HIPK3

Summary

HIPK3 (homeodomain interacting protein kinase 3, HGNC:4915) is a protein-coding gene on chromosome 11p13, encoding Homeodomain-interacting protein kinase 3 (Q9H422). Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression.

Enables protein serine/threonine kinase activity. Involved in mRNA transcription; negative regulation of apoptotic process; and protein phosphorylation. Located in cytosol; nuclear body; and plasma membrane.

Source: NCBI Gene 10114 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 173 total
• Druggable target: yes — 26 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005734

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4915
Approved symbol	HIPK3
Name	homeodomain interacting protein kinase 3
Location	11p13
Locus type	gene with protein product
Status	Approved
Aliases	PKY, DYRK6, YAK1, FIST3
Ensembl gene	ENSG00000110422
Ensembl biotype	protein_coding
OMIM	604424
Entrez	10114

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000303296, ENST00000379016, ENST00000456517, ENST00000525975, ENST00000531504, ENST00000534262, ENST00000905205, ENST00000905206, ENST00000905207, ENST00000923623

RefSeq mRNA: 4 — MANE Select: NM_005734 NM_001048200, NM_001278162, NM_001278163, NM_005734

CCDS: CCDS41634, CCDS7884

Canonical transcript exons

ENST00000303296 — 17 exons

Exon	Start	End
ENSE00000709778	33338757	33338843
ENSE00000709779	33339350	33339534
ENSE00000709780	33340968	33341127
ENSE00000709781	33341563	33341686
ENSE00000709783	33347293	33347414
ENSE00000709787	33347852	33348013
ENSE00000709788	33348166	33348228
ENSE00000709789	33348522	33348818
ENSE00000709791	33349147	33349287
ENSE00000709793	33351608	33351843
ENSE00000709795	33352138	33352265
ENSE00001165658	33347629	33347753
ENSE00001479517	33353092	33357023
ENSE00001479558	33286413	33287511
ENSE00001652501	33328510	33328633
ENSE00003531448	33337075	33337194
ENSE00003848015	33257381	33257889

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 99.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.2863 / max 669.3664, expressed in 1822 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113664	35.3815	1821
113669	4.0731	651
113671	1.4591	616
113668	1.1841	509
113665	1.0108	570
113663	0.8106	481
113666	0.1466	65
113670	0.1300	45
113667	0.0905	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.60	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.46	gold quality
heart right ventricle	UBERON:0002080	99.44	gold quality
biceps brachii	UBERON:0001507	99.41	gold quality
parietal pleura	UBERON:0002400	99.32	gold quality
cauda epididymis	UBERON:0004360	99.29	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.23	gold quality
visceral pleura	UBERON:0002401	99.22	gold quality
germinal epithelium of ovary	UBERON:0001304	99.12	gold quality
gingival epithelium	UBERON:0001949	98.98	gold quality
saphenous vein	UBERON:0007318	98.96	gold quality
vena cava	UBERON:0004087	98.93	gold quality
gingiva	UBERON:0001828	98.89	gold quality
caput epididymis	UBERON:0004358	98.89	gold quality
bronchial epithelial cell	CL:0002328	98.81	gold quality
synovial joint	UBERON:0002217	98.76	gold quality
body of tongue	UBERON:0011876	98.73	gold quality
skin of hip	UBERON:0001554	98.71	gold quality
upper leg skin	UBERON:0004262	98.71	gold quality
mammary duct	UBERON:0001765	98.69	gold quality
superficial temporal artery	UBERON:0001614	98.65	gold quality
pericardium	UBERON:0002407	98.59	gold quality
corpus epididymis	UBERON:0004359	98.59	gold quality
urethra	UBERON:0000057	98.56	gold quality
epithelium of nasopharynx	UBERON:0001951	98.55	gold quality
seminal vesicle	UBERON:0000998	98.51	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.49	gold quality
trabecular bone tissue	UBERON:0002483	98.48	gold quality
renal medulla	UBERON:0000362	98.45	gold quality
cardia of stomach	UBERON:0001162	98.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	21.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUN

miRNA regulators (miRDB)

336 targeting HIPK3, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4514	99.99	67.10	1870
HSA-LET-7F-2-3P	99.98	70.98	2588

Literature-anchored findings (GeneRIF, showing 40)

• JNK regulates the expression of HIPK3 in prostate cancer cells, which leads to increased resistance to Fas receptor-mediated apoptosis by reducing the interaction between FADD and caspase-8 (PMID:14766760)
• This finding has linked three common factors, HIPK3, JNK, and c-Jun, to the cAMP signaling pathway leading to increased steroidogenic gene expression (PMID:17210646)
• Analysis of these mutants revealed that HIPK1, HIPK2 and HIPK3 but not HIPK4 are capable of autophosphorylating on other tyrosines (PMID:25630557)
• circHIPK3 directly binds to miR-124 and inhibits miR-124 activity and cell cycle progression. (PMID:27050392)
• Overexpression of circHIPK3 promoted NCI-H1299 cell proliferation and knock-down of circHIPK3 inhibited cell proliferation. (PMID:28738961)
• Over-expression of circHIPK3 effectively inhibits migration, invasion, and angiogenesis of bladder cancer cells in vitro and suppresses bladder cancer growth and metastasis in vivo Mechanistic studies reveal that circHIPK3 contains two critical binding sites for the microRNA miR-558 and can abundantly sponge miR-558 to suppress the expression of heparanase (HPSE). (PMID:28794202)
• HIPK3 as a novel kinase modulator of autophagy in Huntington disease (HD) cells. Knocking down or knocking out HIPK3 reduces mutant HTT protein levels via enhancing autophagy in HD cells and in vivo in an HD knock-in mouse model. (PMID:29130397)
• The two kinases HIPK3 and MAPK11 effect on Huntingtin (HTT)levels are mutant HTT protein (mHTT)-dependent, providing a feedback mechanism in which mHTT enhances its own level thus contributing to mHTT accumulation and disease progression. (PMID:29151587)
• HIPK1, HIPK2 and HIPK3 interact with the components of the carbon catabolite repressor 4 (CCR4)-negative on TATA (NOT) complex, an important regulator of all the major steps in the mRNA metabolism. it has emerged that HIPKs and their related miRNAs are involved in diabetic nephropathy, gastric cancer chemoresistance, cervical cancer progression, and recombinant protein expression in cultured cells. [Review] (PMID:29793420)
• Higher circulating RNA HIPK3 was an independent predictor of disease free survival and overall survival in epithelial ovarian cancer patients. (PMID:29949144)
• CircHIPK3 regulates human lens epithelial cells function through miR-193a-mediated CRYAA expression (PMID:29959922)
• The CircHIPK3 could promote IGF2BP3 expression via interacting with miR-654 in glioma cells. (PMID:30057315)
• the expression of cir_ITCH and circHIPK3 were significantly downregulated in gastric cancer tumoral tissues compared with their paired adjacent nonneoplastic counterparts; further analyses showed that cir_ITCH and circHIPK3 expression levels were related with numerous clinicopathological features of tumoral tissues (PMID:30866608)
• expression of circHIPK3 may contribute to the development of preeclampsia by leading to the aberrant biological behavior of trophoblast cells (PMID:31421528)
• Upregulation of circHIPK3 promotes the progression of gastric cancer via Wnt/beta-catenin pathway and indicates a poor prognosis. (PMID:31599413)
• circHIPK3 promotes OXA resistance in CRC by sponging miR-637, which is dependent on the inhibition of autophagy-related cell death via STAT3/Bcl-2/beclin1 signalling pathway. (PMID:31631038)
• Circular RNA HIPK3 contributes to hyperglycemia and insulin homeostasis by sponging miR-192-5p and upregulating transcription factor forkhead box O1. (PMID:31875589)
• CircHIPK3 promotes colorectal cancer cells proliferation and metastasis via modulating of miR-1207-5p/FMNL2 signal. (PMID:32046858)
• The data elucidates that circHIPK3 functions as a regulator in the airway remodeling during the asthma development through miR-326/STIM1 axis (PMID:32450169)
• Circular RNA HIPK3 regulates human lens epithelial cell dysfunction by targeting the miR-221-3p/PI3K/AKT pathway in age-related cataract. (PMID:32681842)
• [Circular RNA homeodomain-interacting protein kinase 3 (circHIPK3) promotes growth and metastasis of glioma cells by sponging miR-124-3p]. (PMID:32727645)
• Knockdown of circ_HIPK3 inhibits tumorigenesis of hepatocellular carcinoma via the miR-582-3p/DLX2 axis. (PMID:32977948)
• Identification of HIPK3 as a potential biomarker and an inhibitor of clear cell renal cell carcinoma. (PMID:33495417)
• Circ-HIPK3 regulates YAP1 expression by sponging miR-381-3p to promote oral squamous cell carcinoma development. (PMID:33737493)
• Exosome-mediated transfer of circHIPK3 promotes trastuzumab chemoresistance in breast cancer. (PMID:33775192)
• Circular RNA circHIPK3 Activates Macrophage NLRP3 Inflammasome and TLR4 Pathway in Gouty Arthritis via Sponging miR-561 and miR-192. (PMID:34085163)
• Exosomal circRNA HIPK3 knockdown inhibited cell proliferation and metastasis in prostate cancer by regulating miR-212/BMI-1 pathway. (PMID:34313249)
• Inhibition of HIPK3 by AST487 Ameliorates Mutant HTT-Induced Neurotoxicity and Apoptosis via Enhanced Autophagy. (PMID:34741261)
• Abemaciclib is a potent inhibitor of DYRK1A and HIP kinases involved in transcriptional regulation. (PMID:34785661)
• Endothelial cell-derived exosomal circHIPK3 promotes the proliferation of vascular smooth muscle cells induced by high glucose via the miR-106a-5p/Foxo1/Vcam1 pathway. (PMID:34887361)
• CircHIPK3 contributes to human villous trophoblast growth, migration and invasion via modulating the pathway of miR-346/KCMF1. (PMID:35032791)
• CircHIPK3 prevents chondrocyte apoptosis and cartilage degradation by sponging miR-30a-3p and promoting PON2. (PMID:35716032)
• Circ_0060,144 inhibits the occurrence and development of age-related cataract via the miR-23b-3p/HIPK3 axis. (PMID:35810770)
• circHIPK3 prevents cardiac senescence by acting as a scaffold to recruit ubiquitin ligase to degrade HuR. (PMID:36438474)
• DNA methylation change of HIPK3 in Chinese rheumatoid arthritis and its effect on inflammation. (PMID:36703984)
• Circular RNA HIPK3 facilitates ferroptosis in gestational diabetes mellitus by regulating glutathione peroxidase 4 DNA methylation. (PMID:37253602)
• CircHIPK3 relieves vascular calcification via mediating SIRT1/PGC-1alpha/MFN2 pathway by interacting with FUS. (PMID:38012555)
• Overexpression of microRNA-205-5p promotes cholangiocarcinoma growth by reducing expression of homeodomain-interacting protein kinase 3. (PMID:38105269)
• HIPK3 maintains sensitivity to platinum drugs and prevents disease progression in gastric cancer. (PMID:38246220)
• CircHIPK3/miR-124 affects angiogenesis in early-onset preeclampsia via CPT1A-mediated fatty acid oxidation. (PMID:38904677)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	hipk3b	ENSDARG00000062082
mus_musculus	Hipk3	ENSMUSG00000027177
rattus_norvegicus	Hipk3	ENSRNOG00000011358
drosophila_melanogaster	Hipk	FBGN0035142
caenorhabditis_elegans		WBGENE00013727
caenorhabditis_elegans		WBGENE00185089

Paralogs (12): DYRK4 (ENSG00000010219), CLK1 (ENSG00000013441), HIPK2 (ENSG00000064393), DYRK1B (ENSG00000105204), CLK4 (ENSG00000113240), DYRK2 (ENSG00000127334), DYRK3 (ENSG00000143479), DYRK1A (ENSG00000157540), HIPK4 (ENSG00000160396), HIPK1 (ENSG00000163349), CLK2 (ENSG00000176444), CLK3 (ENSG00000179335)

Protein

Protein identifiers

Homeodomain-interacting protein kinase 3 — Q9H422 (reviewed: Q9H422)

Alternative names: Androgen receptor-interacting nuclear protein kinase, Fas-interacting serine/threonine-protein kinase, Homolog of protein kinase YAK1

All UniProt accessions (2): Q9H422, E9PKD7

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression. Phosphorylates JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD phosphorylation. Enhances androgen receptor-mediated transcription. May act as a transcriptional corepressor for NK homeodomain transcription factors. The phosphorylation of NR5A1 activates SF1 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. In osteoblasts, supports transcription activation: phosphorylates RUNX2 that synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE).

Subunit / interactions. Interacts with Nkx1-2. Interacts with FAS and DAXX. Probably part of a complex consisting of HIPK3, FAS and FADD. Interacts with and stabilizes ligand-bound androgen receptor (AR). Interacts with UBL1/SUMO-1. Binds to NR5A1/SF1, SPEN/MINT and RUNX2.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Overexpressed in multidrug resistant cells. Highly expressed in heart and skeletal muscle, and at lower levels in placenta, pancreas, brain, spleen, prostate, thymus, testis, small intestine, colon and leukocytes. Not found in liver and lung.

Post-translational modifications. Autophosphorylated, but autophosphorylation is not required for catalytic activity. May be sumoylated.

Similarity. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H422-1	1, HIPK3	yes
Q9H422-2	2, FIST

RefSeq proteins (4): NP_001041665, NP_001265091, NP_001265092, NP_005725* (*=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
IPR050494	Ser_Thr_dual-spec_kinase	Family

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 (58 total): helix 17, strand 8, sequence variant 6, region of interest 6, turn 6, sequence conflict 3, binding site 2, cross-link 2, compositionally biased region 2, chain 1, domain 1, active site 1, modified residue 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7O7I	X-RAY DIFFRACTION	2.5
7O7J	X-RAY DIFFRACTION	2.81

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H422-F1	52.66	0.27

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): 322 (proton acceptor)

Ligand- & substrate-binding residues (2): 203–211; 226

Post-translational modifications (3): 359, 27, 1208

Mutagenesis-validated functional residues (1):

Position	Phenotype
226	loss of kinase activity and impaired activation of sf1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 306 (showing top): GOBP_NEGATIVE_REGULATION_OF_MAP_KINASE_ACTIVITY, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_PEPTIDYL_SERINE_MODIFICATION, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_JUN_KINASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, MARTINEZ_RB1_TARGETS_UP, KREPPEL_CD99_TARGETS_DN, GOBP_JNK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_NEGATIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS

GO Biological Process (7): protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), mRNA transcription (GO:0009299), peptidyl-serine phosphorylation (GO:0018105), peptidyl-threonine phosphorylation (GO:0018107), negative regulation of apoptotic process (GO:0043066), negative regulation of JUN kinase activity (GO:0043508)

GO Molecular Function (8): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein tyrosine kinase activity (GO:0004713), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear body (GO:0016604), PML body (GO:0016605), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	3
cellular anatomical structure	3
protein phosphorylation	2
phosphorylation	1
protein modification process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
DNA-templated transcription	1
mRNA metabolic process	1
peptidyl-serine modification	1
peptidyl-threonine modification	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
JUN kinase activity	1
negative regulation of MAP kinase activity	1
regulation of JUN kinase activity	1
negative regulation of JNK cascade	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
nucleoplasm	1
intracellular membraneless organelle	1
nuclear body	1
nuclear lumen	1

Protein interactions and networks

STRING

1726 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HIPK3	SRSF5	Q13243	772
HIPK3	HNRNPH1	P31943	762
HIPK3	TRA2B	P62995	737
HIPK3	FADD	Q13158	690
HIPK3	HNRNPA1	P09651	633
HIPK3	NOTCH1	P46531	629
HIPK3	RBMXL2	O75526	618
HIPK3	SRSF9	Q13242	566
HIPK3	ZNF609	O15014	565
HIPK3	RBMY1A1	P0DJD3	565
HIPK3	SRSF1	Q07955	562
HIPK3	ITCH	Q96J02	543
HIPK3	CNOT1	A5YKK6	536
HIPK3	RBMX	P38159	535
HIPK3	ANKRD52	Q8NB46	502

IntAct

24 interactions, top by confidence:

A	B	Type	Score
TP53	HIPK3	psi-mi:“MI:0915”(physical association)	0.400
NR2F2	HIPK3	psi-mi:“MI:0915”(physical association)	0.370
HIPK3	TOX4	psi-mi:“MI:0915”(physical association)	0.370
HIPK3	HEYL	psi-mi:“MI:0915”(physical association)	0.370
HIPK3	MTMR4	psi-mi:“MI:0915”(physical association)	0.370
TGFB1I1	HIPK3	psi-mi:“MI:0915”(physical association)	0.370
ZYX	HIPK3	psi-mi:“MI:0915”(physical association)	0.370
HIPK3	LIMK2	psi-mi:“MI:0915”(physical association)	0.370
C1QA	HIPK3	psi-mi:“MI:0915”(physical association)	0.370
HIPK3	SIAH1	psi-mi:“MI:0915”(physical association)	0.370
HIPK3	LIMS2	psi-mi:“MI:0915”(physical association)	0.370
ARRB2	HIPK3	psi-mi:“MI:0915”(physical association)	0.370
HIPK3	ZNF107	psi-mi:“MI:0915”(physical association)	0.370
LIMD1	HIPK3	psi-mi:“MI:0915”(physical association)	0.370
SIAH2	HIPK3	psi-mi:“MI:0915”(physical association)	0.370
HIPK3	GORASP1	psi-mi:“MI:0915”(physical association)	0.370
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
rph	HIPK3	psi-mi:“MI:0915”(physical association)	0.000
HIPK3	araB	psi-mi:“MI:0915”(physical association)	0.000
HIPK3	CREB1	psi-mi:“MI:0915”(physical association)	0.000
HIPK3	GLUL	psi-mi:“MI:0915”(physical association)	0.000
GRB2	HIPK3	psi-mi:“MI:0915”(physical association)	0.000
UBE2I	HIPK3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (38): HIPK3 (Affinity Capture-RNA), HIPK3 (Affinity Capture-RNA), HIPK3 (Affinity Capture-RNA), HIPK3 (Two-hybrid), TP73 (Two-hybrid), TP53 (Two-hybrid), SUMO1 (Two-hybrid), FAS (Affinity Capture-Western), FADD (Affinity Capture-Western), PCGF3 (Affinity Capture-MS), HIPK3 (Negative Genetic), HIPK3 (Affinity Capture-MS), HIPK3 (Two-hybrid), HIPK3 (Two-hybrid), HIPK3 (Two-hybrid)

ESM2 similar proteins: A0A5K7RLP0, A1YEX3, A7YWH3, B1WBU4, O15151, O35618, O43298, O88850, P24278, P97303, Q01954, Q0V8G8, Q15916, Q17RG1, Q562E2, Q5RC05, Q5RDQ6, Q5SXH7, Q5TC79, Q5VYS8, Q5W0Q7, Q5XIN1, Q6ZPY5, Q6ZSB9, Q6ZU67, Q7ZUW7, Q7ZYI3, Q8BLK9, Q8BSV3, Q8IW35, Q8K088, Q8N680, Q8N7W2, Q8TCN5, Q8VHI4, Q8WW38, Q90W33, Q96BR9, Q96S38, Q99ME3

Diamond homologs: A4L9P5, A8WJR8, A8X4H1, A8X5H5, B3WFY8, G5EDB2, O14132, O23145, O43781, O55076, O76039, O88850, O88904, P14680, P18265, P18431, P20911, P22518, P24941, P43288, P43289, P48963, P49657, P49759, P49840, P50613, P51136, P51567, P51568, P51952, P83102, Q00526, Q03147, Q04859, Q07538, Q08DZ2, Q09690, Q09815, Q0IJ08, Q10156

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
HIPK3	“up-regulates activity”	HSF1	phosphorylation
HIPK3	“down-regulates activity”	FADD	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	140
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2881 predictions. Top by Δscore:

Variant	Effect	Δscore
11:33338741:T:TA	acceptor_gain	1.0000
11:33338743:A:AG	acceptor_gain	1.0000
11:33338744:T:G	acceptor_gain	1.0000
11:33338745:A:AG	acceptor_gain	1.0000
11:33338745:ATAT:A	acceptor_gain	1.0000
11:33338746:T:G	acceptor_gain	1.0000
11:33338747:A:AG	acceptor_gain	1.0000
11:33338747:AT:A	acceptor_gain	1.0000
11:33338748:T:A	acceptor_gain	1.0000
11:33338748:T:G	acceptor_gain	1.0000
11:33338751:A:AG	acceptor_gain	1.0000
11:33338752:A:G	acceptor_gain	1.0000
11:33338754:A:AG	acceptor_gain	1.0000
11:33338754:AAGA:A	acceptor_loss	1.0000
11:33338755:A:C	acceptor_loss	1.0000
11:33338755:A:G	acceptor_gain	1.0000
11:33338756:G:GC	acceptor_loss	1.0000
11:33338756:GAC:G	acceptor_gain	1.0000
11:33338839:CGCAT:C	donor_gain	1.0000
11:33338840:GCAT:G	donor_gain	1.0000
11:33338840:GCATG:G	donor_gain	1.0000
11:33338841:CAT:C	donor_gain	1.0000
11:33338841:CATG:C	donor_loss	1.0000
11:33338842:AT:A	donor_gain	1.0000
11:33338843:TGTG:T	donor_loss	1.0000
11:33338844:G:GG	donor_gain	1.0000
11:33338845:T:A	donor_loss	1.0000
11:33338846:GAGTA:G	donor_loss	1.0000
11:33338847:AGTAC:A	donor_loss	1.0000
11:33339471:C:G	donor_gain	1.0000

AlphaMissense

7980 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:33287010:T:A	V199D	1.000
11:33287024:G:C	G204R	1.000
11:33287030:G:C	G206R	1.000
11:33287030:G:T	G206C	1.000
11:33287031:G:A	G206D	1.000
11:33287031:G:T	G206V	1.000
11:33287036:T:A	F208I	1.000
11:33287036:T:C	F208L	1.000
11:33287037:T:G	F208C	1.000
11:33287038:T:A	F208L	1.000
11:33287038:T:G	F208L	1.000
11:33287039:G:C	G209R	1.000
11:33287040:G:A	G209D	1.000
11:33287040:G:T	G209V	1.000
11:33287054:T:C	C214R	1.000
11:33287056:C:G	C214W	1.000
11:33287085:C:A	A224E	1.000
11:33287090:A:G	K226E	1.000
11:33287091:A:T	K226I	1.000
11:33287092:A:C	K226N	1.000
11:33287092:A:T	K226N	1.000
11:33287097:T:C	L228S	1.000
11:33287148:T:C	L245S	1.000
11:33287157:T:C	L248P	1.000
11:33287208:T:C	F265S	1.000
11:33287228:T:C	C272R	1.000
11:33287230:T:G	C272W	1.000
11:33287232:T:C	L273S	1.000
11:33287237:T:C	F275L	1.000
11:33287238:T:C	F275S	1.000

dbSNP variants (sampled 300 via entrez): RS1000013233 (11:33283085 C>A,G), RS1000029878 (11:33289876 T>C,G), RS1000049143 (11:33272299 T>C), RS1000065164 (11:33272857 C>T), RS1000067195 (11:33290186 G>A), RS1000165945 (11:33276638 A>G), RS1000167615 (11:33352589 G>A,T), RS1000181513 (11:33306568 G>A), RS1000187429 (11:33318225 AT>A,ATT), RS1000199545 (11:33352350 T>C), RS1000235141 (11:33337829 A>G), RS1000275868 (11:33345673 G>A), RS1000294059 (11:33295922 T>A), RS1000383066 (11:33339842 T>C), RS1000384201 (11:33322063 G>A)

Disease associations

OMIM: gene MIM:604424 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002324_8	Anger	2.000000e-06
GCST007240_14	Obese vs. thin	2.000000e-06
GCST009723_56	Vertical cup-disc ratio (adjusted for vertical disc diameter)	3.000000e-08
GCST009724_76	Vertical cup-disc ratio (multi-trait analysis)	2.000000e-09
GCST012033_14	Sleep (1/3-day periodicity)	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0003015	aggressive behavior
EFO:0007041	obese body mass index status
EFO:0006939	cup-to-disc ratio measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4577 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

26 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 261,551 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2	363
CHEMBL215152	DEFOSBARASERTIB	2	372
CHEMBL475251	R-406	2	762
CHEMBL513909	BI-2536	2	895
CHEMBL521851	PICTILISIB	2	6,071
CHEMBL1908397	KW-2449	1
CHEMBL296468	BMS-387032	1
CHEMBL4225966	SEL-120 FREE BASE	1
CHEMBL494089	GSK-690693	1
CHEMBL5426285	5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-	1
CHEMBL574738	AST-487	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — HIPK subfamily

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
silmitasertib	Inhibition	7.35	pIC50

ChEMBL bioactivities

72 potent at pChembl≥5 of 73 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.40	Kd	4	nM	AST-487
7.42	IC50	38	nM	CHEMBL4750420
7.40	IC50	40	nM	CHEMBL3103192
7.39	Kd	41	nM	SUNITINIB
7.37	Kd	43	nM	FORETINIB
7.35	IC50	45	nM	SILMITASERTIB
7.20	Kd	63	nM	PHA-665752
7.19	IC50	65	nM	CHEMBL4743730
7.18	IC50	66	nM	CHEMBL4743939
7.12	Kd	75	nM	STAUROSPORINE
7.11	Kd	77	nM	RUBOXISTAURIN
7.08	Kd	83	nM	SU-014813
7.00	IC50	100	nM	FORETINIB
7.00	IC50	100	nM	RUBOXISTAURIN
7.00	IC50	100	nM	SORAFENIB
7.00	IC50	100	nM	PHA-665752
6.96	Kd	110	nM	CHEMBL379218
6.90	IC50	125	nM	CHEMBL4797457
6.89	IC50	128	nM	CHEMBL4762964
6.89	IC50	128	nM	CHEMBL4790030
6.89	Kd	130	nM	CHEMBL1241674
6.88	IC50	131.8	nM	SEL-120 FREE BASE
6.80	IC50	159	nM	CHEMBL4754195
6.79	IC50	164	nM	CHEMBL4789951
6.70	IC50	202	nM	STAUROSPORINE
6.70	Kd	200	nM	GSK-690693
6.64	Kd	230	nM	CHEMBL1802358
6.60	Kd	250	nM	LESTAURTINIB
6.55	IC50	283	nM	CHEMBL4778153
6.52	IC50	300	nM	CHEMBL4791451
6.51	Kd	310	nM	PI-103
6.41	Kd	390	nM	SORAFENIB
6.36	IC50	441	nM	CHEMBL4740998
6.36	Kd	440	nM	SORAFENIB
6.32	IC50	476	nM	CHEMBL4777288
6.32	Kd	480	nM	CHEMBL2048872
6.30	IC50	502.9	nM	CHEMBL5561973
6.24	Kd	580	nM	KW-2449
6.23	IC50	591	nM	STAUROSPORINE
6.22	Kd	600	nM	PICTILISIB
6.20	IC50	634	nM	5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-
6.16	IC50	692	nM	CHEMBL4741919
6.15	IC50	710	nM	STAUROSPORINE
6.14	IC50	720	nM	CHEMBL4777533
6.10	Kd	798	nM	CHEMBL4465866
6.09	IC50	807	nM	CHEMBL4778370
6.07	Kd	850	nM	NINTEDANIB
6.00	IC50	1000	nM	TP-030n
5.99	Kd	1030	nM	CHEMBL4576489
5.92	Kd	1200	nM	RUXOLITINIB

PubChem BioAssay actives

68 with measured affinity, of 720 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
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	625023: Binding constant for HIPK3 kinase domain	kd	0.0040	uM
3-naphthalen-2-yl-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733096: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay	ic50	0.0380	uM
N-[2-[2-aminoethyl(methyl)amino]-5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]phenyl]acetamide	1301614: Inhibition of Hipk3 (unknown origin) by quantitative PCR	ic50	0.0400	uM
Sunitinib	507971: Binding affinity to HIPK3	kd	0.0410	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	625023: Binding constant for HIPK3 kinase domain	kd	0.0430	uM
5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylic acid	1705056: Inhibition of recombinant human HIPK3 in presence of ATP at Km concentration by radiometric filter-binding assay	ic50	0.0450	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	625023: Binding constant for HIPK3 kinase domain	kd	0.0630	uM
3-(4-prop-1-en-2-ylphenyl)-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733096: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay	ic50	0.0650	uM
3-(4-methoxyphenyl)-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733096: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay	ic50	0.0660	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	625023: Binding constant for HIPK3 kinase domain	kd	0.0750	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	625023: Binding constant for HIPK3 kinase domain	kd	0.0770	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	625023: Binding constant for HIPK3 kinase domain	kd	0.0830	uM
Sorafenib	1733113: Inhibition of HIPK3 (unknown origin)	ic50	0.1000	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625023: Binding constant for HIPK3 kinase domain	kd	0.1100	uM
5-(1-methylpyrazol-4-yl)-3-[3-(1-methylpyrazol-4-yl)phenyl]furo[3,2-b]pyridine	1733096: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay	ic50	0.1250	uM
3-phenyl-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733096: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay	ic50	0.1280	uM
5-(1-methylpyrazol-4-yl)-3-[3-(1H-pyrazol-5-yl)phenyl]furo[3,2-b]pyridine	1733096: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay	ic50	0.1280	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	625023: Binding constant for HIPK3 kinase domain	kd	0.1300	uM
6,7-dibromo-5-methyl-2-piperazin-1-yl-1,3-diazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraene	2070985: Inhibition of HIPK3 (unknown origin) by ADP-Glo assay	ic50	0.1318	uM
5-(1-methylpyrazol-4-yl)-3-(3-pyridin-4-ylphenyl)furo[3,2-b]pyridine	1722640: Inhibition of human HIPK3 by radiometric assay	ic50	0.1590	uM
5-(1-methylpyrazol-4-yl)-3-[3-(1H-pyrazol-4-yl)phenyl]furo[3,2-b]pyridine	1733096: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay	ic50	0.1640	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	625023: Binding constant for HIPK3 kinase domain	kd	0.2000	uM
(4Z)-2-anilino-4-(1,3-benzodioxol-5-ylmethylidene)-1H-imidazol-5-one	707478: Binding affinity to HIPK3	kd	0.2300	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	507971: Binding affinity to HIPK3	kd	0.2500	uM
3-(4-tert-butylphenyl)-5-(2H-triazol-4-yl)furo[3,2-b]pyridine	1733096: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay	ic50	0.2830	uM
5-(1-methylpyrazol-4-yl)-3-(3-piperidin-4-ylphenyl)furo[3,2-b]pyridine	1733096: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay	ic50	0.3000	uM
3-(6-morpholin-4-yl-8-oxa-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaen-4-yl)phenol	625023: Binding constant for HIPK3 kinase domain	kd	0.3100	uM
3-[4-(1-methylcyclopropyl)phenyl]-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733096: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay	ic50	0.4410	uM
3-(4-tert-butylphenyl)-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733096: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay	ic50	0.4760	uM
5,6-dibromo-4-(difluoromethyl)-1-(oxan-4-yl)-2-piperazin-1-ylbenzimidazole	2070985: Inhibition of HIPK3 (unknown origin) by ADP-Glo assay	ic50	0.5029	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625023: Binding constant for HIPK3 kinase domain	kd	0.5800	uM
4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine	625023: Binding constant for HIPK3 kinase domain	kd	0.6000	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2R)-1-methoxy-4-methylpentan-2-yl]iminoimidazolidin-4-one	2024508: Inhibition of human HIPK3 assessed as remaining activity by eurofins-cerep kinase profiler analysis	ic50	0.6340	uM
3-[3-(1-methylpiperidin-4-yl)phenyl]-5-(1-methylpyrazol-4-yl)furo[3,2-b]pyridine	1733096: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay	ic50	0.6920	uM
3-(4-tert-butylphenyl)-5-(2H-tetrazol-5-yl)furo[3,2-b]pyridine	1733096: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay	ic50	0.7200	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526199: Binding affinity to recombinant N-terminal His-FLAG-GST-tagged HIPK3 (unknown origin) (161 to 562 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.7980	uM
3-(4-phenylphenyl)-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733096: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay	ic50	0.8070	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625023: Binding constant for HIPK3 kinase domain	kd	0.8500	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526199: Binding affinity to recombinant N-terminal His-FLAG-GST-tagged HIPK3 (unknown origin) (161 to 562 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	1.0300	uM
Ruxolitinib	625023: Binding constant for HIPK3 kinase domain	kd	1.2000	uM
3-[4-(2-methylpropyl)phenyl]-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733096: Inhibition of human recombinant HIPK3 using myelin substrate by radiometric scintillation assay	ic50	1.2270	uM
Fedratinib	625023: Binding constant for HIPK3 kinase domain	kd	1.3000	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	625023: Binding constant for HIPK3 kinase domain	kd	2.0000	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	625023: Binding constant for HIPK3 kinase domain	kd	2.3000	uM
Midostaurin	507971: Binding affinity to HIPK3	kd	2.3000	uM
2-[3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]quinazolin-4-yl]amino]-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide	625023: Binding constant for HIPK3 kinase domain	kd	2.5000	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625023: Binding constant for HIPK3 kinase domain	kd	3.2000	uM
Bosutinib	625023: Binding constant for HIPK3 kinase domain	kd	3.2000	uM
2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide	625023: Binding constant for HIPK3 kinase domain	kd	3.4000	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	625023: Binding constant for HIPK3 kinase domain	kd	3.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects localization, decreases expression, increases reaction, increases abundance, increases expression	3
Benzo(a)pyrene	increases expression, decreases expression	3
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
methylmercuric chloride	increases expression	1
bisphenol A	increases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
jinfukang	decreases expression	1
Fulvestrant	increases methylation	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Cisplatin	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Lead	affects expression	1
Lipopolysaccharides	increases expression	1
Methyl Methanesulfonate	increases expression	1
Silicon Dioxide	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	affects expression	1

ChEMBL screening assays

229 unique, capped per target: 229 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004126	Binding	Inhibition of HIPK3 at 1 uM relative to control	Novel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1TP	Abcam HeLa HIPK3 KO	Cancer cell line	Female
CVCL_SR47	HAP1 HIPK3 (-) 1	Cancer cell line	Male
CVCL_SR48	HAP1 HIPK3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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