TSKS

Summary

TSKS (testis specific serine kinase substrate, HGNC:30719) is a protein-coding gene on chromosome 19q13.33, encoding Testis-specific serine kinase substrate (Q9UJT2). May play a role in testicular physiology, most probably in the process of spermatogenesis or spermatid development.

This gene may play a role in testicular physiology, spermatogenesis or spermiogenesis. Expression of the encoded protein is highest in the testis and down-regulated in testicular cancer. The gene is localized to the region 19q13.3 among the related RAS viral oncogene homolog (RRAS) and interferon regulatory factor 3 (IRF3) genes, which are both involved in tumorigenesis pathways and progression.

Source: NCBI Gene 60385 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 107 total
• MANE Select transcript: NM_021733

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30719
Approved symbol	TSKS
Name	testis specific serine kinase substrate
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	TSSKS, PPP1R161
Ensembl gene	ENSG00000126467
Ensembl biotype	protein_coding
OMIM	608253
Entrez	60385

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000246801, ENST00000358830, ENST00000599325

RefSeq mRNA: 1 — MANE Select: NM_021733 NM_021733

CCDS: CCDS12780

Canonical transcript exons

ENST00000246801 — 11 exons

Exon	Start	End
ENSE00000864522	49740059	49740183
ENSE00000864523	49741885	49742020
ENSE00000864524	49744231	49744404
ENSE00000864525	49745202	49745396
ENSE00000864526	49746470	49746798
ENSE00000864527	49747389	49747472
ENSE00000864528	49748085	49748168
ENSE00000864529	49748374	49748469
ENSE00000864530	49762004	49762232
ENSE00001127176	49763078	49763306
ENSE00003017746	49739760	49739932

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 96.75.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1149 / max 108.2604, expressed in 5 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182076	0.0752	5
182075	0.0348	3
182077	0.0050	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	96.75	gold quality
left testis	UBERON:0004533	96.59	gold quality
testis	UBERON:0000473	93.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.02	gold quality
male germ cell	CL:0000015	71.86	gold quality
sperm	CL:0000019	71.35	silver quality
pancreatic ductal cell	CL:0002079	69.39	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	68.95	gold quality
apex of heart	UBERON:0002098	68.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	67.83	gold quality
granulocyte	CL:0000094	67.18	gold quality
adult organism	UBERON:0007023	66.97	gold quality
right atrium auricular region	UBERON:0006631	66.63	gold quality
monocyte	CL:0000576	66.48	gold quality
right coronary artery	UBERON:0001625	66.35	gold quality
mononuclear cell	CL:0000842	66.24	gold quality
leukocyte	CL:0000738	65.96	gold quality
cardiac atrium	UBERON:0002081	65.55	gold quality
omental fat pad	UBERON:0010414	65.34	gold quality
peritoneum	UBERON:0002358	65.31	gold quality
tendon of biceps brachii	UBERON:0008188	65.12	gold quality
body of uterus	UBERON:0009853	64.47	gold quality
adipose tissue of abdominal region	UBERON:0007808	64.19	gold quality
ectocervix	UBERON:0012249	62.86	gold quality
skin of abdomen	UBERON:0001416	62.75	gold quality
left coronary artery	UBERON:0001626	62.11	gold quality
coronary artery	UBERON:0001621	61.95	gold quality
left uterine tube	UBERON:0001303	61.79	gold quality
parotid gland	UBERON:0001831	61.72	gold quality
heart	UBERON:0000948	61.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.40

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• 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

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tsks	ENSMUSG00000059891
rattus_norvegicus	Tsks	ENSRNOG00000020443

Protein

Protein identifiers

Testis-specific serine kinase substrate — Q9UJT2 (reviewed: Q9UJT2)

Alternative names: STK22 substrate 1

All UniProt accessions (2): Q9UJT2, C9K0I0

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in testicular physiology, most probably in the process of spermatogenesis or spermatid development.

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

Tissue specificity. Highly expressed in testis. Expressed at low levels in prostate, female breast, placenta, ovary and thymus.

Post-translational modifications. Phosphorylated on serine residue(s) by STK22A/TSSK1 and STK22B/TSSK2.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UJT2-1	1	yes
Q9UJT2-2	2

RefSeq proteins (1): NP_068379* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028214	TSKS	Family

Pfam: PF15358

UniProt features (15 total): splice variant 3, sequence variant 3, modified residue 3, region of interest 2, compositionally biased region 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJT2-F1	66.05	0.20

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 217, 288, 316

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 45 (showing top): GOCC_MICROTUBULE_ORGANIZING_CENTER, GOCC_CENTRIOLE, GOMF_KINASE_BINDING, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, DCA_UP.V1_UP, GSE14386_UNTREATED_VS_IFNA_TREATED_ACT_PBMC_MS_PATIENT_UP, GSE13547_WT_VS_ZFX_KO_BCELL_ANTI_IGM_STIM_12H_UP, GSE13547_CTRL_VS_ANTI_IGM_STIM_BCELL_2H_DN, GSE14308_NAIVE_CD4_TCELL_VS_INDUCED_TREG_UP, GSE14308_NAIVE_CD4_TCELL_VS_NATURAL_TREG_UP, GSE14769_UNSTIM_VS_40MIN_LPS_BMDM_UP, GSE14769_40MIN_VS_360MIN_LPS_BMDM_DN, GSE15750_WT_VS_TRAF6KO_DAY6_EFF_CD8_TCELL_DN, GSE17721_CPG_VS_GARDIQUIMOD_16H_BMDC_UP

GO Biological Process (0):

GO Molecular Function (2): protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (3): centriole (GO:0005814), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	2
kinase binding	1
binding	1
microtubule organizing center	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

302 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSKS	TSSK2	Q96PF2	976
TSKS	TSSK1B	Q9BXA7	856
TSKS	TSSK3	Q96PN8	720
TSKS	TSSK6	Q9BXA6	720
TSKS	TSSK4	Q6SA08	719
TSKS	RRAS	P10301	701
TSKS	AP2A1	O95782	698
TSKS	RBM12B	Q8IXT5	590
TSKS	NEK4	P51957	585
TSKS	IRF3	Q14653	460
TSKS	TSGA10IP	Q3SY00	400
TSKS	PRR12	Q9ULL5	394
TSKS	DDX25	Q9UHL0	376
TSKS	PRRG2	O14669	374
TSKS	TBC1D21	Q8IYX1	373

IntAct

34 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
AAGAB	AP2A2	psi-mi:“MI:0914”(association)	0.670
ATXN7L3	USP27X	psi-mi:“MI:0914”(association)	0.640
EXOSC3	MTREX	psi-mi:“MI:0914”(association)	0.640
LHX3	LDB1	psi-mi:“MI:0914”(association)	0.570
KRT27	TSKS	psi-mi:“MI:0915”(physical association)	0.560
TPM3	TSKS	psi-mi:“MI:0915”(physical association)	0.560
TSSK1B	TSKS	psi-mi:“MI:0915”(physical association)	0.560
TSKS	RGPD8	psi-mi:“MI:0914”(association)	0.530
ZNF214	LRP4	psi-mi:“MI:0914”(association)	0.530
TSKS	PPP1CA	psi-mi:“MI:0407”(direct interaction)	0.440
ABL1	TSKS	psi-mi:“MI:0915”(physical association)	0.400
FYN	TSKS	psi-mi:“MI:0915”(physical association)	0.400
TSKS	GRB2	psi-mi:“MI:0915”(physical association)	0.400
TSKS	H1-4	psi-mi:“MI:0915”(physical association)	0.400
TSKS	H1-5	psi-mi:“MI:0915”(physical association)	0.400
TSKS	H1-2	psi-mi:“MI:0915”(physical association)	0.400
TSKS	H1-1	psi-mi:“MI:0915”(physical association)	0.400
TSSK2	TSKS	psi-mi:“MI:0915”(physical association)	0.000
TSKS	KRT27	psi-mi:“MI:0915”(physical association)	0.000
TSKS	TPM3	psi-mi:“MI:0915”(physical association)	0.000
TSKS	TSSK2	psi-mi:“MI:0915”(physical association)	0.000
TSKS	TSSK1B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (59): PGGT1B (Affinity Capture-MS), PTRF (Affinity Capture-MS), TRAF3 (Affinity Capture-MS), RGPD8 (Affinity Capture-MS), BLOC1S2 (Affinity Capture-MS), C17orf70 (Affinity Capture-MS), DTNBP1 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), CCDC85B (Affinity Capture-MS), RFWD2 (Affinity Capture-MS), POC1A (Affinity Capture-MS), EXOC1 (Affinity Capture-MS), PRMT3 (Affinity Capture-MS), SNAPIN (Affinity Capture-MS), FNTA (Affinity Capture-MS)

ESM2 similar proteins: A0A140LIT1, A0A1B0GVG4, A0JNH6, A1A5D9, A6NC98, A6NGB0, A6NJZ7, A6NNM3, F6XLV1, O15049, O54887, P0C7N4, P58660, P60531, Q0D2H9, Q0P5D1, Q2KJ21, Q2TAC2, Q3LUD3, Q3T1I3, Q3TMW1, Q3V0F0, Q4QRL3, Q5JTB6, Q5RD60, Q66HR5, Q6NSJ2, Q6PHN1, Q6QZQ4, Q80VM7, Q8BP01, Q8C7U1, Q8CB62, Q8CGU1, Q8CHW5, Q8K2I2, Q8N137, Q8N283, Q8N6Y0, Q8R370

Diamond homologs: O54887, P60531, Q9UJT2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2366 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49740052:T:TA	donor_gain	1.0000
19:49740057:A:AC	donor_gain	1.0000
19:49740058:C:CC	donor_gain	1.0000
19:49740058:CT:C	donor_gain	1.0000
19:49740066:T:TA	donor_gain	1.0000
19:49741876:C:A	donor_gain	1.0000
19:49746474:G:C	donor_gain	1.0000
19:49746601:C:CA	donor_gain	1.0000
19:49746799:C:CC	acceptor_gain	1.0000
19:49748081:TCACC:T	donor_loss	1.0000
19:49748082:CA:C	donor_loss	1.0000
19:49748165:CGCT:C	acceptor_gain	1.0000
19:49748167:CT:C	acceptor_gain	1.0000
19:49748169:C:CC	acceptor_gain	1.0000
19:49748169:C:G	acceptor_gain	1.0000
19:49748175:C:CT	acceptor_gain	1.0000
19:49748465:CCACT:C	acceptor_gain	1.0000
19:49748466:CACT:C	acceptor_gain	1.0000
19:49748466:CACTC:C	acceptor_gain	1.0000
19:49748468:CT:C	acceptor_gain	1.0000
19:49748470:C:CC	acceptor_gain	1.0000
19:49748471:T:A	acceptor_loss	1.0000
19:49761998:CCTCA:C	donor_loss	1.0000
19:49761999:CTCA:C	donor_loss	1.0000
19:49762001:CA:C	donor_loss	1.0000
19:49762228:CCACC:C	acceptor_gain	1.0000
19:49762229:CACC:C	acceptor_gain	1.0000
19:49762229:CACCC:C	acceptor_gain	1.0000
19:49762230:ACC:A	acceptor_gain	1.0000
19:49762231:CC:C	acceptor_gain	1.0000

AlphaMissense

3809 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49747436:C:G	A206P	0.997
19:49763083:G:C	F55L	0.997
19:49763083:G:T	F55L	0.997
19:49763085:A:G	F55L	0.997
19:49747414:A:G	L213S	0.995
19:49747403:A:G	S217P	0.994
19:49763220:A:G	W10R	0.994
19:49763220:A:T	W10R	0.994
19:49748089:A:G	L192P	0.993
19:49763218:C:A	W10C	0.992
19:49763218:C:G	W10C	0.992
19:49748442:C:G	A143P	0.991
19:49763084:A:G	F55S	0.991
19:49746791:A:G	L224P	0.990
19:49748378:A:G	L164P	0.990
19:49748433:A:G	S146P	0.990
19:49748441:G:T	A143D	0.990
19:49763222:A:G	I9T	0.990
19:49763222:A:T	I9N	0.989
19:49747393:A:G	L220P	0.987
19:49763222:A:C	I9S	0.987
19:49740179:A:G	L501P	0.986
19:49748120:C:G	A182P	0.986
19:49740168:C:G	A505P	0.985
19:49763084:A:C	F55C	0.985
19:49763227:C:A	K7N	0.985
19:49763227:C:G	K7N	0.985
19:49748450:A:G	L140S	0.984
19:49747425:T:A	K209N	0.983
19:49747425:T:G	K209N	0.983

dbSNP variants (sampled 300 via entrez): RS1000135677 (19:49759128 A>G), RS1000194068 (19:49759332 G>T), RS1000249138 (19:49753395 A>G), RS1000294591 (19:49763282 T>G), RS1000422743 (19:49764860 C>T), RS1000493988 (19:49752068 T>C), RS1000567041 (19:49752311 G>A), RS1000628134 (19:49759665 G>A), RS1000646542 (19:49745508 C>T), RS1000740895 (19:49757804 C>T), RS1000768849 (19:49747108 GA>G), RS1000853021 (19:49740257 G>A), RS1001154944 (19:49740006 G>A,C,T), RS1001207860 (19:49740807 C>G,T), RS1001250636 (19:49751868 G>T)

Disease associations

OMIM: gene MIM:608253 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008971_41	Urate levels	2.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis