HIPK1

Summary

HIPK1 (homeodomain interacting protein kinase 1, HGNC:19006) is a protein-coding gene on chromosome 1p13.2, encoding Homeodomain-interacting protein kinase 1 (Q86Z02). Serine/threonine-protein kinase involved in transcription regulation and TNF-mediated cellular apoptosis.

The protein encoded by this gene belongs to the Ser/Thr family of protein kinases and HIPK subfamily. It phosphorylates homeodomain transcription factors and may also function as a co-repressor for homeodomain transcription factors. Alternative splicing results in four transcript variants encoding four distinct isoforms.

Source: NCBI Gene 204851 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 136 total
• Druggable target: yes — 21 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_198268

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19006
Approved symbol	HIPK1
Name	homeodomain interacting protein kinase 1
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0630, Myak, MGC26642, Nbak2, MGC33446, MGC33548
Ensembl gene	ENSG00000163349
Ensembl biotype	protein_coding
OMIM	608003
Entrez	204851

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 20 protein_coding

ENST00000340480, ENST00000361587, ENST00000369553, ENST00000369555, ENST00000369558, ENST00000369559, ENST00000369561, ENST00000426820, ENST00000503968, ENST00000514621, ENST00000626993, ENST00000901068, ENST00000901069, ENST00000901070, ENST00000901071, ENST00000901072, ENST00000931241, ENST00000931242, ENST00000931243, ENST00000931244

RefSeq mRNA: 7 — MANE Select: NM_198268 NM_001369806, NM_001369807, NM_001410847, NM_152696, NM_181358, NM_198268, NM_198269

CCDS: CCDS41370, CCDS867, CCDS868, CCDS869, CCDS91025

Canonical transcript exons

ENST00000426820 — 16 exons

Exon	Start	End
ENSE00000784434	113967766	113967948
ENSE00000784435	113968442	113968648
ENSE00001186485	113971824	113971954
ENSE00001186489	113969956	113970197
ENSE00001436280	113966130	113966272
ENSE00001610208	113958066	113958291
ENSE00001612587	113963387	113963521
ENSE00001645886	113954651	113954770
ENSE00001667987	113962317	113962438
ENSE00001696467	113955563	113955649
ENSE00001722917	113956627	113956811
ENSE00001753712	113957124	113957286
ENSE00002224072	113929324	113929532
ENSE00003528342	113952766	113952889
ENSE00003697666	113940382	113941459
ENSE00003770814	113973024	113977869

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.5979 / max 3376.5819, expressed in 1809 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4733	38.2177	1804
4735	0.8849	423
4734	0.6339	306
4732	0.4653	119
4731	0.4012	184
4730	0.3325	66
4739	0.2082	35
4737	0.2020	74
4736	0.1296	40
4740	0.0706	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	98.52	gold quality
cerebellar vermis	UBERON:0004720	97.79	gold quality
epithelium of bronchus	UBERON:0002031	97.78	gold quality
bronchus	UBERON:0002185	97.59	gold quality
endometrium epithelium	UBERON:0004811	97.46	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.39	gold quality
paraflocculus	UBERON:0005351	97.11	gold quality
choroid plexus epithelium	UBERON:0003911	96.96	gold quality
caput epididymis	UBERON:0004358	96.93	gold quality
adult organism	UBERON:0007023	96.86	gold quality
buccal mucosa cell	CL:0002336	96.69	gold quality
thymus	UBERON:0002370	96.67	gold quality
bone marrow	UBERON:0002371	96.08	gold quality
trabecular bone tissue	UBERON:0002483	95.88	gold quality
medial globus pallidus	UBERON:0002477	95.18	gold quality
superficial temporal artery	UBERON:0001614	95.13	gold quality
epithelium of nasopharynx	UBERON:0001951	95.03	gold quality
palpebral conjunctiva	UBERON:0001812	94.97	gold quality
sperm	CL:0000019	94.82	gold quality
bone marrow cell	CL:0002092	94.82	gold quality
pigmented layer of retina	UBERON:0001782	94.75	gold quality
nasal cavity epithelium	UBERON:0005384	94.53	gold quality
blood vessel layer	UBERON:0004797	94.40	gold quality
cauda epididymis	UBERON:0004360	94.34	gold quality
heart right ventricle	UBERON:0002080	94.28	gold quality
nasal cavity mucosa	UBERON:0001826	94.26	gold quality
oral cavity	UBERON:0000167	94.25	gold quality
amniotic fluid	UBERON:0000173	94.16	gold quality
globus pallidus	UBERON:0001875	94.07	gold quality
seminal vesicle	UBERON:0000998	93.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYB, TP53

miRNA regulators (miRDB)

380 targeting HIPK1, 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-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
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-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-4262	100.00	73.26	3931
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298

Literature-anchored findings (GeneRIF, showing 15)

• TNFalpha-induced desumoylation and cytoplasmic translocation of HIPK1 are critical in TNFalpha-induced ASK1-JNK/p38 activation (PMID:15701637)
• c-Myb appears to be phosphorylated by HIPK1 in its negative regulatory domain as supported by both in vivo and in vitro data. (PMID:19646965)
• These findings indicate that the control of HIPK1 stability by Mdm2-NORE1 has a major effect on cell behaviour, and epigenetic inactivation of NORE1 enables adenocarcinoma formation in vivo through HIPK1 stabilization. (PMID:22173032)
• HIPK1 expression was identified only in invasive breast cancer cells with three different patterns: cytoplasmic, nuclear, and both cytoplasmic and nuclear. (PMID:23071292)
• HIPK1 and HIPK2, are transcriptional corepressors that regulate TGF-beta-dependent angiogenesis during embryonic development. (PMID:23565059)
• HIPK1 drives p53 activation to limit colorectal cancer cell growth. (PMID:23676219)
• PAGE4, a regulator of c-Jun transactivation, is phosphorylated by homeodomain-interacting protein kinase 1. (PMID:24559171)
• Analysis of these mutants revealed that HIPK1, HIPK2 and HIPK3 but not HIPK4 are capable of autophosphorylating on other tyrosines (PMID:25630557)
• The data presented here con fi rmed that HIPK1 is involved in the increased expression of recombinant luciferase and the secreted recombinant GPC3-hFc from HEK 293 cells following transfection with miR-22-3p. (PMID:28987030)
• 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)
• MicroRNA-889-3p restrains the proliferation and epithelial-mesenchymal transformation of lung cancer cells via down-regulation of Homeodomain-interacting protein kinase 1. (PMID:34723781)
• Abemaciclib is a potent inhibitor of DYRK1A and HIP kinases involved in transcriptional regulation. (PMID:34785661)
• Downregulation of circ-ZNF644 alleviates LPS-induced HK2 cell injury via miR-335-5p/HIPK1 axis. (PMID:36052886)
• HIPK1 Inhibition Protects against Pathological Cardiac Hypertrophy by Inhibiting the CREB-C/EBPbeta Axis. (PMID:37098980)
• Tyr352 as a Predominant Phosphosite in the Understudied Kinase and Molecular Target, HIPK1: Implications for Cancer Therapy. (PMID:38498023)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	hipk1a	ENSDARG00000063594
danio_rerio	hipk1b	ENSDARG00000077095
mus_musculus	Hipk1	ENSMUSG00000008730
rattus_norvegicus	Hipk1	ENSRNOG00000019333
drosophila_melanogaster	mnb	FBGN0259168
caenorhabditis_elegans		WBGENE00003149
caenorhabditis_elegans		WBGENE00013727
caenorhabditis_elegans		WBGENE00185089

Paralogs (12): DYRK4 (ENSG00000010219), CLK1 (ENSG00000013441), HIPK2 (ENSG00000064393), DYRK1B (ENSG00000105204), HIPK3 (ENSG00000110422), CLK4 (ENSG00000113240), DYRK2 (ENSG00000127334), DYRK3 (ENSG00000143479), DYRK1A (ENSG00000157540), HIPK4 (ENSG00000160396), CLK2 (ENSG00000176444), CLK3 (ENSG00000179335)

Protein

Protein identifiers

Homeodomain-interacting protein kinase 1 — Q86Z02 (reviewed: Q86Z02)

Alternative names: Nuclear body-associated kinase 2

All UniProt accessions (6): D6RC95, D6RF28, Q86Z02, H3BLW0, J3KP92, Q5SQL3

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in transcription regulation and TNF-mediated cellular apoptosis. Plays a role as a corepressor for homeodomain transcription factors. Phosphorylates DAXX and MYB. Phosphorylates DAXX in response to stress, and mediates its translocation from the nucleus to the cytoplasm. Inactivates MYB transcription factor activity by phosphorylation. Prevents MAP3K5-JNK activation in the absence of TNF. TNF triggers its translocation to the cytoplasm in response to stress stimuli, thus activating nuclear MAP3K5-JNK by derepression and promoting apoptosis. May be involved in anti-oxidative stress responses. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. Promotes angiogenesis and to be involved in erythroid differentiation. May be involved in malignant squamous cell tumor formation. Phosphorylates PAGE4 at ‘Thr-51’ which is critical for the ability of PAGE4 to potentiate the transcriptional activator activity of JUN.

Subunit / interactions. Interacts with Nkx1-2, Nkx2-5, MYB, PARK7, DAXX and p53/TP53. Part of a cytoplasmic complex made of HIPK1, DAB2IP and MAP3K5 in response to TNF. This complex formation promotes MAP3K5-JNK activation and subsequent apoptosis.

Subcellular location. Nucleus. Cytoplasm. Nucleus speckle.

Tissue specificity. Ubiquitously expressed with highest levels in skeletal muscle and heart. Overexpressed in breast cancer cell lines. Isoform 2 is highly expressed in testis. Expressed in both androgen-dependent and androgen-independent prostate cancer cells.

Post-translational modifications. Autophosphorylated. Phosphorylated and activated by JNK1. Degraded by PARK7 at the protein level. Sumoylated. When conjugated it is directed to nuclear speckles. SENP1-mediated desumoylation is mediated by TNF in response to stress stimuli, triggering transient translocation from nucleus to cytoplasm.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q86Z02-1	1, HIPK1-alpha	yes
Q86Z02-2	2, HIPK1-beta
Q86Z02-3	3
Q86Z02-4	4

RefSeq proteins (7): NP_001356735, NP_001356736, NP_001397776, NP_689909, NP_852003, NP_938009, NP_938010 (=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 (44 total): region of interest 7, mutagenesis site 7, cross-link 6, splice variant 5, sequence conflict 4, compositionally biased region 3, modified residue 3, sequence variant 3, binding site 2, chain 1, domain 1, active site 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86Z02-F1	52.62	0.28

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): 315 (proton acceptor)

Ligand- & substrate-binding residues (2): 196–204; 219

Post-translational modifications (9): 872, 967, 1200, 25, 25, 120, 124, 991, 1203

Mutagenesis-validated functional residues (7):

Position	Phenotype
25	reduced sumoylation and cytoplasmic subcellular location. impaired sumoylation and cytoplasmic subcellular location; whe
219	loss of kinase activity.
315	loss of kinase activity and impaired map3k5-jnk inactivation.
317	nuclear subcellular location. impaired sumoylation and cytoplasmic subcellular location; when associated with r-25; r-44
440	nuclear subcellular location. impaired sumoylation and cytoplasmic subcellular location; when associated with r-25; r-31
556	nuclear subcellular location. impaired sumoylation and cytoplasmic subcellular location; when associated with r-25; r-31
1203	nuclear subcellular location. impaired sumoylation and cytoplasmic subcellular location; when associated with r-25; r-31

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2032785	YAP1- and WWTR1 (TAZ)-stimulated gene expression
R-HSA-5578768	Physiological factors
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation

MSigDB gene sets: 421 (showing top): GCM_MAP4K4, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, FREAC2_01, GGTGTGT_MIR329, GOBP_RESPONSE_TO_PEPTIDE, GCM_ZNF198, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_DEVELOPMENTAL_INDUCTION, GOBP_NEUROGENESIS, GOBP_NEURAL_RETINA_DEVELOPMENT, FOXO1_01, SP1_Q2_01, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP

GO Biological Process (19): eye development (GO:0001654), protein phosphorylation (GO:0006468), smoothened signaling pathway (GO:0007224), cell population proliferation (GO:0008283), positive regulation of cell population proliferation (GO:0008284), anterior/posterior pattern specification (GO:0009952), regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803), retina layer formation (GO:0010842), neuron differentiation (GO:0030182), adherens junction assembly (GO:0034333), intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:0042771), positive regulation of angiogenesis (GO:0045766), embryonic camera-type eye morphogenesis (GO:0048596), embryonic retina morphogenesis in camera-type eye (GO:0060059), definitive hemopoiesis (GO:0060216), lens induction in camera-type eye (GO:0060235), iris morphogenesis (GO:0061072), endothelial cell apoptotic process (GO:0072577), extrinsic apoptotic signaling pathway (GO:0097191)

GO Molecular Function (9): 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), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), PML body (GO:0016605), nuclear speck (GO:0016607), ciliary basal body (GO:0036064)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Generic Transcription Pathway	1
Cardiac conduction	1
Regulation of TP53 Activity	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	3
cellular anatomical structure	3
cell surface receptor signaling pathway	2
retina morphogenesis in camera-type eye	2
camera-type eye morphogenesis	2
microtubule organizing center	2
sensory organ development	1
visual system development	1
phosphorylation	1
protein modification process	1
cellular process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regionalization	1
regulation of cytokine-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
neural retina development	1
anatomical structure formation involved in morphogenesis	1
cell differentiation	1
generation of neurons	1
cell-cell junction assembly	1
adherens junction organization	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
intrinsic apoptotic signaling pathway by p53 class mediator	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
embryonic camera-type eye development	1
embryonic eye morphogenesis	1
embryonic morphogenesis	1
hemopoiesis	1
lens morphogenesis in camera-type eye	1
developmental induction	1
anatomical structure morphogenesis	1
apoptotic process	1
apoptotic signaling pathway	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1

Protein interactions and networks

STRING

902 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HIPK1	DAXX	Q9UER7	734
HIPK1	PML	P29590	674
HIPK1	PAGE4	O60829	577
HIPK1	TP53	P04637	571
HIPK1	HMBOX1	Q6NT76	491
HIPK1	MDM2	Q00987	483
HIPK1	RITA1	Q96K30	462
HIPK1	TP63	Q9H3D4	428
HIPK1	MEF2C	Q06413	417
HIPK1	NFYB	P25208	396
HIPK1	ARX	Q96QS3	345
HIPK1	ACTR6	Q9GZN1	330
HIPK1	DCAF7	P61962	313
HIPK1	ZEB1	P37275	301
HIPK1	CITED4	Q96RK1	289

IntAct

35 interactions, top by confidence:

A	B	Type	Score
FHL3	HIPK1	psi-mi:“MI:0915”(physical association)	0.740
HIPK1	FHL3	psi-mi:“MI:0915”(physical association)	0.740
FOXP3	FOXP2	psi-mi:“MI:0914”(association)	0.530
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
TP53	HIPK1	psi-mi:“MI:0915”(physical association)	0.510
Rassf5	HIPK1	psi-mi:“MI:0915”(physical association)	0.460
HIPK1	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
DAXX	HIPK1	psi-mi:“MI:0915”(physical association)	0.400
HIPK1	Daxx	psi-mi:“MI:0915”(physical association)	0.400
HIPK1	USP20	psi-mi:“MI:0915”(physical association)	0.400
RASSF5	HIPK1	psi-mi:“MI:0915”(physical association)	0.400
HIPK1	ATP13A2	psi-mi:“MI:0915”(physical association)	0.370
HIPK1	SKIL	psi-mi:“MI:0915”(physical association)	0.370
HIPK1	PRPF40A	psi-mi:“MI:0915”(physical association)	0.370
SNIP1	HIPK1	psi-mi:“MI:0915”(physical association)	0.370
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AHRR	psi-mi:“MI:0914”(association)	0.350
FHL3	COBL	psi-mi:“MI:0914”(association)	0.350
SHARPIN	ZNF609	psi-mi:“MI:0914”(association)	0.350
FHL3		psi-mi:“MI:0914”(association)	0.350
HIPK1	HAX1	psi-mi:“MI:0914”(association)	0.350
HIPK1	MDM2	psi-mi:“MI:0403”(colocalization)	0.270
KHDRBS1	HIPK1	psi-mi:“MI:0915”(physical association)	0.000
APOE	HIPK1	psi-mi:“MI:0915”(physical association)	0.000
HIPK1	GLUL	psi-mi:“MI:0915”(physical association)	0.000
HIPK1	UBE2I	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (52): HIPK1 (Two-hybrid), HIPK1 (Affinity Capture-MS), HIPK1 (Affinity Capture-MS), HIPK1 (Affinity Capture-MS), HIPK1 (Affinity Capture-RNA), TP53 (Affinity Capture-Western), TP53 (Two-hybrid), HIPK1 (Two-hybrid), HIPK1 (Two-hybrid), FHL3 (Two-hybrid), HIPK1 (Affinity Capture-MS), HIPK1 (Biochemical Activity), HIPK1 (Affinity Capture-MS), HIPK1 (Affinity Capture-MS), HIPK1 (Affinity Capture-MS)

ESM2 similar proteins: A0AVK6, A4L9P5, B2GUN4, D2HNW6, D3ZGB1, E1BKK0, E1BP74, E1BZ85, F1LMN3, O14607, O15164, O15550, O70546, O88850, O88904, O94916, Q14B70, Q58CW6, Q58FA4, Q5RJA1, Q5ZKW8, Q64127, Q6B4Z3, Q7Z353, Q7Z3K3, Q84VX4, Q86Z02, Q8BJ34, Q8BZH4, Q8C7R7, Q8HWS3, Q8IXK0, Q8K0L9, Q8N187, Q93073, Q99743, Q99MQ1, Q99PP7, Q9BYH8, Q9ERH7

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

3 interactions.

A	Effect	B	Mechanism
HIPK1	“down-regulates activity”	DAXX	phosphorylation
HIPK1	“up-regulates activity”	PAGE4	phosphorylation
HIPK1	“down-regulates activity”	MYB	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 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.

GO biological processes:

GO term	Partners	Fold	FDR
regulation of apoptotic process	5	14.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	113
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2676 predictions. Top by Δscore:

Variant	Effect	Δscore
1:113929533:G:GG	donor_gain	1.0000
1:113940375:A:AG	acceptor_gain	1.0000
1:113940377:TATA:T	acceptor_loss	1.0000
1:113940378:ATAG:A	acceptor_gain	1.0000
1:113940380:A:AG	acceptor_gain	1.0000
1:113940380:A:AT	acceptor_loss	1.0000
1:113940380:AG:A	acceptor_gain	1.0000
1:113940381:G:GA	acceptor_gain	1.0000
1:113940381:GG:G	acceptor_gain	1.0000
1:113940381:GGT:G	acceptor_gain	1.0000
1:113940381:GGTA:G	acceptor_gain	1.0000
1:113940381:GGTAT:G	acceptor_gain	1.0000
1:113952760:T:TA	acceptor_gain	1.0000
1:113952764:A:AG	acceptor_gain	1.0000
1:113952765:G:GG	acceptor_gain	1.0000
1:113952765:GA:G	acceptor_gain	1.0000
1:113955558:TATA:T	acceptor_loss	1.0000
1:113955559:A:AG	acceptor_gain	1.0000
1:113955560:T:G	acceptor_gain	1.0000
1:113955560:TAGAC:T	acceptor_loss	1.0000
1:113955561:A:AG	acceptor_gain	1.0000
1:113955562:G:GA	acceptor_gain	1.0000
1:113955562:GA:G	acceptor_gain	1.0000
1:113955562:GAC:G	acceptor_gain	1.0000
1:113955562:GACA:G	acceptor_gain	1.0000
1:113955562:GACAC:G	acceptor_gain	1.0000
1:113955613:G:GT	donor_gain	1.0000
1:113955650:G:GG	donor_gain	1.0000
1:113955651:T:G	donor_loss	1.0000
1:113956730:A:G	donor_gain	1.0000

AlphaMissense

7867 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:113940925:A:T	E181V	1.000
1:113940931:T:A	L183H	1.000
1:113940931:T:C	L183P	1.000
1:113940937:C:T	S185F	1.000
1:113940951:T:G	Y190D	1.000
1:113940952:A:C	Y190S	1.000
1:113940958:T:A	V192D	1.000
1:113940966:T:C	F195L	1.000
1:113940967:T:C	F195S	1.000
1:113940968:C:A	F195L	1.000
1:113940968:C:G	F195L	1.000
1:113940970:T:C	L196P	1.000
1:113940972:G:C	G197R	1.000
1:113940972:G:T	G197C	1.000
1:113940973:G:A	G197D	1.000
1:113940973:G:T	G197V	1.000
1:113940978:G:A	G199R	1.000
1:113940978:G:C	G199R	1.000
1:113940978:G:T	G199W	1.000
1:113940979:G:A	G199E	1.000
1:113940979:G:C	G199A	1.000
1:113940979:G:T	G199V	1.000
1:113940984:T:A	F201I	1.000
1:113940984:T:C	F201L	1.000
1:113940984:T:G	F201V	1.000
1:113940985:T:C	F201S	1.000
1:113940985:T:G	F201C	1.000
1:113940986:T:A	F201L	1.000
1:113940986:T:G	F201L	1.000
1:113940987:G:A	G202R	1.000

dbSNP variants (sampled 300 via entrez): RS1000042630 (1:113935236 G>A), RS1000068284 (1:113935092 C>T), RS1000090081 (1:113959259 T>C), RS1000109384 (1:113936685 G>A), RS1000122783 (1:113931824 A>T), RS1000172318 (1:113942098 A>C), RS1000175667 (1:113931538 T>C), RS1000323633 (1:113951877 G>A), RS1000385279 (1:113937546 A>G), RS1000414760 (1:113947983 A>C,G), RS1000481508 (1:113945256 T>A,C), RS1000521447 (1:113935030 T>A), RS1000528 (1:113928567 C>A,G,T), RS1000560594 (1:113939971 T>C), RS1000620351 (1:113964771 T>G)

Disease associations

OMIM: gene MIM:608003 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001937_47	Breast cancer	2.000000e-08
GCST004866_5	Alopecia areata	7.000000e-07
GCST005537_135	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	5.000000e-08
GCST006979_1000	Heel bone mineral density	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5427 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

21 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 252,941 (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
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2	363
CHEMBL475251	R-406	2	762
CHEMBL513909	BI-2536	2	895
CHEMBL521851	PICTILISIB	2	6,071
CHEMBL1908397	KW-2449	1	622
CHEMBL296468	BMS-387032	1	2,075
CHEMBL494089	GSK-690693	1	2,061
CHEMBL5426285	5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-	1	4
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
staurosporine	Inhibition	5.58	pIC50

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[2-(cyclopropanecarbonylamino)-[1,3]thiazolo[5,4-b]pyridin-5-yl]-N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	KD	57 nM	US-8765747: Fused 2-aminothiazole compounds

ChEMBL bioactivities

80 potent at pChembl≥5 of 87 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.44	IC50	0.367	nM	CHEMBL1591531
7.80	IC50	16	nM	CHEMBL4750420
7.48	IC50	33	nM	CHEMBL4743939
7.47	Kd	34	nM	CHEMBL2148124
7.40	IC50	40	nM	CHEMBL3103192
7.29	IC50	51	nM	CHEMBL4743730
7.26	Kd	55	nM	SUNITINIB
7.21	IC50	62	nM	CHEMBL4790030
7.03	Kd	93	nM	PHA-665752
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
6.90	IC50	125	nM	CHEMBL4762964
6.80	Kd	160	nM	CHEMBL4066819
6.77	Kd	170	nM	AST-487
6.75	IC50	177	nM	CHEMBL4789951
6.73	IC50	187	nM	CHEMBL4754195
6.68	IC50	209	nM	CHEMBL4797457
6.66	IC50	220	nM	CHEMBL4740998
6.64	Kd	230	nM	CHEMBL379218
6.64	Kd	230	nM	RUBOXISTAURIN
6.63	IC50	235	nM	CHEMBL4790791
6.61	IC50	248	nM	CHEMBL4777288
6.58	IC50	264	nM	CHEMBL4791451
6.56	IC50	278	nM	CHEMBL4778370
6.54	IC50	285	nM	CHEMBL4778153
6.52	Kd	300	nM	CHEMBL1241674
6.50	Kd	320	nM	CHEMBL1802358
6.45	IC50	354	nM	CHEMBL4741919
6.38	Kd	420	nM	FORETINIB
6.37	Kd	430	nM	KW-2449
6.29	Kd	510	nM	GSK-690693
6.28	Kd	520	nM	BOSUTINIB
6.26	IC50	545	nM	CHEMBL4777533
6.23	Kd	590	nM	LESTAURTINIB
6.21	IC50	621	nM	BISINDOLYLMALEIMIDE IX
6.16	IC50	685	nM	CHEMBL4794825
6.10	IC50	798	nM	CHEMBL5559304
6.09	Kd	820	nM	R-406
6.07	Kd	860	nM	FEDRATINIB
6.04	IC50	922	nM	CHEMBL3780758
6.04	IC50	921	nM	CHEMBL4789373
6.01	Kd	970	nM	SU-014813
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
6.00	Kd	1000	nM	ENZASTAURIN
5.96	Kd	1100	nM	CHEMBL4781866
5.96	Kd	1100	nM	SORAFENIB

PubChem BioAssay actives

69 with measured affinity, of 731 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
methanesulfonic acid;3-[3-[4-(1-methylindol-3-yl)-2,5-dioxopyrrol-3-yl]indol-1-yl]propyl carbamimidothioate	1350978: Inhibition of HIPK1 (unknown origin)	ic50	0.0004	uM
Abemaciclib	1551239: Inhibition of wild-type human partial length HIPK1 (M146 to I555 residues) expressed in mammalian expression system assessed as residual activity at 50 nM by Kinomescan method relative to control	ki	0.0100	uM
3-naphthalen-2-yl-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.0160	uM
3-(4-methoxyphenyl)-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.0330	uM
N-[2-[2-aminoethyl(methyl)amino]-5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]phenyl]acetamide	1301612: Inhibition of Hipk1 (unknown origin) by quantitative PCR	ic50	0.0400	uM
3-(4-prop-1-en-2-ylphenyl)-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.0510	uM
Sunitinib	624726: Binding constant for HIPK1 kinase domain	kd	0.0550	uM
3-phenyl-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.0620	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	624726: Binding constant for HIPK1 kinase domain	kd	0.0930	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	1733111: Inhibition of HIPK1 (unknown origin)	ic50	0.1000	uM
Sorafenib	1733111: Inhibition of HIPK1 (unknown origin)	ic50	0.1000	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	1733111: Inhibition of HIPK1 (unknown origin)	ic50	0.1000	uM
5-(1-methylpyrazol-4-yl)-3-[3-(1H-pyrazol-5-yl)phenyl]furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.1250	uM
8-[[6-(2-methoxyethylcarbamoyl)-3-pyridinyl]oxy]-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474318: Binding affinity to partial length human HIPK1 (M146 to I555 residues) expressed in mammalian expression system by kinome scan assay	kd	0.1600	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	624726: Binding constant for HIPK1 kinase domain	kd	0.1700	uM
5-(1-methylpyrazol-4-yl)-3-[3-(1H-pyrazol-4-yl)phenyl]furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.1770	uM
5-(1-methylpyrazol-4-yl)-3-(3-pyridin-4-ylphenyl)furo[3,2-b]pyridine	1722638: Inhibition of human HIPK1 by radiometric assay	ic50	0.1870	uM
5-(1-methylpyrazol-4-yl)-3-[3-(1-methylpyrazol-4-yl)phenyl]furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.2090	uM
3-[4-(1-methylcyclopropyl)phenyl]-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.2200	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624726: Binding constant for HIPK1 kinase domain	kd	0.2300	uM
3-(1-methylpyrazol-4-yl)-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.2350	uM
3-(4-tert-butylphenyl)-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.2480	uM
5-(1-methylpyrazol-4-yl)-3-(3-piperidin-4-ylphenyl)furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.2640	uM
3-(4-phenylphenyl)-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.2780	uM
3-(4-tert-butylphenyl)-5-(2H-triazol-4-yl)furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.2850	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624726: Binding constant for HIPK1 kinase domain	kd	0.3000	uM
(4Z)-2-anilino-4-(1,3-benzodioxol-5-ylmethylidene)-1H-imidazol-5-one	707481: Binding affinity to HIPK1	kd	0.3200	uM
3-[3-(1-methylpiperidin-4-yl)phenyl]-5-(1-methylpyrazol-4-yl)furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.3540	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624726: Binding constant for HIPK1 kinase domain	kd	0.4300	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	624726: Binding constant for HIPK1 kinase domain	kd	0.5100	uM
Bosutinib	624726: Binding constant for HIPK1 kinase domain	kd	0.5200	uM
3-(4-tert-butylphenyl)-5-(2H-tetrazol-5-yl)furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.5450	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	507969: Binding affinity to HIPK1	kd	0.5900	uM
3-[3-[4-(1-methylindol-3-yl)-2,5-dioxopyrrol-3-yl]indol-1-yl]propyl carbamimidothioate	1531719: Inhibition of human HIPK1 using MBP as substrate by [gamma-33P]-ATP assay	ic50	0.6210	uM
3-[4-(2-methylpropyl)phenyl]-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.6850	uM
N-[(2S)-1-(azetidin-1-yl)propan-2-yl]-3-[2-(3,5-dimethoxyanilino)pyrimidin-4-yl]-1-methylpyrazole-5-carboxamide	2075975: Inhibition of HIPK1 (unknown origin)	ic50	0.7980	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	624726: Binding constant for HIPK1 kinase domain	kd	0.8200	uM
Fedratinib	624726: Binding constant for HIPK1 kinase domain	kd	0.8600	uM
3-(4-benzylphenyl)-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine	1733094: Inhibition of human recombinant HIPK1 using myelin substrate by radiometric scintillation assay	ic50	0.9210	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	624726: Binding constant for HIPK1 kinase domain	kd	0.9700	uM
3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione	624726: Binding constant for HIPK1 kinase domain	kd	1.0000	uM
Momelotinib	2183896: Inhibition of HIPK1 (unknown origin)	ic50	1.0000	uM
4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine	624726: Binding constant for HIPK1 kinase domain	kd	1.1000	uM
N-(4-methyl-2-pyridinyl)-2-naphthalen-2-ylacetamide	1685598: Binding affinity to human HIPK1 (158 to 555 residues) using myelin ba as substrate incubated for 40 mins in presence of [gamma33P]ATP by radiometric scintillation analysis	kd	1.1000	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2R)-1-methoxy-4-methylpentan-2-yl]iminoimidazolidin-4-one	2024506: Inhibition of human HIPK1 assessed as remaining activity by eurofins-cerep kinase profiler analysis	ic50	1.1720	uM
Ruxolitinib	624726: Binding constant for HIPK1 kinase domain	kd	1.2000	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624726: Binding constant for HIPK1 kinase domain	kd	1.3000	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	624726: Binding constant for HIPK1 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	624726: Binding constant for HIPK1 kinase domain	kd	1.7000	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	350274: Inhibition of HIPK1	ic50	2.6390	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases stability, increases phosphorylation, affects cotreatment, decreases expression, increases abundance (+2 more)	3
arsenite	decreases reaction, affects expression, affects binding	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Estradiol	affects expression, increases expression	2
Valproic Acid	decreases expression, decreases methylation	2
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	increases sumoylation	1
testosterone enanthate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
coumarin	decreases phosphorylation	1
arsenic disulfide	decreases expression	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
motexafin gadolinium	affects reaction, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Amphotericin B	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Coumestrol	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lipopolysaccharides	decreases reaction, increases expression, increases reaction, decreases expression	1

ChEMBL screening assays

285 unique, capped per target: 285 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1038412	Binding	Residual activity of HIPK1 at 1 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg 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_SR41	HAP1 HIPK1 (-) 1	Cancer cell line	Male
CVCL_SR42	HAP1 HIPK1 (-) 2	Cancer cell line	Male
CVCL_SR43	HAP1 HIPK1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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