HASPIN

Summary

HASPIN (histone H3 associated protein kinase, HGNC:19682) is a protein-coding gene on chromosome 17p13.2, encoding Serine/threonine-protein kinase haspin (Q8TF76). Serine/threonine-protein kinase that phosphorylates histone H3 at ‘Thr-3’ (H3T3ph) during mitosis.

Enables ATP binding activity and histone H3T3 kinase activity. Involved in several processes, including mitotic sister chromatid cohesion; mitotic spindle assembly checkpoint signaling; and protein localization to chromosome, centromeric region. Located in centrosome; nucleoplasm; and spindle.

Source: NCBI Gene 83903 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 133 total
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_031965

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19682
Approved symbol	HASPIN
Name	histone H3 associated protein kinase
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000177602
Ensembl biotype	protein_coding
OMIM	609240
Entrez	83903

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000325418

RefSeq mRNA: 1 — MANE Select: NM_031965 NM_031965

CCDS: CCDS11036

Canonical transcript exons

ENST00000325418 — 1 exons

Exon	Start	End
ENSE00001287270	3723903	3726699

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 88.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.8709 / max 92.6940, expressed in 1267 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158882	7.8709	1267

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	88.06	silver quality
secondary oocyte	CL:0000655	84.83	gold quality
oocyte	CL:0000023	79.81	gold quality
ventricular zone	UBERON:0003053	77.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.89	gold quality
tibialis anterior	UBERON:0001385	73.44	silver quality
ganglionic eminence	UBERON:0004023	72.58	gold quality
kidney epithelium	UBERON:0004819	72.08	gold quality
bone marrow cell	CL:0002092	71.95	gold quality
sperm	CL:0000019	71.15	gold quality
upper arm skin	UBERON:0004263	71.14	gold quality
ileal mucosa	UBERON:0000331	69.97	gold quality
stromal cell of endometrium	CL:0002255	68.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.49	gold quality
left testis	UBERON:0004533	67.30	gold quality
right testis	UBERON:0004534	67.12	gold quality
testis	UBERON:0000473	66.65	gold quality
vermiform appendix	UBERON:0001154	65.99	gold quality
bone marrow	UBERON:0002371	65.76	gold quality
lymph node	UBERON:0000029	64.47	gold quality
buccal mucosa cell	CL:0002336	63.40	gold quality
rectum	UBERON:0001052	62.06	gold quality
deltoid	UBERON:0001476	61.96	silver quality
colonic epithelium	UBERON:0000397	61.80	gold quality
caecum	UBERON:0001153	61.48	gold quality
mucosa of transverse colon	UBERON:0004991	61.13	gold quality
lower esophagus mucosa	UBERON:0035834	60.41	gold quality
quadriceps femoris	UBERON:0001377	60.23	gold quality
mucosa of paranasal sinus	UBERON:0005030	59.85	gold quality
esophagus mucosa	UBERON:0002469	59.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.92

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting HASPIN, 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-3617-3P	99.98	67.86	918
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-649	97.96	67.21	704
HSA-MIR-10400-3P	97.29	64.66	597
HSA-MIR-4674	97.29	64.62	597
HSA-MIR-4703-3P	96.68	68.61	545
HSA-MIR-5090	93.28	60.86	94
HSA-MIR-6775-5P	92.43	61.00	132
HSA-MIR-6727-5P	92.41	61.98	83

Literature-anchored findings (GeneRIF, showing 31)

• This work reveals a new kinase involved in composing the histone code and adds haspin to the select group of kinases that integrate regulation of chromosome and spindle function during mitosis and meiosis (PMID:15681610)
• Haspin is required to maintain centromeric cohesion during mitosis. (PMID:17084365)
• Haspin-depleted cells reveal that spindle-pole integrity in mitosis requires chromosome cohesion. (PMID:19910498)
• Haspin is a relatively newly discovered kinase that phosphorylates histone H3 during mitosis and appears to play a role in regulating chromosome behavior during cell division. [REVIEW] (PMID:19997740)
• phosphorylation of H3T3 by Haspin is necessary for chromosomal passenger complex(CPC) accumulation at centromeres; Survivin binds to H3T3ph; H3T3ph generated by Haspin positions CPC at centromeres to regulate selected targets of Aurora B during mitosis (PMID:20705812)
• findings show phosphorylation of histone H3-threonine 3 mediated by Haspin cooperates with Bub1-mediated histone 2A-serine 121 phosphorylation in targeting the chromosomal passenger complex to the inner centromere in fission yeast and human cells (PMID:20929775)
• Aurora B phosphorylates Haspin to promote generation of H3T3ph and that Aurora B kinase activity is required for normal chromosomal localization of the CPC, indicating an intimate linkage between Aurora B and Haspin functions in mitosis (PMID:21658950)
• Haspin inhibitors reveal centromeric roles of Aurora B in chromosome movement and spindle checkpoint signaling (PMID:23071152)
• Haspin activity affects the phosphorylation state of proteins involved in gene expression regulation and splicing. (PMID:24732914)
• Haspin kinase plays a key role in maintaining the slowly exchanging centromere Borealin pool. (PMID:25854549)
• This is the first structural model of a bisubstrate inhibitor targeting haspin. The presented structural data represent a model for the future development of more specific haspin inhibitors (PMID:27139824)
• The mitotic histone kinase Haspin binds to the cohesin regulatory subunit Pds5B through a conserved YGA/R motif in its non-catalytic N terminus, which is similar to the recently reported YSR-motif-dependent binding of Wapl to Pds5B. (PMID:28343965)
• The authors’ data identify the HIM of Pds5 as a binding motif for Haspin/Hrk1 in fission yeast. The authors’ analyses also show that human PDS5B binds Haspin through the same HIM-PIM interaction module, indicating that the Haspin localization mechanism is highly conserved. (PMID:28343969)
• Autosomal recessive RP associated with mutations in the male germ cell-associated kinase (MAK) gene is associated with preservation of foveal vision even in advanced stages of retinal degeneration despite similar rates of peripheral visual field loss to other forms of autosomal recessive RP (PMID:29103961)
• The results indicate a kinase-dependent role for Haspin in antagonizing Wapl and protecting centromeric cohesion in mitosis. (PMID:29138236)
• GSG2 upregulation was associated with pancreatic cancer progression. (PMID:31493385)
• HASPIN is involved in the progression of gallbladder carcinoma. (PMID:31987787)
• Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis. (PMID:32027339)
• Genome-wide CRISPR screen uncovers a synergistic effect of combining Haspin and Aurora kinase B inhibition. (PMID:32300176)
• Knockdown of GSG2 inhibits prostate cancer progression in vitro and in vivo. (PMID:32319597)
• GSG2 (Haspin) promotes development and progression of bladder cancer through targeting KIF15 (Kinase-12). (PMID:32439830)
• GSG2 knockdown suppresses cholangiocarcinoma progression by regulating cell proliferation, apoptosis and migration. (PMID:33846801)
• Phosphorylation of H3-Thr3 by Haspin Is Required for Primary Cilia Regulation. (PMID:34299370)
• Loss of haspin suppresses cancer cell proliferation by interfering with cell cycle progression at multiple stages. (PMID:34551143)
• Knockdown of GSG2 Suppresses the Progression of Colorectal Cancer Cells. (PMID:35089075)
• Effects and mechanisms of GSG2 in esophageal cancer progression. (PMID:35939116)
• Knockdown of GSG2 inhibits the development and progression of non-small cell lung cancer in vitro and in vivo. (PMID:35972887)
• GSG2 facilitates the progression of human breast cancer through MDM2-mediated ubiquitination of E2F1. (PMID:37537694)
• GSG2 promotes thyroid cancer via stabilizing AURKB and activating AKT pathway. (PMID:38441546)
• Germ cell-specific gene 2 accelerates cell cycle in epithelial ovarian cancer by inhibiting GSK3alpha-p27 cascade. (PMID:38613588)
• GSG2 promotes progression of human endometrial cancer by regulating PD-1/PD-L1 expression via PI3K-AKT pathway. (PMID:38759367)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	haspin	ENSDARG00000092290
mus_musculus	Haspin	ENSMUSG00000050107
rattus_norvegicus	Haspin	ENSRNOG00000048660
drosophila_melanogaster	pll	FBGN0010441
drosophila_melanogaster	Haspin	FBGN0046706
caenorhabditis_elegans		WBGENE00004029
caenorhabditis_elegans	hasp-1	WBGENE00007258
caenorhabditis_elegans		WBGENE00012159
caenorhabditis_elegans	hasp-2	WBGENE00021214

Paralogs (4): IRAK3 (ENSG00000090376), IRAK2 (ENSG00000134070), IRAK1 (ENSG00000184216), IRAK4 (ENSG00000198001)

Protein

Protein identifiers

Serine/threonine-protein kinase haspin — Q8TF76 (reviewed: Q8TF76)

Alternative names: Germ cell-specific gene 2 protein, H-haspin, Haploid germ cell-specific nuclear protein kinase

All UniProt accessions (1): Q8TF76

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that phosphorylates histone H3 at ‘Thr-3’ (H3T3ph) during mitosis. May act through H3T3ph to both position and modulate activation of AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle.

Subcellular location. Nucleus. Chromosome. Cytoplasm. Cytoskeleton. Spindle.

Tissue specificity. Strongly expressed in testis. Also present in thymus and bone marrow and low levels observed in prostate, intestine, lung, spleen and lymph node. Expressed in fetal skin, liver, kidney and small intestine and also in proliferating but not non-proliferating cell lines.

Post-translational modifications. Autophosphorylated on both serine and threonine residues. Strongly phosphorylated during mitosis but this does not appear to significantly affect its intrinsic kinase activity. Phosphorylation by AURKB is required for full activity toward histone H3 at ‘Ser-3’ in mitosis.

Activity regulation. Constitutive activity that does not require phosphorylation. Specifically inhibited by 3-(1H-indazol-5-yl)-N-propylimidazo[1,2-b]pyridazin-6-amine (CHR-6494).

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TF76-1	1	yes
Q8TF76-2	2

RefSeq proteins (1): NP_114171* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR024604	GSG2_C	Domain

Pfam: PF12330

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 (71 total): strand 17, helix 15, sequence variant 10, mutagenesis site 7, binding site 5, modified residue 5, splice variant 2, region of interest 2, sequence conflict 2, compositionally biased region 2, chain 1, domain 1, turn 1, active site 1

Structure

Experimental structures (PDB)

41 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4QTC	X-RAY DIFFRACTION	1.4
6G3A	X-RAY DIFFRACTION	1.43
6G39	X-RAY DIFFRACTION	1.45
6G36	X-RAY DIFFRACTION	1.46
6G38	X-RAY DIFFRACTION	1.47
6G37	X-RAY DIFFRACTION	1.48
5HTC	X-RAY DIFFRACTION	1.5
6Z57	X-RAY DIFFRACTION	1.5
6Z5E	X-RAY DIFFRACTION	1.5
6G35	X-RAY DIFFRACTION	1.55
6Z5A	X-RAY DIFFRACTION	1.55
7AVQ	X-RAY DIFFRACTION	1.65
5HTB	X-RAY DIFFRACTION	1.7
6Z5C	X-RAY DIFFRACTION	1.75
6Z5D	X-RAY DIFFRACTION	1.75
6G34	X-RAY DIFFRACTION	1.76
7SQM	X-RAY DIFFRACTION	1.78
2VUW	X-RAY DIFFRACTION	1.8
3F2N	X-RAY DIFFRACTION	1.8
6Z58	X-RAY DIFFRACTION	1.8
3DLZ	X-RAY DIFFRACTION	1.85
9FLQ	X-RAY DIFFRACTION	1.85
4OUC	X-RAY DIFFRACTION	1.9
6Z56	X-RAY DIFFRACTION	1.9
6Z5B	X-RAY DIFFRACTION	1.9
9FLR	X-RAY DIFFRACTION	1.91
3E7V	X-RAY DIFFRACTION	2
3FMD	X-RAY DIFFRACTION	2
3IQ7	X-RAY DIFFRACTION	2
6Z59	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TF76-F1	63.64	0.41

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): 649 (proton acceptor)

Ligand- & substrate-binding residues (5): 649–654; 687–689; 490–498; 511; 606–611

Post-translational modifications (5): 58, 93, 97, 143, 147

Mutagenesis-validated functional residues (7):

Position	Phenotype
492	markedly reduced affinity for histone h3 and reduced histone h3 phosphorylation.
511	strongly reduced enzyme activity.
651	strongly reduced enzyme activity, markedly reduced affinity for histone h3.
707	markedly reduced affinity for histone h3 and reduced histone h3 phosphorylation.
709	markedly reduced affinity for histone h3 and reduced histone h3 phosphorylation.
713	markedly reduced affinity for histone h3 and reduced histone h3 phosphorylation.
716	markedly reduced histone h3 phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 207 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_CHROMOSOME_SEPARATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOLDRATH_ANTIGEN_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_ORGANELLE_FISSION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_PROTEIN_LOCALIZATION_TO_CHROMOSOME_CENTROMERIC_REGION, GOBP_REGULATION_OF_CHROMOSOME_SEGREGATION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_SISTER_CHROMATID_COHESION, GOBP_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GOBP_REGULATION_OF_CELL_CYCLE

GO Biological Process (10): mitotic cell cycle (GO:0000278), protein phosphorylation (GO:0006468), mitotic sister chromatid cohesion (GO:0007064), mitotic spindle assembly checkpoint signaling (GO:0007094), intracellular signal transduction (GO:0035556), protein localization to chromosome, centromeric region (GO:0071459), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), chromosome organization (GO:0051276), negative regulation of mitotic cell cycle phase transition (GO:1901991)

GO Molecular Function (10): protein kinase activity (GO:0004672), ATP binding (GO:0005524), histone H3T3 kinase activity (GO:0072354), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), histone kinase activity (GO:0035173)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytoplasm (GO:0005737), centrosome (GO:0005813), spindle (GO:0005819), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	3
intracellular membraneless organelle	3
intracellular anatomical structure	2
cellular anatomical structure	2
cell cycle	1
mitotic nuclear division	1
phosphorylation	1
protein modification process	1
sister chromatid cohesion	1
mitotic cell cycle	1
negative regulation of mitotic metaphase/anaphase transition	1
spindle assembly checkpoint signaling	1
mitotic spindle checkpoint signaling	1
signal transduction	1
protein localization to chromosome	1
cellular component organization	1
chromatin organization	1
organelle organization	1
mitotic cell cycle phase transition	1
negative regulation of mitotic cell cycle	1
negative regulation of cell cycle phase transition	1
regulation of mitotic cell cycle phase transition	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
protein serine/threonine kinase activity	1
histone H3 kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
histone modifying activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
centriole	1
microtubule organizing center	1
microtubule cytoskeleton	1

Protein interactions and networks

STRING

1326 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HASPIN	PDS5A	Q29RF7	910
HASPIN	AURKB	Q96GD4	908
HASPIN	BUB1	O43683	901
HASPIN	KIF2C	Q99661	827
HASPIN	H3-4	Q16695	805
HASPIN	H3C1	P02295	789
HASPIN	H3-7	Q5TEC6	789
HASPIN	H3-5	Q6NXT2	789
HASPIN	H3C14	Q71DI3	789
HASPIN	SGO1	Q5FBB7	785
HASPIN	H3-3A	P06351	783
HASPIN	RCC2	Q9P258	778
HASPIN	INCENP	Q9NQS7	750
HASPIN	PLK1	P53350	742
HASPIN	H2AC19	P20670	741

IntAct

63 interactions, top by confidence:

A	B	Type	Score
P4HA3	FAM171A2	psi-mi:“MI:0914”(association)	0.640
NEUROG3	GXYLT2	psi-mi:“MI:0914”(association)	0.640
HSF2BP	HASPIN	psi-mi:“MI:0915”(physical association)	0.560
HASPIN	MDFI	psi-mi:“MI:0915”(physical association)	0.560
ZNF169	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
LRP1	NME4	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
FBL	ZNF316	psi-mi:“MI:0914”(association)	0.530
VTN	HAT1	psi-mi:“MI:0914”(association)	0.530
HASPIN	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.520
HSP90AB1	HASPIN	psi-mi:“MI:0915”(physical association)	0.520
HASPIN	H3-3A	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
MATR3	BCLAF3	psi-mi:“MI:0914”(association)	0.350
HASPIN	KPNA6	psi-mi:“MI:0914”(association)	0.350
MYC	ILVBL	psi-mi:“MI:0914”(association)	0.350
NCBP3	RSL1D1	psi-mi:“MI:0914”(association)	0.350
EEF1D	VWA8	psi-mi:“MI:0914”(association)	0.350
IL17RA	DDX11L8	psi-mi:“MI:0914”(association)	0.350
APP	ZNF724	psi-mi:“MI:0914”(association)	0.350
SIRT6	HDAC3	psi-mi:“MI:0914”(association)	0.350
THBS3	APBB1	psi-mi:“MI:0914”(association)	0.350
RPL28	SDCBP	psi-mi:“MI:0914”(association)	0.350
TNFRSF19	NOP56	psi-mi:“MI:0914”(association)	0.350
RBM4B	ZNF324	psi-mi:“MI:0914”(association)	0.350

BioGRID (145): GSG2 (Affinity Capture-MS), GSG2 (Affinity Capture-MS), KPNA6 (Affinity Capture-MS), FBXL6 (Affinity Capture-MS), HERC5 (Affinity Capture-MS), THAP11 (Affinity Capture-MS), EHMT1 (Affinity Capture-MS), GSG2 (Affinity Capture-MS), GSG2 (Affinity Capture-MS), GSG2 (Affinity Capture-MS), GSG2 (Affinity Capture-MS), GSG2 (Affinity Capture-MS), GSG2 (Affinity Capture-MS), GSG2 (Affinity Capture-MS), GSG2 (Affinity Capture-MS)

ESM2 similar proteins: A0AUV4, A0JM98, A1A5Q6, A2KF29, B1WAS2, C0HKC8, C0HKC9, O60285, O70551, O88866, P51957, P57058, P57059, Q2T9U5, Q4R9F7, Q5R7G9, Q5RD27, Q5REX1, Q5XHI9, Q60670, Q641K5, Q66HE5, Q68UT7, Q6IFT4, Q6P3R8, Q6REY9, Q6VZ17, Q80VH0, Q8BI55, Q8BLD6, Q8BZN4, Q8C0N0, Q8C0V7, Q8C0X8, Q8CFH6, Q8NE63, Q8TF76, Q96SB4, Q9H093, Q9H0K1

Diamond homologs: O13924, O80528, Q2KIP2, Q8TF76, Q9Z0R0, P83103, Q54LU8

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
AURKB	“up-regulates activity”	HASPIN	phosphorylation
HASPIN	“up-regulates activity”	H3C1	phosphorylation
CDK1	“up-regulates activity”	HASPIN	phosphorylation
HASPIN	“up-regulates activity”	PLK1	binding
PLK1	“up-regulates activity”	HASPIN	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	122
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

83 predictions. Top by Δscore:

Variant	Effect	Δscore
17:3723910:TTTGA:T	donor_gain	0.7100
17:3725074:TTTGG:T	donor_gain	0.6800
17:3725094:T:TA	donor_gain	0.6700
17:3723912:TGA:T	donor_gain	0.6400
17:3726347:A:AC	donor_gain	0.6100
17:3726348:C:CC	donor_gain	0.6100
17:3724340:T:TA	donor_gain	0.6000
17:3723911:TTGA:T	donor_gain	0.5700
17:3725997:TA:T	donor_gain	0.5700
17:3724435:C:A	donor_gain	0.5500
17:3726347:ACTGC:A	donor_gain	0.5200
17:3726348:CTGCC:C	donor_gain	0.5200
17:3724587:C:A	donor_gain	0.4400
17:3724509:T:TA	donor_gain	0.4200
17:3726347:ACTG:A	donor_gain	0.4100
17:3726348:CTGC:C	donor_gain	0.4100
17:3724663:C:A	donor_gain	0.4000
17:3723918:T:TA	donor_gain	0.3800
17:3726343:T:TA	donor_gain	0.3800
17:3724380:G:T	donor_gain	0.3600
17:3724567:C:CA	donor_gain	0.3600
17:3725082:AAAAC:A	acceptor_gain	0.3600
17:3724262:A:T	donor_gain	0.3500
17:3724348:T:TA	donor_gain	0.3500
17:3726484:A:C	acceptor_gain	0.3500
17:3726485:C:CC	acceptor_gain	0.3500
17:3724965:G:GT	donor_gain	0.3400
17:3725063:GAAT:G	acceptor_gain	0.3400
17:3725360:TAG:T	acceptor_gain	0.3400
17:3725719:A:C	acceptor_gain	0.3400

AlphaMissense

5222 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:3725878:G:C	R648P	0.999
17:3725995:A:T	D687V	0.999
17:3726010:G:C	R692P	0.999
17:3725881:A:T	D649V	0.998
17:3725995:A:C	D687A	0.998
17:3725996:C:A	D687E	0.998
17:3725996:C:G	D687E	0.998
17:3726165:T:A	W744R	0.998
17:3726165:T:C	W744R	0.998
17:3725468:A:C	K511N	0.997
17:3725468:A:T	K511N	0.997
17:3725601:T:C	F556L	0.997
17:3725603:T:A	F556L	0.997
17:3725603:T:G	F556L	0.997
17:3725869:T:C	F645S	0.997
17:3725881:A:C	D649A	0.997
17:3725994:G:C	D687H	0.997
17:3726132:T:A	W733R	0.997
17:3726132:T:C	W733R	0.997
17:3725431:T:C	F499S	0.996
17:3725629:T:A	V565D	0.996
17:3725842:T:C	L636P	0.996
17:3725868:T:C	F645L	0.996
17:3725870:T:A	F645L	0.996
17:3725870:T:G	F645L	0.996
17:3725875:A:G	H647R	0.996
17:3725882:C:A	D649E	0.996
17:3725882:C:G	D649E	0.996
17:3725995:A:G	D687G	0.996
17:3726134:G:C	W733C	0.996

dbSNP variants (sampled 300 via entrez): RS1000062386 (17:3723509 C>A,T), RS1000427717 (17:3724280 C>A,G), RS1001267272 (17:3722650 G>A), RS1001468124 (17:3722493 A>G), RS1001898592 (17:3726398 A>T), RS1002095178 (17:3726643 C>T), RS1003316116 (17:3724739 G>A,C), RS1003701167 (17:3722631 G>A), RS1004506129 (17:3723870 G>A,C,T), RS1004762446 (17:3726951 A>G), RS1005111933 (17:3722952 G>A), RS1005690355 (17:3726788 C>T), RS1006165176 (17:3723804 C>A,G,T), RS1007050128 (17:3727046 A>C,G), RS1007169272 (17:3722911 A>T)

Disease associations

OMIM: gene MIM:609240 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST012431_14	Parkinson’s disease	1.000000e-14
GCST012431_8	Parkinson’s disease	2.000000e-15

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075163 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,951 (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
CHEMBL5173264	INE-963	2	6
CHEMBL1952329	SGI-1776	1	400
CHEMBL269538	HARMINE	1	4,346
CHEMBL4076837	SENEXIN B	1	104
CHEMBL4225966	SEL-120 FREE BASE	1	91
CHEMBL5426285	5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-	1	4

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Haspin family

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

Ligand	Action	Affinity	Parameter
SGI-1776	Inhibition	7.47	pIC50

Binding affinities (BindingDB)

94 measured of 97 human assays (97 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
ARC-3429	KD	0.019 nM
ARC-3430	KD	0.1 nM
5-cyclopropyl-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	0.48 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclohexane]-4-carboxamide	IC50	0.77 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-(2-fluoroethyl)spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclobutane]-4-carboxamide	IC50	0.827 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethyl-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.09 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclobutane]-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3,7,7-trimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
13-chloro-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(13),2(6),4,9,11-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-(2-fluoroethyl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7-cyclohexyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclobutane]-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-methylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclobutane]-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-methylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclohexane]-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
(7S)-7-cyclohexyl-3-ethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
(7R)-7-cyclohexyl-3-ethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
5-chloro-3-ethylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-oxane]-4-carboxamide	IC50	2.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
5-cyclopropyl-3-ethyl-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	2.65 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclohexane]-4-carboxylic acid	IC50	3.01 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethyl-1’-(2,2,2-trifluoroethyl)spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-piperidine]-4-carboxamide	IC50	3.14 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
(7S)-7-(oxan-4-yl)-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	4.46 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-oxane]-4-carboxamide	IC50	4.58 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-methylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-oxane]-4-carboxamide	IC50	6.1 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
1’-acetylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-piperidine]-4-carboxamide	IC50	7.48 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclohexane]-4-carboxamide	IC50	8.22 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
(7S)-7-cyclohexyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	8.5 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
ARC-3384	KD	11 nM
3-(2-methoxyethyl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	11.5 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	11.9 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethyl-5-(3-methoxyphenyl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	13.9 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7-methyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	14.4 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
ARC-3380	KD	14.9 nM
3-ethyl-5-(2-methoxyphenyl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	16.4 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
5-chloro-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	16.6 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethyl-7,7-dimethyl-5-[2-(trifluoromethyl)phenyl]-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	16.7 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
(7R)-7-cyclohexyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	19.3 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7,7-dimethyl-3-(2,2,2-trifluoroethyl)-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	19.4 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7,7-dimethyl-5-(4-sulfamoylphenyl)-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxylic acid	IC50	20.7 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-(2-methoxyethyl)spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-oxane]-4-carboxamide	IC50	20.9 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
5-ethenyl-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	29.5 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7-methyl-7-propan-2-yl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	31.1 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
13-chloro-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(13),2(6),4,9,11-pentaene-4-carboxylic acid	IC50	31.4 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
1’-(2,2,2-trifluoroethyl)spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-piperidine]-4-carboxamide	IC50	40.5 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
5-(3,6-dihydro-2H-pyran-4-yl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	70.5 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7,7-dimethyl-5-(4-sulfamoylphenyl)-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	81.3 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
5-(3,6-dihydro-2H-pyran-4-yl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxylic acid	IC50	86.6 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-(2-fluoroethyl)-5-(2-methoxyphenyl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	97.3 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7,7-dimethyl-5-phenyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	107 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
5-(2-hydroxyphenyl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	112 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
1’-(3,3,3-trifluoropropyl)spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-piperidine]-4-carboxamide	IC50	120 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors

ChEMBL bioactivities

243 potent at pChembl≥5 of 251 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.72	Kd	0.019	nM	CHEMBL5199572
9.81	IC50	0.155	nM	CHEMBL5574055
9.38	Kd	0.42	nM	CHEMBL5194339
9.26	Kd	0.55	nM	CHEMBL5440655
8.80	IC50	1.6	nM	CHEMBL4791276
8.70	IC50	2	nM	CHEMBL5178368
8.52	IC50	3	nM	CHEMBL5201780
8.52	IC50	3	nM	CHEMBL5186093
8.52	IC50	3	nM	CHEMBL5178368
8.52	IC50	3	nM	CHEMBL5563528
8.40	IC50	4	nM	CHEMBL4064608
8.40	Kd	4	nM	CHEMBL5169980
8.40	IC50	4	nM	CHEMBL5178368
8.30	IC50	5	nM	CHEMBL5201904
8.30	IC50	5	nM	IODOTUBERCIDIN
8.30	IC50	5	nM	CHEMBL5575484
8.22	IC50	6	nM	CHEMBL4446681
8.15	IC50	7	nM	CHEMBL5566424
8.05	IC50	8.91	nM	CHEMBL4793447
8.05	IC50	8.82	nM	CHEMBL4785886
8.02	IC50	9.56	nM	CHEMBL4777356
8.01	IC50	9.8	nM	CHEMBL4776812
8.00	Kd	10	nM	CHEMBL5179988
8.00	IC50	10	nM	CHEMBL5095897
7.96	IC50	11	nM	CHEMBL5179988
7.92	IC50	12	nM	CHEMBL4278808
7.92	IC50	12	nM	CHEMBL5188318
7.89	IC50	12.8	nM	CHEMBL4781993
7.87	IC50	13.6	nM	CHEMBL5561973
7.85	IC50	14	nM	CHEMBL4642838
7.85	IC50	14	nM	CHEMBL4278808
7.82	Kd	15	nM	CHEMBL4848254
7.80	IC50	15.9	nM	CHEMBL4785713
7.78	IC50	16.5	nM	CHEMBL5826420
7.76	IC50	17.5	nM	CHEMBL4797007
7.72	IC50	19	nM	STAUROSPORINE
7.65	IC50	22.4	nM	CHEMBL4779550
7.63	IC50	23.6	nM	CHEMBL6191865
7.62	IC50	24.2	nM	CHEMBL4789603
7.59	IC50	25.6	nM	CHEMBL4795368
7.58	IC50	26.6	nM	CHEMBL6022963
7.58	IC50	26.2	nM	CHEMBL4789125
7.56	IC50	27.6	nM	CHEMBL4780792
7.55	IC50	28	nM	CHEMBL6173699
7.51	IC50	30.6	nM	CHEMBL6191307
7.50	IC50	32	nM	STAUROSPORINE
7.50	IC50	32	nM	CHEMBL5187817
7.50	IC50	31.8	nM	CHEMBL4789863
7.50	IC50	31.7	nM	CHEMBL6191783
7.47	IC50	34	nM	SGI-1776

PubChem BioAssay actives

154 with measured affinity, of 892 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
(2R)-4-[[(5S)-6-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-amino-6-azaniumyl-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-(diaminomethylideneazaniumyl)-1-oxopentan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-azaniumylpropanoyl]amino]-5-(diaminomethylideneazaniumyl)pentanoyl]amino]-6-oxohexyl]amino]-2-[6-[[(2S,3S,4R,5R)-5-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolane-2-carbonyl]amino]hexanoylamino]-4-oxobutanoate	1802698: Equilibrium Binding/Displacement Assay with Fluorescence Anisotropy from Article 10.1002/cbic.201600697: “Slowly on, Slowly off: Bisubstrate-Analogue Conjugates of 5-Iodotubercidin and Histone H3 Peptide Targeting Protein Kinase Haspin.”	kd	<0.0001	uM
(4S)-4-[[(2S)-2-[[(2S)-6-[[(3R)-3-[6-[[(2S,3S,4R,5R)-5-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolane-2-carbonyl]amino]hexanoylamino]-3-carboxypropanoyl]amino]-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-[[(2S,3S)-1-[[(2S)-1-[[(2R)-1,6-diamino-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	1846289: Binding affinity to haspin (unknown origin) assessed as dissociation constant	kd	<0.0001	uM
(2R)-4-[[(5S)-6-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-amino-6-[[3-carboxy-4-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]benzoyl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-[[amino(azaniumylidene)methyl]amino]-1-oxopentan-2-yl]amino]-5-[[(2S)-5-[[amino(azaniumylidene)methyl]amino]-2-[[(2S)-2-azaniumylpropanoyl]amino]pentanoyl]amino]-6-oxohexyl]amino]-2-[6-[[(2S,3S,4R,5R)-5-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolane-2-carbonyl]amino]hexanoylamino]-4-oxobutanoate	1802698: Equilibrium Binding/Displacement Assay with Fluorescence Anisotropy from Article 10.1002/cbic.201600697: “Slowly on, Slowly off: Bisubstrate-Analogue Conjugates of 5-Iodotubercidin and Histone H3 Peptide Targeting Protein Kinase Haspin.”	kd	0.0001	uM
(2R,3R,4S,5R)-2-(4-amino-5-ethynylpyrrolo[2,3-d]pyrimidin-7-yl)-5-(azidomethyl)thiolane-3,4-diol	2110489: Inhibition of recombinant human N-terminal GST-tagged haspin (470 to end residues) expressed in baculovirus infected Sf9 cells using histone H3 peptide as substrate by ADP-Glo kinase assay	ic50	0.0002	uM
3-(1H-indazol-5-yl)-N-propylimidazo[1,2-b]pyridazin-6-amine	2003942: Inhibition of haspin (unknown origin) assessed as dissociation constant	kd	0.0002	uM
(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-[[(3R)-4-amino-3-[6-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carbonyl]amino]hexanoylamino]-4-oxobutanoyl]amino]-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-N-[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]pentanediamide	1846303: Binding affinity to N-terminal his6-tagged human recombinant Haspin (470 to 798 residues) assessed as dissociation constant	kd	0.0004	uM
N-[(5-methyl-1H-imidazol-2-yl)methyl]-4-(8,9,10,11-tetrahydro-3H-pyrazolo[4,5-a]phenanthridin-7-yl)benzamide	2003942: Inhibition of haspin (unknown origin) assessed as dissociation constant	kd	0.0006	uM
(2R)-4-[[(5S)-6-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-amino-6-[[3-carboxy-4-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]benzoyl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-[[amino(azaniumylidene)methyl]amino]-1-oxopentan-2-yl]amino]-5-[[(2S)-5-[[amino(azaniumylidene)methyl]amino]-2-[[(2S)-2-azaniumylpropanoyl]amino]pentanoyl]amino]-6-oxohexyl]amino]-2-[6-[[(2S,3S,4R,5R)-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolane-2-carbonyl]amino]hexanoylamino]-4-oxobutanoate	1802699: Kinetic Assay with Fluorescence Anisotropy from Article 10.1002/cbic.201600697: “Slowly on, Slowly off: Bisubstrate-Analogue Conjugates of 5-Iodotubercidin and Histone H3 Peptide Targeting Protein Kinase Haspin.”	kd	0.0028	uM
1-[5-(2,4-difluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-4-methylpiperidin-4-amine	1903457: Inhibition of human Haspin kinase domain using histone H3 biotin peptide as substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 90 mins by luminescence based analysis	ic50	0.0030	uM
10-nitropyrido[3,4-g]quinolin-2-amine	1909328: Inhibition of recombinant human Haspin (470 to 798 residues) expressed in bacterial expression system using ARTKQTARKSTGGKAPRKQLA as substrate measured after 30 mins in presence of ATP by ADP-Glo assay	ic50	0.0030	uM
N-[[4-(aminomethyl)phenyl]methyl]-3-[[(4-hydroxyphenyl)methyl-methylamino]methyl]-1-methylindole-5-carboxamide	2110490: Inhibition of human haspin preincubated for 30 mins followed by ATP and ULight-histone H3 peptide/ULight-eIF4E binding protein addition and measured after 2 hrs by LANCE Ultra TR-FRET assay	ic50	0.0030	uM
N-(4-morpholin-4-ylcyclohexyl)-5-(oxan-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1471973: Inhibition of recombinant N-terminal His6-tagged human haspin (471 end residues) expressed in baculovirus infected Sf21 insect cells	ic50	0.0040	uM
(2S,3S,4R,5R)-5-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolane-2-carboxylic acid	1846305: Binding affinity to a TEV-cleavable N-terminal His6-tagged human recombinant haspin (470 to 798 residues) assessed as dissociation constant	kd	0.0040	uM
N-(4-fluorophenyl)-3-[[(3-hydroxyphenyl)methyl-methylamino]methyl]-1-methylindole-5-carboxamide	2110490: Inhibition of human haspin preincubated for 30 mins followed by ATP and ULight-histone H3 peptide/ULight-eIF4E binding protein addition and measured after 2 hrs by LANCE Ultra TR-FRET assay	ic50	0.0050	uM
4-N-[5-(6-methoxy-3-pyridinyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl]cyclohexane-1,4-diamine	1903457: Inhibition of human Haspin kinase domain using histone H3 biotin peptide as substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 90 mins by luminescence based analysis	ic50	0.0050	uM
(2R,3R,4S,5R)-2-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)oxolane-3,4-diol	2110487: Inhibition of haspin (unknown origin)	ic50	0.0050	uM
N-(4-fluorophenyl)-1-methyl-3-[[methyl-[2-(4-phenylphenyl)ethyl]amino]methyl]indole-5-carboxamide	2110490: Inhibition of human haspin preincubated for 30 mins followed by ATP and ULight-histone H3 peptide/ULight-eIF4E binding protein addition and measured after 2 hrs by LANCE Ultra TR-FRET assay	ic50	0.0060	uM
3-[(benzylamino)methyl]-N-(4-fluorophenyl)-1-methylindole-5-carboxamide	2110490: Inhibition of human haspin preincubated for 30 mins followed by ATP and ULight-histone H3 peptide/ULight-eIF4E binding protein addition and measured after 2 hrs by LANCE Ultra TR-FRET assay	ic50	0.0070	uM
(2R)-4-[[(5S)-6-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2R)-1-amino-6-[[3-carboxy-4-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]benzoyl]amino]-1-oxohexan-2-yl]amino]-1-oxo-6-(tetradecanoylamino)hexan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-[[amino(azaniumylidene)methyl]amino]-1-oxopentan-2-yl]amino]-5-[[(2S)-5-[[amino(azaniumylidene)methyl]amino]-2-[[(2S)-2-azaniumylpropanoyl]amino]pentanoyl]amino]-6-oxohexyl]amino]-2-[6-[[(2S,3S,4R,5R)-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolane-2-carbonyl]amino]hexanoylamino]-4-oxobutanoate	1802698: Equilibrium Binding/Displacement Assay with Fluorescence Anisotropy from Article 10.1002/cbic.201600697: “Slowly on, Slowly off: Bisubstrate-Analogue Conjugates of 5-Iodotubercidin and Histone H3 Peptide Targeting Protein Kinase Haspin.”	kd	0.0084	uM
1-N-[5-(2,4-difluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-2-methylpropane-1,2-diamine	1903482: Binding affinity to human HASPIN	kd	0.0100	uM
3-(2,7-dimethoxyacridin-9-yl)sulfanylpropan-1-amine	2110487: Inhibition of haspin (unknown origin)	ic50	0.0100	uM
3-fluoro-4-(8,9,10,11-tetrahydro-3H-pyrazolo[4,5-a]phenanthridin-7-yl)phenol	1417230: Inhibition of Haspin (unknown origin) after 3 hrs by ADP-Glo assay	ic50	0.0120	uM
2-methylsulfanylpyrido[3,4-g]quinazolin-10-amine	1909328: Inhibition of recombinant human Haspin (470 to 798 residues) expressed in bacterial expression system using ARTKQTARKSTGGKAPRKQLA as substrate measured after 30 mins in presence of ATP by ADP-Glo assay	ic50	0.0120	uM
5,6-dibromo-4-(difluoromethyl)-1-(oxan-4-yl)-2-piperazin-1-ylbenzimidazole	2070988: Inhibition of HASPIN (unknown origin) by ADP-Glo assay	ic50	0.0136	uM
(2Z)-6-hydroxy-2-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)-1-benzofuran-3-one	1659938: Inhibition of human recombinant Haspin (470 to 798 residues) expressed in bacteria using Histone H3 and ARTKQTARKSTGGKAPRKQLA as substrate in presence of ATP incubated for 50 mins by ADP-GloTM assay	ic50	0.0140	uM
N,N-dimethyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine	1752098: Binding affinity to wild-type human partial length HASPIN (I452 to K798 residues) expressed in mammalian expression system measured after 1 hr by competitive binding assay	kd	0.0150	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	1612688: Inhibition of human haspin using Histone H3 as substrate by [gamma-33P]-ATP assay	ic50	0.0190	uM
1-[5-(2-fluoro-4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-4-methylpiperidin-4-amine	1903457: Inhibition of human Haspin kinase domain using histone H3 biotin peptide as substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 90 mins by luminescence based analysis	ic50	0.0320	uM
N-[(1-methylpiperidin-4-yl)methyl]-3-[3-(trifluoromethoxy)phenyl]imidazo[1,2-b]pyridazin-6-amine	706708: Inhibition of haspin	ic50	0.0340	uM
2-(4-fluorophenyl)-N-[5-(4-pyridin-3-ylthiophen-2-yl)-3-pyridinyl]acetamide	1417224: Inhibition of recombinant human Haspin expressed in Baculovirus expression system by Adapta assay	ic50	0.0360	uM
2-methyl-6-pyridin-4-yl-3-[3-(trifluoromethoxy)phenyl]imidazo[1,2-b]pyridazine	2075065: Binding affinity to biotinylated super-streptavidin biosensor immobilised Haspin (unknown origin) assessed as dissociation constant by biolayer interferometry	kd	0.0393	uM
1-[5-(cyclohexen-1-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-4-methylpiperidin-4-amine	1903457: Inhibition of human Haspin kinase domain using histone H3 biotin peptide as substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 90 mins by luminescence based analysis	ic50	0.0450	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	2070988: Inhibition of HASPIN (unknown origin) by ADP-Glo assay	ic50	0.0460	uM
2-methoxy-10-nitropyrido[3,4-g]quinazoline	1909328: Inhibition of recombinant human Haspin (470 to 798 residues) expressed in bacterial expression system using ARTKQTARKSTGGKAPRKQLA as substrate measured after 30 mins in presence of ATP by ADP-Glo assay	ic50	0.0500	uM
2-propan-2-ylsulfanylpyrido[3,4-g]quinazolin-10-amine	1909328: Inhibition of recombinant human Haspin (470 to 798 residues) expressed in bacterial expression system using ARTKQTARKSTGGKAPRKQLA as substrate measured after 30 mins in presence of ATP by ADP-Glo assay	ic50	0.0560	uM
1-ethylpyrazolo[5,4-g]isoquinolin-9-amine	2107092: Inhibition of recombinant human Haspin kinase domain (470 to 798 residues) expressed in bacteria using histone H3 (1 to 21) peptide as substrate incubated for 30 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0620	uM
2-propylsulfanylpyrido[3,4-g]quinazolin-10-amine	1909328: Inhibition of recombinant human Haspin (470 to 798 residues) expressed in bacterial expression system using ARTKQTARKSTGGKAPRKQLA as substrate measured after 30 mins in presence of ATP by ADP-Glo assay	ic50	0.0650	uM
N-(4-fluorophenyl)-1-methyl-3-[(naphthalen-1-ylmethylamino)methyl]indole-5-carboxamide	2110490: Inhibition of human haspin preincubated for 30 mins followed by ATP and ULight-histone H3 peptide/ULight-eIF4E binding protein addition and measured after 2 hrs by LANCE Ultra TR-FRET assay	ic50	0.0650	uM
2-butylsulfanylpyrido[3,4-g]quinazolin-10-amine	1909328: Inhibition of recombinant human Haspin (470 to 798 residues) expressed in bacterial expression system using ARTKQTARKSTGGKAPRKQLA as substrate measured after 30 mins in presence of ATP by ADP-Glo assay	ic50	0.0690	uM
1H-pyrrolo[3,2-g]isoquinoline-3-carbonitrile	2107092: Inhibition of recombinant human Haspin kinase domain (470 to 798 residues) expressed in bacteria using histone H3 (1 to 21) peptide as substrate incubated for 30 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0750	uM
3-pyridin-4-yl-1H-pyrrolo[3,2-g]isoquinoline	2107092: Inhibition of recombinant human Haspin kinase domain (470 to 798 residues) expressed in bacteria using histone H3 (1 to 21) peptide as substrate incubated for 30 mins in presence of ATP by ADP-Glo kinase assay	ic50	0.0760	uM
N-[5-(4-pyridin-3-ylthiophen-2-yl)-3-pyridinyl]cyclopropanecarboxamide	1408874: Inhibition of human GST-tagged haspin expressed in baculovirus expression system in presence of 100 uM ATP	ic50	0.0763	uM
(2E)-6-hydroxy-2-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)-3,4-dihydronaphthalen-1-one	1659938: Inhibition of human recombinant Haspin (470 to 798 residues) expressed in bacteria using Histone H3 and ARTKQTARKSTGGKAPRKQLA as substrate in presence of ATP incubated for 50 mins by ADP-GloTM assay	ic50	0.0770	uM
1-[5-(6-methoxy-2-pyridinyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-4-methylpiperidin-4-amine	1903457: Inhibition of human Haspin kinase domain using histone H3 biotin peptide as substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 90 mins by luminescence based analysis	ic50	0.0780	uM
8-[[6-(2-methoxyethylcarbamoyl)-3-pyridinyl]oxy]-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474316: Binding affinity to partial length wild-type human HASPIN (I452 to K798 residues) expressed in bacterial expression system by kinome scan assay	kd	0.0860	uM
2-ethylsulfanyl-10-nitropyrido[3,4-g]quinazoline	1909328: Inhibition of recombinant human Haspin (470 to 798 residues) expressed in bacterial expression system using ARTKQTARKSTGGKAPRKQLA as substrate measured after 30 mins in presence of ATP by ADP-Glo assay	ic50	0.0910	uM
4-[7-methoxy-1-(trifluoromethyl)pyrido[3,4-b]indol-9-yl]butan-1-amine	655305: Inhibition of human recombinant N-terminal MBP-tagged haspin kinase expressed in Escherichia coli DE3 after 10 mins by TR-FRET assay	ic50	0.1000	uM
N-(4-fluorophenyl)-1-methyl-3-[(2-phenylethylamino)methyl]indole-5-carboxamide	2110490: Inhibition of human haspin preincubated for 30 mins followed by ATP and ULight-histone H3 peptide/ULight-eIF4E binding protein addition and measured after 2 hrs by LANCE Ultra TR-FRET assay	ic50	0.1050	uM
2-(2,6-dioxopiperidin-3-yl)-5-[4-[2-[1-[4-oxo-4-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]butanoyl]piperidin-4-yl]ethyl]piperazin-1-yl]isoindole-1,3-dione	1723779: Inhibition of GSG2 (unknown origin)	ic50	0.1100	uM
10-nitro-2-propan-2-ylsulfanylpyrido[3,4-g]quinazoline	1909328: Inhibition of recombinant human Haspin (470 to 798 residues) expressed in bacterial expression system using ARTKQTARKSTGGKAPRKQLA as substrate measured after 30 mins in presence of ATP by ADP-Glo assay	ic50	0.1140	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
aflatoxin B2	decreases methylation	1
coumarin	decreases phosphorylation	1
chromium hexavalent ion	increases abundance, decreases expression	1
2-palmitoylglycerol	increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Troglitazone	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Coumestrol	affects cotreatment, increases expression	1
Demecolcine	decreases expression	1
Oxygen	decreases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases expression	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

280 unique, capped per target: 273 binding, 5 admet, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1067026	Binding	Inhibition of human haspin at 0.1 uM	Identification of potent and selective VEGFR receptor tyrosine kinase inhibitors having new amide isostere headgroups. — Bioorg Med Chem Lett
CHEMBL4275974	ADMET	Inhibition of human GST-tagged haspin expressed in baculovirus expression system at 1.25 uM in presence of 100 uM ATP relative to control	Development of novel amide-derivatized 2,4-bispyridyl thiophenes as highly potent and selective Dyrk1A inhibitors. Part II: Identification of the cyclopropylamide moiety as a key modification. — Eur J Med Chem
CHEMBL5160033	Toxicity	Inhibition of human Haspin kinase domain using histone H3 biotin peptide as substrate preincubated with enzyme for 30 mins followed by substrate and ATP addition for 90 mins by luminescence based analysis	Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SQ63	HAP1 GSG2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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