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
• GTEx eGene: eQTL in 19 tissues, sQTL in 3 (q < 0.05)
• ChEMBL bioactivity: 18 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 0.77 (unconstrained)
• MANE Select transcript: NM_080836
• Notable: 71 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 5 — 4 protein_coding, 1 nonsense_mediated_decay

MANE Select: ENST00000381482

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 5: 1

ENST00000381482, ENST00000493263, ENST00000926982, ENST00000968998, ENST00001134146

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.

Highest expression (Bgee): secondary oocyte, oviduct epithelium, endothelial cell, Brodmann (1909) area 23, oocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

STK35 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 19 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 22 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	1.6e-42	-0.92	20:2104363:G:C
Cells Cultured fibroblasts	eqtl	6.2e-16	-0.21	20:2150388:C:T
Nerve Tibial	eqtl	1.6e-10	-0.21	20:2143478:C:T
Artery Tibial	eqtl	1.3e-07	-0.18	20:2144458:A:G
Testis	eqtl	1.9e-05	+0.19	20:2162586:G:A
Skin Sun Exposed Lower leg	eqtl	2.9e-05	-0.15	20:2161559:T:A
Thyroid	eqtl	3.5e-04	+0.18	20:2162586:G:A
Cells EBV-transformed lymphocytes	eqtl	5.0e-04	-0.23	20:2149878:A:C
Brain Cerebellar Hemisphere	eqtl	7.6e-04	-0.27	20:2131744:T:C
Adipose Subcutaneous	eqtl	5.4e-03	-0.17	20:2127773:C:T
Artery Aorta	eqtl	5.8e-03	-0.19	20:2143478:C:T
Brain Cerebellum	eqtl	8.6e-03	-0.26	20:2142303:A:G
Brain Cortex	eqtl	1.0e-02	+0.27	20:2068452:A:G
Esophagus Mucosa	eqtl	1.6e-02	+0.26	20:2149094:A:G
Brain Anterior cingulate cortex BA24	eqtl	1.9e-02	+0.27	20:2953752:C:T
Esophagus Muscularis	eqtl	1.9e-02	+0.16	20:2168414:C:T
Brain Caudate basal ganglia	eqtl	2.5e-02	-0.24	20:2144907:C:T
Brain Hypothalamus	eqtl	2.9e-02	+0.95	20:1770672:A:G
Esophagus Mucosa	sqtl	4.2e-02	+0.25	20:2758937:T:C
Colon Sigmoid	eqtl	4.3e-02	-0.19	20:1876767:G:A

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

showing 100 of 256 tissues 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
globus pallidus	UBERON:0001875	95.25	gold quality
middle temporal gyrus	UBERON:0002771	95.23	gold quality
penis	UBERON:0000989	95.21	gold quality
buccal mucosa cell	CL:0002336	95.00	gold quality
skin of hip	UBERON:0001554	94.99	gold quality
synovial joint	UBERON:0002217	94.99	gold quality
colonic mucosa	UBERON:0000317	94.89	gold quality
layer of synovial tissue	UBERON:0007616	94.75	gold quality
nipple	UBERON:0002030	94.67	gold quality
mammalian vulva	UBERON:0000997	94.62	gold quality
cartilage tissue	UBERON:0002418	94.61	gold quality
upper arm skin	UBERON:0004263	94.38	gold quality
bronchial epithelial cell	CL:0002328	94.33	gold quality
jejunal mucosa	UBERON:0000399	94.25	gold quality
bronchus	UBERON:0002185	94.19	gold quality
upper leg skin	UBERON:0004262	94.17	gold quality
cerebellar vermis	UBERON:0004720	94.00	gold quality
cardia of stomach	UBERON:0001162	93.83	gold quality
pylorus	UBERON:0001166	93.77	gold quality
epithelium of mammary gland	UBERON:0003244	93.54	gold quality
mammary duct	UBERON:0001765	93.49	gold quality
urethra	UBERON:0000057	93.35	gold quality
thymus	UBERON:0002370	93.04	gold quality
saphenous vein	UBERON:0007318	93.04	gold quality
trabecular bone tissue	UBERON:0002483	92.45	gold quality
jejunum	UBERON:0002115	92.44	gold quality
trachea	UBERON:0003126	92.19	gold quality
lateral globus pallidus	UBERON:0002476	91.96	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.94	gold quality
cauda epididymis	UBERON:0004360	91.94	gold quality
left ventricle myocardium	UBERON:0006566	91.90	gold quality
superior surface of tongue	UBERON:0007371	91.86	gold quality
heart right ventricle	UBERON:0002080	91.83	gold quality
corpus epididymis	UBERON:0004359	91.64	gold quality
decidua	UBERON:0002450	91.45	gold quality
renal medulla	UBERON:0000362	91.27	gold quality
ventral tegmental area	UBERON:0002691	91.19	gold quality
lower lobe of lung	UBERON:0008949	91.17	gold quality
tongue	UBERON:0001723	91.16	gold quality
caput epididymis	UBERON:0004358	91.10	gold quality
superficial temporal artery	UBERON:0001614	90.97	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.65	gold quality
substantia nigra pars compacta	UBERON:0001965	90.38	gold quality
body of tongue	UBERON:0011876	90.21	gold quality
seminal vesicle	UBERON:0000998	90.20	gold quality
myocardium	UBERON:0002349	90.20	gold quality
mammary gland	UBERON:0001911	90.02	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.95	gold quality
dorsal plus ventral thalamus	UBERON:0001897	89.92	gold quality
thoracic mammary gland	UBERON:0005200	89.89	gold quality
entorhinal cortex	UBERON:0002728	89.77	gold quality
occipital lobe	UBERON:0002021	89.40	gold quality
superior vestibular nucleus	UBERON:0007227	89.21	gold quality
placenta	UBERON:0001987	89.18	gold quality
pericardium	UBERON:0002407	89.15	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.04	gold quality
primary visual cortex	UBERON:0002436	88.96	gold quality
parietal lobe	UBERON:0001872	88.68	gold quality
vastus lateralis	UBERON:0001379	88.66	gold quality
quadriceps femoris	UBERON:0001377	88.59	gold quality
medulla oblongata	UBERON:0001896	88.42	gold quality
postcentral gyrus	UBERON:0002581	88.29	gold quality
inferior vagus X ganglion	UBERON:0005363	87.41	gold quality
superior frontal gyrus	UBERON:0002661	87.38	gold quality
biceps brachii	UBERON:0001507	87.14	gold quality
adrenal tissue	UBERON:0018303	87.11	gold quality
lower esophagus mucosa	UBERON:0035834	86.59	gold quality
fallopian tube	UBERON:0003889	86.46	gold quality
kidney epithelium	UBERON:0004819	86.40	silver quality
nasal cavity mucosa	UBERON:0001826	86.32	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

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Retina	tissue	110.2
Postcentral gyrus	tissue	32.8
Locus coeruleus	tissue	22.0
Nucleus accumbens	tissue	21.9
Hippocampus	tissue	21.5	low
Choroid plexus	tissue	17.2
Cerebral cortex	tissue	16.2	low
Somatosensory cortex	tissue	16.2
Prefrontal cortex	tissue	15.3
Motor cortex	tissue	15.2
Occipital cortex	tissue	14.8
Insular cortex	tissue	14.8
Hippocampal formation	tissue	14.7
Entorhinal cortex	tissue	14.7
Temporal cortex	tissue	14.4
Retrosplenial and cingulate cortex	tissue	13.7
Retrosplenial cortex	tissue	13.1
Testis	tissue	13.0	medium
Cerebellum	tissue	13.0	low
Amygdala	tissue	12.8
Thalamus	tissue	12.7
Frontal cortex	tissue	12.1
Superior colliculi	tissue	12.0
Septum	tissue	11.9
Basal ganglia	tissue	11.7	low
Hypothalamus	tissue	11.5
Ventral forebrain	tissue	11.5
Midbrain	tissue	11.3
Pons	tissue	11.2
Esophagus	tissue	11.1	medium
Periaqueductal gray	tissue	10.5
Putamen	tissue	10.2
Substantia nigra	tissue	9.9
Olfactory bulb	tissue	9.9
Pituitary gland	tissue	9.5
Medulla oblongata	tissue	9.5
Skin 1	tissue	9.3	medium
Vagina	tissue	8.8	low
Pancreas	tissue	8.8	medium
Caudate putamen	tissue	8.8
Corpus callosum	tissue	8.6
Spinal cord	tissue	8.5
Adipose tissue	tissue	8.4	not detected
Adrenal gland	tissue	8.2	medium
Bone marrow	tissue	8.1	low
Thyroid gland	tissue	8.0	medium
Salivary gland	tissue	7.7	high
Rectum	tissue	7.7	high
Breast	tissue	7.4	high
Heart muscle	tissue	7.4	medium
Parathyroid gland	tissue	7.3	high
Smooth muscle	tissue	7.3	medium
Fallopian tube	tissue	7.3	medium
Small intestine	tissue	7.2	high
Tonsil	tissue	7.1	medium
Colon	tissue	6.8	high
Duodenum	tissue	6.7	high
Endometrium 1	tissue	6.6	medium
Lung	tissue	6.6	low
Gallbladder	tissue	6.6	high

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Centromedial thalamic nucleus (38.4), Ventral posterolateral thalamic nucleus (38.3), Pulvinar (34.4), Lateral geniculate body (33.2), Precentral gyrus (31.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT3

miRNA regulators (miRDB)

Targeting STK35 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 244 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.00678, LOEUF 0.768, missense Z 1.07 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000381482 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
20:2,101,882–2,103,088	389 / 320.0	1.22	no
20:2,103,089–2,116,704	97 / 146.4	0.66	no
20:2,116,705–2,117,375	109 / 280.3	0.39	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1914583) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
anophthalmia	1
cornea opacity	1
hyperactivity	1
increased startle reflex	1
abnormal vocalization	1
increased vertical activity	1
increased circulating alanine transaminase level	1
abnormal bone structure	1
cornea vascularization	1
decreased mean corpuscular hemoglobin	1
decreased grip strength	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RER6	99.7%	Diamond
Xenopus laevis	Q6NU47	97.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC03086	ncRNA	388780
SIRPA	protein-coding	140885
PDYN	protein-coding	5173
PDYN-AS1	ncRNA	727993

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): A0A0C4DGC9, Q8TDR2

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)

• 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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear bodies; nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

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)

Position	Role
360	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
208–216	ATP
231	ATP

Mutagenesis-validated functional residues (1)

Position	Phenotype
231	no autophosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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 (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737)

GO top-level categories

26 GO namespaces:

Category	Terms
negative regulation of cell cycle G2/M phase transition	2
protein kinase activity	2
nuclear lumen	2
cellular anatomical structure	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
anion 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 membraneless organelle	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
nucleoplasm	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 570 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STK35	PDLIM1	O00151	934
STK35	ACTN1	P12814	634
STK35	ACTN4	O43707	567
STK35	ACTN2	P35609	565
STK35	VCL	P18206	543
STK35	ZFP62	Q8NB50	484
STK35	CWF19L2	Q2TBE0	478
STK35	ANKIB1	Q9P2G1	434
STK35	IFT27	Q9BW83	400
STK35	FRMD4A	Q9P2Q2	370
STK35	SPRN	Q5BIV9	357
STK35	ZNF343	Q6P1L6	357
STK35	STK33	Q9BYT3	356
STK35	STK40	Q8N2I9	311
STK35	PHPT1	Q9NRX4	297

IntAct

Human interaction partners of STK35 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
OSBPL3	physical association	0.560	3
HSP90AA1	association	0.530	4

BioGRID (53 interactions; top human partners by supporting records): CTDSPL2 (Affinity Capture-MS; 6 records), CDC37 (Affinity Capture-MS; 4 records), C1orf174 (Affinity Capture-MS; 3 records), HSP90AA1 (Affinity Capture-MS; 3 records), HSP90AB1 (Affinity Capture-MS; 3 records), NEDD4L (Affinity Capture-MS; 3 records), CDC37L1 (Affinity Capture-MS; 2 records), FKBP5 (Affinity Capture-MS; 2 records), HSP90AA4P (Affinity Capture-MS; 2 records), HSP90AA5P (Affinity Capture-MS; 2 records), HSP90AB3P (Affinity Capture-MS; 2 records), HSP90AB4P (Affinity Capture-MS; 2 records), PDLIM1 (Two-hybrid; 2 records), PRR14L (Affinity Capture-MS; 2 records), TFCP2 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 2 of 3 signaling interactions:

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

Disease & clinical

Genetic variants

Variant evidence for STK35: 71 ClinVar records (0 pathogenic / likely pathogenic); 8 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 19 predictions of 370):

Position(s)	Effect	Δscore	Sites
20:2103366–2103367	donor_loss	1.0000	5
20:2113287	donor_gain	0.9900
20:2116664–2116665	acceptor_loss	0.9900	6
20:2143889	donor_gain	0.9900
20:2117296	donor_gain	0.9700
20:2116658	acceptor_gain	0.9600
20:2117363	donor_gain	0.9500
20:2102550	donor_gain	0.9400
20:2117388	donor_gain	0.9300
20:2143892	donor_gain	0.9200

AlphaMissense

1,535 missense substitutions predicted likely pathogenic (of 3,438 scored), across 298 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M422	9	0.987	0.999
M509	9	0.975	0.999
M315	9	0.964	0.999
M278	9	0.936	0.999
D360	8	1.000	1.000
D381	8	1.000	1.000
D436	8	1.000	1.000
H358	8	0.999	1.000
N365	8	0.999	1.000
F382	8	0.998	1.000
H352	8	0.997	0.999
F438	8	0.993	1.000
F313	8	0.986	1.000
H280	8	0.981	0.998
H258	8	0.979	0.996
S385	8	0.977	1.000
F420	8	0.970	0.999
F248	8	0.969	0.999
D364	8	0.965	0.997
D419	8	0.964	0.990

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	4.97e-05

Disease associations

OMIM: gene MIM:609370 | disease phenotypes:

GWAS associations

8 associations:

Study	Trait	p-value
GCST010002_333	Refractive error	1e-12
GCST90013442_32	Keratoconus	3e-11
GCST90002400_383	Plateletcrit	1e-10
GCST010988_185	Adult body size	7e-10
GCST90020029_1480	Waist circumference adjusted for body mass index	2e-8
GCST90013410_61	Basal cell carcinoma	3e-8
GCST002441_7	Immune response to measles-mumps-rubella vaccine	3e-7
GCST008178_6	Early spontaneous preterm birth	1e-6

EFO canonical traits (from GWAS)

4 canonical traits:

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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 229,102 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

18 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL5416410	DASATINIB	4	674
CHEMBL180022	NERATINIB	4	9,891
CHEMBL502835	NINTEDANIB	4	8,978
CHEMBL535	SUNITINIB	4	80,232
CHEMBL24828	VANDETANIB	4	43,290
CHEMBL428690	ALVOCIDIB	3	28,145
CHEMBL377300	BRIVANIB	3	1,784
CHEMBL31965	CANERTINIB	3	8,307
CHEMBL491473	CEDIRANIB	3	9,464
CHEMBL603469	LESTAURTINIB	3
CHEMBL572881	MOTESANIB	3	4,820
CHEMBL1230609	FORETINIB	2	3,230
CHEMBL475251	R-406	2	787
CHEMBL1721885	SU-014813	2	375
CHEMBL574738	AST-487	1	468
CHEMBL1908397	KW-2449	1	655

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — NKF4 family

Binding affinities (BindingDB)

19 measured of 75 human assays (76 total across all organisms); most potent 19 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
CEP-701	KD	3.4 nM
Staurosporine, 8	IC50	6.5 nM
N-[4-[[(2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	KI	15 nM	US-10981896: Indolinone derivatives as inhibitors of maternal embryonic leucine zipper kinase
CHEMBL1240703	KD	15 nM
2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide	IC50	17 nM
PKC-412	KD	110 nM
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	KD	120 nM	US-9145414: 1,2,4-triazine-6-carboxamide derivative
CHEMBL1908397	KD	650 nM
4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide	KD	740 nM
(9S)-9-[(dimethylamino)methyl]-6,7,10,11-tetrahydro-9H,18H-5,21:12,17-di(metheno)dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecine-18,20(19H)-dione	IC50	743 nM
CHEMBL4564337	KD	1000 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
3-(4-morpholin-4-ylpyrido[2,3]furo[2,4-b]pyrimidin-2-yl)phenol	KD	2400 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
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
SUNITINIB MALATE	KD	3500 nM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide	KD	3900 nM	US-20250129067: PLATELET-DERIVED GROWTH FACTOR RECEPTOR (PDGFR) ALPHA INHIBITORS AND USES THEREOF
(4-chlorophenyl)-[4-(4-pyridylmethyl)phthalazin-1-yl]amine	KD	8800 nM

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	affects cotreatment, increases expression	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for STK35 across ~30M SureChEMBL compounds — explore on Sugi Predict.