical cancer. (PMID:27665472)
• our results present the first evidence that site-specific promoter methylation contributes to the repression of FRK more so in basal B breast cancers. (PMID:28077797)
• Targetable fusions of the FRK tyrosine kinase in ALK-negative anaplastic large cell lymphoma. (PMID:29026208)
• FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes epithelial-mesenchymal transition and metastasis (PMID:31251822)
• These results indicate that FRK inhibits human glioma growth via regulating ITGB1/FAK signaling. (PMID:31395336)
• Activated BRK-mediated degradation of SMAD4 is associated with the repression of tumor suppressor gene FRK. (PMID:31681835)
• TRIM44 promotes cell proliferation by regulating FRK. (PMID:31883420)
• Down-Regulation of miR-2053 Inhibits the Development and Progression of Esophageal Carcinoma by Targeting Fyn-Related Kinase (FRK). (PMID:31894485)
• Recurrent chromosomal rearrangements of ROS1, FRK and IL6 activating JAK/STAT pathway in inflammatory hepatocellular adenomas. (PMID:31907296)
• Furry protein suppresses nuclear localization of yes-associated protein (YAP) by activating NDR kinase and binding to YAP. (PMID:31996378)
• GATA6 activated long non-coding RNA PCAT1 maintains stemness of non-small cell lung cancer by mediating FRK. (PMID:33277858)
• FRK inhibits glioblastoma progression via phosphorylating YAP and inducing its ubiquitylation and degradation by Siah1. (PMID:35723276)
• Hemifacial microsomia is linked to a rare homozygous variant V162I in FRK and validated in zebrafish. (PMID:36070195)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	frk	ENSDARG00000027807
mus_musculus	Frk	ENSMUSG00000019779
rattus_norvegicus	Frk	ENSRNOG00000000543

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), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), SYK (ENSG00000165025), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)

Protein

Protein identifiers

Tyrosine-protein kinase FRK — P42685 (reviewed: P42685)

Alternative names: FYN-related kinase, Nuclear tyrosine protein kinase RAK, Protein-tyrosine kinase 5

All UniProt accessions (1): P42685

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on ‘Tyr-336’, which in turn prevents its ubiquitination and degradation, possibly by reducing its binding to NEDD4. May function as a tumor suppressor.

Subunit / interactions. Interacts (via the SH3-domain) with PTEN. Interacts with RB1.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Predominantly expressed in epithelial derived cell lines and tissues, especially normal liver, kidney, breast and colon.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P42685-1	1	yes
P42685-2	2

RefSeq proteins (1): NP_002022* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000980	SH2	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001452	SH3_domain	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR035805	SH2_Frk	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR050198	Non-receptor_tyrosine_kinases	Family

Pfam: PF00017, PF00018, 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 (18 total): modified residue 4, domain 3, sequence variant 3, splice variant 2, binding site 2, chain 1, mutagenesis site 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42685-F1	83.41	0.60

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): 354 (proton acceptor)

Ligand- & substrate-binding residues (2): 240–248; 262

Post-translational modifications (4): 387, 37, 40, 178

Mutagenesis-validated functional residues (1):

Position	Phenotype
262	loss of ability to phosphorylate pten.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-8948751	Regulation of PTEN stability and activity

MSigDB gene sets: 134 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOZGIT_ESR1_TARGETS_DN, AAGCCAT_MIR135A_MIR135B, CAGCAGG_MIR370, MORF_EPHA7, DOUGLAS_BMI1_TARGETS_DN, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, CUI_TCF21_TARGETS_2_DN, GOMF_SIGNALING_RECEPTOR_BINDING, WALLACE_PROSTATE_CANCER_RACE_DN, RIGGI_EWING_SARCOMA_PROGENITOR_UP, MORF_IL9, MORF_DCC, GOCC_SECRETORY_VESICLE

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), cell differentiation (GO:0030154), pattern recognition receptor signaling pathway (GO:0002221), cytoplasmic pattern recognition receptor signaling pathway (GO:0002753), protein phosphorylation (GO:0006468), symbiont-mediated suppression of cytoplasmic pattern recognition receptor signaling pathway (GO:0039537), negative regulation of innate immune response (GO:0045824)

GO Molecular Function (9): protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), signaling receptor binding (GO:0005102), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (9): extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), azurophil granule lumen (GO:0035578), specific granule lumen (GO:0035580), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
PTEN Regulation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
secretory granule lumen	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
enzyme-linked receptor protein signaling pathway	1
cellular developmental process	1
innate immune response-activating signaling pathway	1
positive regulation of cytokine production	1
pattern recognition receptor signaling pathway	1
intracellular receptor signaling pathway	1
phosphorylation	1
protein modification process	1
symbiont-mediated suppression of host pathogen-associated molecular pattern receptor signaling pathway	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
innate immune response	1
regulation of innate immune response	1
negative regulation of immune response	1
protein kinase activity	1
protein tyrosine kinase activity	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
vacuolar lumen	1

Protein interactions and networks

STRING

1782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FRK	RAPGEF1	Q13905	676
FRK	CRK	P46108	573
FRK	TK1	P04183	562
FRK	COL10A1	Q03692	542
FRK	UGP2	Q16851	532
FRK	SLC16A8	O95907	464
FRK	RAD51B	O15315	434
FRK	ABL1	P00519	432
FRK	NGF	P01138	418
FRK	GPI	P06744	418
FRK	LYN	P07948	409
FRK	FYN	P06241	406
FRK	HMCN1	Q96RW7	405
FRK	FILIP1L	Q4L180	401
FRK	LCK	P06239	401

IntAct

56 interactions, top by confidence:

A	B	Type	Score
FRK	BNIP2	psi-mi:“MI:0915”(physical association)	0.830
BNIP2	FRK	psi-mi:“MI:0915”(physical association)	0.830
SF3B4	FRK	psi-mi:“MI:0915”(physical association)	0.670
FRK	SF3B4	psi-mi:“MI:0915”(physical association)	0.670
PTEN	FRK	psi-mi:“MI:0915”(physical association)	0.640
FRK	PTEN	psi-mi:“MI:0915”(physical association)	0.640
PTEN	FRK	psi-mi:“MI:0217”(phosphorylation reaction)	0.640
FRK	PTEN	psi-mi:“MI:0217”(phosphorylation reaction)	0.640
CSK	FRK	psi-mi:“MI:0914”(association)	0.640
EGFR	FRK	psi-mi:“MI:0915”(physical association)	0.550
FRK	RB1	psi-mi:“MI:0407”(direct interaction)	0.540
FRK	RB1	psi-mi:“MI:0915”(physical association)	0.540
CSK	MATK	psi-mi:“MI:0914”(association)	0.530
FRK	ABI1	psi-mi:“MI:0407”(direct interaction)	0.440
	FRK	psi-mi:“MI:0217”(phosphorylation reaction)	0.440

BioGRID (74): FRK (Two-hybrid), SF3B4 (Two-hybrid), FRK (Two-hybrid), FRK (Affinity Capture-MS), FRK (Two-hybrid), BNIP2 (Two-hybrid), FRK (PCA), FRK (Affinity Capture-Luminescence), FRK (Affinity Capture-MS), FRK (Affinity Capture-MS), SKAP2 (PCA), BNIP2 (Two-hybrid), RB1 (Reconstituted Complex), RB1 (Affinity Capture-Western), FRK (Affinity Capture-MS)

ESM2 similar proteins: A0JNB0, A1Y2K1, F1LM93, F1RDG9, G5EE56, O45539, P00523, P00524, P00525, P00526, P00527, P00528, P05480, P06241, P07947, P09324, P09769, P10936, P12931, P13115, P13116, P13406, P14084, P14085, P14234, P17713, P24604, P25020, P27446, P27447, P31693, P39688, P42680, P42681, P42685, P42686, P42690, P63185, Q04736, Q05876

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

8 interactions.

A	Effect	B	Mechanism
regorafenib	“down-regulates activity”	FRK	“chemical inhibition”
FRK	“up-regulates quantity by stabilization”	BRCA1	phosphorylation
FRK	“down-regulates quantity by destabilization”	YAP1	phosphorylation
FRK	“up-regulates quantity by stabilization”	PTEN	phosphorylation
FRK	“up-regulates activity”	PTEN	phosphorylation
FRK	“down-regulates activity”	EGFR	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 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
Regulation of actin dynamics for phagocytic cup formation	5	31.8×	2e-04
Signaling by Receptor Tyrosine Kinases	7	12.5×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein phosphorylation	10	20.6×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2056 predictions. Top by Δscore:

Variant	Effect	Δscore
6:115942648:A:T	acceptor_gain	1.0000
6:115944273:C:CT	donor_gain	1.0000
6:115944274:T:TT	donor_gain	1.0000
6:115956446:G:C	donor_gain	1.0000
6:115956450:A:AC	donor_gain	1.0000
6:115956451:C:CC	donor_gain	1.0000
6:115956474:T:TA	donor_gain	1.0000
6:115956608:AACCT:A	acceptor_loss	1.0000
6:115956609:ACCTG:A	acceptor_loss	1.0000
6:115956610:CCTG:C	acceptor_loss	1.0000
6:115956611:C:A	acceptor_loss	1.0000
6:115956611:C:CC	acceptor_gain	1.0000
6:115956612:T:G	acceptor_loss	1.0000
6:115967610:T:TA	donor_gain	1.0000
6:115967719:TC:T	acceptor_loss	1.0000
6:115967720:C:CA	acceptor_loss	1.0000
6:115967727:A:C	acceptor_gain	1.0000
6:115968571:TTCAC:T	donor_loss	1.0000
6:115968572:TCAC:T	donor_loss	1.0000
6:115968573:CA:C	donor_loss	1.0000
6:115968740:C:CC	acceptor_gain	1.0000
6:116003872:CTTAC:C	donor_loss	1.0000
6:116003874:TAC:T	donor_loss	1.0000
6:116003875:A:C	donor_loss	1.0000
6:116003994:ACCAC:A	acceptor_gain	1.0000
6:116003995:CCAC:C	acceptor_gain	1.0000
6:116003995:CCACC:C	acceptor_gain	1.0000
6:116003996:CAC:C	acceptor_gain	1.0000
6:116003996:CACC:C	acceptor_gain	1.0000
6:116003997:AC:A	acceptor_gain	1.0000

AlphaMissense

3314 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:115943131:A:G	W399R	1.000
6:115943131:A:T	W399R	1.000
6:115967564:T:A	K262N	1.000
6:115967564:T:G	K262N	1.000
6:115943077:A:G	W417R	0.999
6:115943077:A:T	W417R	0.999
6:115943129:C:A	W399C	0.999
6:115943129:C:G	W399C	0.999
6:115944268:A:C	D372E	0.999
6:115944268:A:T	D372E	0.999
6:115944322:A:C	D354E	0.999
6:115944322:A:T	D354E	0.999
6:115944323:T:A	D354V	0.999
6:115944323:T:C	D354G	0.999
6:115944323:T:G	D354A	0.999
6:115944326:C:A	R353I	0.999
6:115967565:T:A	K262I	0.999
6:115967566:T:C	K262E	0.999
6:115967615:A:C	F245L	0.999
6:115967615:A:T	F245L	0.999
6:115967617:A:G	F245L	0.999
6:115942492:A:C	F480L	0.998
6:115942492:A:T	F480L	0.998
6:115942494:A:G	F480L	0.998
6:115942524:A:G	W470R	0.998
6:115942524:A:T	W470R	0.998
6:115943067:C:T	G420E	0.998
6:115943075:C:A	W417C	0.998
6:115943075:C:G	W417C	0.998
6:115943082:T:A	D415V	0.998

dbSNP variants (sampled 300 via entrez): RS1000012783 (6:116090745 A>AC), RS1000018695 (6:116061981 AAAAG>A), RS1000027326 (6:116023457 C>T), RS1000100882 (6:116022183 C>A), RS1000110943 (6:116053629 G>A,C), RS1000140752 (6:116042350 C>T), RS1000142988 (6:116023114 C>T), RS1000162326 (6:115944463 G>A), RS1000162367 (6:115996320 C>T), RS1000173836 (6:116086802 T>C), RS1000223504 (6:115995291 G>A), RS1000252366 (6:116094534 C>T), RS1000269736 (6:116008136 T>A,C), RS1000280486 (6:115953116 T>A,C), RS1000280743 (6:116003133 C>A,T)

Disease associations

OMIM: gene MIM:606573 | disease phenotypes: MIM:164210

GenCC curated gene-disease

Mondo (1): craniofacial microsomia 1 (MONDO:0958175)

Orphanet (1): Goldenhar syndrome (Orphanet:374)

HPO phenotypes

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

GWAS associations

41 associations (top):

Study	Trait	p-value
GCST000759_9	LDL cholesterol	3.000000e-09
GCST000760_2	Cholesterol, total	2.000000e-10
GCST001100_6	Age-related macular degeneration	1.000000e-08
GCST001791_12	Urate levels	7.000000e-07
GCST002221_50	Cholesterol, total	1.000000e-09
GCST002222_5	LDL cholesterol	2.000000e-07
GCST003075_11	Cognitive decline rate in late mild cognitive impairment	3.000000e-08
GCST003075_125	Cognitive decline rate in late mild cognitive impairment	9.000000e-08
GCST003678_18	C-reactive protein levels or total cholesterol levels (pleiotropy)	2.000000e-12
GCST003679_8	C-reactive protein levels or LDL-cholesterol levels (pleiotropy)	8.000000e-12
GCST003992_12	Photic sneeze reflex	2.000000e-09
GCST004233_23	LDL cholesterol levels	2.000000e-09
GCST004235_76	Total cholesterol levels	2.000000e-13
GCST005037_4	Appendicular lean mass	9.000000e-06
GCST006658_19	Longevity	9.000000e-06
GCST007094_9	Diastolic blood pressure	2.000000e-08
GCST007576_191	Chronotype	4.000000e-08
GCST007614_43	C-reactive protein levels	3.000000e-10
GCST008070_13	HDL cholesterol levels	6.000000e-06
GCST008078_106	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-13
GCST008078_21	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	8.000000e-12
GCST008079_152	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-15
GCST008079_21	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5.000000e-13
GCST008086_29	LDL cholesterol levels in current drinkers	7.000000e-07
GCST008086_71	LDL cholesterol levels in current drinkers	8.000000e-09
GCST008477_15	Emphysema annual change measurement in smokers (adjusted lung density)	5.000000e-06
GCST008477_31	Emphysema annual change measurement in smokers (adjusted lung density)	3.000000e-06
GCST009211_3	Choroid plexus volume	1.000000e-06
GCST010002_333	Refractive error	2.000000e-36
GCST010204_92	Low density lipoprotein cholesterol levels	1.000000e-18

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004531	urate measurement
EFO:0007710	cognitive decline measurement
EFO:0004458	C-reactive protein measurement
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0004980	appendicular lean mass
EFO:0006336	diastolic blood pressure
EFO:0008328	chronotype measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0007626	emphysema imaging measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004469	HOMA-B
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363074 (PROTEIN FAMILY), CHEMBL4223 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

71 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 393,790 (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
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289494	TIVOZANIB	4	4,455
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1421	DASATINIB ANHYDROUS	4	55,003
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL225072	PEMETREXED	4	55,761
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3286830	LORLATINIB	4	3,598
CHEMBL3348923	TOVORAFENIB	4	834
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL3936761	ZANUBRUTINIB	4	2,484
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4
CHEMBL5416410	DASATINIB	4
CHEMBL553	ERLOTINIB	4
CHEMBL576982	QUIZARTINIB	4
CHEMBL601719	CRIZOTINIB	4
CHEMBL608533	MIDOSTAURIN	4
CHEMBL939	GEFITINIB	4
CHEMBL941	IMATINIB	4
CHEMBL101253	VATALANIB	3
CHEMBL1908391	MASITINIB	3

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Src family

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
bosutinib	Inhibition	8.66	pIC50
eCF506	Inhibition	8.55	pIC50

Binding affinities (BindingDB)

26 measured of 45 human assays (45 total across all organisms); most potent 26 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
Staurosporine	KD	1.7 nM
4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole	KD	9.8 nM
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	IC50	10 nM	US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof
4-[4-(4-fluorophenyl)-2-(4-methanesulfinylphenyl)-1H-imidazol-5-yl]pyridine	KD	12 nM
BMS-354825	KD	27 nM
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide	IC50	33 nM
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
PKC-412	KD	190 nM
AMG 706	KD	300 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methyl-phenyl)urea	KD	450 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
3-[4-(benzylamino)-3-methoxyphenyl]-1-[2-[4-(dimethylamino)piperidin-1-yl]ethyl]pyrazolo[3,4-d]pyrimidin-4-amine	IC50	550 nM	US-10294227: Compounds
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	KD	1000 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
ERLOTINIB HYDROCHLORIDE	KD	1200 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
CI-1033	KD	1700 nM
GEFITINIB	IC50	2300 nM	US-9416123: Kinase modulators for the treatment of cancer
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
N-[3-({5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl}carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide	IC50	3400 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
1-methyl-5-[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]pyridin-4-yl]oxy-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine	KD	4500 nM
(4-chlorophenyl)-[4-(4-pyridylmethyl)phthalazin-1-yl]amine	KD	8800 nM

ChEMBL bioactivities

394 potent at pChembl≥5 of 395 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.51	Kd	0.31	nM	DASATINIB
9.00	Kd	1	nM	CHEMBL400402
9.00	Ki	1	nM	CHEMBL1984162
9.00	Ki	1	nM	CHEMBL1993661
8.90	Ki	1.259	nM	CHEMBL1981047
8.89	IC50	1.3	nM	PONATINIB
8.85	Kd	1.4	nM	BOSUTINIB
8.70	Ki	1.995	nM	CHEMBL1992306
8.70	Ki	1.995	nM	ILORASERTIB
8.66	IC50	2.2	nM	BOSUTINIB
8.60	Ki	2.512	nM	TAE-684
8.60	Ki	2.512	nM	CHEMBL1988387
8.60	Ki	2.512	nM	CHEMBL1964692
8.50	Ki	3.162	nM	CHEMBL1970142
8.50	Ki	3.162	nM	CHEMBL1996979
8.50	Ki	3.162	nM	CHEMBL306380
8.50	Ki	3.162	nM	CHEMBL1994938
8.42	Kd	3.8	nM	FORETINIB
8.40	Ki	3.981	nM	CHEMBL1989708
8.40	Ki	3.981	nM	CHEMBL259922
8.39	Kd	4.1	nM	CHEMBL386051
8.34	IC50	4.56	nM	STAUROSPORINE
8.34	Kd	4.571	nM	DASATINIB ANHYDROUS
8.30	Kd	5	nM	DASATINIB
8.30	Kd	5	nM	DASATINIB ANHYDROUS
8.30	Ki	5.012	nM	CHEMBL1998585
8.30	Ki	5.012	nM	CHEMBL2004716
8.30	Ki	5.012	nM	CHEMBL1982466
8.22	Kd	6	nM	CHEMBL450519
8.20	Ki	6.31	nM	CHEMBL1988717
8.20	Ki	6.31	nM	CHEMBL1989708
8.20	Ki	6.31	nM	CHEMBL1090356
8.16	Kd	6.9	nM	CHEMBL5415503
8.10	Ki	7.943	nM	CHEMBL213505
8.00	Ki	10	nM	CHEMBL1974328
8.00	Ki	10	nM	CHEMBL1993424
7.99	IC50	10.3	nM	STAUROSPORINE
7.92	Kd	12	nM	CHEMBL504075
7.90	Ki	12.59	nM	CHEMBL2005886
7.90	Ki	12.59	nM	R-406
7.80	IC50	16	nM	CHEMBL466397
7.80	Ki	15.85	nM	CHEMBL1987034
7.80	Ki	15.85	nM	CHEMBL1977148
7.80	Ki	15.85	nM	CHEMBL2001485
7.80	Ki	15.85	nM	CHEMBL1993243
7.80	Ki	15.85	nM	CHEMBL508928
7.80	Ki	15.85	nM	ENTRECTINIB
7.77	IC50	17	nM	STAUROSPORINE
7.72	IC50	19	nM	CHEMBL4798527
7.70	Ki	19.95	nM	LINIFANIB

PubChem BioAssay actives

167 with measured affinity, of 1499 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
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	436019: Binding constant for FRK kinase domain	kd	0.0003	uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1425007: 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	0.0010	uM
Ponatinib	1716397: Binding affinity to human FRK using poly[Glu:Tyr] (4:1) as substrate by radiometric hotspot kinase assay	ic50	0.0013	uM
Bosutinib	624855: Binding constant for FRK kinase domain	kd	0.0014	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	624855: Binding constant for FRK kinase domain	kd	0.0038	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624855: Binding constant for FRK kinase domain	kd	0.0041	uM
Dasatinib	2148399: Binding affinity to human FRK incubated for 45 mins by Kinobead based pull down assay	kd	0.0046	uM
(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	1715339: Inhibition of human FRK using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0046	uM
3-(4-amino-7-piperidin-4-ylpyrrolo[2,3-d]pyrimidin-5-yl)phenol	389097: Binding affinity to human FRK	kd	0.0060	uM
N-[3-[2-[2-ethoxy-4-(4-methylpiperazin-1-yl)anilino]-7-oxo-8-[[(2R)-oxolan-2-yl]methyl]pyrido[2,3-d]pyrimidin-6-yl]phenyl]-3-(trifluoromethyl)benzamide	1988540: Binding affinity to FRK (unknown origin) assessed as dissociation constant by KINOME scan assay	kd	0.0069	uM
N-[3-[(1S)-1-[(6-chloropyrazin-2-yl)amino]ethyl]phenyl]-3-methylbenzamide	392579: Inhibition of FRK	kd	0.0120	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	2167084: Inhibition of N-terminal 6His-tagged recombinant human PTK5 (218 to end residues) expressed in baculovirus infected Sf21 cells by filter binding assay	ic50	0.0160	uM
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	1734749: Inhibition of human recombinant PTK5 (218 to end residues) using GGEEEEYFELVKKKK as substrate incubated for 40 mins in presence of [gamma33P-ATP] by radiometric scintillation counting analysis	ic50	0.0190	uM
3-cyano-N-[2,4-difluoro-3-[2-(3-methoxy-1H-pyrazolo[5,4-b]pyridin-5-yl)ethynyl]phenyl]benzenesulfonamide	1486190: Binding affinity to partial length human FRK expressed in Escherichia coli BL21 by active-site-dependent competition assay	kd	0.0220	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	436019: Binding constant for FRK kinase domain	kd	0.0260	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	624855: Binding constant for FRK kinase domain	kd	0.0270	uM
Ibrutinib	1714864: Inhibition of FRK (unknown origin)	ic50	0.0292	uM
1-[3-tert-butyl-1-(4-chlorophenyl)pyrazol-5-yl]-3-[4-[(6,6-dimethyl-7-oxo-8H-pyrimido[5,4-b][1,4]oxazin-4-yl)amino]-3-methylphenyl]urea	1822458: Inhibition of human PTK5 in presence of ATP by radiometric assay	ic50	0.0320	uM
4-[8-amino-3-[(6R,8aS)-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721752: Inhibition of FRK (unknown origin)	ic50	0.0340	uM
4-[3-[(6R,8aS)-1,1-dimethyl-3-oxo-6,7,8,8a-tetrahydro-5H-[1,3]oxazolo[3,4-a]pyridin-6-yl]-8-aminoimidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721752: Inhibition of FRK (unknown origin)	ic50	0.0360	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	2168207: Inhibition of human wild type FRK using PolyEY as substrate preincubated for 2 hrs followed by ATP addition and measured every 2 mins for 2.5 hrs by spectrophotometric analysis	ic50	0.0370	uM
2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine	2161829: Inhibition of human N-terminal GST-fused FRK catalytic domain (223 to 505(end) residues) expressed in baculovirus expression system using Srctide as substrate measured after 1 hr by off-chip mobility shift assay relative to control	ic50	0.0400	uM
4-amino-8-(5-methyl-1H-indazol-6-yl)cinnoline-3-carboxamide	1230685: Inhibition of human recombinant Frk	ic50	0.0410	uM
4-[8-amino-3-[(6R,8aS)-3-oxo-1,5,6,7,8,8a-hexahydro-[1,3]oxazolo[3,4-a]pyridin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721752: Inhibition of FRK (unknown origin)	ic50	0.0460	uM
1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[4-(6,7,8,9-tetrahydropyrimido[5,4-b][1,4]oxazepin-4-ylamino)phenyl]urea	1735635: Inhibition of recombinant human PTK5 (218 to end residues) using GGEEEEYFELVKKKK as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting based radiometry assay	ic50	0.0510	uM
Brigatinib	2182821: Inhibition of human FRK using RLGRDKYKTLRQIRQ as substrate in presence of [gamma33P]-ATP by HotSpot assay	ic50	0.0520	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	2187706: Inhibition of GST-tagged recombinant full length FRK (unknown origin) expressed in baculovirus expression system	ic50	0.0530	uM
Lorlatinib	1153118: Inhibition of FRK (unknown origin) by TR-FRET-based Z’-LYTE assay	ic50	0.0530	uM
methyl 5-[[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]methylamino]-1H-pyrrolo[2,3-b]pyridine-2-carboxylate	1301829: Inhibition of GST-tagged full length human recombinant FRK expressed in baculovirus using Fluorescein-Poly GT as substrate	ic50	0.0620	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	624855: Binding constant for FRK kinase domain	kd	0.0680	uM
4-[8-amino-3-[(3R)-1-(oxan-4-yl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488582: Inhibition of FRK (unknown origin)	ic50	0.0850	uM
Nilotinib	624855: Binding constant for FRK kinase domain	kd	0.0860	uM
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-yl-1,3-thiazol-2-yl)amino]phenyl]benzamide	624855: Binding constant for FRK kinase domain	kd	0.0870	uM
N-(3,3-dimethyl-1,2-dihydroindol-6-yl)-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide	436019: Binding constant for FRK kinase domain	kd	0.0990	uM
4-[8-amino-3-[(3R,6S)-1-(cyclopropanecarbonyl)-6-methylpiperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711658: Inhibition of human FRK	ic50	0.1110	uM
N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	1425007: 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	0.1120	uM
N-(3-tert-butylphenyl)-3-[4-(cyclopropylmethylcarbamoyl)phenyl]-4-methylbenzamide	389097: Binding affinity to human FRK	kd	0.1220	uM
4-[8-amino-3-[(2R)-4-(oxan-4-yl)morpholin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488582: Inhibition of FRK (unknown origin)	ic50	0.1320	uM
Tivozanib	1425007: 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	0.1450	uM
4-[8-amino-3-[(3R)-1-(2-methoxyacetyl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488582: Inhibition of FRK (unknown origin)	ic50	0.1510	uM
4-[8-amino-3-[(6R,8aS)-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-3-methoxy-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721752: Inhibition of FRK (unknown origin)	ic50	0.1540	uM
Vandetanib	436019: Binding constant for FRK kinase domain	kd	0.1700	uM
Tovorafenib	1425007: 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	0.1720	uM
4-[8-amino-3-[(3R)-1-(3-methyloxetane-3-carbonyl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711658: Inhibition of human FRK	ic50	0.1870	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	256598: Average Binding Constant for FRK; NA=Not Active at 10 uM	kd	0.1900	uM
Fedratinib	624855: Binding constant for FRK kinase domain	kd	0.2000	uM
4-[8-amino-3-[(2R)-4-(2-methoxyacetyl)morpholin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488582: Inhibition of FRK (unknown origin)	ic50	0.2140	uM
5-(3-ethylsulfonylphenyl)-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide	1425007: 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	0.2220	uM
1-[4-(6,7-dimethoxyquinolin-4-yl)oxy-2-methoxyphenyl]-3-[1-(1,3-thiazol-2-yl)ethyl]urea	624855: Binding constant for FRK kinase domain	kd	0.3100	uM
N-[4-[(2-amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide	1425007: 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	0.3300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, increases reaction, affects cotreatment, decreases expression	5
Tetrachlorodibenzodioxin	decreases reaction, affects cotreatment, decreases expression	3
afimoxifene	increases expression, decreases response to substance	2
Air Pollutants	increases abundance, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
glycidyl methacrylate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
resorcinol	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ON 01910	increases phosphorylation	1
ponatinib	decreases activity	1
Dasatinib	affects binding	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Caffeine	affects phosphorylation	1
Cycloheximide	decreases expression, decreases reaction	1
Doxorubicin	decreases expression	1
Quercetin	decreases expression	1
Dihydrotestosterone	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases expression	1

ChEMBL screening assays

271 unique, capped per target: 269 binding, 1 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5719121	Binding	Inhibition of Src family in human RPMI-8226 cells assessed as reduction of cell growth incubated for 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay	Small molecule inhibitor screen identifies synergistic activity of the bromodomain inhibitor CPI203 and bortezomib in drug resistant myeloma. — Oncotarget
CHEMBL1964118	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FRK	PubChem BioAssay data set
CHEMBL4414922	ADMET	Inhibition of human FRK using poly[Glu:Tyr] (4:1) as substrate preincubated for 60 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by filter binding method	Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1MM	Abcam K-562 FRK KO	Cancer cell line	Female
CVCL_D2J7	Abcam Raji FRK KO	Cancer cell line	Male
CVCL_UQ54	Abcam Jurkat FRK KO	Cancer cell line	Male

Clinical trials (associated diseases)

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