TSSK1B

Summary

TSSK1B (testis specific serine kinase 1B, HGNC:14968) is a protein-coding gene on chromosome 5q22.2, encoding Testis-specific serine/threonine-protein kinase 1 (Q9BXA7). Testis-specific serine/threonine-protein kinase required during spermatid development.

TSSK1 belongs to a family of serine/threonine kinases highly expressed in testis (Hao et al., 2004 [PubMed 15044604]).

Source: NCBI Gene 83942 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 2 total
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_032028

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14968
Approved symbol	TSSK1B
Name	testis specific serine kinase 1B
Location	5q22.2
Locus type	gene with protein product
Status	Approved
Aliases	SPOGA4, FKSG81
Ensembl gene	ENSG00000212122
Ensembl biotype	protein_coding
OMIM	610709
Entrez	83942

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000390666

RefSeq mRNA: 1 — MANE Select: NM_032028 NM_032028

CCDS: CCDS4112

Canonical transcript exons

ENST00000390666 — 1 exons

Exon	Start	End
ENSE00001508579	113432553	113434989

Expression profiles

Bgee: expression breadth broad, 24 present calls, max score 91.28.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1601 / max 148.8580, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62983	0.1156	3
62982	0.0445	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	91.28	gold quality
left testis	UBERON:0004533	91.17	gold quality
testis	UBERON:0000473	87.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.89	gold quality
adult organism	UBERON:0007023	60.87	silver quality
buccal mucosa cell	CL:0002336	59.96	gold quality
myocardium	UBERON:0002349	54.41	gold quality
male germ cell	CL:0000015	52.29	gold quality
medial globus pallidus	UBERON:0002477	52.05	gold quality
sperm	CL:0000019	51.19	gold quality
globus pallidus	UBERON:0001875	49.44	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
stromal cell of endometrium	CL:0002255	49.08	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
quadriceps femoris	UBERON:0001377	48.79	gold quality
thymus	UBERON:0002370	48.78	gold quality
epithelial cell of pancreas	CL:0000083	48.55	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
oviduct epithelium	UBERON:0004804	48.50	gold quality
vastus lateralis	UBERON:0001379	48.42	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting TSSK1B, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-103A-2-5P	99.39	67.72	1577

Literature-anchored findings (GeneRIF, showing 2)

• Report evolution of testis-specific kinases TSSK1B and TSSK2 in primates. (PMID:23258646)
• Role of testisspecific serine kinase 1B in undiagnosed male infertility. (PMID:35485285)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tssk1	ENSMUSG00000041566
caenorhabditis_elegans		WBGENE00012638
caenorhabditis_elegans	tag-344	WBGENE00015230
caenorhabditis_elegans		WBGENE00044388

Paralogs (17): NUAK1 (ENSG00000074590), PRKAA1 (ENSG00000132356), TSSK4 (ENSG00000139908), HUNK (ENSG00000142149), SIK1 (ENSG00000142178), BRSK1 (ENSG00000160469), SIK3 (ENSG00000160584), PRKAA2 (ENSG00000162409), TSSK3 (ENSG00000162526), NUAK2 (ENSG00000163545), SNRK (ENSG00000163788), MELK (ENSG00000165304), SIK2 (ENSG00000170145), BRSK2 (ENSG00000174672), NIM1K (ENSG00000177453), TSSK6 (ENSG00000178093), TSSK2 (ENSG00000206203)

Protein

Protein identifiers

Testis-specific serine/threonine-protein kinase 1 — Q9BXA7 (reviewed: Q9BXA7)

Alternative names: Serine/threonine-protein kinase 22A

All UniProt accessions (2): A0ZT98, Q9BXA7

UniProt curated annotations — full annotation on UniProt →

Function. Testis-specific serine/threonine-protein kinase required during spermatid development. Phosphorylates ‘Ser-288’ of TSKS. Involved in the late stages of spermatogenesis, during the reconstruction of the cytoplasm. During spermatogenesis, required for the transformation of a ring-shaped structure around the base of the flagellum originating from the chromatoid body.

Subunit / interactions. Interacts with TSSK2. Interacts with HSP90; this interaction stabilizes TSSK1.

Subcellular location. Cytoplasm. Cytoplasmic vesicle. Secretory vesicle. Acrosome. Cell projection. Cilium. Flagellum.

Tissue specificity. Testis-specific. Present in sperm (at protein level).

Post-translational modifications. Autophosphorylated. Ubiquitinated; HSP90 activity negatively regulates ubiquitination and degradation.

Activity regulation. Kinase activity is specifically inhibited by 2 classes of compounds: biphenyl compounds (1,1’-(biphenyl-4,4’-diyl)bis(2,2-dihydroxyethanone)) and 1,2,7-trialky-1H-imidazo[4,5-g]quinoxalin-6-one. Activated by phosphorylation on Thr-174 and potentially by autophosphorylation.

Miscellaneous. TSSK1B might be used as a target for male contraception or and intra-vaginal spermicides.

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

RefSeq proteins (1): NP_114417* (*=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 (17 total): sequence variant 6, mutagenesis site 2, binding site 2, chain 1, domain 1, sequence conflict 1, region of interest 1, compositionally biased region 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXA7-F1	81.27	0.68

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): 136 (proton acceptor)

Ligand- & substrate-binding residues (2): 18–26; 41

Post-translational modifications (1): 174

Mutagenesis-validated functional residues (2):

Position	Phenotype
174	loss of kinase activity.
174	constitutively active.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 77 (showing top): GOCC_SECRETORY_GRANULE, SP3_Q3, GOBP_MALE_GAMETE_GENERATION, GRE_C, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GATA1_03, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, YY1_01, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, AP2GAMMA_01, MODULE_342, GOCC_SECRETORY_VESICLE, GOCC_MOTILE_CILIUM, GOCC_ACROSOMAL_VESICLE, GOCC_CILIUM

GO Biological Process (4): protein phosphorylation (GO:0006468), spermatid development (GO:0007286), spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

GO Molecular Function (11): magnesium ion binding (GO:0000287), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein-containing complex binding (GO:0044877), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (6): acrosomal vesicle (GO:0001669), motile cilium (GO:0031514), cytoplasm (GO:0005737), cilium (GO:0005929), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
binding	2
cellular anatomical structure	2
phosphorylation	1
protein modification process	1
germ cell development	1
spermatid differentiation	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
metal ion binding	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
cation binding	1
secretory granule	1
cilium	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1675 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSSK1B	TSKS	Q9UJT2	856
TSSK1B	FBN1	P35555	729
TSSK1B	MFAP1	P55081	649
TSSK1B	COL1A2	P02464	634
TSSK1B	CCN2	P29279	634
TSSK1B	CALY	Q9NYX4	555
TSSK1B	CCL7	P80098	549
TSSK1B	HPX	P02790	490
TSSK1B	TGFB1	P01137	478
TSSK1B	CAPZA3	Q96KX2	465
TSSK1B	CRABP1	P29762	453
TSSK1B	SIGLEC1	Q9BZZ2	452
TSSK1B	FGF7	P21781	435
TSSK1B	SNRNP70	P08621	434
TSSK1B	LY6E	Q16553	404

IntAct

31 interactions, top by confidence:

A	B	Type	Score
FAM229B	TSSK1B	psi-mi:“MI:0915”(physical association)	0.670
FOXN1	TSSK1B	psi-mi:“MI:0915”(physical association)	0.600
EFS	TSSK1B	psi-mi:“MI:0915”(physical association)	0.560
TSSK1B	EFS	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	TSSK1B	psi-mi:“MI:0915”(physical association)	0.560
TSSK1B	TSKS	psi-mi:“MI:0915”(physical association)	0.560
HSP90AB1	TSSK1B	psi-mi:“MI:0915”(physical association)	0.560
TSSK1B	HSPA8	psi-mi:“MI:0914”(association)	0.530
POC1A	TXNDC9	psi-mi:“MI:0914”(association)	0.480
	TSSK1B	psi-mi:“MI:0407”(direct interaction)	0.440
YWHAE	TSSK1B	psi-mi:“MI:0915”(physical association)	0.400
SFN	TSSK1B	psi-mi:“MI:0915”(physical association)	0.400
TSSK1B	AIP	psi-mi:“MI:0914”(association)	0.350
ABI3	TBKBP1	psi-mi:“MI:0914”(association)	0.350
TSSK1B	HERC4	psi-mi:“MI:0914”(association)	0.350
TSSK1B	FOXN1	psi-mi:“MI:0915”(physical association)	0.000
TSSK1B	EFS	psi-mi:“MI:0915”(physical association)	0.000
TSSK1B	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
TSKS	TSSK1B	psi-mi:“MI:0915”(physical association)	0.000
TSSK1B	FAM229B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (56): TSSK1B (Two-hybrid), HSPA8 (Affinity Capture-MS), HSPA6 (Affinity Capture-MS), HSPA2 (Affinity Capture-MS), TUFM (Affinity Capture-MS), CEP131 (Affinity Capture-MS), GPHN (Affinity Capture-MS), CRYBG3 (Affinity Capture-MS), BORA (Affinity Capture-MS), GAPVD1 (Affinity Capture-MS), SNX24 (Affinity Capture-MS), TSSK1B (Synthetic Lethality), CRYBG3 (Affinity Capture-MS), CEP131 (Affinity Capture-MS), GPHN (Affinity Capture-MS)

ESM2 similar proteins: A7MBL8, F1QGZ6, O14757, O35099, O35280, O35942, O54785, O54863, O54992, O96017, P45983, P45984, P49186, P49187, P51955, P53350, P53666, P53668, P53669, P53670, P53671, P53779, P62205, P70032, Q07832, Q14680, Q15835, Q28GW8, Q2RAX3, Q2TA25, Q32L23, Q3SZW1, Q61241, Q61831, Q61846, Q62673, Q63651, Q6DE87, Q6NU47, Q8AYC9

Diamond homologs: A0A194W8T8, A0A5K1K8H0, A2VDU3, A5PKJ4, A6QGC0, A7J1T2, A8WWX1, B7XHR6, G5EEN4, O14427, O43283, O43318, O54863, O59697, O61122, O75914, O88643, P07334, P0C8E4, P0CD62, P23647, P27636, P34722, P35465, P40376, P48562, P50527, Q01389, Q02595, Q03002, Q03497, Q08E52, Q0WPH8, Q10056, Q13153, Q13164, Q13177, Q17850, Q1HKZ5, Q29502

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TSSK1B	“up-regulates activity”	TSSK1B	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

92 predictions. Top by Δscore:

Variant	Effect	Δscore
5:113433401:T:TA	donor_gain	0.9300
5:113433413:T:TA	donor_gain	0.9000
5:113433299:G:T	donor_gain	0.7900
5:113433652:T:TA	donor_gain	0.7700
5:113433343:A:C	donor_gain	0.7000
5:113433639:T:C	donor_gain	0.6200
5:113433776:T:TA	donor_gain	0.6100
5:113433648:G:GA	donor_gain	0.5800
5:113433397:G:A	donor_gain	0.5100
5:113433303:C:T	donor_gain	0.4900
5:113433157:G:A	donor_gain	0.4700
5:113433646:C:CT	donor_gain	0.4600
5:113433647:T:TT	donor_gain	0.4600
5:113433296:C:A	donor_gain	0.4400
5:113433298:TG:T	donor_gain	0.4100
5:113433677:T:TA	donor_gain	0.3900
5:113433653:C:A	donor_gain	0.3800
5:113432887:T:A	donor_gain	0.3600
5:113433302:C:CT	donor_gain	0.3600
5:113433059:ACT:A	acceptor_gain	0.3500
5:113433300:AC:A	donor_gain	0.3500
5:113433301:CC:C	donor_gain	0.3500
5:113433665:C:CT	donor_gain	0.3500
5:113433571:C:CT	acceptor_gain	0.3400
5:113432963:A:C	donor_gain	0.3300
5:113433055:TAATA:T	acceptor_gain	0.3300
5:113433058:TA:T	acceptor_gain	0.3300
5:113433589:G:C	donor_gain	0.3300
5:113433060:C:CC	acceptor_gain	0.3200
5:113433601:A:T	acceptor_gain	0.3200

AlphaMissense

2417 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:113434242:A:G	W200R	0.975
5:113434242:A:T	W200R	0.975
5:113434029:A:G	W271R	0.974
5:113434029:A:T	W271R	0.974
5:113434574:A:T	V89D	0.974
5:113434754:G:T	A29D	0.970
5:113434387:C:A	K151N	0.965
5:113434387:C:G	K151N	0.965
5:113434135:G:C	F235L	0.964
5:113434135:G:T	F235L	0.964
5:113434137:A:G	F235L	0.964
5:113434717:C:A	K41N	0.964
5:113434717:C:G	K41N	0.964
5:113434027:C:A	W271C	0.963
5:113434027:C:G	W271C	0.963
5:113434315:G:C	F175L	0.961
5:113434315:G:T	F175L	0.961
5:113434317:A:G	F175L	0.961
5:113434237:G:C	S201R	0.960
5:113434237:G:T	S201R	0.960
5:113434239:T:G	S201R	0.960
5:113434097:A:G	L248P	0.957
5:113434724:G:T	A39E	0.957
5:113434196:G:T	P215H	0.955
5:113434721:A:T	I40N	0.955
5:113434725:C:G	A39P	0.955
5:113434820:A:T	L7H	0.948
5:113434232:C:T	G203D	0.946
5:113434755:C:G	A29P	0.946
5:113434481:A:G	L120P	0.944

dbSNP variants (sampled 300 via entrez): RS1000090875 (5:113432525 T>G), RS1000631148 (5:113432737 A>G), RS1001026181 (5:113436443 T>A), RS1001273526 (5:113436933 A>G), RS1002950300 (5:113435535 TC>T), RS1003976747 (5:113434771 A>G), RS1004101492 (5:113432974 T>C,G), RS1004173724 (5:113432693 T>G), RS1005929379 (5:113435500 G>T), RS1005982164 (5:113435684 T>A), RS1006565421 (5:113432794 T>C,G), RS1007448347 (5:113434883 C>A), RS10075447 (5:113432339 A>C,G), RS1008133158 (5:113432130 G>A,C,T), RS1008373434 (5:113434040 A>C)

Disease associations

OMIM: gene MIM:610709 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000982_1	F-cell distribution in sickle cell anaemia	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004576	fetal hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6003 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 131,903 (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
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1967878	CENISERTIB	2	358
CHEMBL475251	R-406	2	762
CHEMBL1084546	PF-00562271	1	399
CHEMBL1908397	KW-2449	1	622

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Testis specific kinase (TSSK) family

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
ceritinib	Inhibition	7.64	pIC50
compound 20 [PMID: 30998356]	Inhibition	6.66	pIC50

Binding affinities (BindingDB)

3 measured of 3 human assays (3 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
PKC-412	KD	190 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

ChEMBL bioactivities

98 potent at pChembl≥5 of 106 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.33	IC50	0.0473	nM	STAUROSPORINE
10.28	IC50	0.052	nM	STAUROSPORINE
10.22	IC50	0.0607	nM	STAUROSPORINE
9.66	IC50	0.217	nM	CHEMBL4546504
8.60	Ki	2.512	nM	CHEMBL1971029
8.36	IC50	4.4	nM	BRIGATINIB
8.20	Ki	6.31	nM	CHEMBL2001751
8.10	Ki	7.943	nM	CHEMBL1993661
7.80	Ki	15.85	nM	CHEMBL1995813
7.75	Kd	18	nM	CHEMBL4465866
7.72	Kd	19	nM	CHEMBL4576489
7.70	IC50	20	nM	CHEMBL4550702
7.64	IC50	23	nM	CERITINIB
7.62	Kd	24	nM	STAUROSPORINE
7.60	Kd	25	nM	TAE-684
7.50	Ki	31.62	nM	CHEMBL1987034
7.50	Ki	31.62	nM	CHEMBL1998159
7.50	Ki	31.62	nM	TAE-684
7.46	IC50	35	nM	CHEMBL5085753
7.30	Ki	50.12	nM	CHEMBL1983111
7.30	Ki	50.12	nM	GSK-269962A
7.20	Ki	63.1	nM	CHEMBL1966628
7.20	Ki	63.1	nM	CHEMBL1969523
7.10	Ki	79.43	nM	CHEMBL1982957
7.10	Ki	79.43	nM	CHEMBL1974328
7.10	Ki	79.43	nM	CHEMBL2001239
7.01	Kd	98	nM	LESTAURTINIB
7.00	Ki	100	nM	R-406
7.00	Ki	100	nM	CHEMBL1974870
7.00	Ki	100	nM	CENISERTIB
7.00	Ki	100	nM	CHEMBL1991063
6.90	Ki	125.9	nM	CHEMBL1986943
6.90	Ki	125.9	nM	CHEMBL1241473
6.80	Ki	158.5	nM	CHEMBL1999931
6.77	IC50	170	nM	CHEMBL6167751
6.70	Ki	199.5	nM	CHEMBL1975128
6.70	Ki	199.5	nM	CHEMBL1969588
6.70	Ki	199.5	nM	CHEMBL1996817
6.70	Ki	199.5	nM	CHEMBL1990885
6.70	Ki	199.5	nM	GW843682X
6.68	IC50	210	nM	CHEMBL2334586
6.60	Ki	251.2	nM	CHEMBL1997129
6.60	Ki	251.2	nM	CHEMBL1965836
6.60	Ki	251.2	nM	CHEMBL592030
6.60	Ki	251.2	nM	CHEMBL1997846
6.50	Ki	316.2	nM	CHEMBL1973540
6.33	Kd	470	nM	CHEMBL464552
6.30	Ki	501.2	nM	CHEMBL1970104
6.30	Ki	501.2	nM	DOVITINIB
6.30	Ki	501.2	nM	CHEMBL1970903

PubChem BioAssay actives

35 with measured affinity, of 1227 total; 26 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	1715161: Inhibition of human STK22D using KKKVSRSGLYRSPSMPENLNRPR as substrate by [gamma-33P]-ATP assay	ic50	<0.0001	uM
4-[[5-chloro-4-(4-hydroxy-4-methylcyclohexyl)oxy-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-N,N-dimethyl-3-[(2R)-1,1,1-trifluoropropan-2-yl]oxybenzamide	1551605: Inhibition of recombinant human full length His-tagged TSSK1 expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0002	uM
N-[(1R,2S)-2-aminocyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637139: Inhibition of full-length recombinant human His-tagged STK22D expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0010	uM
Brigatinib	2182799: Inhibition of human TSSK1 using KKKVSRSGLYRSPSMPENLNRPR as substrate in presence of [gamma33P]-ATP by HotSpot assay	ic50	0.0044	uM
4-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637139: Inhibition of full-length recombinant human His-tagged STK22D expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0100	uM
N-[(1R,6R)-6-amino-2,2-difluorocyclohexyl]-4-(6-chloropyrazolo[1,5-a]pyrimidin-3-yl)-5-methylthiophene-2-carboxamide	1637139: Inhibition of full-length recombinant human His-tagged STK22D expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0100	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	1526226: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged TSSK1B (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0180	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	1526226: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged TSSK1B (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0190	uM
4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637139: Inhibition of full-length recombinant human His-tagged STK22D expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.0200	uM
Ceritinib	758001: Inhibition of STK22D (unknown origin) after 60 mins	ic50	0.0230	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	625142: Binding constant for TSSK1B kinase domain	kd	0.0250	uM
2-(2,6-diethylphenyl)-7-[2-[2-methoxy-4-[4-(6-methyl-2,6-diazaspiro[3.3]heptane-2-carbonyl)piperidin-1-yl]anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one	1815054: Inhibition of TSSK1 (unknown origin) by Z-lyte assay	ic50	0.0350	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	508120: Binding affinity to TSSK1B	kd	0.0980	uM
4-(4-amino-3,5,12-triazatetracyclo[9.7.0.02,7.013,18]octadeca-1(11),2,4,6,13(18),14,16-heptaen-16-yl)-2-methylbut-3-yn-2-ol	1856577: Inhibition of human wild type TSSK1	ic50	0.2100	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	625142: Binding constant for TSSK1B kinase domain	kd	0.4700	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	625142: Binding constant for TSSK1B kinase domain	kd	1.0000	uM
Momelotinib	2183927: Inhibition of STK22D (unknown origin)	ic50	1.0000	uM
Fedratinib	625142: Binding constant for TSSK1B kinase domain	kd	1.3000	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	625142: Binding constant for TSSK1B kinase domain	kd	2.1000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625142: Binding constant for TSSK1B kinase domain	kd	2.3000	uM
2-anilino-7-[(1S)-4-hydroxy-2,3-dihydro-1H-inden-1-yl]-5,5-dimethylpyrrolo[2,3-d]pyrimidin-6-one	1336053: Inhibition of human recombinant full length His-tagged STK22D expressed in baculovirus expression system	ic50	3.1170	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625142: Binding constant for TSSK1B kinase domain	kd	3.2000	uM
Bosutinib	625142: Binding constant for TSSK1B kinase domain	kd	4.6000	uM
Midostaurin	435940: Binding constant for full-length TSSK1	kd	4.8000	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625142: Binding constant for TSSK1B kinase domain	kd	6.1000	uM
Sunitinib	435940: Binding constant for full-length TSSK1	kd	6.3000	uM

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Valproic Acid	increases methylation	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

275 unique, capped per target: 274 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001349	Binding	Inhibition of TSSK1 at 10 uM	Achieving multi-isoform PI3K inhibition in a series of substituted 3,4-dihydro-2H-benzo[1,4]oxazines. — Bioorg Med Chem Lett
CHEMBL1963753	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: STK22D	PubChem BioAssay data set

Clinical trials (associated diseases)

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