HCK

Summary

HCK (HCK proto-oncogene, Src family tyrosine kinase, HGNC:4840) is a protein-coding gene on chromosome 20q11.21, encoding Tyrosine-protein kinase HCK (P08631). Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell s….

The protein encoded by this gene is a member of the Src family of tyrosine kinases. This protein is primarily hemopoietic, particularly in cells of the myeloid and B-lymphoid lineages. It may help couple the Fc receptor to the activation of the respiratory burst. In addition, it may play a role in neutrophil migration and in the degranulation of neutrophils. Multiple isoforms with different subcellular distributions are produced due to both alternative splicing and the use of alternative translation initiation codons, including a non-AUG (CUG) codon.

Source: NCBI Gene 3055 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autoinflammation with pulmonary and cutaneous vasculitis (Moderate, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 120 total — 1 pathogenic, 1 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈6% of expected missense variation)
• GTEx eGene: eQTL in 10 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 12
• Drug target: yes — 1 curated mechanism-of-action drug, 5 via a complex or family; 61 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 1 — Bosutinib
• Approved drugs acting on a complex or family including it: 1 — Dasatinib Anhydrous (SRC)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.80 (unconstrained)
• MANE Select transcript: NM_002110
• Interaction hub: 2,032 STRING partners (top 7% of genes corpus-wide)
• Notable: 120 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4840
Approved symbol	HCK
Name	HCK proto-oncogene, Src family tyrosine kinase
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	JTK9
Ensembl gene	ENSG00000101336
Ensembl biotype	protein_coding
OMIM	142370
Entrez	3055

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000375852

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 4

ENST00000375852, ENST00000262651, ENST00000375862, ENST00000470092, ENST00000486475, ENST00000518730, ENST00000520553, ENST00000629881, ENST00001133261

RefSeq mRNA: 6 — MANE Select: NM_002110 NM_001172129, NM_001172130, NM_001172131, NM_001172132, NM_001172133, NM_002110

CCDS: CCDS33460, CCDS54453, CCDS54455, CCDS54456

Canonical transcript exons

ENST00000375852 — 13 exons

Exon	Start	End
ENSE00001468583	32101317	32101856
ENSE00003486521	32079774	32079877
ENSE00003490553	32071662	32071782
ENSE00003517859	32052242	32052486
ENSE00003519607	32086628	32086807
ENSE00003544962	32099004	32099135
ENSE00003561437	32084391	32084543
ENSE00003579002	32074623	32074721
ENSE00003607915	32073716	32073818
ENSE00003635422	32073319	32073361
ENSE00003647034	32093863	32094016
ENSE00003662889	32088568	32088644
ENSE00003667821	32083894	32084043

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 99.08.

FANTOM5 (CAGE): breadth broad, TPM avg 42.4830 / max 2094.1838, expressed in 695 samples.

Highest expression (Bgee): monocyte, mononuclear cell, leukocyte, granulocyte, blood.

Genetic regulation across tissues (GTEx eQTL / sQTL)

HCK is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

15 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	sqtl	8.8e-24	+0.82	20:32030862:C:G
Brain Cerebellum	sqtl	2.7e-07	+0.74	20:32030984:T:C
Whole Blood	sqtl	3.8e-07	-1.36	20:32085310:C:T
Whole Blood	eqtl	4.2e-05	-0.06	20:32042239:C:T
Breast Mammary Tissue	eqtl	2.7e-03	-0.18	20:32053726:G:A
Brain Anterior cingulate cortex BA24	eqtl	3.6e-03	-0.69	20:32940243:A:G
Spleen	sqtl	4.2e-03	-1.78	20:32085310:C:T
Skin Sun Exposed Lower leg	eqtl	6.9e-03	-0.44	20:32086254:T:C
Brain Cerebellum	eqtl	7.1e-03	+0.32	20:32005839:C:T
Adipose Subcutaneous	eqtl	1.5e-02	-0.07	20:32033787:G:C
Uterus	eqtl	2.3e-02	-1.73	20:32098878:AG:A
Adipose Subcutaneous	sqtl	2.7e-02	+0.29	20:31723455:G:C
Spleen	eqtl	3.2e-02	+0.29	20:31734233:C:T
Cells Cultured fibroblasts	eqtl	3.4e-02	+0.45	20:33047992:A:G
Brain Cerebellar Hemisphere	eqtl	3.8e-02	+0.26	20:32026700:A:T

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
184012	41.3885	690
184013	0.8633	198
184011	0.2312	148

Top tissues by expression

showing 100 of 291 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.08	gold quality
mononuclear cell	CL:0000842	99.00	gold quality
leukocyte	CL:0000738	98.99	gold quality
granulocyte	CL:0000094	98.94	gold quality
blood	UBERON:0000178	98.87	gold quality
spleen	UBERON:0002106	96.82	gold quality
bone marrow	UBERON:0002371	94.43	gold quality
vermiform appendix	UBERON:0001154	94.21	gold quality
trabecular bone tissue	UBERON:0002483	93.68	gold quality
middle frontal gyrus	UBERON:0002702	93.47	gold quality
bone marrow cell	CL:0002092	92.91	gold quality
periodontal ligament	UBERON:0008266	92.54	gold quality
frontal pole	UBERON:0002795	91.11	gold quality
upper lobe of left lung	UBERON:0008952	90.14	gold quality
upper lobe of lung	UBERON:0008948	89.68	gold quality
paraflocculus	UBERON:0005351	89.54	gold quality
right lung	UBERON:0002167	89.47	gold quality
lymph node	UBERON:0000029	89.30	gold quality
caecum	UBERON:0001153	89.19	gold quality
lung	UBERON:0002048	87.25	gold quality
palpebral conjunctiva	UBERON:0001812	87.21	gold quality
lower lobe of lung	UBERON:0008949	86.96	gold quality
layer of synovial tissue	UBERON:0007616	86.47	gold quality
decidua	UBERON:0002450	86.09	gold quality
epithelium of nasopharynx	UBERON:0001951	85.69	gold quality
right coronary artery	UBERON:0001625	85.40	gold quality
mucosa of transverse colon	UBERON:0004991	85.15	gold quality
amniotic fluid	UBERON:0000173	84.85	gold quality
gall bladder	UBERON:0002110	84.49	gold quality
Brodmann (1909) area 10	UBERON:0013541	84.33	gold quality
rectum	UBERON:0001052	82.51	gold quality
eye	UBERON:0000970	82.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.02	gold quality
omental fat pad	UBERON:0010414	81.73	gold quality
peritoneum	UBERON:0002358	81.69	gold quality
superficial temporal artery	UBERON:0001614	81.56	gold quality
synovial joint	UBERON:0002217	81.55	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.47	gold quality
small intestine Peyer’s patch	UBERON:0003454	80.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.15	gold quality
mucosa of urinary bladder	UBERON:0001259	80.06	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.91	gold quality
right adrenal gland	UBERON:0001233	79.53	gold quality
left adrenal gland	UBERON:0001234	79.51	gold quality
left uterine tube	UBERON:0001303	79.50	gold quality
small intestine	UBERON:0002108	79.47	gold quality
apex of heart	UBERON:0002098	79.25	gold quality
right adrenal gland cortex	UBERON:0035827	79.18	gold quality
left adrenal gland cortex	UBERON:0035825	79.14	gold quality
spinal cord	UBERON:0002240	79.02	gold quality
smooth muscle tissue	UBERON:0001135	78.95	gold quality
placenta	UBERON:0001987	78.94	gold quality
subcutaneous adipose tissue	UBERON:0002190	78.76	gold quality
transverse colon	UBERON:0001157	78.53	gold quality
descending thoracic aorta	UBERON:0002345	78.42	gold quality
visceral pleura	UBERON:0002401	78.36	gold quality
ileal mucosa	UBERON:0000331	78.31	gold quality
left coronary artery	UBERON:0001626	78.17	gold quality
coronary artery	UBERON:0001621	78.12	gold quality
adrenal cortex	UBERON:0001235	78.05	gold quality
duodenum	UBERON:0002114	78.01	gold quality
colonic mucosa	UBERON:0000317	77.97	gold quality
adipose tissue	UBERON:0001013	77.93	gold quality
thoracic aorta	UBERON:0001515	77.81	gold quality
connective tissue	UBERON:0002384	77.54	gold quality
ascending aorta	UBERON:0001496	77.45	gold quality
adrenal gland	UBERON:0002369	77.42	gold quality
intestine	UBERON:0000160	77.08	gold quality
tonsil	UBERON:0002372	76.96	gold quality
pleura	UBERON:0000977	76.78	gold quality
large intestine	UBERON:0000059	76.66	gold quality
colon	UBERON:0001155	76.38	gold quality
germinal epithelium of ovary	UBERON:0001304	76.34	gold quality
parietal pleura	UBERON:0002400	76.01	gold quality
nasal cavity epithelium	UBERON:0005384	75.94	silver quality
cerebellar vermis	UBERON:0004720	75.54	silver quality
urinary bladder	UBERON:0001255	75.52	gold quality
endometrium epithelium	UBERON:0004811	75.42	silver quality
mucosa of stomach	UBERON:0001199	75.25	gold quality
liver	UBERON:0002107	74.68	gold quality
tibial nerve	UBERON:0001323	74.49	gold quality
oral cavity	UBERON:0000167	74.31	gold quality
jejunal mucosa	UBERON:0000399	74.24	gold quality
sigmoid colon	UBERON:0001159	74.22	gold quality
aorta	UBERON:0000947	73.90	gold quality
right atrium auricular region	UBERON:0006631	73.82	gold quality
right lobe of liver	UBERON:0001114	73.59	gold quality
cardiac atrium	UBERON:0002081	73.29	gold quality
pericardium	UBERON:0002407	73.11	gold quality
heart	UBERON:0000948	73.00	gold quality
upper leg skin	UBERON:0004262	72.99	gold quality
heart left ventricle	UBERON:0002084	72.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	72.89	gold quality
cauda epididymis	UBERON:0004360	72.84	gold quality
anatomical system	UBERON:0000467	72.77	gold quality
multicellular organism	UBERON:0000468	72.76	gold quality
material anatomical entity	UBERON:0000465	72.73	gold quality
skin of hip	UBERON:0001554	72.73	gold quality
caput epididymis	UBERON:0004358	72.72	gold quality
cardiac ventricle	UBERON:0002082	72.68	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	495.23
E-CURD-122	yes	76.43
E-MTAB-6678	yes	27.41
E-MTAB-9221	yes	26.38
E-ANND-3	yes	25.98
E-HCAD-13	yes	24.30
E-MTAB-6701	yes	22.10
E-MTAB-9467	yes	18.73
E-MTAB-9067	yes	14.74
E-MTAB-8410	yes	14.21
E-CURD-88	yes	13.23
E-MTAB-9801	yes	6.24
E-MTAB-5061	no	498.96

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Appendix	tissue	94.2	not detected
Spleen	tissue	73.2	low
Bone marrow	tissue	51.4	medium
Lung	tissue	43.3	medium
Tonsil	tissue	36.7	low
Lymph node	tissue	36.1	low
Urinary bladder	tissue	30.5	not detected
Choroid plexus	tissue	24.9
Smooth muscle	tissue	23.5	not detected
Adipose tissue	tissue	23.0	not detected
Placenta	tissue	19.6	not detected
Small intestine	tissue	16.7	not detected
Hypothalamus	tissue	15.2
Duodenum	tissue	14.2	not detected
Thymus	tissue	13.5
Periaqueductal gray	tissue	13.5
Gallbladder	tissue	13.4	not detected
Liver	tissue	13.1	not detected
Rectum	tissue	12.7	not detected
Colon	tissue	11.9	not detected
Septum	tissue	10.7
Spinal cord	tissue	9.7
Pons	tissue	9.6
Substantia nigra	tissue	9.1
Adrenal gland	tissue	8.7	not detected
Medulla oblongata	tissue	8.4
Corpus callosum	tissue	7.0
Midbrain	tissue	6.8
Tongue	tissue	6.4
Locus coeruleus	tissue	6.4
Stomach 1	tissue	6.3	not detected
Esophagus	tissue	6.3	not detected
Thalamus	tissue	6.2
Ventral forebrain	tissue	6.2
Amygdala	tissue	6.1
Hippocampus	tissue	6.0	not detected
Breast	tissue	5.5	not detected
Skin 1	tissue	5.4	not detected
Superior colliculi	tissue	5.3
Putamen	tissue	5.2
Cervix	tissue	5.1	not detected
Basal ganglia	tissue	5.0	not detected
Hippocampal formation	tissue	5.0
Salivary gland	tissue	4.8	not detected
Seminal vesicle	tissue	4.4
Pancreas	tissue	4.3	not detected
Nucleus accumbens	tissue	4.3
Fallopian tube	tissue	4.0	not detected
Vagina	tissue	3.8	not detected
Heart muscle	tissue	3.7	not detected
Cerebral cortex	tissue	3.6	not detected
Insular cortex	tissue	3.6
Prefrontal cortex	tissue	3.5
Entorhinal cortex	tissue	3.5
Temporal cortex	tissue	3.5
Retrosplenial and cingulate cortex	tissue	3.2
Retrosplenial cortex	tissue	3.2
Motor cortex	tissue	3.1
Pituitary gland	tissue	3.0
Endometrium 1	tissue	2.9	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Lateral funiculus (white matter) (21.0), Nucleus raphe pallidus (16.9), Nucleus gracilis (14.5), Nucleus rhomboideus (14.0), Cervical spinal cord, ventral horn (13.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF6, PML, RARA, SP1, SPI1

miRNA regulators (miRDB)

Targeting HCK by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

18 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-4752	98.71	68.04	833
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-3654	96.43	66.55	646

Functional genomics

gnomAD constraint: pLI 1.79e-07, LOEUF 0.795, missense Z 1.87 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000375852 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈6% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
20:32,052,425–32,084,453	318 / 336.0	0.95	no
20:32,084,454–32,086,636	13 / 38.8	0.34	yes (p 3.5e-05)
20:32,086,637–32,101,340	160 / 237.5	0.67	no
20:32,101,341–32,101,516	77 / 85.0	0.91	no

Literature-anchored findings (GeneRIF, showing 40)

• Alternate use of a non-AUG (CUG), and an in-frame, downstream AUG translation initiation codon, results in the production of two isoforms with different subcellular localization. (PMID:10967098)
• A dominant negative form of Hck, in an interaction that is SH3 domain dependent, blocks HIV-1 Nef induced MHC class I downregulation. (PMID:11500821)
• SH3-dependent stimulation of Src-family kinase autophosphorylation without tail release from the SH2 domain in vivo (PMID:11976726)
• The interaction of the Bcr-Abl tyrosine kinase with this protein is mediated by multiple binding domains. (PMID:12592324)
• These results suggest that CSF-induced and HIV-1-mediated regulation of Hck and C/EBPbeta represent the heterogeneous susceptibility of tissue macrophages to HIV-1 infection. (PMID:12900520)
• C3G and Hck interact physically and functionally in vivo to activate kinase-dependent and caspase-mediated apoptosis, which is independent of catalytic domain of C3G (PMID:14551197)
• SRC kinases LYN & HCK let engaged b2 integrins form focal-adhesion-like structures needed for stable shear-resistant PMN adhesion. SRC-dependent outside-in signalling is needed for integrin adhesiveness triggered by a classical chemoattractant like IL-8. (PMID:14969582)
• Gab2 docking proteins in IL-6-induced proliferation and survival of multiple myeloma cells. (PMID:15010462)
• In humans, the cytoplasmic domain of ADAM15v2 strongly interacts with Lck and Hck and regulates leukocyte function. (PMID:15263807)
• HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and thereby inhibits M-CSF functions in monocytes/macrophages. (PMID:15626739)
• data support the existence of multiple active conformations of Src family member Hck kinase that may generate unique downstream signals (PMID:16210316)
• The free energy surface shows that the N-terminal end of HCK acts as a reversible two-state conformational switch coupling the catalytic domain to the regulatory modules. (PMID:16271895)
• Data suggest that the insertion/deletion polymorphism could be a functional polymorphism of the Hck gene, may contribute to COPD pathogenesis and modify COPD-related phenotypes. (PMID:17024369)
• The structure of the HckSH3:PD1 complex reveals novel features of SH3 ligand binding and yields new insights into the structural basics of SH3-ligand interactions. (PMID:17141806)
• p73 is identified as a novel substrate and interacting partner of Hck and it regulates p73 through mechanisms that are dependent on either catalytic activity or protein interaction domains. (PMID:17535448)
• hematopoietic cell kinase (hct) phosphorylates fems-like tyrosine kinase 3(FLT3) in the JM region and inhibits its maturation (PMID:17668209)
• Nef perturbs the intracellular maturation and the trafficking of nascent Fms, through a unique mechanism that required both the activation of Hck and the aberrant spatial regulation of the active Hck (PMID:17893228)
• Alternate use of a non-AUG (CUG), and an in-frame, downstream AUG translation initiation codon, results in the production of 2 isoforms in mouse and human. (PMID:1875927)
• Hck has a nonredundant function as a key downstream signaling partner for Bcr-Abl and may represent a potential drug target in CML (PMID:18794796)
• HCK and BIN1 plays critical roles in AHI-1-mediated leukemic transformation of cutaneous T-Cell Lymphoma. (PMID:19211505)
• This finding establishes an intriguing link between the pathogenesis of Nef and a newly emerging concept that the Golgi-localized Src kinases regulate the Golgi function. (PMID:19585521)
• Taken together, PKR and Hck were critical for DON-induced ribosomal recruitment of p38, its subsequent phosphorylation, and, ultimately, p38-driven proinflammatory cytokine expression. (PMID:20181660)
• Nef participates in HIV-1-induced multinucleated giant cells formation via a p61Hck- and lysosomal enzyme-dependent pathway (PMID:20488787)
• Identification and biophysical assessment of the molecular recognition mechanisms between the human haemopoietic cell kinase Src homology domain 3 and ALG-2-interacting protein X. (PMID:20670214)
• BSS-SAXS reconstruction is used to reveal the structural organization of Hck in solution and the different shifts in the equilibrium population of assembly states upon the binding of different signaling peptides (PMID:20798061)
• Data show that the structures and relative orientations of the SH2 and SH3 domains down-regulated Hck. (PMID:20810664)
• Hck activation at the Golgi apparatus causes the HIV-1 Nef-induced c-Fms proto-oncogene N-glycosylation defect. (PMID:21567396)
• Hck acts as a key regulator controlling gene expression in alternatively activated monocytes/macrophages. (PMID:21878628)
• Loss of HCK is associated with acute promyelocytic leukemia. (PMID:21993313)
• we show that Hck, has a pre-eminent role in LPS/TLR4-induced TNF and IL-6 production. (PMID:22021612)
• There were significant differences in the genotype and allele distribution of -627 G/T polymorphism in Hck gene between cases and controls. (PMID:22185326)
• the activation of Hck, Lyn and c-Src by Nef is highly conserved among all major clades of HIV-1 (PMID:22393415)
• This particular binding mode enables Hck SH3 to sense a specific non-canonical residue situated in the SH3 RT-loop of the kinase. (PMID:22641034)
• The SRC family tyrosine kinase HCK and the ETS family transcription factors SPIB and EHF regulate transcytosis across a human follicle-associated epithelium model. (PMID:23439650)
• Data indicate that combined treatment using SFK (LYN, HCK, or FGR) and c-KIT inhibitor dasatinib dasatinib and chemotherapy provides a novel approach to increasing p53 activity and enhancing targeting of acute myeloid leukemia (AML) stem cells. (PMID:23896410)
• Interaction between Nef and Hck is important for Nef-dependent modulation of viral infectivity. (PMID:24051604)
• Interaction with the Src homology (SH3-SH2) region of the Hck structures the HIV-1 Nef dimer for kinase activation and effector recruitment. (PMID:25122770)
• we provide evidence for involvement of HCK and FGR in FCRL4-mediated immunoregulation and for the functional importance of posttranslational modifications of the FCRL4 molecule. (PMID:25972488)
• HCK represents a novel target for therapeutic development in MYD88-mutated Waldenstrom macroglobulinemia and activated-B cell diffuse large B-cell lymphoma, and possibly other diseases driven by mutated MYD88. (PMID:27143257)
• three-dimensional (3D) QSAR pharmacophore models were generated for Hck based on experimentally known inhibitors. A best pharmacophore model, Hypo1, was developed with high correlation coefficient (0.975), Low RMS deviation (0.60) and large cost difference (49.31), containing three ring aromatic and one hydrophobic aliphatic feature (PMID:27485399)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hck	ENSDARG00000058647
mus_musculus	Hck	ENSMUSG00000003283
rattus_norvegicus	Hck	ENSRNOG00000009331

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), JAK2 (ENSG00000096968), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), BMX (ENSG00000102010), CSK (ENSG00000103653), TYK2 (ENSG00000105397), JAK3 (ENSG00000105639), FRK (ENSG00000111816), 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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96052) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 23 distinct phenotype terms.

Mouse phenotype (MP)	Records
atelectasis	1
thick pulmonary interalveolar septum	1
overexpanded pulmonary alveolus	1
abnormal immune system physiology	1
impaired macrophage phagocytosis	1
abnormal inflammatory response	1
lung inflammation	1
respiratory distress	1
emphysema	1
increased lung adenocarcinoma incidence	1
abnormal pulmonary alveolus morphology	1
abnormal macrophage physiology	1
abnormal neutrophil physiology	1
pulmonary hyperplasia	1
increased eosinophil cell number	1
abnormal enzyme/coenzyme activity	1
pulmonary fibrosis	1
abnormal alveolar macrophage morphology	1
increased circulating tumor necrosis factor level	1
increased interleukin-5 secretion	1
abnormal respiratory epithelium morphology	1
respiratory epithelium hypertrophy	1
decreased lung elastance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	P00523	100.0%	Diamond
Coturnix japonica	P34908	100.0%	Diamond
Bos taurus	A0JNB0	99.6%	Diamond
Sus scrofa	A1Y2K1	99.4%	Diamond
Pan troglodytes	P0C0K6	99.3%	Diamond
Xenopus laevis	P87379	98.7%	Diamond
Calliphora vicina	P11681	98.6%	Diamond
Macaca fascicularis	Q1KL86	98.0%	Diamond
Apteryx australis	P87347	96.5%	Diamond
Moloney murine sarcoma virus (STRAIN HT-1)	P07331	100.0%	Diamond
Avian retrovirus IC10	P10533	100.0%	Diamond
Avian sarcoma virus PR2257	P15054	100.0%	Diamond
Rous-associated virus type 1	P27966	100.0%	Diamond
Avian sarcoma virus S2	P14085	99.8%	Diamond
Moloney murine sarcoma virus	P00538	99.7%	Diamond
Moloney murine sarcoma virus (strain TS110)	P32593	99.7%	Diamond
Avian sarcoma virus S1	P14084	99.6%	Diamond
Feline sarcoma virus (STRAIN HARDY-ZUCKERMAN 2)	P10447	99.3%	Diamond
Gardner-Arnstein feline sarcoma virus	P00542	99.1%	Diamond
Rous sarcoma virus (strain Schmidt-Ruppin A)	P00524	99.0%	Diamond
Avian sarcoma virus RASV1441	P00525	99.0%	Diamond
Rous sarcoma virus - Prague C	P00526	99.0%	Diamond
Rous sarcoma virus (strain H-19)	P25020	99.0%	Diamond
Rous sarcoma virus (strain Schmidt-Ruppin E)	P63185	99.0%	Diamond
Y73 sarcoma virus	P00527	98.9%	Diamond
Myeloproliferative sarcoma virus (CLONE TS159)	P10421	98.8%	Diamond
Abelson murine leukemia virus	P00521	98.7%	Diamond
Moloney murine sarcoma virus (STRAIN M1)	P00537	98.0%	Diamond
Rous sarcoma virus (strain PA101T)	P31693	95.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CCM2L	protein-coding	140706
TM9SF4	protein-coding	9777
XKR7	protein-coding	343702
PLAGL2	protein-coding	5326

Protein

Protein identifiers

Tyrosine-protein kinase HCK — P08631 (reviewed: P08631)

Alternative names: Hematopoietic cell kinase, Hemopoietic cell kinase, p59-HCK/p60-HCK, p59Hck, p61Hck

All UniProt accessions (5): P08631, H0Y3C5, H7BXG4, H7C5P9, J3KPD6

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.

Subunit / interactions. Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with VAV1, WAS and RAPGEF1. This interaction stimulates its tyrosine-kinase activity. Interacts with ARRB1 and ARRB2. Interacts with ADAM15. Interacts with FASLG. Interacts with CBL. Interacts with FCGR1A; the interaction may be indirect. Interacts with IL6ST. Interacts (via SH3 domain) with ELMO1. Interacts (via SH3 domain) with TP73. Interacts with YAP1. Interacts with ABL1 and ITGB1, and thereby recruits ABL1 to activated ITGB1. Interacts (via SH3 domain) with WDCP. (Microbial infection) Interacts (via SH3 domain) with HEV ORF3 protein. (Microbial infection) Interacts (via SH3 domain) with HIV-1 Nef and Vif.

Subcellular location. Lysosome. Membrane. Cell projection. Podosome membrane. Cytoplasm. Cytosol Cell membrane. Caveola. Cell junction. Focal adhesion. Cytoskeleton. Golgi apparatus. Cytoplasmic vesicle. Nucleus Cytoplasmic vesicle. Secretory vesicle. Cytosol.

Tissue specificity. Detected in monocytes and neutrophils (at protein level). Expressed predominantly in cells of the myeloid and B-lymphoid lineages. Highly expressed in granulocytes. Detected in tonsil.

Post-translational modifications. Phosphorylated on several tyrosine residues. Autophosphorylated. Becomes rapidly phosphorylated upon activation of the immunoglobulin receptors FCGR1A and FCGR2A. Phosphorylation by the BCR-ABL fusion protein mediates activation of HCK. Phosphorylation at Tyr-411 increases kinase activity. Phosphorylation at Tyr-522 inhibits kinase activity. Kinase activity is not required for phosphorylation at Tyr-522, suggesting that this site is a target of other kinases. Ubiquitinated by CBL, leading to its degradation via the proteasome. Isoform 2 palmitoylation at position 2 requires prior myristoylation. Palmitoylation at position 3 is required for caveolar localization of isoform 2.

Disease relevance. Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity. Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation. Autoinflammation with pulmonary and cutaneous vasculitis (AIPCV) [MIM:620296] An autosomal dominant disorder characterized by cutaneous vasculitis and chronic pulmonary inflammation that evolves to fibrosis. AIPCV manifests soon after birth with petechial skin lesions, followed by progressive pulmonary involvement causing restrictive lung disease and respiratory insufficiency. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Subject to autoinhibition, mediated by intramolecular interactions involving the SH2 and SH3 domains. Kinase activity is also regulated by phosphorylation at regulatory tyrosine residues. Phosphorylation at Tyr-411 is required for optimal activity. Phosphorylation at Tyr-522 inhibits kinase activity. Inhibited by PP1 and A-770041.

Domain organisation. The SH3 domain mediates binding to HIV-1 Nef.

Induction. Up-regulated during myeloid cell differentiation. The highest levels are detected in fully differentiated phagocytes. Up-regulated by IL2.

Miscellaneous. Initiates from a CTG codon. Initiates from a CTG codon.

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

Isoforms (4)

UniProt ID	Names	Canonical?
P08631-1	1, p60-HCK, p61Hck	yes
P08631-2	2, p59-HCK, p59Hck
P08631-3	3
P08631-4	4

RefSeq proteins (6): NP_001165600, NP_001165601, NP_001165602, NP_001165603, NP_001165604, NP_002101* (*=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
IPR035851	HCK_SH2	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)

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

UniProt features (102 total): strand 29, helix 25, mutagenesis site 9, modified residue 7, sequence conflict 6, sequence variant 5, turn 5, lipid moiety-binding region 3, domain 3, initiator methionine 2, splice variant 2, binding site 2, chain 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

showing 30 of 42 structures by resolution:

PDB	Title	Method	Resolution (Å)
5H0B	Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor …	X-RAY DIFFRACTION	1.65
5ZJ6	Crystal structure of HCK kinase complexed with a pyrrolo-pyrimidine inhibitor …	X-RAY DIFFRACTION	1.7
5H0H	Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor …	X-RAY DIFFRACTION	1.72
5H0G	Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor …	X-RAY DIFFRACTION	1.8
9BYJ	Crystal Structure of Hck in complex with the Src-family kinase inhibitor A-419259	X-RAY DIFFRACTION	1.8
4U5W	Crystal Structure of HIV-1 Nef-SF2 Core Domain in Complex with the Src Family Kinase Hck …	X-RAY DIFFRACTION	1.86
5H09	Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor …	X-RAY DIFFRACTION	1.95
1QCF	CRYSTAL STRUCTURE OF HCK IN COMPLEX WITH A SRC FAMILY-SELECTIVE TYROSINE KINASE INHIBITOR	X-RAY DIFFRACTION	2
2HK5	Hck Kinase in Complex with Lck targetted Inhibitor PG-1009247	X-RAY DIFFRACTION	2
3REA	HIV-1 Nef protein in complex with engineered Hck-SH3 domain	X-RAY DIFFRACTION	2
4ORZ	HIV-1 Nef protein in complex with single domain antibody sdAb19 and an engineered Hck SH3 …	X-RAY DIFFRACTION	2
5H0E	Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor …	X-RAY DIFFRACTION	2.1
2C0T	Src family kinase Hck with bound inhibitor A-641359	X-RAY DIFFRACTION	2.15
3VS3	Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor …	X-RAY DIFFRACTION	2.17
3VRZ	Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor …	X-RAY DIFFRACTION	2.22
9Y58	Nef SF2 dimerization mutant bound to Hck SH3	X-RAY DIFFRACTION	2.25
2C0I	Src family kinase Hck with bound inhibitor A-420983	X-RAY DIFFRACTION	2.3
9Y9K	HIV-1 Nef SF2 Core Domain Bound To The Human Hck SH3 Domain	X-RAY DIFFRACTION	2.34
3RBB	HIV-1 NEF protein in complex with engineered HCK SH3 domain	X-RAY DIFFRACTION	2.35
3VS6	Crystal structure of HCK complexed with a pyrazolo-pyrimidine inhibitor tert-butyl …	X-RAY DIFFRACTION	2.37
3VS1	Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor …	X-RAY DIFFRACTION	2.46
3VRY	Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor …	X-RAY DIFFRACTION	2.48
1AD5	SRC FAMILY KINASE HCK-AMP-PNP COMPLEX	X-RAY DIFFRACTION	2.6
1BU1	SRC FAMILY KINASE HCK SH3 DOMAIN	X-RAY DIFFRACTION	2.6
3VS2	Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor …	X-RAY DIFFRACTION	2.61
3NHN	Crystal structure of the SRC-family kinase HCK SH3-SH2-linker regulatory region	X-RAY DIFFRACTION	2.61
8F2P	Nef SF2 dimerization mutant bound to Hck SH3	X-RAY DIFFRACTION	2.63
3VS4	Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor …	X-RAY DIFFRACTION	2.75
5NUH	Crystal structure of SIVmac239 Nef bound to an engineered Hck SH3 domain	X-RAY DIFFRACTION	2.78
2C0O	Src family kinase Hck with bound inhibitor A-770041	X-RAY DIFFRACTION	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08631-F1	83.93	0.68

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 4ORZ

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, Predicted intracellular proteins, Disease related genes, Potential drug targets

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; cytosol; plasma membrane

Antibody reliability (HPA): IH approved · IF supported

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)

Position	Role
381	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
268–276	ATP
290	ATP

Post-translational modifications (10)

Type	Positions
Phosphothreonine	36, 202
N-myristoyl glycine	2, 2
S-palmitoyl cysteine	3
Phosphotyrosine	51, 209, 411, 522
Phosphoserine	462

Mutagenesis-validated functional residues (9)

Position	Phenotype
3	slight palmitoylation, cytoplasmic and caveolar localization; in isoform 1;.
3	abolishes palmitoylation and localization at the cell membrane.
23	myristoylation and palmitoylation are abolished, leading to entirely cytoplasmic localization; in isoform 2.
24	palmitoylation is abolished, some cytoplasmic and no calveolar localization; in isoform 2.
290	loss of kinase activity.
305	loss of kinase activity.
381	loss of kinase activity.
411	reduced catalytic activity and higher affinity for target peptides.
522	constitutively activated kinase, leading to cellular transformation.

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 28; 14 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

28 pathways:

ID	Pathway	Evidence
R-HSA-9664323	FCGR3A-mediated IL10 synthesis ⚕	curated
R-HSA-9664422	FCGR3A-mediated phagocytosis ⚕	curated
R-HSA-164944	Nef and signal transduction ⚕	curated
R-HSA-2029481	FCGR activation	curated
R-HSA-9662851	Anti-inflammatory response favouring Leishmania parasite infection ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-162906	HIV Infection ⚕	—
R-HSA-162909	Host Interactions of HIV factors ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9658195	Leishmania infection ⚕	—
R-HSA-9664433	Leishmania parasite growth and survival ⚕	—
R-HSA-9664417	Leishmania phagocytosis ⚕	—
R-HSA-9664407	Parasite infection ⚕	—
R-HSA-9824443	Parasitic Infection Pathways ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-9607240	FLT3 Signaling	—
R-HSA-9706374	FLT3 signaling through SRC family kinases	electronic
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis	—
R-HSA-168256	Immune System	—
R-HSA-9705462	Inactivation of CSF3 (G-CSF) signaling	electronic
R-HSA-168249	Innate Immune System	—
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling	—
R-HSA-912631	Regulation of signaling by CBL	electronic
R-HSA-9680350	Signaling by CSF1 (M-CSF) in myeloid cells	electronic
R-HSA-9674555	Signaling by CSF3 (G-CSF)	electronic
R-HSA-449147	Signaling by Interleukins	—
R-HSA-164952	The role of Nef in HIV-1 replication and disease pathogenesis	—

MSigDB gene sets: 546 (showing top): GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, MODULE_169, GOBP_REGULATION_OF_PODOSOME_ASSEMBLY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, MODULE_45, BIOCARTA_BARRESTIN_SRC_PATHWAY

GO Biological Process (34): leukocyte migration involved in immune response (GO:0002522), innate immune response-activating signaling pathway (GO:0002758), negative regulation of inflammatory response to antigenic stimulus (GO:0002862), protein phosphorylation (GO:0006468), inflammatory response (GO:0006954), cell adhesion (GO:0007155), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), integrin-mediated signaling pathway (GO:0007229), mesoderm development (GO:0007498), positive regulation of cell population proliferation (GO:0008284), regulation of cell shape (GO:0008360), peptidyl-tyrosine phosphorylation (GO:0018108), cytokine-mediated signaling pathway (GO:0019221), cell differentiation (GO:0030154), positive regulation of actin filament polymerization (GO:0030838), lipopolysaccharide-mediated signaling pathway (GO:0031663), regulation of actin cytoskeleton organization (GO:0032956), intracellular signal transduction (GO:0035556), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), negative regulation of apoptotic process (GO:0043066), leukocyte degranulation (GO:0043299), respiratory burst after phagocytosis (GO:0045728), protein autophosphorylation (GO:0046777), regulation of inflammatory response (GO:0050727), regulation of phagocytosis (GO:0050764), type II interferon-mediated signaling pathway (GO:0060333), regulation of podosome assembly (GO:0071801), immune system process (GO:0002376), exocytosis (GO:0006887), phagocytosis (GO:0006909), response to stress (GO:0006950), innate immune response (GO:0045087), leukocyte migration (GO:0050900), cellular response to lipid (GO:0071396)

GO Molecular Function (11): phosphotyrosine residue binding (GO:0001784), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), signaling receptor binding (GO:0005102), ATP binding (GO:0005524), 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 (16): nucleus (GO:0005634), lysosome (GO:0005764), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), caveola (GO:0005901), focal adhesion (GO:0005925), cytoplasmic side of plasma membrane (GO:0009898), transport vesicle (GO:0030133), cell projection (GO:0042995), cytoplasm (GO:0005737), actin filament (GO:0005884), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), membrane raft (GO:0045121)

Reactome top-level categories

15 top-level categories:

Category	Pathways
Cytokine Signaling in Immune system	3
Immune System	2
The role of Nef in HIV-1 replication and disease pathogenesis	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
Interleukin-3, Interleukin-5 and GM-CSF signaling	1
Anti-inflammatory response favouring Leishmania parasite infection	1
Leishmania phagocytosis	1
Signaling by CSF3 (G-CSF)	1
FLT3 Signaling	1
Viral Infection Pathways	1
HIV Infection	1
Host Interactions of HIV factors	1
Innate Immune System	1
Signaling by Interleukins	1
Disease	1

GO top-level categories

showing 60 of 74 GO namespaces:

Category	Terms
cellular anatomical structure	4
cell surface receptor signaling pathway	3
cytoplasm	3
intracellular anatomical structure	2
binding	2
intracellular membrane-bounded organelle	2
endomembrane system	2
immune effector process	1
immune response	1
leukocyte migration	1
activation of innate immune response	1
immune response-activating signaling pathway	1
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1
negative regulation of immune response	1
phosphorylation	1
protein modification process	1
defense response	1
cellular process	1
enzyme-linked receptor protein signaling pathway	1
tissue development	1
animal gross anatomical part developmental process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of cell morphogenesis	1
regulation of biological quality	1
protein phosphorylation	1
cellular response to cytokine stimulus	1
cellular developmental process	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
cellular response to lipopolysaccharide	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
signal transduction	1
Fc receptor mediated stimulatory signaling pathway	1
phagocytosis	1
Fc-gamma receptor signaling pathway	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
protein phosphorylated amino acid binding	1
protein kinase activity	1
protein tyrosine kinase activity	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion 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
transferase activity, transferring phosphorus-containing groups	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 18 of 61 annotations. The rest are phylogenetic / computational / electronic (IEA).

18 experimentally-supported GO terms:

GO term	NS	Evidence
intracellular signal transduction	BP	mutant phenotype
negative regulation of apoptotic process	BP	mutant phenotype
peptidyl-tyrosine phosphorylation	BP	mutant phenotype
positive regulation of cell population proliferation	BP	mutant phenotype
protein autophosphorylation	BP	mutant phenotype
regulation of actin cytoskeleton organization	BP	mutant phenotype
regulation of cell shape	BP	mutant phenotype
regulation of phagocytosis	BP	mutant phenotype
regulation of podosome assembly	BP	direct assay
caveola	CC	direct assay
cytoplasmic side of plasma membrane	CC	mutant phenotype
cytosol	CC	direct assay
focal adhesion	CC	mutant phenotype
lysosome	CC	direct assay
plasma membrane	CC	direct assay
lipid binding	MF	experiment
phosphotyrosine residue binding	MF	physical interaction
protein tyrosine kinase activity	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 2,032 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HCK	ARL2	P36404	618
HCK	PTPRA	P18433	596
HCK	UNC119	Q13432	560
HCK	SH3KBP1	Q96B97	559
HCK	CCKBR	P32239	552
HCK	TM9SF4	Q92544	513
HCK	CBL	P22681	510
HCK	PTGES3	Q15185	497
HCK	TCF15	Q12870	496
HCK	CDC37	Q16543	490
HCK	STIP1	P31948	490
HCK	TCIRG1	Q13488	487
HCK	PACS1	Q6VY07	474
HCK	PTPN1	P18031	465
HCK	PLAGL2	Q9UPG8	463

IntAct

Human interaction partners of HCK in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 66 partners by confidence:

Partner	Interaction type	MIscore	Records
KHDRBS1	physical association	0.780	4
WAS	physical association	0.720	8
ADAM15	direct interaction	0.710	4
PDCD6IP	physical association	0.710	4
SOS1	physical association	0.690	4
HSP90AB1	physical association	0.670	1
EGFR	physical association	0.650	3
ASAP1	physical association	0.610	2
GOPC	physical association	0.560	3
KRT40	physical association	0.560	3
KRTAP10-9	physical association	0.560	3
MTUS2	physical association	0.560	3
NOTCH2NLA	physical association	0.560	3
ADAM12	direct interaction	0.560	2
ELMO1	physical association	0.520	4
PAK2	physical association	0.520	2
NLRP12	physical association	0.510	4
ALOX5	phosphorylation reaction	0.440	2
ERBB3	direct interaction	0.440	2
KIT	direct interaction	0.440	2
ABI1	direct interaction	0.440	1
ADAM19	direct interaction	0.440	1
ADAM22	direct interaction	0.440	1
AR	direct interaction	0.440	1
GAB1	direct interaction	0.440	1
K15-M	direct interaction	0.440	1
MET	direct interaction	0.440	1
PRRG4	direct interaction	0.440	1
SPRR2A	direct interaction	0.440	1
ABL1	physical association	0.400	5

BioGRID (216 interactions; top human partners by supporting records): CBL (Affinity Capture-Western; 7 records), ADAM15 (Biochemical Activity; 3 records), CDC37 (Affinity Capture-Western; 3 records), EGFR (Two-hybrid; 3 records), HSP90AA1 (Affinity Capture-MS; 3 records), KHDRBS1 (Protein-peptide; 3 records), LYN (Affinity Capture-MS; 3 records), RAPGEF1 (Two-hybrid; 3 records), SRC (Affinity Capture-MS; 3 records), TP73 (Affinity Capture-Western; 3 records), BCR (Affinity Capture-Western; 2 records), BTK (Reconstituted Complex; 2 records), CSF3R (Affinity Capture-Western; 2 records), ELMO1 (Affinity Capture-Western; 2 records), ERBB3 (Reconstituted Complex; 2 records)

SIGNOR signaling

showing 19 of 37 signaling interactions:

A	Effect	B	Mechanism
HCK	up-regulates	ADAM15	phosphorylation
HCK	unknown	ADAM15	phosphorylation
HCK	up-regulates	ELMO1	phosphorylation
HCK	up-regulates	RAPGEF1	phosphorylation
HCK	“up-regulates activity”	HCK	phosphorylation
HCK	“up-regulates activity”	BCR-ABL	phosphorylation
HCK	“down-regulates activity”	TBK1	phosphorylation
HCK	“up-regulates activity”	GLI1	phosphorylation
HCK	up-regulates	BCR-ABL	phosphorylation
HCK	down-regulates	HCK	phosphorylation
HCK	up-regulates	HCK	phosphorylation
HCK	unknown	CBL	phosphorylation
HCK	“up-regulates activity”	PLCG1	phosphorylation
HCK	“up-regulates activity”	PLCG2	phosphorylation
HCK	“up-regulates activity”	CSF3R	phosphorylation
HCK	“up-regulates activity”	STAT3	phosphorylation
HCK	“up-regulates activity”	WAS	phosphorylation
GNAI1	“up-regulates activity”	HCK	binding
GNAS	“up-regulates activity”	HCK	binding

Protein complexes (CORUM) (5)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

5 complexes by size:

Complex	Subunits	Members
★ FCER1G-FCGR1A-HCK complex	3	FCER1G, FCGR1A, HCK
★ HCK-NLRP12 complex	2	HCK, NLRP12
★ HCK-SKAP2 complex	2	HCK, SKAP2
★ HCK-TP73 complex	2	HCK, TP73
★ HCK-TBK1 complex	2	HCK, TBK1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 66 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
Constitutive Signaling by EGFRvIII	5	62.6×	8e-07
Signaling by ERBB2 ECD mutants	5	58.9×	9e-07
DAP12 signaling	8	51.7×	9e-10
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	5	50.1×	1e-06
Signaling by ALK	5	50.1×	1e-06
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	45.5×	2e-06
Signaling by ERBB2 KD Mutants	6	44.5×	4e-07
Downstream signal transduction	6	40.1×	7e-07

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	9	37.2×	2e-09
cell surface receptor protein tyrosine kinase signaling pathway	8	23.2×	5e-07
T cell receptor signaling pathway	9	22.8×	8e-08
phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	21.1×	7e-05
male gonad development	5	13.0×	3e-03
actin filament organization	5	9.9×	6e-03
cell migration	9	9.2×	7e-05
intracellular signal transduction	10	6.3×	3e-04

Disease & clinical

Genetic variants

Variant evidence for HCK: 120 ClinVar records (2 pathogenic / likely pathogenic); 7 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	72
Likely benign	20
Benign	7

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
809243	NM_002110.5(HCK):c.1555G>T (p.Glu519Ter)	Likely pathogenic	criteria provided, single submitter	1
2446380	NM_002110.5(HCK):c.1545C>A (p.Tyr515Ter)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore HCK’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 1,166):

Position(s)	Effect	Δscore	Sites
20:32071783–32071784	donor_loss	1.0000	5
20:32073317–32073318	acceptor_loss	1.0000	4
20:32073819	donor_loss	1.0000	2
20:32074613	acceptor_gain	1.0000
20:32074621–32074622	acceptor_loss	1.0000	4
20:32074722–32074723	donor_loss	1.0000	3
20:32083888	acceptor_gain	1.0000
20:32083892–32083893	acceptor_loss	1.0000	5
20:32084531	donor_gain	1.0000
20:32086617	acceptor_gain	1.0000

AlphaMissense

1,566 missense substitutions predicted likely pathogenic (of 3,472 scored), across 343 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M369	9	0.973	0.998
M309	9	0.947	0.998
M336	9	0.870	0.992
D381	8	0.999	1.000
D399	8	0.999	1.000
H379	8	0.998	1.000
N386	8	0.998	1.000
D439	8	0.998	0.999
H197	8	0.995	0.999
F400	8	0.993	0.999
F302	8	0.989	0.999
F419	8	0.988	0.999
F273	8	0.987	1.000
F504	8	0.986	0.999
F434	8	0.982	1.000
H314	8	0.954	0.990
D96	8	0.940	0.976
F443	8	0.938	0.996
D513	8	0.934	0.980
S173	8	0.914	0.995

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:142370 | disease phenotypes: MIM:620296

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
autoinflammation with pulmonary and cutaneous vasculitis	Moderate	Autosomal dominant	3

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
Autoinflammatory disorders	amber
Primary immunodeficiency or monogenic inflammatory bowel disease	amber
Pulmonary Fibrosis, Familial	amber
Rare genetic inflammatory skin disorders	amber

Mondo (1): autoinflammation with pulmonary and cutaneous vasculitis (MONDO:0957204)

HPO phenotypes

12 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000967	Petechiae
HP:0000979	Purpura
HP:0001744	Splenomegaly
HP:0001903	Anemia
HP:0002091	Restrictive ventilatory defect
HP:0002240	Hepatomegaly
HP:0002788	Recurrent upper respiratory tract infections
HP:0002878	Respiratory failure
HP:0003623	Neonatal onset
HP:0006515	Interstitial pneumonitis
HP:0200029	Vasculitis in the skin

GWAS associations

7 associations:

Study	Trait	p-value
GCST90013406_103	Liver enzyme levels (alkaline phosphatase)	4e-14
GCST001725_63	Inflammatory bowel disease	6e-10
GCST003720_22	Migraine	1e-8
GCST010988_192	Adult body size	1e-8
GCST010796_1004	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-8
GCST007611_10	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	4e-8
GCST010796_1005	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-8

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004327	electrocardiography
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363074 (PROTEIN FAMILY), CHEMBL3234 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the HCK protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
BOSUTINIB	Small molecule	4

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes HCK — the drug acts on the assembly or class, not necessarily on this subunit alone.

5 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
DASATINIB ANHYDROUS	SRC	10	4
ENMD-981693	SRC	10	2
ILORASERTIB	SRC	10	2
TG100-801	SRC	10	2
XL-228	SRC	10	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 619,431 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 61 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL1173655	AFATINIB	4	15,878
CHEMBL3545311	BRIGATINIB	4	5,988
CHEMBL2105717	CABOZANTINIB	4	11,799
CHEMBL2028663	DABRAFENIB	4	13,060
CHEMBL5416410	DASATINIB	4	674
CHEMBL1421	DASATINIB ANHYDROUS	4	55,947
CHEMBL553	ERLOTINIB	4	109,860
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL939	GEFITINIB	4	119,425
CHEMBL3301622	GILTERITINIB	4	2,542
CHEMBL1873475	IBRUTINIB	4	8,363
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL180022	NERATINIB	4	9,891
CHEMBL255863	NILOTINIB	4	39,362
CHEMBL502835	NINTEDANIB	4	8,978
CHEMBL477772	PAZOPANIB	4	16,241
CHEMBL1171837	PONATINIB	4	9,435
CHEMBL1336	SORAFENIB	4	87,476
CHEMBL535	SUNITINIB	4	80,232
CHEMBL24828	VANDETANIB	4
CHEMBL483158	ALISERTIB	3
CHEMBL415049	BARASERTIB	3
CHEMBL377300	BRIVANIB	3
CHEMBL31965	CANERTINIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL1908391	MASITINIB	3
CHEMBL572881	MOTESANIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL217092	SARACATINIB	3
CHEMBL3544983	TESEVATINIB	3
CHEMBL495727	AT-9283	2
CHEMBL3545396	BMS-690514	2
CHEMBL402548	DANUSERTIB	2
CHEMBL215152	DEFOSBARASERTIB	2
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1230609	FORETINIB	2
CHEMBL3989914	GLESATINIB	2
CHEMBL3039525	GOLVATINIB	2
CHEMBL3695568	JNJ-49095397	2
CHEMBL564829	MILCICLIB	2
CHEMBL119385	NEFLAMAPIMOD	2
CHEMBL607707	PELITINIB	2
CHEMBL475251	R-406	2
CHEMBL558752	RAF-265	2
CHEMBL1738757	REBASTINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL572878	TOZASERTIB	2
CHEMBL574737	UCN-01	2
CHEMBL551064	AEW-541	1
CHEMBL3545360	ASP-3026	1
CHEMBL574738	AST-487	1
CHEMBL2041933	AZD-7762	1
CHEMBL482967	CYC-116	1
CHEMBL1908397	KW-2449	1
CHEMBL259084	MLN-8054	1
CHEMBL1084546	PF-00562271	1
CHEMBL3544932	TAK-901	1

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Src family

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
compound 2 [PMID: 15546730]	Inhibition	8.7	pIC50
eCF506	Inhibition	8.55	pIC50
PP121	Inhibition	8.1	pIC50
pexmetinib	Inhibition	7.59	pIC50
ibrutinib	Inhibition	7.54	pIC50

Binding affinities (BindingDB)

320 measured of 487 human assays (503 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL3808884	EC50	0.04 nM
3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide	EC50	0.05 nM
CHEMBL4075002	IC50	0.257 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
AP-26113	IC50	0.37 nM
N-(2,6-dimethylphenyl)-2-[[2-[[(3S)-1-propanoylpyrrolidin-3-yl]amino]pyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	IC50	0.5 nM	US-10844077: Thiazolyl-containing compounds for treating proliferative diseases
N-(2,6-dimethylphenyl)-2-[[2-[[(3S)-1-prop-2-enoylpyrrolidin-3-yl]amino]pyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	IC50	0.6 nM	US-10844077: Thiazolyl-containing compounds for treating proliferative diseases
1-[(2R)-2-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one	IC50	0.8 nM	US-20240317756: INHIBITORS OF BRUTON’S TYROSINE KINASE
Jak Inhibitor 1	EC50	1 nM
N-(2-chloro-6-methylphenyl)-2-[[1-[(1-prop-2-enoylpyrrolidin-3-yl)methyl]pyrazol-3-yl]amino]-1,3-thiazole-5-carboxamide	IC50	1.1 nM	US-10844077: Thiazolyl-containing compounds for treating proliferative diseases
5-(2-fluoro-4-phenoxyphenyl)-7-[4-(4-methylpiperazin-1-yl)cyclohexyl]imidazo[5,1-f][1,2,4]triazin-4-amine	IC50	1.1 nM	US-11963960: Compounds for treating or inhibiting recurrence of acute myeloid leukemia
N-[4-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexyl]prop-2-enamide	IC50	1.1 nM	US-9181263: Inhibitors of bruton’s tyrosine kinase
CHEMBL5271284	IC50	1.2 nM
N-(2,6-dimethylphenyl)-2-[[2-[[(3R)-1-prop-2-enoylpyrrolidin-3-yl]amino]pyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	IC50	1.38 nM	US-10844077: Thiazolyl-containing compounds for treating proliferative diseases
N-(2-chloro-6-methylphenyl)-2-[[6-(morpholin-4-ylmethyl)-2-[[(3S)-1-prop-2-enoylpyrrolidin-3-yl]amino]pyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	IC50	1.61 nM	US-10844077: Thiazolyl-containing compounds for treating proliferative diseases
N-(2,6-dimethylphenyl)-2-[[6-(morpholin-4-ylmethyl)-2-[[(3S)-1-prop-2-enoylpyrrolidin-3-yl]amino]pyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	IC50	1.63 nM	US-10844077: Thiazolyl-containing compounds for treating proliferative diseases
Staurosporine	KD	1.7 nM
N-(2-chloro-6-methylphenyl)-2-[[2-[[(3S)-1-prop-2-enoylpyrrolidin-3-yl]amino]pyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	IC50	1.74 nM	US-10844077: Thiazolyl-containing compounds for treating proliferative diseases
N-(2,6-dimethylphenyl)-2-[[2-[[(3R)-1-prop-2-enoylpiperidin-3-yl]amino]pyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	IC50	1.9 nM	US-10844077: Thiazolyl-containing compounds for treating proliferative diseases
3-(7-amino-3-(4-(4-methylpiperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-6-yl)phenol	IC50	2 nM
CHEMBL5415503	IC50	2.1 nM
CHEMBL4210294	IC50	2.6 nM
4-(2,6-dichloro-phenyl)-8-[4-(2-diethylamino-ethoxy)-phenylamino]-1,2-dihydro-3a,7,9,9b-tetraaza-cyclopenta[a]naphthalen-3-one	IC50	3 nM
CHEMBL4204499	IC50	3.1 nM
CEP-701	KD	3.4 nM
CHEMBL4095434	IC50	3.5 nM
N-(3-(1-(6-aminopyrimidin-4-yl)-1H-benzo[d]imidazol-2-ylamino)-4-methylphenyl)-5-tert-butylthiophene-2-carboxamide	IC50	4 nM
3-(2-Fluoro-4-phenoxyphenyl)-1-((trans)-4-(4-methylpiperazin-1-yl) cyclohexyl)-1H-pyrazolo [3,4-d] pyrimidin-4-amine	IC50	4.1 nM	US-11963960: Compounds for treating or inhibiting recurrence of acute myeloid leukemia
CHEMBL4214689	IC50	5 nM
CHEMBL4218162	IC50	5 nM
5-(2-fluoro-4-phenoxyphenyl)-7-[4-[(3S)-3-methylpiperazin-1-yl]cyclohexyl]imidazo[5,1-f][1,2,4]triazin-4-amine	IC50	5 nM	US-11963960: Compounds for treating or inhibiting recurrence of acute myeloid leukemia
3-(2-fluoro-4-phenoxyphenyl)-1-[4-[(3S)-3-methylpiperazin-1-yl]cyclohexyl]pyrazolo[3,4-d]pyrimidin-4-amine	IC50	5.1 nM	US-11963960: Compounds for treating or inhibiting recurrence of acute myeloid leukemia
4-[4-[(5-tert-butyl-2-quinolin-6-ylpyrazol-3-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	IC50	5.5 nM
N-(2-chloro-6-methylphenyl)-2-[[2-[(1-prop-2-enoylazepan-3-yl)amino]pyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	IC50	5.52 nM	US-10844077: Thiazolyl-containing compounds for treating proliferative diseases
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	IC50	5.6 nM	US-8822500: Tyrosine kinase inhibitors
CHEMBL5278149	IC50	5.7 nM
Staurosporine, 8	IC50	6.5 nM
CHEMBL4087733	IC50	7.6 nM
CHEMBL4465866	KD	8 nM
CHEMBL4576489	KD	8 nM
CHEMBL4071932	IC50	8.9 nM
1-[3-[[4-[(5-phenoxy-[1,3]thiazolo[5,4-b]pyridin-2-yl)amino]pyrimidin-2-yl]amino]azepan-1-yl]prop-2-en-1-one	IC50	9.06 nM	US-10844077: Thiazolyl-containing compounds for treating proliferative diseases
CHEMBL3586447	IC50	11 nM
CHEMBL4213227	IC50	11 nM
N-[4-[4-[[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]carbamoylamino]naphthalen-1-yl]oxy-2-pyridinyl]-2-methoxyacetamide	IC50	12 nM	US-9724347: 1-pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl)oxy)napththalen-1-yl) ureas as P38 MAP knase inhibitors
CHEMBL4203527	IC50	12 nM
CHEMBL4061078	IC50	13 nM
CHEMBL4203767	IC50	13 nM
CHEMBL4093003	IC50	14 nM
N-[4-[[(2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	KI	15 nM	US-10981896: Indolinone derivatives as inhibitors of maternal embryonic leucine zipper kinase

ChEMBL bioactivities

624 potent at pChembl≥5 of 653 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.96	IC50	0.11	nM	PONATINIB
9.74	IC50	0.18	nM	CHEMBL1241676
9.59	IC50	0.257	nM	CHEMBL4075002
9.59	IC50	0.26	nM	CHEMBL4075002
9.50	Ki	0.3162	nM	DASATINIB
9.46	Kd	0.35	nM	DASATINIB
9.40	IC50	0.4	nM	CHEMBL45177
9.37	IC50	0.4266	nM	CHEMBL45177
9.37	IC50	0.43	nM	CHEMBL45177
9.23	IC50	0.59	nM	CHEMBL6030654
9.23	IC50	0.59	nM	CHEMBL5941829
9.14	IC50	0.73	nM	CHEMBL5760397
9.00	IC50	1	nM	CHEMBL3647967
8.79	IC50	1.64	nM	CHEMBL5846343
8.74	IC50	1.8	nM	CHEMBL4208645
8.72	IC50	1.9	nM	STAUROSPORINE
8.71	IC50	1.94	nM	CHEMBL5829834
8.70	IC50	2	nM	CHEMBL364623
8.70	IC50	2	nM	CHEMBL1090979
8.70	IC50	2	nM	CHEMBL1241484
8.70	IC50	2	nM	CHEMBL1241581
8.65	IC50	2.23	nM	STAUROSPORINE
8.62	IC50	2.42	nM	CHEMBL5854945
8.61	IC50	2.43	nM	CHEMBL6027766
8.55	IC50	2.8	nM	CHEMBL4568087
8.52	IC50	3	nM	CHEMBL3695574
8.52	IC50	3	nM	CHEMBL3695593
8.52	IC50	3	nM	CHEMBL1214131
8.52	IC50	3	nM	CHEMBL3695569
8.52	IC50	3	nM	CHEMBL3695579
8.52	IC50	3	nM	CHEMBL3695583
8.52	IC50	3	nM	CHEMBL1214132
8.52	IC50	3	nM	CHEMBL3695592
8.52	IC50	3	nM	CHEMBL1214134
8.52	IC50	3	nM	CHEMBL4515441
8.52	IC50	3.03	nM	STAUROSPORINE
8.52	IC50	3	nM	CHEMBL4798527
8.49	IC50	3.2	nM	BOSUTINIB
8.48	Kd	3.3	nM	CHEMBL386051
8.47	Kd	3.4	nM	BOSUTINIB
8.46	IC50	3.467	nM	CHEMBL4095434
8.46	IC50	3.5	nM	CHEMBL4095434
8.43	IC50	3.7	nM	IBRUTINIB
8.43	IC50	3.7	nM	CHEMBL4066401
8.40	IC50	4	nM	CHEMBL3695578
8.40	IC50	4	nM	CHEMBL3695591
8.40	IC50	4	nM	CHEMBL3695586
8.40	IC50	4	nM	CHEMBL3695580
8.40	IC50	4	nM	CHEMBL3695581
8.40	IC50	4	nM	CHEMBL3695577

PubChem BioAssay actives

494 with measured affinity, of 1933 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
Ponatinib	1716394: Binding affinity to human HCK using KVEKIGEGTYGVVYK as substrate by radiometric hotspot kinase assay	ic50	0.0001	uM
5-(4-amino-1-cyclopentylpyrazolo[3,4-d]pyrimidin-3-yl)-2-chlorophenol	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0002	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435311: Binding constant for HCK kinase domain	kd	0.0003	uM
5-(4-phenoxyphenyl)-7-[4-(4-propan-2-ylpiperazin-1-yl)cyclohexyl]pyrrolo[2,3-d]pyrimidin-4-amine	1487300: Inhibition of HCK (unknown origin)	ic50	0.0003	uM
7-[4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine	1366202: Inhibition of recombinant human HCK SH3-SH2-KD (75 to 526 residues) after 20 mins by mobility shift assay	ic50	0.0004	uM
1-[4-(4-methylpiperazin-1-yl)cyclohexyl]-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-4-amine	1872714: Inhibition of HCK (unknown origin)	ic50	0.0005	uM
N-[3-[2-[4-(2-aminoethoxy)anilino]quinazolin-6-yl]-4-methylphenyl]-3-(trifluoromethyl)benzamide	1799897: Fluorescence Assay from Article 10.1021/cb300623a: “A Hexylchloride-Based Catch-and-Release System for Chemical Proteomic Applications.”	ic50	0.0005	uM
tert-butyl N-[4-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]carbamate	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0010	uM
(2S)-2-[[4-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl]amino]-3-hydroxypropanoic acid	1366202: Inhibition of recombinant human HCK SH3-SH2-KD (75 to 526 residues) after 20 mins by mobility shift assay	ic50	0.0018	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	1531717: Inhibition of human HCK using KVEKIGEGTYGVVYK as substrate by [gamma-33P]-ATP assay	ic50	0.0019	uM
N-(2-chloro-6-methylphenyl)-2-[(2,6-dimethylpyrimidin-4-yl)amino]-1,3-thiazole-5-carboxamide	240535: inhibitory activity against Hck kinase	ic50	0.0020	uM
3-(4-amino-3-methoxyphenyl)-1-cyclopentylpyrazolo[3,4-d]pyrimidin-4-amine	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0020	uM
5-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-2-chlorophenol	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0020	uM
N-[(1R,2S)-2-aminocyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637083: Inhibition of full-length human N-terminal GST-tagged HCK expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0028	uM
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	1734744: Inhibition of human HCK (230 to 497 residues) using GGMEDIYFEFMGGKKK as substrate incubated for 40 mins in presence of [gamma33P-ATP] by radiometric scintillation counting analysis	ic50	0.0030	uM
N-(2-chloro-6-methylphenyl)-2-[4-(4-methylpiperazin-1-yl)anilino]-4-[2-(prop-2-enoylamino)anilino]pyrimidine-5-carboxamide	1560506: Inhibition of HCK (unknown origin)	ic50	0.0030	uM
Bosutinib	507439: Inhibition of HCK	ic50	0.0032	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624857: Binding constant for HCK kinase domain	kd	0.0033	uM
2-[4-[4-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl]piperazin-1-yl]ethanol	1487300: Inhibition of HCK (unknown origin)	ic50	0.0035	uM
2-[[4-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl]amino]acetic acid	1366202: Inhibition of recombinant human HCK SH3-SH2-KD (75 to 526 residues) after 20 mins by mobility shift assay	ic50	0.0037	uM
Ibrutinib	1714868: Inhibition of HCK (unknown origin)	ic50	0.0037	uM
5-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-2-bromophenol	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0040	uM
(2S)-2-[[4-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl]amino]-4-methylpentanoic acid	1366202: Inhibition of recombinant human HCK SH3-SH2-KD (75 to 526 residues) after 20 mins by mobility shift assay	ic50	0.0044	uM
3-(4-amino-1-cyclopentylpyrazolo[3,4-d]pyrimidin-3-yl)-5-fluorophenol	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0044	uM
5-(4-amino-1-cyclopentylpyrazolo[3,4-d]pyrimidin-3-yl)-2-fluorophenol	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0045	uM
1-cyclopentyl-3-(1H-indol-6-yl)pyrazolo[3,4-d]pyrimidin-4-amine	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0050	uM
1-tert-butyl-3-(4-chlorophenyl)pyrazolo[3,4-d]pyrimidin-4-amine	325799: Inhibition of Hck	ic50	0.0050	uM
5-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-2-methylphenol	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0051	uM
(3S)-3-[[4-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl]amino]oxolan-2-one	1366202: Inhibition of recombinant human HCK SH3-SH2-KD (75 to 526 residues) after 20 mins by mobility shift assay	ic50	0.0054	uM
1-cyclopentyl-3-(1H-indol-5-yl)pyrazolo[3,4-d]pyrimidin-4-amine	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0054	uM
5-[4-amino-1-(3-methylcyclopentyl)pyrazolo[3,4-d]pyrimidin-3-yl]-2-fluorophenol	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0057	uM
5-(4-amino-1-cyclobutylpyrazolo[3,4-d]pyrimidin-3-yl)-2-chlorophenol	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0058	uM
6-amino-7-(4-phenoxyphenyl)-9-[(3S)-1-prop-2-enoylpiperidin-3-yl]purin-8-one	1425017: 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	0.0060	uM
(2R)-2-[[4-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl]amino]-3-hydroxypropanoic acid	1366202: Inhibition of recombinant human HCK SH3-SH2-KD (75 to 526 residues) after 20 mins by mobility shift assay	ic50	0.0063	uM
N-[3-[[3-[6-[4-[2-[[2-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]acetyl]amino]ethoxy]anilino]pyrimidin-4-yl]-2-pyridinyl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide	1799543: In Vitro Activity Assay from Article 10.1016/j.chembiol.2010.01.008: “Affinity reagents that target a specific inactive form of protein kinases.”	ic50	0.0063	uM
(2S)-2-[[4-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl]amino]propanoic acid	1366202: Inhibition of recombinant human HCK SH3-SH2-KD (75 to 526 residues) after 20 mins by mobility shift assay	ic50	0.0069	uM
(2S)-2-[[4-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl]amino]-3-(4-hydroxyphenyl)propanoic acid	1366202: Inhibition of recombinant human HCK SH3-SH2-KD (75 to 526 residues) after 20 mins by mobility shift assay	ic50	0.0074	uM
(2S)-2-[[4-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl]amino]-3-phenylpropanoic acid	1366202: Inhibition of recombinant human HCK SH3-SH2-KD (75 to 526 residues) after 20 mins by mobility shift assay	ic50	0.0075	uM
2-[[4-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl]amino]acetamide	1487300: Inhibition of HCK (unknown origin)	ic50	0.0076	uM
3-[7-amino-3-[4-(4-methylpiperazin-1-yl)phenyl]pyrazolo[1,5-a]pyrimidin-6-yl]phenol	484554: Inhibition of HCK	ic50	0.0080	uM
1-cyclopentyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[3,4-d]pyrimidin-4-amine	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0080	uM
5-[4-amino-1-[(3R)-oxolan-3-yl]pyrazolo[3,4-d]pyrimidin-3-yl]-2-chlorophenol	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0080	uM
N-[3-[[3-[4-[4-[2-[5-[3-(2-fluoro-10,12-dimethyl-1-aza-3-azonia-2-boratricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)propanoylamino]pentanoylamino]ethoxy]anilino]-1,3,5-triazin-2-yl]-2-pyridinyl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide	1799543: In Vitro Activity Assay from Article 10.1016/j.chembiol.2010.01.008: “Affinity reagents that target a specific inactive form of protein kinases.”	kd	0.0087	uM
5-[4-amino-1-[(3S)-oxolan-3-yl]pyrazolo[3,4-d]pyrimidin-3-yl]-2-chlorophenol	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0088	uM
5-(4-phenoxyphenyl)-7-[4-(pyridin-4-ylmethylamino)cyclohexyl]pyrrolo[2,3-d]pyrimidin-4-amine	1487300: Inhibition of HCK (unknown origin)	ic50	0.0089	uM
5-(4-amino-1-cyclobutylpyrazolo[3,4-d]pyrimidin-3-yl)-2-bromophenol	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0089	uM
N-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-3-chloro-4-[(4-ethylpiperazin-1-yl)methyl]benzamide	469071: Inhibition of HCK	ic50	0.0090	uM
3-[2-[2-amino-5-(1-methylpyrazol-4-yl)-3-pyridinyl]ethynyl]-N-[3,5-bis(trifluoromethyl)phenyl]-4-methylbenzamide	1779903: Inhibition of human recombinant HCK (230 to 497) by radiometric scintillation counting analysis	ic50	0.0090	uM
tert-butyl 5-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)indole-1-carboxylate	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0090	uM
5-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-2-fluorophenol	507080: Inhibition of recombinant HCK by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0092	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	6
Tretinoin	increases expression	3
sodium arsenite	affects cotreatment, decreases expression, affects binding, increases reaction	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Benzo(a)pyrene	increases methylation, increases mutagenesis	2
Nickel	decreases expression, increases expression	2
3,4,5-trimethoxybenzaldehyde	affects binding, decreases activity	1
Asian ginseng	decreases expression, decreases reaction, affects cotreatment	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases phosphorylation	1
deoxynivalenol	increases phosphorylation	1
lead acetate	affects cotreatment, decreases expression	1
4-bis(2-chloroethyl)aminobenzaldehyde	affects binding, decreases reaction, decreases activity, decreases phosphorylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
sulforaphane	increases expression	1
chromous chloride	affects cotreatment, decreases expression	1
cobaltous chloride	increases expression	1
pyrrolidine dithiocarbamic acid	decreases reaction, increases expression, affects cotreatment	1
chromic oxide	affects cotreatment, decreases expression	1
bathocuproine sulfonate	decreases reaction, increases expression, affects cotreatment	1
aflatoxin B2	increases methylation	1
triphenyltin	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
clothianidin	increases expression	1

ChEMBL screening assays

431 unique, capped per target: 429 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*
CHEMBL1963709	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: HCK	PubChem BioAssay data set
CHEMBL4414993	ADMET	Inhibition of human HCK at 1 uM using poly[Glu:Tyr] (4:1) as substrate preincubated for 15 to 20 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

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9G2	Ubigene HEK293 HCK KO	Transformed cell line	Female
CVCL_F6GE	EDITGENE HCK Knockout HAP1 Cell Line	Cancer cell line	Male
CVCL_SQ96	HAP1 HCK (-) 1	Cancer cell line	Male
CVCL_SQ97	HAP1 HCK (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for HCK across ~30M SureChEMBL compounds — explore on Sugi Predict.