HUNK

Summary

HUNK (hormonally up-regulated Neu-associated kinase, HGNC:13326) is a protein-coding gene on chromosome 21q22.11, encoding Hormonally up-regulated neu tumor-associated kinase (P57058).

Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in intracellular signal transduction. Predicted to act upstream of or within protein phosphorylation. Predicted to be active in cytoplasm.

Source: NCBI Gene 30811 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 107 total — 1 pathogenic
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014586

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13326
Approved symbol	HUNK
Name	hormonally up-regulated Neu-associated kinase
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000142149
Ensembl biotype	protein_coding
OMIM	606532
Entrez	30811

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000270112, ENST00000430354, ENST00000439107, ENST00000465574, ENST00000931898

RefSeq mRNA: 1 — MANE Select: NM_014586 NM_014586

CCDS: CCDS13610

Canonical transcript exons

ENST00000270112 — 11 exons

Exon	Start	End
ENSE00000952493	31940165	31940220
ENSE00000952494	31946036	31946171
ENSE00000952495	31958843	31958970
ENSE00001025753	31995768	31995948
ENSE00001025754	31974555	31974717
ENSE00001025755	31924468	31924760
ENSE00001025758	31968250	31968385
ENSE00001191620	31998526	32004064
ENSE00001191626	31873020	31873935
ENSE00003508200	31990129	31990176
ENSE00003547885	31983526	31983609

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 90.45.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7707 / max 44.3780, expressed in 488 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188792	0.5973	299
188794	0.4948	259
188796	0.3159	170
188793	0.1932	110
188795	0.1694	95

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	90.45	gold quality
ventricular zone	UBERON:0003053	81.53	gold quality
buccal mucosa cell	CL:0002336	79.39	gold quality
embryo	UBERON:0000922	79.34	gold quality
pancreatic ductal cell	CL:0002079	78.91	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.78	gold quality
cortical plate	UBERON:0005343	76.47	gold quality
middle temporal gyrus	UBERON:0002771	75.97	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.22	gold quality
sperm	CL:0000019	74.88	gold quality
male germ cell	CL:0000015	74.53	gold quality
endothelial cell	CL:0000115	73.26	silver quality
rectum	UBERON:0001052	72.25	gold quality
body of pancreas	UBERON:0001150	71.96	gold quality
gluteal muscle	UBERON:0002000	71.95	gold quality
mucosa of sigmoid colon	UBERON:0004993	71.79	silver quality
triceps brachii	UBERON:0001509	71.78	gold quality
primary visual cortex	UBERON:0002436	71.00	gold quality
prefrontal cortex	UBERON:0000451	70.80	gold quality
pancreas	UBERON:0001264	70.73	gold quality
olfactory bulb	UBERON:0002264	70.54	gold quality
cervix squamous epithelium	UBERON:0006922	70.40	gold quality
stromal cell of endometrium	CL:0002255	70.31	gold quality
smooth muscle tissue	UBERON:0001135	70.08	gold quality
islet of Langerhans	UBERON:0000006	69.57	gold quality
type B pancreatic cell	CL:0000169	69.43	gold quality
colonic mucosa	UBERON:0000317	69.29	gold quality
metanephros cortex	UBERON:0010533	68.98	gold quality
occipital lobe	UBERON:0002021	68.96	gold quality
placenta	UBERON:0001987	68.56	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	25.31
E-ANND-3	yes	5.70
E-CURD-89	no	10.29
E-GEOD-124858	no	3.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

165 targeting HUNK, 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-9-5P	100.00	72.28	2361
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772

Literature-anchored findings (GeneRIF, showing 10)

• Overproduction of MAK-V/Hunk in human breast cancer may be used fore more precise molecular typing. (PMID:15575376)
• a gene expression signature that distinguishes Hunk-wild type from Hunk-deficient tumors predicts clinical outcome in women with breast cancer (PMID:19717424)
• Data show that HUNK reconstitution in basal breast cancer cell lines prevented protein phosphatase 2-A (PP2A from binding to CFL-1. (PMID:20133759)
• Hunk is required for HER2/neu-induced mammary tumorigenesis (PMID:21393859)
• Our findings indicate that therapeutically targeting HUNK is a potential strategy for overcoming resistance and that resistant breast cancer cells maintain HUNK expression to drive tumorigenesis (PMID:25515931)
• Recent work demonstrates a role for Hunk in HER2(+)/ErbB2(+) breast cancer progression, including drug resistance to HER2/ErbB2 inhibitors, with Hunk potentially acting downstream of HER2/ErbB2 and the PI3K/Akt pathway. [review] (PMID:28189783)
• HUNK phosphorylates EGFR to regulate breast cancer metastasis. (PMID:31597954)
• Rubicon as a novel substrate of HUNK. (PMID:31752345)
• HUNK inhibits epithelial-mesenchymal transition of CRC via direct phosphorylation of GEF-H1 and activating RhoA/LIMK-1/CFL-1. (PMID:37193711)
• HUNK inhibits cargo uptake and lysosomal traffic in the caveolar pathway via the AGAP3/ARF6. (PMID:38071109)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hunk	ENSMUSG00000053414
rattus_norvegicus	Hunk	ENSRNOG00000002092
drosophila_melanogaster	Snrk	FBGN0033915
drosophila_melanogaster	Nuak	FBGN0262617
caenorhabditis_elegans		WBGENE00012638
caenorhabditis_elegans	ZK524.4	WBGENE00013994
caenorhabditis_elegans	tag-344	WBGENE00015230
caenorhabditis_elegans		WBGENE00044388

Paralogs (17): NUAK1 (ENSG00000074590), PRKAA1 (ENSG00000132356), TSSK4 (ENSG00000139908), SIK1 (ENSG00000142178), BRSK1 (ENSG00000160469), SIK3 (ENSG00000160584), PRKAA2 (ENSG00000162409), TSSK3 (ENSG00000162526), NUAK2 (ENSG00000163545), SNRK (ENSG00000163788), MELK (ENSG00000165304), SIK2 (ENSG00000170145), BRSK2 (ENSG00000174672), NIM1K (ENSG00000177453), TSSK6 (ENSG00000178093), TSSK2 (ENSG00000206203), TSSK1B (ENSG00000212122)

Protein

Protein identifiers

Hormonally up-regulated neu tumor-associated kinase — P57058 (reviewed: P57058)

Alternative names: B19, Serine/threonine-protein kinase MAK-V

All UniProt accessions (3): P57058, H7C2X2, H7C3H0

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

RefSeq proteins (1): NP_055401* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR034671	Hunk	Domain

Pfam: PF00069

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (16 total): sequence variant 4, region of interest 4, compositionally biased region 3, binding site 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P57058-F1	62.83	0.34

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): 186 (proton acceptor)

Ligand- & substrate-binding residues (2): 68–76; 91

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 84 (showing top): PEREZ_TP63_TARGETS, LIAO_METASTASIS, SANSOM_APC_TARGETS_UP, PEREZ_TP53_AND_TP63_TARGETS, LIAO_HAVE_SOX4_BINDING_SITES, DOUGLAS_BMI1_TARGETS_UP, ATGTCAC_MIR489, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, chr21q22, VERNELL_RETINOBLASTOMA_PATHWAY_UP, CUI_TCF21_TARGETS_2_UP, SANSOM_APC_TARGETS, GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_KINASE_ACTIVITY, GOMF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY

GO Biological Process (3): signal transduction (GO:0007165), intracellular signal transduction (GO:0035556), protein phosphorylation (GO:0006468)

GO Molecular Function (8): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
protein kinase activity	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
phosphorylation	1
protein modification process	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
cellular anatomical structure	1

Protein interactions and networks

STRING

1121 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HUNK	URB1	O60287	549
HUNK	SYNJ1	O43426	517
HUNK	RABEP1	Q15276	503
HUNK	MYC	P01106	490
HUNK	SCAF4	O95104	480
HUNK	MIS18A	Q9NYP9	447
HUNK	EVA1C	P58658	412
HUNK	ZBTB21	Q9ULJ3	412
HUNK	PAXBP1	Q9Y5B6	394
HUNK	VPS26C	O14972	363
HUNK	YARS1	P54577	347
HUNK	TMEM273	Q5T292	343
HUNK	KBTBD12	Q3ZCT8	331
HUNK	DONSON	Q9NYP3	325
HUNK	PTTG1IP	P53801	324

IntAct

105 interactions, top by confidence:

A	B	Type	Score
HIF1AN	GMDS	psi-mi:“MI:0914”(association)	0.640
HUNK	LIMK1	psi-mi:“MI:0915”(physical association)	0.570
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530
CFL1	HUNK	psi-mi:“MI:0915”(physical association)	0.520
Dlg4	HUNK	psi-mi:“MI:0407”(direct interaction)	0.440
HUNK	PPP2CA	psi-mi:“MI:0915”(physical association)	0.400
HUNK	PPP2R1A	psi-mi:“MI:0915”(physical association)	0.400
HUNK	H1-1	psi-mi:“MI:0915”(physical association)	0.400
PIP	RBM47	psi-mi:“MI:0914”(association)	0.350
HUNK	TRAPPC10	psi-mi:“MI:0914”(association)	0.350
HUNK	MCHR1	psi-mi:“MI:0915”(physical association)	0.000
HUNK	CAMK1	psi-mi:“MI:0915”(physical association)	0.000
HUNK	APBA2	psi-mi:“MI:0915”(physical association)	0.000
HUNK	MBD1	psi-mi:“MI:0915”(physical association)	0.000
HUNK	NAPA	psi-mi:“MI:0915”(physical association)	0.000
HUNK	PICK1	psi-mi:“MI:0915”(physical association)	0.000
HUNK	MOAP1	psi-mi:“MI:0915”(physical association)	0.000
HUNK	ASCL1	psi-mi:“MI:0915”(physical association)	0.000
HUNK	ZNF76	psi-mi:“MI:0915”(physical association)	0.000
HUNK	NEUROD2	psi-mi:“MI:0915”(physical association)	0.000
HUNK	ABLIM1	psi-mi:“MI:0915”(physical association)	0.000
HUNK	OLR1	psi-mi:“MI:0915”(physical association)	0.000
HUNK	CCAR1	psi-mi:“MI:0915”(physical association)	0.000
HUNK	PTPRA	psi-mi:“MI:0915”(physical association)	0.000
HUNK	RAB5B	psi-mi:“MI:0915”(physical association)	0.000
HUNK	STMN1	psi-mi:“MI:0915”(physical association)	0.000
HUNK	IFT88	psi-mi:“MI:0915”(physical association)	0.000
HUNK	SLC6A1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (108): HUNK (Two-hybrid), HIST1H1A (Proximity Label-MS), HUNK (Affinity Capture-RNA), C7orf43 (Affinity Capture-MS), TRAPPC6B (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS), TRAPPC4 (Affinity Capture-MS), HUNK (Affinity Capture-MS), RPS6KA6 (Affinity Capture-MS), HUNK (Affinity Capture-MS), TRAPPC10 (Affinity Capture-MS), AGAP3 (Affinity Capture-MS), TRAPPC1 (Affinity Capture-MS), DNAJA1 (Two-hybrid), ZNF292 (Two-hybrid)

ESM2 similar proteins: A0AUV4, A1A5Q6, A1A5R7, A2KF29, B1WAS2, C0HKC8, C0HKC9, D3ZML2, O60285, O74536, O88831, O88866, P41279, P51956, P57058, P97756, Q20443, Q2T9U5, Q5R7G9, Q5XHI9, Q60670, Q63562, Q641K5, Q66HE5, Q68UT7, Q6P431, Q6VZ17, Q7T0B0, Q7T0B1, Q7TNJ7, Q7TNL4, Q8BHI9, Q8BZN4, Q8C078, Q8C0N0, Q8C0V7, Q8C0X8, Q8CIP4, Q8IY84, Q8K4K4

Diamond homologs: A0A5B9GBF0, A0AAR7, A1IVT7, A2XUW1, A6ZQG7, A6ZZF6, A7TGR2, A8WYE4, A8XQD5, A8XWC4, B1H3E1, B2DD29, D3ZML2, D3ZSZ3, E1BMN8, E2QWQ2, G1XJZ4, O14019, O14328, O14757, O45818, O54949, O59763, O61661, O64812, O88866, O96821, P0CP69, P0DP15, P22211, P25333, P32485, P34117, P34208, P34244, P36002, P36004, P38970, P45894, P53233

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HUNK	“up-regulates activity”	ITM2A	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	89
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
59011	GRCh38/hg38 21q22.11(chr21:31339386-32311519)x1	Pathogenic

SpliceAI

2042 predictions. Top by Δscore:

Variant	Effect	Δscore
21:31873933:AAG:A	donor_loss	1.0000
21:31873934:AGGT:A	donor_loss	1.0000
21:31873935:GGTG:G	donor_loss	1.0000
21:31873937:T:A	donor_loss	1.0000
21:31924464:TTAG:T	acceptor_loss	1.0000
21:31924465:TA:T	acceptor_loss	1.0000
21:31924466:A:AG	acceptor_gain	1.0000
21:31924466:A:T	acceptor_loss	1.0000
21:31924466:AG:A	acceptor_gain	1.0000
21:31924466:AGGT:A	acceptor_gain	1.0000
21:31924466:AGGTG:A	acceptor_gain	1.0000
21:31924467:G:A	acceptor_gain	1.0000
21:31924467:G:GA	acceptor_gain	1.0000
21:31924467:GGT:G	acceptor_gain	1.0000
21:31924467:GGTG:G	acceptor_gain	1.0000
21:31924467:GGTGG:G	acceptor_gain	1.0000
21:31924756:CACAG:C	donor_loss	1.0000
21:31924759:AGGTA:A	donor_loss	1.0000
21:31924760:GGT:G	donor_loss	1.0000
21:31924761:GTAA:G	donor_loss	1.0000
21:31924762:T:G	donor_loss	1.0000
21:31946136:G:GT	donor_gain	1.0000
21:31958839:TCA:T	acceptor_loss	1.0000
21:31958840:CA:C	acceptor_loss	1.0000
21:31958841:A:AG	acceptor_gain	1.0000
21:31958841:A:G	acceptor_loss	1.0000
21:31958841:AGAG:A	acceptor_gain	1.0000
21:31958842:G:GG	acceptor_gain	1.0000
21:31958842:GA:G	acceptor_gain	1.0000
21:31958842:GAGG:G	acceptor_gain	1.0000

AlphaMissense

4700 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:31873850:G:T	G59V	1.000
21:31873859:T:C	L62P	1.000
21:31873879:G:C	G69R	1.000
21:31873880:G:A	G69D	1.000
21:31873885:G:A	G71S	1.000
21:31873885:G:C	G71R	1.000
21:31873885:G:T	G71C	1.000
21:31873886:G:A	G71D	1.000
21:31873886:G:T	G71V	1.000
21:31873891:T:A	F73I	1.000
21:31873891:T:C	F73L	1.000
21:31873891:T:G	F73V	1.000
21:31873892:T:C	F73S	1.000
21:31873892:T:G	F73C	1.000
21:31873893:T:A	F73L	1.000
21:31873893:T:G	F73L	1.000
21:31873894:G:C	A74P	1.000
21:31873895:C:A	A74D	1.000
21:31873895:C:T	A74V	1.000
21:31873900:G:A	V76M	1.000
21:31873900:G:C	V76L	1.000
21:31873900:G:T	V76L	1.000
21:31873901:T:A	V76E	1.000
21:31873901:T:C	V76A	1.000
21:31873904:G:C	R77P	1.000
21:31873909:G:A	G79R	1.000
21:31873909:G:C	G79R	1.000
21:31873909:G:T	G79W	1.000
21:31873910:G:A	G79E	1.000
21:31873913:T:C	L80P	1.000

dbSNP variants (sampled 300 via entrez): RS1000002829 (21:31935314 C>T), RS1000036994 (21:31882859 T>C), RS1000049682 (21:31940340 CTTTT>C), RS1000094066 (21:31964329 A>G), RS1000110478 (21:31980047 T>G), RS1000186931 (21:31939982 C>T), RS1000197579 (21:31984798 C>G), RS1000210747 (21:31994423 TAG>T), RS1000216450 (21:31938528 C>T), RS1000218403 (21:31987874 A>C), RS1000240969 (21:31981566 T>A), RS1000243468 (21:31885797 C>T), RS1000318194 (21:31938799 A>G,T), RS1000353368 (21:31911069 G>A), RS1000355036 (21:31985635 C>G,T)

Disease associations

OMIM: gene MIM:606532 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000520_4	Vitiligo	2.000000e-06
GCST000885_1	Response to antipsychotic treatment in schizophrenia (reasoning)	5.000000e-07
GCST001033_7	Type 2 diabetes	4.000000e-06
GCST003256_1	Joint damage progression in ACPA-negative rheumatoid arthritis	4.000000e-09
GCST010577_12	Crohn’s disease	1.000000e-06
GCST011741_64	LDL cholesterol levels in HIV infection	1.000000e-05

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004350	reasoning
EFO:0005413	joint damage measurement
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795165 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 177,497 (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
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2	363
CHEMBL513909	BI-2536	2	895
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL1908397	KW-2449	1	622

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — HUNK subfamily

ChEMBL bioactivities

22 potent at pChembl≥5 of 22 total, top 19 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.43	Kd	3.7	nM	SU-014813
6.62	Kd	240	nM	MIDOSTAURIN
6.46	Kd	350	nM	TAE-684
6.39	Kd	410	nM	DOVITINIB
6.34	Kd	460	nM	KW-2449
6.30	Kd	500	nM	SUNITINIB
6.24	Kd	570	nM	LESTAURTINIB
6.21	Kd	620	nM	STAUROSPORINE
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.85	Kd	1400	nM	PHA-665752
5.82	Kd	1500	nM	AXITINIB
5.39	Kd	4100	nM	VANDETANIB
5.30	Kd	5000	nM	BOSUTINIB
5.27	Kd	5400	nM	FORETINIB
5.19	Kd	6400	nM	CANERTINIB
5.01	Kd	9700	nM	BI-2536
5.01	Kd	9800	nM	TOZASERTIB

PubChem BioAssay actives

19 with measured affinity, of 123 total; 16 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
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	625084: Binding constant for HUNK kinase domain	kd	0.0037	uM
Midostaurin	507974: Binding affinity to HUNK	kd	0.2400	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	625084: Binding constant for HUNK kinase domain	kd	0.3500	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	625084: Binding constant for HUNK kinase domain	kd	0.4100	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625084: Binding constant for HUNK kinase domain	kd	0.4600	uM
Sunitinib	507974: Binding affinity to HUNK	kd	0.5000	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507974: Binding affinity to HUNK	kd	0.5700	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	625084: Binding constant for HUNK kinase domain	kd	0.6200	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	625084: Binding constant for HUNK kinase domain	kd	1.4000	uM
Axitinib	625084: Binding constant for HUNK kinase domain	kd	1.5000	uM
Vandetanib	625084: Binding constant for HUNK kinase domain	kd	4.1000	uM
Bosutinib	625084: Binding constant for HUNK kinase domain	kd	5.0000	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	625084: Binding constant for HUNK kinase domain	kd	5.4000	uM
N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide	625084: Binding constant for HUNK kinase domain	kd	6.4000	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	625084: Binding constant for HUNK kinase domain	kd	9.7000	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	625084: Binding constant for HUNK kinase domain	kd	9.8000	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects expression, decreases expression	5
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases methylation	1
sotorasib	affects cotreatment, increases expression	1
pirinixic acid	increases activity, increases expression, affects binding	1
bisphenol A	decreases expression	1
terbufos	increases methylation	1
benzo(e)pyrene	decreases methylation	1
belinostat	decreases expression	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
incobotulinumtoxinA	decreases expression	1
trametinib	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Methapyrilene	decreases methylation	1
Parathion	increases methylation	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
Acrylamide	increases expression	1

ChEMBL screening assays

66 unique, capped per target: 66 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1166020	Binding	Inhibition of HUNK at 1 uM	Synthesis and structure-activity relationships of 1,2,3,4-tetrahydropyrido[2,3-b]pyrazines as potent and selective inhibitors of the anaplastic lymphoma kinase. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1CG	Ubigene SW480 HUNK KO	Cancer cell line	Male
CVCL_SR88	HAP1 HUNK (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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