STK35

Summary

STK35 (serine/threonine kinase 35, HGNC:16254) is a protein-coding gene on chromosome 20p13, encoding Serine/threonine-protein kinase 35 (Q8TDR2).

The protein encoded by this gene is a kinase that is predominantly found in the nucleus. However, it can interact with PDLIM1/CLP-36 in the cytoplasm and localize to actin stress fibers. The encoded protein may be a regulator of actin stress fibers in nonmuscle cells.

Source: NCBI Gene 140901 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 71 total
• Druggable target: yes — 18 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_080836

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16254
Approved symbol	STK35
Name	serine/threonine kinase 35
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	bA550O8.2, CLIK1, STK35L1
Ensembl gene	ENSG00000125834
Ensembl biotype	protein_coding
OMIM	609370
Entrez	140901

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000381482, ENST00000493263, ENST00000926982, ENST00000968998

RefSeq mRNA: 1 — MANE Select: NM_080836 NM_080836

CCDS: CCDS13024

Canonical transcript exons

ENST00000381482 — 4 exons

Exon	Start	End
ENSE00001165390	2116666	2117415
ENSE00001488779	2143784	2148555
ENSE00001488817	2101827	2102175
ENSE00003504142	2102768	2103365

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.3055 / max 180.7164, expressed in 1751 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183139	3.4617	1546
183138	1.1068	783
183134	1.0403	668
183136	0.6663	198
183135	0.5862	354
208972	0.3278	125
183137	0.1164	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.58	gold quality
oviduct epithelium	UBERON:0004804	99.32	gold quality
endothelial cell	CL:0000115	98.77	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.72	gold quality
oocyte	CL:0000023	98.62	gold quality
amniotic fluid	UBERON:0000173	98.60	gold quality
esophagus squamous epithelium	UBERON:0006920	98.49	gold quality
parietal pleura	UBERON:0002400	98.18	gold quality
epithelial cell of pancreas	CL:0000083	98.05	gold quality
gingival epithelium	UBERON:0001949	98.05	gold quality
gingiva	UBERON:0001828	97.78	gold quality
parotid gland	UBERON:0001831	97.70	gold quality
palpebral conjunctiva	UBERON:0001812	97.45	gold quality
visceral pleura	UBERON:0002401	97.45	gold quality
epithelium of nasopharynx	UBERON:0001951	96.87	gold quality
tendon of biceps brachii	UBERON:0008188	96.84	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.73	gold quality
oral cavity	UBERON:0000167	96.71	gold quality
germinal epithelium of ovary	UBERON:0001304	96.54	gold quality
tibia	UBERON:0000979	96.45	gold quality
medial globus pallidus	UBERON:0002477	96.05	gold quality
ileal mucosa	UBERON:0000331	96.00	gold quality
adult organism	UBERON:0007023	95.75	gold quality
pharyngeal mucosa	UBERON:0000355	95.62	gold quality
sperm	CL:0000019	95.58	gold quality
nasal cavity epithelium	UBERON:0005384	95.56	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.54	gold quality
pigmented layer of retina	UBERON:0001782	95.53	gold quality
pancreatic ductal cell	CL:0002079	95.37	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	4.94
E-ANND-3	yes	4.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT3

miRNA regulators (miRDB)

244 targeting STK35, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 6)

• results establish the CLP-36 PDZ-LIM protein as an adapter, recruiting the Clik1 kinase to actin stress fibers in nonmuscle cells, and suggest that Clik1 represents a novel regulator of actin stress fibers (PMID:11973348)
• analysis of the STK35L proteins in human and in sea squirts (PMID:19756140)
• by regulating CDKN2A and inhibiting G1- to S-phase transition STK35L1 may act as a central kinase linking the cell cycle and migration of endothelial cells (PMID:21283756)
• constitutive overexpression of STK35 proteins enhances caspase-independent cell death under oxidative stress conditions. (PMID:21964068)
• STK35 knockdown enhanced apoptosis. Expression of the active forms and the activity of two major executioner caspases, caspase 3 and caspase 7, were also increased in osteosarcoma cells with STK35 silenced. (PMID:29414823)
• SCP4-STK35/PDIK1L complex is a dual phospho-catalytic signaling dependency in acute myeloid leukemia. (PMID:35021089)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	stk35l	ENSDARG00000057497
danio_rerio	stk35	ENSDARG00000086856
mus_musculus	Stk35	ENSMUSG00000037885
rattus_norvegicus	Stk35	ENSRNOG00000006002

Paralogs (8): EIF2AK2 (ENSG00000055332), EIF2AK1 (ENSG00000086232), PKMYT1 (ENSG00000127564), EIF2AK4 (ENSG00000128829), WEE1 (ENSG00000166483), EIF2AK3 (ENSG00000172071), PDIK1L (ENSG00000175087), WEE2 (ENSG00000214102)

Protein

Protein identifiers

Serine/threonine-protein kinase 35 — Q8TDR2 (reviewed: Q8TDR2)

Alternative names: CLP-36-interacting kinase 1, PDLIM1-interacting kinase 1, Serine/threonine-protein kinase 35 L1

All UniProt accessions (2): Q8TDR2, A0A0C4DGC9

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with PDLIM1/CLP-36.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Tissue specificity. Expressed in testis.

Post-translational modifications. Autophosphorylated.

Miscellaneous. Association with PDLIM1 is controversial.

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

RefSeq proteins (1): NP_543026* (*=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
IPR050339	CC_SR_Kinase	Family

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 (12 total): sequence conflict 3, compositionally biased region 2, binding site 2, chain 1, domain 1, region of interest 1, active site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDR2-F1	67.52	0.37

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): 360 (proton acceptor)

Ligand- & substrate-binding residues (2): 208–216; 231

Mutagenesis-validated functional residues (1):

Position	Phenotype
231	no autophosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 237 (showing top): E2F_Q4, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, E2F4DP1_01, AAGCCAT_MIR135A_MIR135B, GOBP_CELL_CYCLE_PHASE_TRANSITION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, AREB6_01, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE, PATIL_LIVER_CANCER, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GTGCCTT_MIR506, E2F1DP1_01, E2F_Q3, MCAATNNNNNGCG_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_MEIOTIC_CELL_CYCLE

GO Biological Process (3): negative regulation of G2/M transition of mitotic cell cycle (GO:0010972), negative regulation of G2/MI transition of meiotic cell cycle (GO:0110031), protein phosphorylation (GO:0006468)

GO Molecular Function (8): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), nuclear body (GO:0016604)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of cell cycle G2/M phase transition	2
protein kinase activity	2
nuclear lumen	2
cellular anatomical structure	2
intracellular membraneless organelle	2
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
negative regulation of mitotic cell cycle phase transition	1
G2/MI transition of meiotic cell cycle	1
regulation of G2/MI transition of meiotic cell cycle	1
negative regulation of meiotic cell cycle phase transition	1
phosphorylation	1
protein modification process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
nucleoplasm	1

Protein interactions and networks

STRING

1378 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STK35	PDLIM1	O00151	941
STK35	ACTN1	P12814	628
STK35	ACTN4	O43707	571
STK35	ACTN2	P35609	568
STK35	VCL	P18206	509
STK35	A0A0A0MSP3	A0A0A0MSP3	489
STK35	CWF19L2	Q2TBE0	453
STK35	FRMD4A	Q9P2Q2	423
STK35	ZFP62	Q8NB50	414
STK35	ZNF343	Q6P1L6	404
STK35	ANKIB1	Q9P2G1	369
STK35	IPP	Q9Y573	360
STK35	STK33	Q9BYT3	354
STK35	STK40	Q8N2I9	338
STK35	IFT27	Q9BW83	326

IntAct

15 interactions, top by confidence:

A	B	Type	Score
STK35	OSBPL3	psi-mi:“MI:0915”(physical association)	0.560
STK35	HSP90AA1	psi-mi:“MI:0914”(association)	0.530
C1orf174	AHCYL1	psi-mi:“MI:0914”(association)	0.530
STK35	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
C1orf174	H2AC11	psi-mi:“MI:0914”(association)	0.350
CDC37	MAP2K7	psi-mi:“MI:0914”(association)	0.350
C1orf174	POLRMT	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
STK35	OSBPL3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (53): CTDSPL2 (Affinity Capture-MS), HSP90AB3P (Affinity Capture-MS), HSP90AA5P (Affinity Capture-MS), HSP90AB4P (Affinity Capture-MS), CDC37L1 (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS), C1orf174 (Affinity Capture-MS), UBP1 (Affinity Capture-MS), CDC37 (Affinity Capture-MS), HSP90AA1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), TFCP2 (Affinity Capture-MS), PRR14L (Affinity Capture-MS), STK35 (Two-hybrid)

ESM2 similar proteins: A4Q9F3, A8IHN8, D3YYI7, M0R7T9, O09112, O60347, O88751, P51509, Q09YL6, Q0IHH1, Q13202, Q13505, Q14190, Q147X3, Q17QD9, Q3TZ87, Q3UPL5, Q3V1H9, Q5TGI4, Q5VUJ9, Q5VV17, Q5XI57, Q61079, Q6A039, Q6PDS0, Q6ZVT0, Q7Z7K6, Q80UW0, Q86YJ5, Q8C4U2, Q8CES0, Q8N554, Q8N8J7, Q8TC41, Q8TDR2, Q8WWW0, Q96AQ8, Q96ET8, Q96KN8, Q96MM7

Diamond homologs: A0A2I0BVG8, A0A509ALV6, A3B529, A8X6H4, A8XA58, F4I1N8, O08605, O15865, O60145, O65554, O70150, O74536, O80673, P06782, P08414, P0DP15, P13234, P13863, P22216, P34117, P34556, P43291, P51958, P52389, P53681, P54645, P54646, P62343, P62344, P62345, P92937, P92958, Q00372, Q00526, Q02723, Q03428, Q08942, Q09136, Q09137, Q13131

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
STK35	“form complex”	STK35/PDIK1L	binding
CTDSPL2	“up-regulates quantity by stabilization”	STK35	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

780 predictions. Top by Δscore:

Variant	Effect	Δscore
20:2103362:AAAGG:A	donor_loss	1.0000
20:2103363:AAGG:A	donor_loss	1.0000
20:2103364:AGGT:A	donor_loss	1.0000
20:2103366:GTAGG:G	donor_loss	1.0000
20:2103367:T:A	donor_loss	1.0000
20:2113285:GGT:G	donor_gain	1.0000
20:2113286:GT:G	donor_gain	0.9900
20:2113287:T:G	donor_gain	0.9900
20:2113287:TT:T	donor_gain	0.9900
20:2116662:TTA:T	acceptor_loss	0.9900
20:2116663:TA:T	acceptor_loss	0.9900
20:2116664:A:AT	acceptor_loss	0.9900
20:2117386:GGC:G	donor_gain	0.9900
20:2143889:C:T	donor_gain	0.9900
20:2143895:G:GT	donor_gain	0.9900
20:2103366:G:GG	donor_gain	0.9800
20:2116658:T:TA	acceptor_gain	0.9800
20:2116664:A:AG	acceptor_gain	0.9800
20:2116665:G:GG	acceptor_gain	0.9800
20:2116665:GGA:G	acceptor_gain	0.9800
20:2143846:T:TA	donor_gain	0.9800
20:2143847:G:GA	donor_gain	0.9800
20:2116665:GGAGA:G	acceptor_gain	0.9700
20:2117296:A:G	donor_gain	0.9700
20:2116663:TAGG:T	acceptor_gain	0.9600
20:2116664:AG:A	acceptor_gain	0.9600
20:2116664:AGGA:A	acceptor_gain	0.9600
20:2116664:AGGAG:A	acceptor_gain	0.9600
20:2116665:GG:G	acceptor_gain	0.9600
20:2116665:GGAG:G	acceptor_gain	0.9600

AlphaMissense

3438 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:2103099:G:A	G209E	1.000
20:2103159:C:A	A229E	1.000
20:2103162:T:A	V230D	1.000
20:2103164:A:G	K231E	1.000
20:2103166:G:C	K231N	1.000
20:2103166:G:T	K231N	1.000
20:2103201:T:C	L243P	1.000
20:2103207:T:C	L245P	1.000
20:2103222:C:A	A250D	1.000
20:2103225:T:C	L251P	1.000
20:2103274:C:G	C267W	1.000
20:2103279:T:C	L269P	1.000
20:2103345:T:C	L291P	1.000
20:2103363:A:T	K297I	1.000
20:2116705:T:C	L311P	1.000
20:2116707:T:A	W312R	1.000
20:2116707:T:C	W312R	1.000
20:2116711:T:C	F313S	1.000
20:2116714:T:A	V314D	1.000
20:2116726:G:A	C318Y	1.000
20:2116727:T:G	C318W	1.000
20:2116741:T:C	L323P	1.000
20:2116804:T:C	L344P	1.000
20:2116825:T:C	L351P	1.000
20:2116843:T:A	V357E	1.000
20:2116845:C:G	H358D	1.000
20:2116846:A:G	H358R	1.000
20:2116847:C:A	H358Q	1.000
20:2116847:C:G	H358Q	1.000
20:2116849:G:C	R359T	1.000

dbSNP variants (sampled 300 via entrez): RS1000064061 (20:2136766 T>A,C), RS1000081791 (20:2142952 C>G), RS1000178718 (20:2121175 A>G), RS1000219183 (20:2134853 T>C), RS1000285475 (20:2129285 C>A,T), RS1000291460 (20:2135126 A>G,T), RS1000309631 (20:2102903 G>A), RS1000338156 (20:2140946 C>T), RS1000374190 (20:2136970 G>A,C,T), RS1000446359 (20:2129452 C>T), RS1000508655 (20:2122662 T>C), RS1000558250 (20:2133636 A>G), RS1000639159 (20:2102104 G>A,T), RS1000740936 (20:2127923 G>C,T), RS1000774807 (20:2102338 G>A)

Disease associations

OMIM: gene MIM:609370 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002441_7	Immune response to measles-mumps-rubella vaccine	3.000000e-07
GCST008178_8	Early spontaneous preterm birth	1.000000e-06
GCST010002_58	Refractive error	1.000000e-12
GCST010988_315	Adult body size	7.000000e-10
GCST90002400_110	Plateletcrit	1.000000e-10
GCST90013410_61	Basal cell carcinoma	3.000000e-08
GCST90013442_32	Keratoconus	3.000000e-11
GCST90020029_50	Waist circumference adjusted for body mass index	2.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0006917	spontaneous preterm birth
EFO:0007985	platelet crit
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5651 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

18 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 223,131 (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
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
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL377300	BRIVANIB	3	1,721
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL572881	MOTESANIB	3	4,642
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2	363
CHEMBL475251	R-406	2	762
CHEMBL1908397	KW-2449	1	622
CHEMBL574738	AST-487	1	451

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — NKF4 family

ChEMBL bioactivities

26 potent at pChembl≥5 of 26 total, top 24 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	Kd	2	nM	BOSUTINIB
8.27	Kd	5.4	nM	CEDIRANIB
8.09	Kd	8.2	nM	SU-014813
7.80	Kd	16	nM	AST-487
7.58	Kd	26	nM	BRIVANIB
7.25	Kd	56	nM	VANDETANIB
6.85	Kd	140	nM	STAUROSPORINE
6.64	Kd	230	nM	FORETINIB
6.58	Kd	260	nM	TAE-684
6.44	Kd	360	nM	CHEMBL386051
6.35	Kd	450	nM	ALVOCIDIB
6.30	Kd	500	nM	CHEMBL1241674
6.21	Kd	610	nM	CRIZOTINIB
6.20	Kd	630	nM	KW-2449
6.11	Kd	770	nM	DASATINIB
6.09	Kd	810	nM	LESTAURTINIB
6.09	Kd	810	nM	NINTEDANIB
5.89	Kd	1300	nM	CHEMBL4564337
5.89	Kd	1300	nM	SUNITINIB
5.85	Kd	1400	nM	R-406
5.54	Kd	2900	nM	CANERTINIB
5.50	Kd	3200	nM	CHEMBL1908395
5.35	Kd	4500	nM	NERATINIB
5.27	Kd	5400	nM	MOTESANIB

PubChem BioAssay actives

26 with measured affinity, of 148 total; 24 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
Bosutinib	624711: Binding constant for STK35 kinase domain	kd	0.0020	uM
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline	624711: Binding constant for STK35 kinase domain	kd	0.0054	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	624711: Binding constant for STK35 kinase domain	kd	0.0082	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	624711: Binding constant for STK35 kinase domain	kd	0.0160	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	624711: Binding constant for STK35 kinase domain	kd	0.0260	uM
Vandetanib	624711: Binding constant for STK35 kinase domain	kd	0.0560	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	624711: Binding constant for STK35 kinase domain	kd	0.1400	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	624711: Binding constant for STK35 kinase domain	kd	0.2300	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	624711: Binding constant for STK35 kinase domain	kd	0.2600	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624711: Binding constant for STK35 kinase domain	kd	0.3600	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	624711: Binding constant for STK35 kinase domain	kd	0.4500	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624711: Binding constant for STK35 kinase domain	kd	0.5000	uM
Crizotinib	624711: Binding constant for STK35 kinase domain	kd	0.6100	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624711: Binding constant for STK35 kinase domain	kd	0.6300	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	624711: Binding constant for STK35 kinase domain	kd	0.7700	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	508096: Binding affinity to STK35	kd	0.8100	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624711: Binding constant for STK35 kinase domain	kd	0.8100	uM
5-(6-bromo-5-methoxy-1H-indol-3-yl)-2-(1H-pyrrol-2-yl)-1,3-oxazole	1541243: Binding affinity to wild-type human partial length STK35 (G182 to A534 residues) expressed in bacterial expression system by active-site directed competition binding assay based Kinomescan method	kd	1.3000	uM
Sunitinib	508096: Binding affinity to STK35	kd	1.3000	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	624711: Binding constant for STK35 kinase domain	kd	1.4000	uM
N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide	624711: Binding constant for STK35 kinase domain	kd	2.9000	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624711: Binding constant for STK35 kinase domain	kd	3.2000	uM
Neratinib	624711: Binding constant for STK35 kinase domain	kd	4.5000	uM
N-(3,3-dimethyl-1,2-dihydroindol-6-yl)-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide	624711: Binding constant for STK35 kinase domain	kd	5.4000	uM

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	increases methylation	1
cobaltous chloride	increases expression	1
nickel sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	increases expression, affects cotreatment	1
Theophylline	affects cotreatment, increases expression	1
Thimerosal	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Valproic Acid	affects expression	1

ChEMBL screening assays

94 unique, capped per target: 94 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1059367	Binding	Inhibition of STK35 assessed as enzyme activity at 1 uM relative to untreated control	Selective inhibitors of the mutant B-Raf pathway: discovery of a potent and orally bioavailable aminoisoquinoline. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3IG	Abcam HEK293T STK35 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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