TSSK2

Summary

TSSK2 (testis specific serine kinase 2, HGNC:11401) is a protein-coding gene on chromosome 22q11.21, encoding Testis-specific serine/threonine-protein kinase 2 (Q96PF2). Testis-specific serine/threonine-protein kinase required during spermatid development.

TSSK2 belongs to a family of serine/threonine kinases highly expressed in testis (Hao et al., 2004 [PubMed 15044604]).

Source: NCBI Gene 23617 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 2 total — 1 pathogenic
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_053006

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11401
Approved symbol	TSSK2
Name	testis specific serine kinase 2
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Aliases	SPOGA2, FLJ38613
Ensembl gene	ENSG00000206203
Ensembl biotype	protein_coding
OMIM	610710
Entrez	23617

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000399635

RefSeq mRNA: 1 — MANE Select: NM_053006 NM_053006

CCDS: CCDS13755

Canonical transcript exons

ENST00000399635 — 1 exons

Exon	Start	End
ENSE00001539405	19131308	19132622

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 97.30.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4066 / max 415.4493, expressed in 7 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191035	0.3530	5
191036	0.0384	3
191034	0.0153	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.30	gold quality
right testis	UBERON:0004534	97.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.86	gold quality
testis	UBERON:0000473	94.40	gold quality
adult organism	UBERON:0007023	93.38	gold quality
sperm	CL:0000019	87.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.77	gold quality
male germ cell	CL:0000015	86.20	gold quality
frontal pole	UBERON:0002795	72.95	gold quality
middle frontal gyrus	UBERON:0002702	72.47	gold quality
paraflocculus	UBERON:0005351	72.41	gold quality
tibialis anterior	UBERON:0001385	62.30	silver quality
endometrium epithelium	UBERON:0004811	62.11	gold quality
cerebellar vermis	UBERON:0004720	56.89	gold quality
ganglionic eminence	UBERON:0004023	54.31	gold quality
cortical plate	UBERON:0005343	53.83	gold quality
thymus	UBERON:0002370	53.61	gold quality
metanephric glomerulus	UBERON:0004736	53.53	gold quality
quadriceps femoris	UBERON:0001377	53.04	gold quality
cauda epididymis	UBERON:0004360	52.88	gold quality
deltoid	UBERON:0001476	52.55	silver quality
vastus lateralis	UBERON:0001379	51.53	gold quality
embryo	UBERON:0000922	51.47	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.97	gold quality
ventricular zone	UBERON:0003053	50.84	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.84	gold quality
layer of synovial tissue	UBERON:0007616	49.72	gold quality
kidney epithelium	UBERON:0004819	49.42	gold quality
buccal mucosa cell	CL:0002336	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31.83
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TCF3

miRNA regulators (miRDB)

18 targeting TSSK2, 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-4778-3P	99.93	70.40	1818
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-299-5P	98.56	71.14	1140
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-500A-3P	97.60	67.48	595
HSA-MIR-203B-5P	97.24	68.54	543
HSA-MIR-6718-5P	97.24	68.15	553
HSA-MIR-550B-2-5P	96.56	64.61	646
HSA-MIR-24-1-5P	95.57	65.85	492
HSA-MIR-24-2-5P	95.57	66.16	484

Literature-anchored findings (GeneRIF, showing 4)

• Data show that human testis-specific serine/threonine (Ser/Thr) kinase (TSSK) 1 and 2 messages are expressed exclusively in the testis and suggest that this family of kinases might play a role in sperm function. (PMID:15044604)
• associated with male idiopathic infertility (PMID:19926886)
• Report evolution of testis-specific kinases TSSK1B and TSSK2 in primates. (PMID:23258646)
• n vitro phosphorylation experiments carried out with TSKS (isoform 1) fragments revealed particularly strong phosphorylation of a recombinant N-terminal region representing aa 1-150 of TSKS, indicating that the N-terminus of human TSKS is phosphorylated by human TSSK2. (PMID:26777341)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tssk2	ENSMUSG00000045521
rattus_norvegicus	Tssk1b	ENSRNOG00000068894
drosophila_melanogaster	Snrk	FBGN0033915
caenorhabditis_elegans		WBGENE00012638
caenorhabditis_elegans	ZK524.4	WBGENE00013994
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), TSSK1B (ENSG00000212122)

Protein

Protein identifiers

Testis-specific serine/threonine-protein kinase 2 — Q96PF2 (reviewed: Q96PF2)

Alternative names: DiGeorge syndrome protein G, Serine/threonine-protein kinase 22B

All UniProt accessions (2): A0ZT99, Q96PF2

UniProt curated annotations — full annotation on UniProt →

Function. Testis-specific serine/threonine-protein kinase required during spermatid development. Phosphorylates TSKS at ‘Ser-288’ and SPAG16. 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 TSSK1B. Interacts with HSP90; this interaction stabilizes TSSK2.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole.

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

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

Activity regulation. Activated by phosphorylation on Thr-174, 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_443732* (*=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

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

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 (16 total): sequence variant 6, sequence conflict 2, compositionally biased region 2, binding site 2, chain 1, domain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PF2-F1	82.84	0.70

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

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 144 (showing top): MYAATNNNNNNNGGC_UNKNOWN, MORF_MSH3, GOCC_SECRETORY_GRANULE, MORF_BRCA1, AREB6_01, RACCACAR_AML_Q6, GOBP_MALE_GAMETE_GENERATION, MORF_RAD51L3, GOCC_MICROTUBULE_ORGANIZING_CENTER, CATRRAGC_UNKNOWN, AAACCAC_MIR140, AML_Q6, MORF_PRKCA, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GNF2_CCNA1

GO Biological Process (5): protein phosphorylation (GO:0006468), spermatid development (GO:0007286), protein autophosphorylation (GO:0046777), 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 (5): acrosomal vesicle (GO:0001669), nucleus (GO:0005634), cytoplasm (GO:0005737), centriole (GO:0005814), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
binding	2
intracellular membraneless organelle	2
phosphorylation	1
protein modification process	1
germ cell development	1
spermatid differentiation	1
protein phosphorylation	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
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
microtubule organizing center	1

Protein interactions and networks

STRING

1779 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSSK2	TSKS	Q9UJT2	976
TSSK2	MFAP1	P55081	668
TSSK2	FBN1	P35555	639
TSSK2	CALY	Q9NYX4	565
TSSK2	CCN2	P29279	506
TSSK2	SPAG6	O75602	482
TSSK2	SEPTIN5	Q99719	450
TSSK2	ODF1	Q14990	445
TSSK2	DGCR6L	Q9BY27	444
TSSK2	CRABP1	P29762	438
TSSK2	SIGLEC1	Q9BZZ2	436
TSSK2	TNP1	P09430	434
TSSK2	KLHL10	Q6JEL2	429
TSSK2	SNRNP70	P08621	428
TSSK2	IZUMO1	Q8IYV9	423

IntAct

30 interactions, top by confidence:

A	B	Type	Score
TSSK2	TSKS	psi-mi:“MI:0915”(physical association)	0.700
TSKS	TSSK2	psi-mi:“MI:0915”(physical association)	0.700
TSSK2	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
TSEN15	TSSK2	psi-mi:“MI:0915”(physical association)	0.560
FAM229B	TSSK2	psi-mi:“MI:0915”(physical association)	0.560
TSSK2	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.560
PTPRD	TSSK2	psi-mi:“MI:0407”(direct interaction)	0.440
	TSSK2	psi-mi:“MI:0407”(direct interaction)	0.440
TSSK2	TSKS	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
TSKS	TSSK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PKM	TSSK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
YWHAE	TSSK2	psi-mi:“MI:0915”(physical association)	0.400
SFN	TSSK2	psi-mi:“MI:0915”(physical association)	0.400
SKIC2	TSSK2	psi-mi:“MI:0915”(physical association)	0.370
TSSK2	SERPINA1	psi-mi:“MI:0914”(association)	0.350
TSSK2	TSKS	psi-mi:“MI:0915”(physical association)	0.000
TSSK2	LZTS2	psi-mi:“MI:0915”(physical association)	0.000
TSSK2	TSEN15	psi-mi:“MI:0915”(physical association)	0.000
TSKS	TSSK2	psi-mi:“MI:0915”(physical association)	0.000
TSSK2	FAM229B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): TSSK2 (Reconstituted Complex), TSKS (Two-hybrid), TSSK2 (Affinity Capture-Western), TSSK2 (Biochemical Activity), TSKS (Biochemical Activity), TSSK2 (Two-hybrid), TSSK2 (Two-hybrid), TSSK2 (Two-hybrid), TSSK2 (Two-hybrid), SERPINA1 (Affinity Capture-MS), APOA1 (Affinity Capture-MS), ORM1 (Affinity Capture-MS), TTR (Affinity Capture-MS), TF (Affinity Capture-MS), HSP90AA1 (Affinity Capture-MS)

ESM2 similar proteins: A2XFF4, B8BBT7, O15530, O22971, O54863, O96017, P51567, P52304, P53351, P92958, Q02723, Q0JI49, Q14680, Q28GW8, Q38997, Q3SZW1, Q5HZ38, Q5JLS2, Q5R4L1, Q61241, Q61846, Q6DE87, Q6H7U5, Q6PFQ0, Q6SA08, Q852Q0, Q852Q1, Q852Q2, Q86YV6, Q8BG48, Q8C1R0, Q91821, Q91822, Q93V58, Q93Z30, Q96PF2, Q9BXA7, Q9C562, Q9D411, Q9JJX8

Diamond homologs: A0AAR7, A1Z9X0, A8WRV1, B5X4Z9, F1MH24, F1SPM8, G5ECQ3, O14976, O15021, O35942, O43066, O54863, O60307, O61267, P09216, P0C1X8, P0C263, P10830, P13678, P28708, P34885, P38080, P40494, P41719, P51955, P53974, P92937, P97874, Q02156, Q08217, Q09815, Q12152, Q2M2I8, Q3U214, Q3UHJ0, Q54VV7, Q55DU7, Q5A961, Q5JLQ9, Q5W736

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
455788	NC_000022.10:g.(?18900668)(19770565_?)del	Pathogenic

SpliceAI

178 predictions. Top by Δscore:

Variant	Effect	Δscore
22:19132253:T:G	acceptor_gain	0.7200
22:19132252:T:TG	acceptor_gain	0.7000
22:19131548:CTGA:C	donor_gain	0.6800
22:19131907:A:AG	acceptor_gain	0.6500
22:19131547:A:AC	donor_gain	0.6400
22:19131548:C:CC	donor_gain	0.6400
22:19131439:G:GT	acceptor_gain	0.6000
22:19131440:T:TT	acceptor_gain	0.6000
22:19131893:G:GA	acceptor_gain	0.6000
22:19131894:C:A	acceptor_gain	0.5900
22:19132275:G:GT	acceptor_gain	0.5900
22:19132276:T:TT	acceptor_gain	0.5900
22:19131626:A:AC	donor_gain	0.5800
22:19131627:C:CC	donor_gain	0.5800
22:19131635:TTGAG:T	donor_gain	0.5800
22:19131891:C:CA	acceptor_gain	0.5600
22:19131892:A:AA	acceptor_gain	0.5600
22:19131905:TCATC:T	acceptor_gain	0.5500
22:19131906:CATCC:C	acceptor_gain	0.5500
22:19132260:G:A	acceptor_gain	0.5400
22:19131908:TCC:T	acceptor_gain	0.5300
22:19131909:CCTC:C	acceptor_gain	0.5200
22:19131888:G:GA	acceptor_gain	0.5100
22:19132272:C:T	acceptor_gain	0.5000
22:19131570:T:TA	donor_gain	0.4900
22:19131628:G:C	donor_gain	0.4900
22:19131551:A:AC	donor_gain	0.4700
22:19131552:C:CC	donor_gain	0.4700
22:19131550:G:T	donor_gain	0.4500
22:19132280:GCGC:G	acceptor_gain	0.4500

AlphaMissense

2378 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:19131803:G:C	R135P	0.997
22:19131997:T:A	W200R	0.996
22:19131997:T:C	W200R	0.996
22:19132043:C:A	P215H	0.996
22:19131485:C:A	A29D	0.994
22:19131515:C:A	A39D	0.994
22:19132142:T:C	L248P	0.994
22:19131824:T:C	L142P	0.993
22:19131999:G:C	W200C	0.993
22:19131999:G:T	W200C	0.993
22:19131922:T:C	F175L	0.992
22:19131924:C:A	F175L	0.992
22:19131924:C:G	F175L	0.992
22:19131950:C:A	P184H	0.992
22:19131852:G:C	K151N	0.991
22:19131852:G:T	K151N	0.991
22:19132042:C:T	P215S	0.991
22:19132210:T:A	W271R	0.991
22:19132210:T:C	W271R	0.991
22:19131522:G:C	K41N	0.990
22:19131522:G:T	K41N	0.990
22:19131565:T:C	F56L	0.990
22:19131567:C:A	F56L	0.990
22:19131567:C:G	F56L	0.990
22:19131806:A:C	D136A	0.990
22:19131806:A:T	D136V	0.989
22:19131827:T:C	L143P	0.989
22:19131861:C:A	D154E	0.989
22:19131861:C:G	D154E	0.989
22:19131868:T:C	F157L	0.989

dbSNP variants (sampled 300 via entrez): RS1000322876 (22:19131568 C>G,T), RS1001266142 (22:19130079 A>C,G), RS1001731346 (22:19130450 A>G), RS1003082166 (22:19132975 C>T), RS1004306113 (22:19130014 C>T), RS1005094210 (22:19131282 G>A), RS1005200672 (22:19130901 C>T), RS1007176029 (22:19131292 C>A), RS1007201326 (22:19132799 C>G), RS1007316056 (22:19133044 T>A,C), RS1007534633 (22:19131113 G>A,C), RS1008594262 (22:19130040 C>T), RS1008996523 (22:19130594 T>C), RS1009999817 (22:19131536 A>G), RS1010118571 (22:19131815 G>A,T)

Disease associations

OMIM: gene MIM:610710 | disease phenotypes: MIM:188400

GenCC curated gene-disease

Mondo (1): DiGeorge syndrome (MONDO:0008564)

Orphanet (1): 22q11.2 deletion syndrome (Orphanet:567)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008171_26	Platelet aggregation	3.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004062	DiGeorge Syndrome	C05.660.207.103.500; C14.240.400.021.500; C14.280.400.044.500; C15.604.451.249.500; C16.131.077.019.500; C16.131.240.400.021.500; C16.131.260.019.500; C16.131.482.249.500; C16.131.621.207.103.500; C16.320.180.019.500; C19.642.482.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6014 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 6,029 (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
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1980391	RG-1530	1	37

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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 2c [PMID: 24900538]	Inhibition	7.51	pIC50

ChEMBL bioactivities

48 potent at pChembl≥5 of 49 total, top 48 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.48	IC50	3.32	nM	STAUROSPORINE
8.46	IC50	3.44	nM	STAUROSPORINE
8.37	IC50	4.32	nM	STAUROSPORINE
8.00	Ki	10	nM	TAE-684
8.00	Ki	10	nM	CHEMBL1971029
7.51	IC50	30.6	nM	CHEMBL2151321
7.40	Ki	39.81	nM	CHEMBL1978448
7.20	Ki	63.1	nM	GW843682X
7.10	Ki	79.43	nM	CHEMBL1998159
7.10	Ki	79.43	nM	CHEMBL1991078
7.10	Ki	79.43	nM	CHEMBL1974328
7.00	Ki	100	nM	CHEMBL1995813
7.00	Ki	100	nM	CHEMBL1993661
6.86	IC50	138	nM	BRIGATINIB
6.80	Ki	158.5	nM	CHEMBL539474
6.80	Ki	158.5	nM	CHEMBL1969523
6.70	Ki	199.5	nM	CHEMBL1987034
6.60	Ki	251.2	nM	CHEMBL1983111
6.60	Ki	251.2	nM	CENISERTIB
6.50	Ki	316.2	nM	CHEMBL2006263
6.30	Ki	501.2	nM	CHEMBL1997129
6.30	Ki	501.2	nM	CHEMBL1975138
6.30	Ki	501.2	nM	CHEMBL2001239
6.20	Ki	631	nM	CHEMBL1990885
6.20	Ki	631	nM	CHEMBL1825138
6.10	Ki	794.3	nM	CHEMBL1966628
6.10	Ki	794.3	nM	CHEMBL2000832
6.10	Ki	794.3	nM	CHEMBL2004544
6.10	Ki	794.3	nM	CHEMBL1241473
6.10	Ki	794.3	nM	CHEMBL1997349
6.10	Ki	794.3	nM	CHEMBL2001751
6.03	IC50	944	nM	CHEMBL5085753
6.00	Ki	1000	nM	ALSTERPAULLONE
6.00	Ki	1000	nM	CHEMBL526133
6.00	Ki	1000	nM	RG-1530
5.90	Ki	1259	nM	CHEMBL519697
5.90	Ki	1259	nM	CHEMBL1964687
5.90	Ki	1259	nM	CHEMBL1992922
5.90	Ki	1259	nM	CHEMBL583144
5.90	Ki	1259	nM	CHEMBL2000354
5.90	Ki	1259	nM	CHEMBL1989805
5.90	Ki	1259	nM	CHEMBL1969588
5.90	Ki	1259	nM	CHEMBL1995740
5.80	Ki	1585	nM	CHEMBL1975233
5.80	Ki	1585	nM	CHEMBL592030
5.80	Ki	1585	nM	CHEMBL1988838
5.80	Ki	1585	nM	CHEMBL1974870
5.05	IC50	8900	nM	CHEMBL2381116

PubChem BioAssay actives

7 with measured affinity, of 483 total; 5 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	1715135: Inhibition of human TSSK2 using KKKVSRSGLYRSPSMPENLNRPR as substrate by [gamma-33P]-ATP assay	ic50	0.0033	uM
N-[(1S)-1-(5-fluoro-2-pyridinyl)ethyl]-3-(3-propan-2-yloxy-1H-pyrazol-5-yl)imidazo[4,5-b]pyridin-5-amine	692419: Inhibition of TSSK2	ic50	0.0306	uM
Brigatinib	2182837: Inhibition of human TSSK2 using KKKVSRSGLYRSPSMPENLNRPR as substrate in presence of [gamma33P]-ATP by HotSpot assay	ic50	0.1380	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	1815053: Inhibition of TSSK2 (unknown origin) by Z-lyte assay	ic50	0.9440	uM
2-(5-methoxy-3-oxo-1H-isoindol-2-yl)-N-(4-piperazin-1-yl-3-pyridinyl)-1,3-thiazole-4-carboxamide	746300: Inhibition of human TSSK2	ic50	8.9000	uM

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
tetrabromobisphenol A	increases expression	1
CGP 52608	increases reaction, affects binding	1
jinfukang	affects cotreatment, decreases expression	1
Amphotericin B	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1

ChEMBL screening assays

150 unique, capped per target: 149 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1036954	Binding	Inhibition of TSSK2 at 1 uM	Structure-guided design of potent and selective pyrimidylpyrrole inhibitors of extracellular signal-regulated kinase (ERK) using conformational control. — J Med Chem
CHEMBL1963716	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: STK22B	PubChem BioAssay data set

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TU99	HAP1 TSSK2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00395538	PHASE3	TERMINATED	Effects of PTH Replacement on Bone in Hypoparathyroidism
NCT00576407	PHASE2	COMPLETED	Thymus Transplantation in DiGeorge Syndrome #668
NCT00576836	PHASE2	COMPLETED	Thymus Transplantation Dose in DiGeorge #932
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT05149898	PHASE2	COMPLETED	Open-Label Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With 22q11.2 Deletion Syndrome (INSPIRE)
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT00566488	PHASE1	COMPLETED	Parathyroid and Thymus Transplantation in DiGeorge #931
NCT00579709	PHASE1	COMPLETED	Thymus Transplantation With Immunosuppression
NCT00849888	PHASE1	TERMINATED	Serum-Free Thymus Transplantation in DiGeorge Anomaly
NCT02895906	PHASE1	COMPLETED	Safety and Efficacy Study of NFC-1 in Subjects Aged 12-17 Years With 22q11.2DS & Associated Neuropsychiatric Conditions
NCT00579527	PHASE1/PHASE2	COMPLETED	Phase I/II Thymus Transplantation With Immunosuppression #950
NCT00004351	Not specified	COMPLETED	Study of Phenotype and Genotype Correlations in Patients With Contiguous Gene Deletion Syndromes
NCT00005102	Not specified	UNKNOWN	Immunologic Evaluation in Patients With DiGeorge Syndrome or Velocardiofacial Syndrome
NCT00105274	Not specified	COMPLETED	Velocardiofacial (VCFS; 22q11.2; DiGeorge) Syndrome Study
NCT00278005	Not specified	TERMINATED	Infection in DiGeorge Following CHD Surgery
NCT00556530	Not specified	RECRUITING	Examining Genetic Factors That Affect the Severity of 22q11.2 Deletion Syndrome
NCT00916955	Not specified	COMPLETED	Genetic Modifiers for 22q11.2 Syndrome
NCT01220531	Not specified	COMPLETED	Thymus Transplantation Safety-Efficacy
NCT01781923	Not specified	COMPLETED	Cognitive Remediation in 22q11DS
NCT02381457	Not specified	COMPLETED	SNP-based Microdeletion and Aneuploidy RegisTry (SMART)
NCT02430584	Not specified	UNKNOWN	Whole Blood Specimen Collection From Pregnant Subjects
NCT02460328	Not specified	COMPLETED	Resolution of Primary Immune Defect in 22q11.2 Deletion Syndrome
NCT02787486	Not specified	COMPLETED	Expanded Noninvasive Genomic Medical Assessment: The Enigma Study
NCT03284060	Not specified	TERMINATED	Social Cognition Training and Cognitive Remediation
NCT04141540	Not specified	COMPLETED	Molecular Variants Associated With Schizophrenia: Differential Analysis of Monozygotic Twins With Variable Phenotypic 22q11
NCT04373226	Not specified	TERMINATED	Arithmetic Abilities in Children With 22q11.2DS
NCT04639388	Not specified	RECRUITING	Understanding of Psychotic Disorders in Children With 22q11.2DS
NCT04639960	Not specified	TERMINATED	Neuroprotective Effects of Risperdal on Brain and Cognition in 22q11 Deletion Syndrome
NCT04647500	Not specified	COMPLETED	Effects of Methylphenidate on Brain and Cognition in 22q11 Deletion Syndrome
NCT05924347	Not specified	RECRUITING	Early Scoliotic Changes in Children at Increased Risk for Scoliosis Development
NCT07493096	Not specified	RECRUITING	Intensive Multimodal Neurorehabilitation Targeting Neuroplasticity in Pediatric Neurodevelopmental and Chromosomal Disorders