STK33

Summary

STK33 (serine/threonine kinase 33, HGNC:14568) is a protein-coding gene on chromosome 11p15.4, encoding Serine/threonine-protein kinase 33 (Q9BYT3). Serine/threonine protein kinase required for spermatid differentiation and male fertility.

Enables protein serine/threonine kinase activity. Involved in spermatogenesis. Predicted to be located in manchette. Predicted to be active in nucleus. Implicated in colorectal cancer; depressive disorder; and spermatogenic failure 93.

Source: NCBI Gene 65975 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 93 (Limited, GenCC)
• GWAS associations: 22
• Clinical variants (ClinVar): 102 total — 1 pathogenic
• Phenotypes (HPO): 11
• Druggable target: yes — 22 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001352389

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14568
Approved symbol	STK33
Name	serine/threonine kinase 33
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000130413
Ensembl biotype	protein_coding
OMIM	607670
Entrez	65975

Gene structure

Transcript identifiers

Ensembl transcripts: 57 — 53 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000315204, ENST00000358872, ENST00000396672, ENST00000418597, ENST00000422559, ENST00000431279, ENST00000444064, ENST00000447869, ENST00000454443, ENST00000457885, ENST00000473980, ENST00000486305, ENST00000524760, ENST00000526360, ENST00000526517, ENST00000532336, ENST00000534493, ENST00000687296, ENST00000910635, ENST00000910636, ENST00000910637, ENST00000910638, ENST00000910639, ENST00000910640, ENST00000910641, ENST00000910642, ENST00000910643, ENST00000910644, ENST00000910645, ENST00000910646, ENST00000910647, ENST00000910648, ENST00000910649, ENST00000933820, ENST00000933821, ENST00000933822, ENST00000933823, ENST00000933824, ENST00000967113, ENST00000967114, ENST00000967115, ENST00000967116, ENST00000967117, ENST00000967118, ENST00000967119, ENST00000967120, ENST00000967121, ENST00000967122, ENST00000967123, ENST00000967124, ENST00000967125, ENST00000967126, ENST00000967127, ENST00000967128, ENST00000967129, ENST00000967130, ENST00000967131

RefSeq mRNA: 17 — MANE Select: NM_001352389 NM_001289058, NM_001289059, NM_001289061, NM_001352387, NM_001352388, NM_001352389, NM_001352390, NM_001352391, NM_001352392, NM_001352393, NM_001352394, NM_001352395, NM_001352396, NM_001352397, NM_001352398, NM_001352399, NM_030906

CCDS: CCDS73253, CCDS73254, CCDS7789

Canonical transcript exons

ENST00000687296 — 16 exons

Exon	Start	End
ENSE00000988570	8474681	8475066
ENSE00001125293	8473163	8473276
ENSE00001482457	8594083	8594228
ENSE00001608708	8476687	8476751
ENSE00001745457	8477250	8477283
ENSE00003477425	8454744	8454832
ENSE00003507163	8440678	8440753
ENSE00003577469	8436027	8436139
ENSE00003595380	8435494	8435579
ENSE00003601545	8452822	8452906
ENSE00003626379	8413495	8413692
ENSE00003679174	8464709	8464822
ENSE00003680236	8461805	8461909
ENSE00003788066	8457341	8457479
ENSE00003927988	8480410	8480614
ENSE00003932187	8391870	8392710

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 98.62.

FANTOM5 (CAGE): breadth broad, TPM avg 3.8445 / max 98.5029, expressed in 790 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118500	3.1933	750
118499	0.4783	292
118498	0.1177	41
118497	0.0553	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.62	gold quality
adenohypophysis	UBERON:0002196	94.51	gold quality
bronchial epithelial cell	CL:0002328	94.44	gold quality
left testis	UBERON:0004533	93.88	gold quality
right testis	UBERON:0004534	93.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.52	gold quality
sperm	CL:0000019	93.23	gold quality
bronchus	UBERON:0002185	92.55	gold quality
pituitary gland	UBERON:0000007	92.35	gold quality
testis	UBERON:0000473	92.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.83	gold quality
ventricular zone	UBERON:0003053	91.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.81	gold quality
fallopian tube	UBERON:0003889	87.73	gold quality
oviduct epithelium	UBERON:0004804	86.67	gold quality
left lobe of thyroid gland	UBERON:0001120	86.59	gold quality
caput epididymis	UBERON:0004358	86.48	gold quality
thyroid gland	UBERON:0002046	86.07	gold quality
right lobe of thyroid gland	UBERON:0001119	86.02	gold quality
left ovary	UBERON:0002119	85.54	gold quality
right adrenal gland cortex	UBERON:0035827	84.93	gold quality
left adrenal gland cortex	UBERON:0035825	84.63	gold quality
right ovary	UBERON:0002118	84.56	gold quality
right atrium auricular region	UBERON:0006631	84.54	gold quality
right adrenal gland	UBERON:0001233	84.25	gold quality
smooth muscle tissue	UBERON:0001135	84.19	gold quality
left adrenal gland	UBERON:0001234	84.08	gold quality
body of uterus	UBERON:0009853	83.91	gold quality
left uterine tube	UBERON:0001303	83.69	gold quality
heart left ventricle	UBERON:0002084	83.28	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	2695.49
E-CURD-119	yes	26.56
E-MTAB-10287	yes	25.61
E-GEOD-130148	yes	10.99
E-ANND-3	yes	10.84
E-CURD-11	no	100.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting STK33, 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-302E	99.96	70.74	2669
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-5197-5P	99.64	69.08	1494

Literature-anchored findings (GeneRIF, showing 13)

• STK33/Stk33 expression pattern resembles those of some related members of the calcium/calmodulin dependent kinase group (PMID:16176263)
• STK33 downregulation or dominant mutant overexpression had no effect on KRAS signaling or survival of cancer cells. (PMID:21742770)
• The STK33-linked SNP rs4929949 is associated with obesity and BMI in two independent cohorts of Swedish and Greek children. (PMID:23967198)
• STK33 plays an essential role in hepatocellular proliferation and liver tumorigenesis. STK33 may bind directly to c-Myc and increase its transcriptional activity. (PMID:25398772)
• Results show that STK33 is a potential oncogene and a promising diagnostic marker for hypopharyngeal squamous cell carcinoma (HSCC). STK33 may promote tumorigenesis and progression of HSCC, and serve as a valuable molecular target for treatment of HSCC. (PMID:25603720)
• STK33 can promote cell migration and invasion and suppress p53 gene expression in the NL9980 and L9981 large cell lung cancer cell lines. In addition, this protein also promotes epithelial-mesenchymal transition. (PMID:25662617)
• STK33 is a potential oncogene and plays an important role in tumorigenesis of HSCC via regulation of numerous genes. (PMID:27414193)
• inhibition of STK33 in small cell lung carcinoma cells suppressed the cell proliferation and invasion while induced cell apoptosis (PMID:28895411)
• Dysregulated HIF1alpha/STK33 signaling promotes pancreatic ductal adenocarcinoma (PDAC) growth and progression, this suggests that STK33 is a candidate therapeutic target to improve PDAC treatment. (PMID:29038348)
• STK33 has pro-tumor function and is a critical downstream mediator of KLF4 in gastric cancer. STK33 may serve as a potential prognostic marker and therapeutic target for gastric cancer. (PMID:29367428)
• Data show that serine/threonine kinase 33 (STK33) can bind with extracellular signal-regulated kinase 2 (ERK2) and take part in the regulation of ERKs signaling pathway. (PMID:30760631)
• Novel frameshift mutation in STK33 is associated with asthenozoospermia and multiple morphological abnormalities of the flagella. (PMID:34155512)
• Interaction between STK33 and autophagy promoted renal cell carcinoma metastasis by regulating mTOR/ULK1 signaling pathway. (PMID:37101009)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	stk33	ENSDARG00000054318
mus_musculus	Stk33	ENSMUSG00000031027
rattus_norvegicus	Stk33	ENSRNOG00000014590
caenorhabditis_elegans		WBGENE00019321

Paralogs (22): CAMKK1 (ENSG00000004660), CAMK1G (ENSG00000008118), CAMK2B (ENSG00000058404), CAMK2A (ENSG00000070808), MYLK2 (ENSG00000101306), CAMKK2 (ENSG00000110931), STK11 (ENSG00000118046), PNCK (ENSG00000130822), DCLK1 (ENSG00000133083), CAMK1 (ENSG00000134072), MYLK3 (ENSG00000140795), CAMK2D (ENSG00000145349), MYLK4 (ENSG00000145949), PSKH2 (ENSG00000147613), CAMK2G (ENSG00000148660), PHKG2 (ENSG00000156873), PSKH1 (ENSG00000159792), DCLK3 (ENSG00000163673), CAMKV (ENSG00000164076), PHKG1 (ENSG00000164776), DCLK2 (ENSG00000170390), CAMK1D (ENSG00000183049)

Protein

Protein identifiers

Serine/threonine-protein kinase 33 — Q9BYT3 (reviewed: Q9BYT3)

All UniProt accessions (11): Q9BYT3, A0A0C4DH60, B4DDH2, C9J319, C9J5G1, C9J6X7, C9J8B1, C9JCS6, E9PNP9, F8WAK5, H0YEZ7

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine protein kinase required for spermatid differentiation and male fertility. Promotes sperm flagella assembly during spermatogenesis by mediating phosphorylation of fibrous sheath proteins AKAP3 and AKAP4. Also phosphorylates vimentin/VIM, thereby regulating the dynamic behavior of the intermediate filament cytoskeleton.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Cytoskeleton. Perinuclear region.

Tissue specificity. Highly expressed in testis, fetal lung and heart, followed by pituitary gland, kidney, interventricular septum, pancreas, heart, trachea, thyroid gland and uterus. Weak hybridization signals were observed in the following tissues: amygdala, aorta, esophagus, colon ascending, colon transverse, skeletal muscle, spleen, peripheral blood leukocyte, lymph node, bone marrow, placenta, prostate, liver, salivary gland, mammary gland, some tumor cell lines, fetal brain, fetal liver, fetal spleen and fetal thymus. No signal at all was detectable in RNA from tissues of the nervous system.

Post-translational modifications. Autophosphorylated.

Disease relevance. Spermatogenic failure 93 (SPGF93) [MIM:620849] An autosomal recessive, male infertility disorder characterized by asthenozoospermia and multiple morphologic abnormalities of the sperm flagella. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Specifically inhibited by CDD-2807 ((3-([1,1’-Biphenyl]-2-ylethynyl)-1H-indazol-5-yl)(2,6-diazaspiro[3.5]nonan-2-yl)methanone).

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BYT3-1	1	yes
Q9BYT3-2	2

RefSeq proteins (17): NP_001275987, NP_001275988, NP_001275990, NP_001339316, NP_001339317, NP_001339318, NP_001339319, NP_001339320, NP_001339321, NP_001339322, NP_001339323, NP_001339324, NP_001339325, NP_001339326, NP_001339327, NP_001339328, NP_112168 (=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

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 (22 total): sequence variant 7, region of interest 3, compositionally biased region 3, binding site 2, sequence conflict 2, chain 1, domain 1, modified residue 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8VF6	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYT3-F1	67.88	0.43

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): 238 (proton acceptor)

Ligand- & substrate-binding residues (2): 145; 122–130

Post-translational modifications (1): 407

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 160 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, MODULE_301, GOBP_NEGATIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_DNA_DAMAGE_RESPONSE, GOBP_MITOTIC_DNA_INTEGRITY_CHECKPOINT_SIGNALING

GO Biological Process (8): spermatogenesis (GO:0007283), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), mitotic DNA damage checkpoint signaling (GO:0044773), protein autophosphorylation (GO:0046777), negative regulation of protein polyubiquitination (GO:1902915), manchette assembly (GO:1905198), protein phosphorylation (GO:0006468), cell differentiation (GO:0030154)

GO Molecular Function (7): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): manchette (GO:0002177), nucleus (GO:0005634), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein kinase activity	2
developmental process involved in reproduction	1
male gamete generation	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
DNA damage checkpoint signaling	1
mitotic cell cycle	1
mitotic DNA integrity checkpoint signaling	1
protein phosphorylation	1
protein polyubiquitination	1
negative regulation of protein ubiquitination	1
regulation of protein polyubiquitination	1
spermatid development	1
cellular component assembly	1
phosphorylation	1
protein modification process	1
cellular developmental process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
microtubule cytoskeleton	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1527 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STK33	LMO1	P25800	669
STK33	KRAS	P01116	648
STK33	TP53	P04637	542
STK33	RPS6	P08227	540
STK33	PELI1	Q96FA3	474
STK33	TTC36	A6NLP5	472
STK33	RIC3	Q7Z5B4	462
STK33	SDR42E1	Q8WUS8	447
STK33	TUB	P50607	437
STK33	FAM167B	Q9BTA0	430
STK33	DIP2C	Q9Y2E4	427
STK33	CPNE6	O95741	417
STK33	ANKS1B	Q7Z6G8	416
STK33	CCDC8	Q9H0W5	404
STK33	PSMA1	P25786	400

IntAct

11 interactions, top by confidence:

A	B	Type	Score
PKM	STK33	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
LRRK2	STK33	psi-mi:“MI:0407”(direct interaction)	0.440
STK33	CALU	psi-mi:“MI:0915”(physical association)	0.400
GLYCTK	STK33	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
STK33	SCO2	psi-mi:“MI:0914”(association)	0.350
MGARP	BTAF1	psi-mi:“MI:0914”(association)	0.350
SLC22A11	CNOT1	psi-mi:“MI:0914”(association)	0.350
	PSMD12	psi-mi:“MI:0914”(association)	0.350
EEF1D	STK33	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (105): STK33 (Synthetic Lethality), STK33 (Affinity Capture-MS), STK33 (Affinity Capture-MS), STK33 (Affinity Capture-Western), HPD (Biochemical Activity), STK33 (Biochemical Activity), STK33 (Proximity Label-MS), STK33 (Affinity Capture-MS), STK33 (Proximity Label-MS), STK33 (Affinity Capture-MS), SCO2 (Affinity Capture-MS), GLUD1 (Affinity Capture-MS), HSP90AA1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS), HCK (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3S724, A4IGM9, A4IIW7, A5GFW1, B0VXL7, B6A7Q3, C0RW22, D7UQM5, F4I4F2, O08605, O14965, O35495, O55099, O59790, O70126, O80673, O94921, P18266, P27466, P49841, P59241, P97477, Q00771, Q0VD22, Q13555, Q16566, Q2TA06, Q501Q9, Q58D94, Q5XIT0, Q66JF3, Q6BVA0, Q6C3J2, Q6CWQ4, Q6DE08, Q6DGS3, Q6GPL3, Q6Z8C8, Q755C4, Q7YRC6

Diamond homologs: A0A2I0BVG8, A0A509AFG4, A0A509AHB6, A0A509ALV6, A0A509AQE6, A0A5K1K8H0, A2XFF4, A8X6H4, B8BBT7, E9PT87, F4JBP3, O15865, O22932, O61267, O70150, O80673, P05986, P08414, P13234, P18654, P22216, P22517, P25323, P27466, P28582, P34101, P40376, P51812, P53681, P53684, P62343, P62344, P62345, P92958, P93759, Q00771, Q09170, Q0D715, Q0VD22, Q10KY3

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
STK33	“up-regulates activity”	MAPK1	phosphorylation
STK33	“down-regulates quantity by destabilization”	HPD	phosphorylation
STK33	“up-regulates quantity by stabilization”	AKAP3	phosphorylation
STK33	“up-regulates quantity by stabilization”	AKAP4	phosphorylation
STK33	“up-regulates activity”	STK33	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	79
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3238650	NM_001352389.2(STK33):c.1235del (p.Thr412fs)	Pathogenic

SpliceAI

3229 predictions. Top by Δscore:

Variant	Effect	Δscore
11:8392711:C:CC	acceptor_gain	1.0000
11:8435492:A:AC	donor_gain	1.0000
11:8435493:C:CT	donor_gain	1.0000
11:8435580:C:CC	acceptor_gain	1.0000
11:8436021:ACTT:A	donor_loss	1.0000
11:8436023:TTACC:T	donor_loss	1.0000
11:8436024:TACCA:T	donor_loss	1.0000
11:8436025:A:AC	donor_gain	1.0000
11:8436025:A:T	donor_loss	1.0000
11:8436025:AC:A	donor_gain	1.0000
11:8436026:C:CA	donor_gain	1.0000
11:8436026:CC:C	donor_gain	1.0000
11:8436026:CCA:C	donor_gain	1.0000
11:8436026:CCACA:C	donor_gain	1.0000
11:8436135:GTAAT:G	acceptor_gain	1.0000
11:8436137:AAT:A	acceptor_gain	1.0000
11:8436138:AT:A	acceptor_gain	1.0000
11:8436140:C:CC	acceptor_gain	1.0000
11:8440676:A:AC	donor_gain	1.0000
11:8440677:C:CC	donor_gain	1.0000
11:8440677:CAA:C	donor_gain	1.0000
11:8457486:T:C	acceptor_gain	1.0000
11:8457486:T:TC	acceptor_gain	1.0000
11:8457488:A:AC	acceptor_gain	1.0000
11:8457488:A:C	acceptor_gain	1.0000
11:8457490:A:C	acceptor_gain	1.0000
11:8457492:A:AC	acceptor_gain	1.0000
11:8457492:A:C	acceptor_gain	1.0000
11:8457494:A:AC	acceptor_gain	1.0000
11:8457494:A:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000009115 (11:8468792 A>G), RS1000027131 (11:8540715 A>G), RS1000043561 (11:8401492 G>A,T), RS1000053697 (11:8466231 T>C), RS1000059383 (11:8435868 C>A,T), RS1000080583 (11:8540447 T>C), RS1000082750 (11:8582355 T>A), RS1000091387 (11:8420644 G>T), RS1000097865 (11:8577152 T>C), RS1000102656 (11:8382320 T>C), RS1000107423 (11:8501682 A>G), RS1000115584 (11:8475241 C>A,T), RS1000120647 (11:8592225 T>C,G), RS1000120991 (11:8511075 T>C), RS1000153055 (11:8397182 C>A,T)

Disease associations

OMIM: gene MIM:607670 | disease phenotypes: MIM:620849

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 93	Limited	Autosomal recessive

Mondo (1): spermatogenic failure 93 (MONDO:0971000)

Orphanet (0):

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000798	Oligozoospermia
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:0012207	Reduced sperm motility
HP:0032558	Absent sperm flagella
HP:0032559	Short sperm flagella
HP:0032560	Coiled sperm flagella
HP:0033393	Irregularly shaped sperm tail
HP:0034011	Reduced progressive sperm motility
HP:0034811	Bent sperm flagella

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST000298_6	Body mass index	1.000000e-06
GCST003485_7	Response to fenofibrate (HDL cholesterol levels)	2.000000e-06
GCST004557_17	Body mass index	2.000000e-10
GCST004557_200	Body mass index	2.000000e-09
GCST004557_229	Body mass index	9.000000e-11
GCST004557_99	Body mass index	1.000000e-09
GCST004558_14	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-09
GCST004558_149	Body mass index (joint analysis main effects and physical activity interaction)	2.000000e-10
GCST004558_171	Body mass index (joint analysis main effects and physical activity interaction)	8.000000e-09
GCST004558_97	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-08
GCST004559_12	Body mass index in physically active individuals	2.000000e-08
GCST004559_130	Body mass index in physically active individuals	1.000000e-07
GCST004559_50	Body mass index in physically active individuals	1.000000e-07
GCST004559_92	Body mass index in physically active individuals	1.000000e-08
GCST004746_23	Small cell lung carcinoma	7.000000e-07
GCST004904_92	Body mass index	5.000000e-11
GCST005950_10	Body mass index x sex x age interaction (4df test)	6.000000e-11
GCST005951_51	Body mass index	8.000000e-11
GCST005953_4	Body mass index (age <50)	4.000000e-11
GCST008759_11	Intake of total sugars	6.000000e-06
GCST010136_6	Fruit consumption	9.000000e-09
GCST010988_458	Adult body size	2.000000e-14

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007805	HDL cholesterol change measurement
EFO:0008002	physical activity measurement
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0010158	sugar consumption measurement
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6005 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

22 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 305,594 (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
CHEMBL180022	NERATINIB	4	9,404
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL377300	BRIVANIB	3	1,721
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL491473	CEDIRANIB	3	9,098
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
CHEMBL607707	PELITINIB	2	6,340
CHEMBL1908397	KW-2449	1
CHEMBL574738	AST-487	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CAMK-unique family

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

Ligand	Action	Affinity	Parameter
compound 1 [PMID: 21742770]	Inhibition	8.15	pIC50

Binding affinities (BindingDB)

163 measured of 208 human assays (235 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
5-(1,4-diazepan-1-ylsulfonyl)isoquinoline	KD	50 nM	US-11198680: Rho kinase inhibitor BA-1049 (R) and active metabolites thereof
(2Z)-2-[4-(diethylamino)benzylidene]-1,3-diketo-indane-5-carboxylic acid	EC50	60 nM
(2E)-2-[4-(diethylamino)benzylidene]-1,3-diketo-indane-5-carboxylic acid	EC50	100 nM
cid_5289419	IC50	110 nM
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
2-(1-propyl-4-pyridinylidene)indene-1,3-dione	IC50	296 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
SMR000652046	EC50	416 nM
(2-anilinopyrimidin-4-yl)-phenyl-amine	IC50	423 nM	US-9249124: Aurora kinase inhibitors and methods of making and using thereof
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methyl-phenyl)urea	KD	450 nM
N-[4-[[3-[2,6-bis(chloranyl)-3,5-dimethoxy-phenyl]-7-[4-(diethylamino)butylamino]-2-oxidanylidene-4H-pyrimido[4,5-d]pyrimidin-1-yl]methyl]phenyl]prop-2-enamide	EC50	618 nM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dione	KD	700 nM
(6E)-6-[6-amino-4-(ethylamino)-1H-1,3,5-triazin-2-ylidene]-4-chloro-1-cyclohexa-2,4-dienone	EC50	847 nM
N-[4-[[2-[[4-(dimethylamino)cyclohexyl]amino]-9-propan-2-yl-purin-6-yl]amino]phenyl]prop-2-enamide	EC50	883 nM
2-(1-ethyl-4-pyridinylidene)indene-1,3-dione	IC50	1200 nM
SMR000414386	EC50	1240 nM
cid_6701	IC50	1310 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
4-[5-(4-ethoxyphenyl)-1,2-oxazol-3-yl]-N-(3-methoxypropyl)butanamide	IC50	1420 nM
(2Z)-2-(3,4-dihydroxybenzylidene)-6-hydroxy-coumaran-3-one	IC50	1530 nM
SMR000590970	EC50	1860 nM
3,6,7-trimethoxyphenanthrene-2,5-diol	IC50	1950 nM
(3Z)-3-[(3,4-dimethoxyanilino)methylene]oxindole	IC50	1970 nM
N-[2-(3-oxo-4H-quinoxalin-2-yl)phenyl]-2-thiophenecarboxamide	EC50	2100 nM
(5E)-5-(2,4-dihydroxybenzylidene)thiazolidine-2,4-quinone	IC50	2200 nM
MLS001165417	EC50	2240 nM
cid_6097961	EC50	2430 nM
1-[6-(1-hydroxyiminoethyl)-9-propyl-3-carbazolyl]ethanone oxime	EC50	2480 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
3-[4-[(Z)-3-(4-bromophenyl)-3-oxoprop-1-enyl]-3-(4-methylphenyl)pyrazol-1-yl]propanoic acid	IC50	2600 nM
(1Z)-1-[(4-hydroxyanilino)methylidene]-2-naphthalenone	EC50	2840 nM
cid_16746003	EC50	2860 nM
(3Z)-3-(1H-imidazol-5-ylmethylene)oxindole	IC50	2870 nM
SMR000217101	EC50	3040 nM
(3Z)-3-[(3,4,5-trimethoxyanilino)methylene]oxindole	IC50	3130 nM
SMR000273743	EC50	3460 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM
13-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-2,5,9-trimethyl-4-thia-2,6,9,12,14-pentazatricyclo[8.4.0.03,7]tetradeca-1(14),3(7),5,10,12-pentaen-8-one	IC50	3610 nM	US-12365696: Small-molecule focal adhesion kinase (FAK) inhibitors
MLS001212262	EC50	3760 nM
cid_24818812	EC50	3820 nM
5-(4-Hydroxy-3-methoxy-benzylidene)-2-(2-methoxy-phenylimino)-thiazolidin-4-one	EC50	4000 nM
MLS000080844	EC50	4050 nM
3-hydroxypyrido[1,2-a]indole-10-carbonitrile	EC50	4590 nM
4-N,4-N-diethyl-1-N-(4-morpholin-4-ylquinazolin-2-yl)benzene-1,4-diamine	EC50	4710 nM
(4Z)-4-[[(7-chloro-4-quinolinyl)hydrazo]methylidene]-2-hydroxy-1-cyclohexa-2,5-dienone	IC50	4730 nM
cid_3097937	EC50	4910 nM
(5E)-3-amino-5-[(2E)-1-cyano-2-(3-ethoxy-4-keto-cyclohexa-2,5-dien-1-ylidene)ethylidene]-3-pyrazoline-4-carbonitrile	IC50	5240 nM
3-[(Z)-(2-ethyl-1H-imidazol-5-yl)methylidene]-1H-indol-2-one	EC50	5250 nM

ChEMBL bioactivities

82 potent at pChembl≥5 of 84 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.74	Kd	1.8	nM	STAUROSPORINE
8.49	Kd	3.2	nM	TAE-684
8.22	Kd	6	nM	CHEMBL4576489
8.15	IC50	7	nM	CHEMBL2203524
8.10	Kd	8	nM	CHEMBL4465866
7.96	IC50	11	nM	CHEMBL2203525
7.85	IC50	14	nM	CHEMBL2204239
7.77	Kd	17	nM	SUNITINIB
7.58	Kd	26	nM	LESTAURTINIB
7.44	IC50	36.3	nM	STAUROSPORINE
7.43	Kd	37	nM	BOSUTINIB
7.42	IC50	38.4	nM	STAUROSPORINE
7.38	IC50	41.6	nM	STAUROSPORINE
7.16	Kd	70	nM	CHEMBL464552
7.12	IC50	76	nM	CHEMBL2203528
7.11	IC50	78	nM	CHEMBL2204241
7.01	Kd	98	nM	FORETINIB
6.96	IC50	110	nM	CHEMBL2204238
6.89	Kd	130	nM	SU-014813
6.85	Kd	140	nM	KW-2449
6.82	IC50	150	nM	CHEMBL2203530
6.80	IC50	160	nM	CHEMBL2204235
6.77	IC50	170	nM	CHEMBL1992679
6.72	Kd	190	nM	MIDOSTAURIN
6.66	Kd	220	nM	FEDRATINIB
6.66	Kd	220	nM	CHEMBL379218
6.60	IC50	250	nM	CHEMBL2204237
6.60	Ki	251.2	nM	CHEMBL1967116
6.57	IC50	270	nM	CHEMBL2204240
6.55	IC50	280	nM	CHEMBL1543343
6.52	IC50	300	nM	CHEMBL2203531
6.42	IC50	380	nM	CHEMBL2203526
6.39	IC50	410	nM	CHEMBL2204236
6.28	IC50	530	nM	CHEMBL2203527
6.27	Kd	540	nM	CEDIRANIB
6.24	IC50	580	nM	CHEMBL2203529
6.20	Ki	631	nM	CHEMBL1970317
6.11	Kd	780	nM	CHEMBL1908395
6.08	Kd	840	nM	PHA-665752
6.03	Kd	940	nM	NERATINIB
6.01	IC50	980	nM	CHEMBL2203532
6.01	Kd	970	nM	R-406
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.96	Kd	1100	nM	BI-2536
5.96	Kd	1100	nM	NINTEDANIB
5.92	Kd	1200	nM	AST-487
5.85	Kd	1400	nM	VANDETANIB
5.80	IC50	1600	nM	CHEMBL2204234

PubChem BioAssay actives

73 with measured affinity, of 694 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
(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	436053: Binding constant for full-length STK33	kd	0.0018	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625138: Binding constant for STK33 kinase domain	kd	0.0032	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526272: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged STK33 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0060	uM
N-[3-methoxy-4-(4-methylpiperazin-1-yl)phenyl]-1-(4-methoxyphenyl)pyrazolo[5,4-b]pyridin-6-amine	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.0070	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526272: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged STK33 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0080	uM
N-[[(2S,4R)-4-[(4-methylisoquinolin-5-yl)sulfonylamino]pyrrolidin-2-yl]methyl]acetamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.0110	uM
N-[2-(3-oxo-4H-quinoxalin-2-yl)-4-propan-2-ylphenyl]thiophene-2-carboxamide	1859105: Inhibition of recombinant STK33 (unknown origin)	ic50	0.0140	uM
Sunitinib	436053: Binding constant for full-length STK33	kd	0.0170	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	508095: Binding affinity to STK33	kd	0.0260	uM
Bosutinib	625138: Binding constant for STK33 kinase domain	kd	0.0370	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	625138: Binding constant for STK33 kinase domain	kd	0.0700	uM
N-[2-(3-oxo-4H-quinoxalin-2-yl)phenyl]pyridine-2-carboxamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.0760	uM
N-[5-fluoro-2-(3-oxo-4H-quinoxalin-2-yl)phenyl]thiophene-2-carboxamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.0780	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	625138: Binding constant for STK33 kinase domain	kd	0.0980	uM
N-[2-(3-oxo-4H-quinoxalin-2-yl)-4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.1100	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	436053: Binding constant for full-length STK33	kd	0.1300	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625138: Binding constant for STK33 kinase domain	kd	0.1400	uM
4-fluoro-N-[2-(3-oxo-4H-quinoxalin-2-yl)phenyl]benzamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.1500	uM
N-[4-chloro-2-(3-oxo-4H-quinoxalin-2-yl)phenyl]thiophene-2-carboxamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.1600	uM
N-[2-(3-oxo-4H-quinoxalin-2-yl)phenyl]benzamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.1700	uM
Midostaurin	625138: Binding constant for STK33 kinase domain	kd	0.1900	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625138: Binding constant for STK33 kinase domain	kd	0.2200	uM
Fedratinib	625138: Binding constant for STK33 kinase domain	kd	0.2200	uM
N-[4-methoxy-2-(3-oxo-4H-quinoxalin-2-yl)phenyl]thiophene-2-carboxamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.2500	uM
N-[5-chloro-2-(3-oxo-4H-quinoxalin-2-yl)phenyl]thiophene-2-carboxamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.2700	uM
N-[2-(3-oxo-4H-quinoxalin-2-yl)phenyl]thiophene-2-carboxamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.2800	uM
4-chloro-N-[2-(3-oxo-4H-quinoxalin-2-yl)phenyl]benzamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.3000	uM
5-chloro-N-[2-(3-oxo-4H-quinoxalin-2-yl)phenyl]thiophene-2-carboxamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.3800	uM
N-[4-fluoro-2-(3-oxo-4H-quinoxalin-2-yl)phenyl]thiophene-2-carboxamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.4100	uM
N-[2-(3-oxo-4H-quinoxalin-2-yl)phenyl]-1,3-thiazole-2-carboxamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.5300	uM
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline	625138: Binding constant for STK33 kinase domain	kd	0.5400	uM
N-[2-(3-oxo-4H-quinoxalin-2-yl)phenyl]pyridine-3-carboxamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.5800	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625138: Binding constant for STK33 kinase domain	kd	0.7800	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	625138: Binding constant for STK33 kinase domain	kd	0.8400	uM
Neratinib	625138: Binding constant for STK33 kinase domain	kd	0.9400	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	625138: Binding constant for STK33 kinase domain	kd	0.9700	uM
4-methoxy-N-[2-(3-oxo-4H-quinoxalin-2-yl)phenyl]benzamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	0.9800	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	625138: Binding constant for STK33 kinase domain	kd	1.1000	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625138: Binding constant for STK33 kinase domain	kd	1.1000	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	436053: Binding constant for full-length STK33	kd	1.2000	uM
Vandetanib	436053: Binding constant for full-length STK33	kd	1.4000	uM
N-[2-(6,7-dimethyl-3-oxo-4H-quinoxalin-2-yl)phenyl]thiophene-2-carboxamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	1.6000	uM
N-[2-(6,7-difluoro-3-oxo-4H-quinoxalin-2-yl)phenyl]thiophene-2-carboxamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	1.6000	uM
3-[2-(pyridin-2-ylmethylamino)phenyl]-1H-quinoxalin-2-one	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	1.6000	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	436053: Binding constant for full-length STK33	kd	1.7000	uM
Sorafenib	436053: Binding constant for full-length STK33	kd	2.4000	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	625138: Binding constant for STK33 kinase domain	kd	2.6000	uM
(2R)-1-[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxypropan-2-ol	625138: Binding constant for STK33 kinase domain	kd	3.2000	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	436053: Binding constant for full-length STK33	kd	3.8000	uM
N-[2-(6,7-dichloro-3-oxo-4H-quinoxalin-2-yl)phenyl]thiophene-2-carboxamide	712545: Inhibition of N-terminal 6His-tagged full length human recombinant STK33 using myelin basic protein as substrate incubated for 15 mins before initiation of kinase reaction measured after 1 hr by ADP-glo assay	ic50	4.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	4
Air Pollutants	affects cotreatment, increases abundance, increases expression	3
Tretinoin	decreases expression, increases expression	2
Valproic Acid	affects expression, increases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
propionaldehyde	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
nickel sulfate	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Methotrexate	increases expression	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Vanadates	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, increases expression	1
Volatile Organic Compounds	affects cotreatment, increases expression	1

ChEMBL screening assays

214 unique, capped per target: 213 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1043822	Binding	Residual activity of STK33 at 1 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem
CHEMBL1963730	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: STK33	PubChem BioAssay data set

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XT98	HAP1 STK33 (-) 1	Cancer cell line	Male
CVCL_XT99	HAP1 STK33 (-) 2	Cancer cell line	Male
CVCL_XU00	HAP1 STK33 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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