STK38

Summary

STK38 (serine/threonine kinase 38, HGNC:17847) is a protein-coding gene on chromosome 6p21.31, encoding Serine/threonine-protein kinase 38 (Q15208). Serine/threonine-protein kinase that acts as a negative regulator of MAP3K1/2 signaling.

This gene encodes a member of the AGC serine/threonine kinase family of proteins. The kinase activity of this protein is regulated by autophosphorylation and phosphorylation by other upstream kinases. This protein has been shown to function in the cell cycle and apoptosis. This protein has also been found to regulate the protein stability and transcriptional activity of the MYC oncogene. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 11329 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 54 total
• Phenotypes (HPO): 1
• Druggable target: yes — 9 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_007271

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17847
Approved symbol	STK38
Name	serine/threonine kinase 38
Location	6p21.31
Locus type	gene with protein product
Status	Approved
Aliases	NDR, NDR1
Ensembl gene	ENSG00000112079
Ensembl biotype	protein_coding
OMIM	606964
Entrez	11329

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000229812, ENST00000850860, ENST00000869135, ENST00000869136, ENST00000869137, ENST00000869138, ENST00000869139, ENST00000970356

RefSeq mRNA: 2 — MANE Select: NM_007271 NM_001305102, NM_007271

CCDS: CCDS4822

Canonical transcript exons

ENST00000229812 — 14 exons

Exon	Start	End
ENSE00000748942	36496711	36496805
ENSE00000748945	36497780	36497875
ENSE00000748952	36499873	36499990
ENSE00000748955	36506583	36506644
ENSE00000748958	36507500	36507602
ENSE00000748962	36517717	36517840
ENSE00000748967	36524341	36524463
ENSE00000748970	36525591	36525642
ENSE00001233802	36547190	36547479
ENSE00001233821	36540072	36540207
ENSE00002305375	36515338	36515492
ENSE00002310103	36521734	36521817
ENSE00002313336	36498363	36498486
ENSE00004282537	36493892	36495914

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 97.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.0596 / max 516.4937, expressed in 1820 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73355	27.4709	1814
73354	7.7471	1538
73353	1.1036	266
73351	0.4423	235
73352	0.2958	95

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	97.95	gold quality
oocyte	CL:0000023	97.80	gold quality
secondary oocyte	CL:0000655	97.64	gold quality
granulocyte	CL:0000094	97.52	gold quality
nasal cavity epithelium	UBERON:0005384	96.97	gold quality
amniotic fluid	UBERON:0000173	96.94	gold quality
leukocyte	CL:0000738	96.66	gold quality
epithelium of nasopharynx	UBERON:0001951	96.63	gold quality
nasopharynx	UBERON:0001728	96.61	gold quality
mononuclear cell	CL:0000842	96.57	gold quality
monocyte	CL:0000576	96.52	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.34	gold quality
jejunal mucosa	UBERON:0000399	96.30	gold quality
blood	UBERON:0000178	96.25	gold quality
pharyngeal mucosa	UBERON:0000355	96.22	gold quality
bronchial epithelial cell	CL:0002328	96.12	gold quality
bronchus	UBERON:0002185	96.03	gold quality
epithelium of bronchus	UBERON:0002031	96.00	gold quality
skin of hip	UBERON:0001554	95.73	gold quality
trabecular bone tissue	UBERON:0002483	95.69	gold quality
oral cavity	UBERON:0000167	95.62	gold quality
colonic mucosa	UBERON:0000317	95.36	gold quality
pylorus	UBERON:0001166	95.09	gold quality
superior surface of tongue	UBERON:0007371	94.95	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.91	gold quality
urethra	UBERON:0000057	94.85	gold quality
mucosa of transverse colon	UBERON:0004991	94.75	gold quality
lower esophagus mucosa	UBERON:0035834	94.59	gold quality
eye	UBERON:0000970	93.99	gold quality
visceral pleura	UBERON:0002401	93.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1

miRNA regulators (miRDB)

86 targeting STK38, 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-4668-3P	100.00	68.74	2635
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606

Literature-anchored findings (GeneRIF, showing 31)

• NDR1 and NDR2 serine-threonine kinases are regulated by mob proteins (PMID:15067004)
• an insert within the catalytic domain between subdomains VII and VIII is autoinhibitory, and the binding of human MOB1 to the N-terminal domain of NDR induces the release of this autoinhibition. (PMID:15197186)
• The NDR1 and NDR2 kinases were incorporated into HIV-1 particles and were cleaved by the HIV-1 protease. (PMID:15582665)
• In vivo activation of human NDR by membrane-bound hMOBs is dependent on their interaction and occurs solely at the membrane. (PMID:16135814)
• These data indicate that NDR-driven centrosome duplication requires Cdk2 activity and that Cdk2-induced centrosome amplification is affected upon reduction of NDR activity. (PMID:17317633)
• phosphorylation of MOB1 at Thr74 by MST2 is essential to make a complex of MOB1, MST2 and NDR1, and to fully activate NDR1 (PMID:18362890)
• findings identify NDR1/2 as novel proapoptotic kinases and key members of the RASSF1A/MST1 signaling cascade (PMID:19062280)
• Results suggest that MST2-, Fry-, and MOB2-mediated activation of NDR1 is crucial for the fidelity of mitotic chromosome alignment in mammalian cells. (PMID:19327996)
• Data indicate that human MOB2 is a negative regulator of human NDR kinases in biochemical and biological settings. (PMID:20624913)
• These findings establish a novel MST3-NDR-p21 axis as an important regulator of G(1)/S progression of mammalian cells. (PMID:21262772)
• Findings show a biological role for MICAL-1 in apoptosis and define a novel negative regulatory mechanism of MST-NDR signaling. (PMID:21730291)
• GSK-3beta inhibits full activation of STK38, and STK38 activation is required to prevent cell death in response to oxidative stress (PMID:22142472)
• Findings suggest a function of NDR1, which may regulate NF-kappaB activation by its kinase activity. (PMID:22674419)
• STK38 regulates MYC protein stability and turnover in a kinase activity-dependent manner. STK38 kinase inactivation abrogates apoptosis following B-cell receptor activation, whereas its silencing significantly decreases MYC levels and increases apoptosis. (PMID:23178486)
• a novel and intimate link between the protein kinase NDR1 and TGFbeta signaling (PMID:23840619)
• 17-allylamino-17-demethoxygeldanamycin down-regulates STK38, modulating radiosensitivity. (PMID:23886587)
• cyclin D1 has a role in promoting cell cycle progression by enhancing NDR1/2 kinase activity independent of Cdk4 (PMID:23897809)
• STK38-mediated phosphorylation of CDC25A at Ser-76 and the subsequent degradation of CDC25A are required to promote DNA damage-induced G2/M checkpoint activation. (PMID:25936524)
• PLK1-mediated phosphorylation protects the binding of Mob1 to NDR1 and subsequent NDR1 activation (PMID:26057687)
• Data establish STK38 as a conserved regulator of autophagy in human cells and flies. (PMID:26387716)
• Data show that STK38 supports Ras-driven transformation through promoting detachment-induced autophagy. (PMID:27283898)
• Study provides evidence for an inhibitory role of SOCS2 in TNFalpha induced NF-kappa B activation, identifies NDR1 as a novel substrate of SOCS2, and demonstrates that SOCS2 and TNFalpha induced NF-kappa B signaling are linked through NDR1. (PMID:28216640)
• Relied on its interaction with serine/threonine-protein kinase 38 (Stk38) to inhibit ubiquitination. (PMID:29549164)
• The activation segment of NDR1 influences interaction with MST1/MST2 and Furry. (PMID:29983373)
• Downregulated NDR1 protein kinase inhibits innate immune response by initiating an miR146a-STAT1 feedback loop. (PMID:30018336)
• our results reveal STK38 as an activator of XPO1, behaving as a gatekeeper of nuclear export. These observations establish a novel mechanism of XPO1-dependent cargo export regulation by phosphorylation of XPO1’s C-terminal auto-inhibitory domain. (PMID:31544310)
• The STK38-XPO1 axis, a new actor in physiology and cancer. (PMID:33145612)
• STK38 is a PPARgamma-interacting protein promoting adipogenesis. (PMID:34670478)
• NDR1 increases NOTCH1 signaling activity by impairing Fbw7 mediated NICD degradation to enhance breast cancer stem cell properties. (PMID:35508987)
• Prognostic and Immunological Role of STK38 across Cancers: Friend or Foe? (PMID:36232893)
• Microautophagy regulated by STK38 and GABARAPs is essential to repair lysosomes and prevent aging. (PMID:37987447)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	stk38b	ENSDARG00000018516
danio_rerio	stk38a	ENSDARG00000019973
mus_musculus	Stk38	ENSMUSG00000024006
rattus_norvegicus	Stk38	ENSRNOG00000000519
drosophila_melanogaster	trc	FBGN0003744
caenorhabditis_elegans		WBGENE00004727

Paralogs (1): STK38L (ENSG00000211455)

Protein

Protein identifiers

Serine/threonine-protein kinase 38 — Q15208 (reviewed: Q15208)

Alternative names: NDR1 protein kinase, Nuclear Dbf2-related kinase 1

All UniProt accessions (1): Q15208

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that acts as a negative regulator of MAP3K1/2 signaling. Converts MAP3K2 from its phosphorylated form to its non-phosphorylated form and inhibits autophosphorylation of MAP3K2. Acts as an ufmylation ‘reader’ in a kinase-independent manner: specifically recognizes and binds mono-ufmylated histone H4 in response to DNA damage, promoting the recruitment of SUV39H1 to the double-strand breaks, resulting in ATM activation.

Subunit / interactions. Homodimeric S100B binds two molecules of STK38. Interacts with MOB1 and MOB2. Interacts with MAP3K1 and MAP3K2 (via the kinase catalytic domain). Forms a tripartite complex with MOBKL1B and STK3/MST2. Interacts with MICAL1; leading to inhibit the protein kinase activity by antagonizing activation by MST1/STK4.

Subcellular location. Nucleus. Cytoplasm. Chromosome.

Tissue specificity. Ubiquitously expressed with highest levels observed in peripheral blood leukocytes.

Post-translational modifications. ISGylated. Phosphorylated by STK3/MST2 and this is enhanced by MOBKL1B.

Activity regulation. Activated by binding of S100B which releases autoinhibitory N-lobe interactions, enabling ATP to bind and the autophosphorylation of Ser-281. Thr-444 then undergoes calcium-dependent phosphorylation by STK24/MST3. Interactions between phosphorylated Thr-444 and the N-lobe promote additional structural changes that complete the activation of the kinase. Autoinhibition is also released by the binding of MOB1/MOBKL1A and MOB2/HCCA2 to the N-terminal of STK38.

Domain organisation. The UFM1-interacting motif (UFIM) specifically recognizes and binds ufmylated histone H4.

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

RefSeq proteins (2): NP_001292031, NP_009202* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain
IPR050839	Rho-assoc_Ser/Thr_Kinase	Family

Pfam: PF00069, PF00433

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 (54 total): helix 21, strand 9, modified residue 5, mutagenesis site 5, sequence variant 3, domain 2, turn 2, binding site 2, initiator methionine 1, chain 1, region of interest 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6BXI	X-RAY DIFFRACTION	2.2
1PSB	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15208-F1	84.80	0.50

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): 212 (proton acceptor)

Ligand- & substrate-binding residues (2): 95–103; 118

Post-translational modifications (5): 74, 264, 281, 444, 2

Mutagenesis-validated functional residues (5):

Position	Phenotype
74	decreases autophosphorylation and kinase activity. reduced binding of s100b.
118	loss of autophosphorylation and kinase activity.
281	loss of autophosphorylation and kinase activity.
306–311	abolished binding to ufmylated histone h4.
444	decreases autophosphorylation and kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-9013418	RHOBTB2 GTPase cycle
R-HSA-9013422	RHOBTB1 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9706574	RHOBTB GTPase Cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 306 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_NEGATIVE_REGULATION_OF_MAP_KINASE_ACTIVITY, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, GNF2_CASP8, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, RORA1_01, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_CELL_CYCLE_PHASE_TRANSITION, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GTGCCTT_MIR506, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN

GO Biological Process (9): DNA damage checkpoint signaling (GO:0000077), protein phosphorylation (GO:0006468), DNA damage response (GO:0006974), intracellular signal transduction (GO:0035556), protein modification process (GO:0036211), negative regulation of MAP kinase activity (GO:0043407), postsynapse organization (GO:0099173), chromatin organization (GO:0006325), negative regulation of metabolic process (GO:0009892)

GO Molecular Function (15): magnesium ion binding (GO:0000287), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), mitogen-activated protein kinase kinase kinase binding (GO:0031435), cadherin binding (GO:0045296), protein serine kinase activity (GO:0106310), ubiquitin-like protein reader activity (GO:0140035), histone reader activity (GO:0140566), UFM1-modified protein reader activity (GO:0141185), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), site of double-strand break (GO:0035861), glutamatergic synapse (GO:0098978), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RHOBTB GTPase Cycle	2
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
RHO GTPase cycle	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
cellular component organization	2
protein kinase activity	2
cellular anatomical structure	2
DNA integrity checkpoint signaling	1
signal transduction in response to DNA damage	1
phosphorylation	1
protein modification process	1
cellular response to stress	1
signal transduction	1
protein metabolic process	1
macromolecule modification	1
MAP kinase activity	1
regulation of MAP kinase activity	1
negative regulation of MAPK cascade	1
negative regulation of protein serine/threonine kinase activity	1
synapse organization	1
metabolic process	1
regulation of metabolic process	1
negative regulation of cellular process	1
metal ion binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein kinase binding	1
cell adhesion molecule binding	1
protein-macromolecule adaptor activity	1
modification-dependent protein binding	1
nucleosome	1
histone binding	1
chromatin-protein adaptor activity	1
ubiquitin-like protein reader activity	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
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cation binding	1

Protein interactions and networks

STRING

2118 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STK38	MOB2	Q70IA6	845
STK38	MOB1A	Q9H8S9	729
STK38	MICAL1	Q8TDZ2	723
STK38	FRYL	O94915	698
STK38	RBM24	Q9BX46	689
STK38	MOB4	Q9Y3A3	671
STK38	MOB3A	Q96BX8	632
STK38	MOB1B	Q7L9L4	608
STK38	SAV1	Q9H4B6	541
STK38	BAG3	O95817	540
STK38	MOB3C	Q70IA8	505
STK38	RAB3IP	Q96QF0	499
STK38	PPM1B	O75688	479
STK38	TRAF3	Q13114	472
STK38	SUV39H1	O43463	468

IntAct

107 interactions, top by confidence:

A	B	Type	Score
RICTOR	MTOR	psi-mi:“MI:0914”(association)	0.970
MAPKAP1	MTOR	psi-mi:“MI:0914”(association)	0.860
MOB1B	LATS1	psi-mi:“MI:0914”(association)	0.840
NCK1	NCK2	psi-mi:“MI:0914”(association)	0.730
STK38	MOB2	psi-mi:“MI:0914”(association)	0.710
MOB2	STK38	psi-mi:“MI:0915”(physical association)	0.710
STK38	S100B	psi-mi:“MI:0407”(direct interaction)	0.610
STK38	S100B	psi-mi:“MI:0915”(physical association)	0.610
STK38	BANP	psi-mi:“MI:0915”(physical association)	0.560
STK38	MOB1A	psi-mi:“MI:0915”(physical association)	0.560
CRK	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
MARVELD2	GAP43	psi-mi:“MI:0914”(association)	0.530
STK38	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.520
HSP90AB1	STK38	psi-mi:“MI:0915”(physical association)	0.520
STK38	CTDP1	psi-mi:“MI:0915”(physical association)	0.520
PEBP1	STK38	psi-mi:“MI:0915”(physical association)	0.500
CAV1	STK38	psi-mi:“MI:0915”(physical association)	0.500
STK38	NCK1	psi-mi:“MI:0915”(physical association)	0.500
STK38	EGFR	psi-mi:“MI:2364”(proximity)	0.480
EHMT2	KDM1A	psi-mi:“MI:0914”(association)	0.460
steC	SCD	psi-mi:“MI:0914”(association)	0.460
Stk38	STK38	psi-mi:“MI:0915”(physical association)	0.400
Chek2		psi-mi:“MI:0915”(physical association)	0.400

BioGRID (240): MOB2 (Affinity Capture-MS), MOB1A (Affinity Capture-MS), MPP1 (Co-fractionation), STK38 (Affinity Capture-MS), HIST2H2AC (Biochemical Activity), HIST2H2BE (Biochemical Activity), HIST1H3E (Biochemical Activity), STK38 (Affinity Capture-MS), STK38 (Affinity Capture-MS), STK38 (Affinity Capture-MS), STK38 (Affinity Capture-Western), STK38 (Affinity Capture-Western), STK38 (Affinity Capture-Western), STK38 (Affinity Capture-MS), STK38 (Affinity Capture-MS)

ESM2 similar proteins: A2VDV2, A8XJL7, O13310, O75582, O97627, P00518, P07934, P13286, P18652, P18653, P18654, P21146, P23443, P26817, P26818, P26819, P35626, P51812, P54645, P67998, P67999, Q09639, Q12706, Q15208, Q21734, Q2L6W9, Q2LZZ7, Q39030, Q3UYH7, Q54IH8, Q5F3L1, Q5R4K3, Q5R8M1, Q64682, Q6PFQ0, Q6TGC6, Q6TJY3, Q7TPS0, Q7TSE6, Q8BGW6

Diamond homologs: A2VDV2, A8WVU9, A8XJL7, E9PSL7, F4HPN2, F4HYG2, F4J6F6, M3TYT0, O01583, O13310, O14578, O15021, O45797, O54874, O60307, O75116, O77819, O94487, O95835, P00517, P05131, P05383, P0C1B1, P12688, P17612, P18961, P22204, P22694, P25321, P27791, P31034, P32328, P36887, P38679, P38938, P49025, P53894, P54265, P54644, P68180

SIGNOR signaling

30 interactions.

A	Effect	B	Mechanism
STK24	up-regulates	STK38	phosphorylation
STK38	up-regulates	STK38	phosphorylation
STK38	“down-regulates activity”	YAP1	phosphorylation
STK38	“down-regulates quantity by destabilization”	CDKN1A	phosphorylation
PLK1	“down-regulates activity”	STK38	phosphorylation
STK38	“up-regulates activity”	XPO1	phosphorylation
STK38	“up-regulates activity”	RBM24	phosphorylation
MAP3K2	“up-regulates quantity by stabilization”	STK38	phosphorylation
GSK3B	“down-regulates activity”	STK38	phosphorylation
STK38	“down-regulates quantity”	CDC25A	phosphorylation
STK38	“up-regulates activity”	HEY1	phosphorylation
STK4	“up-regulates activity”	STK38	phosphorylation
STK38	“down-regulates activity”	MYC	phosphorylation
STK38	“up-regulates activity”	PANX2	phosphorylation
STK38	“up-regulates activity”	PI4KB	phosphorylation
STK38	“up-regulates activity”	AAK1	phosphorylation
STK38	“up-regulates activity”	RAB11FIP5	phosphorylation
STK38	“up-regulates activity”	RAB3IP	phosphorylation
PRKACA	“down-regulates activity”	STK38	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	39.5×	5e-06
Signaling by high-kinase activity BRAF mutants	8	29.9×	7e-08
Signaling by RAS mutants	6	29.9×	2e-06
MAP2K and MAPK activation	8	26.9×	1e-07
VEGFR2 mediated vascular permeability	5	24.0×	5e-05
Signaling by moderate kinase activity BRAF mutants	8	23.9×	1e-07
Paradoxical activation of RAF signaling by kinase inactive BRAF	8	23.9×	1e-07
Signaling downstream of RAS mutants	8	23.9×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	5	15.0×	5e-03
positive regulation of cell growth	6	11.3×	5e-03
phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	10.9×	1e-02
intracellular protein localization	7	7.5×	5e-03
positive regulation of ERK1 and ERK2 cascade	8	7.0×	5e-03
positive regulation of gene expression	15	6.0×	4e-05
negative regulation of apoptotic process	12	4.3×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2263 predictions. Top by Δscore:

Variant	Effect	Δscore
6:36495913:CA:C	acceptor_gain	1.0000
6:36495915:C:CC	acceptor_gain	1.0000
6:36496705:TGTTA:T	donor_loss	1.0000
6:36496706:GTTAC:G	donor_loss	1.0000
6:36496707:TTACC:T	donor_loss	1.0000
6:36496708:TA:T	donor_loss	1.0000
6:36496709:ACC:A	donor_loss	1.0000
6:36496710:C:A	donor_loss	1.0000
6:36496802:CTCT:C	acceptor_gain	1.0000
6:36496804:CT:C	acceptor_gain	1.0000
6:36496806:C:CC	acceptor_gain	1.0000
6:36496810:C:CT	acceptor_gain	1.0000
6:36496811:A:T	acceptor_gain	1.0000
6:36496821:A:C	acceptor_gain	1.0000
6:36497818:A:AC	donor_gain	1.0000
6:36497819:C:CC	donor_gain	1.0000
6:36497876:C:CA	acceptor_loss	1.0000
6:36497877:T:G	acceptor_loss	1.0000
6:36506581:A:AC	donor_gain	1.0000
6:36506582:C:CA	donor_gain	1.0000
6:36506582:CTAG:C	donor_gain	1.0000
6:36506645:C:CC	acceptor_gain	1.0000
6:36507498:A:AC	donor_gain	1.0000
6:36507499:C:CC	donor_gain	1.0000
6:36521728:CTTTA:C	donor_loss	1.0000
6:36521729:TTTAC:T	donor_loss	1.0000
6:36521730:TTACC:T	donor_loss	1.0000
6:36521731:TAC:T	donor_loss	1.0000
6:36521733:C:A	donor_loss	1.0000
6:36521733:CCTG:C	donor_gain	1.0000

AlphaMissense

3121 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:36495862:G:C	F440L	1.000
6:36495862:G:T	F440L	1.000
6:36495864:A:G	F440L	1.000
6:36496739:A:C	F413L	1.000
6:36496739:A:T	F413L	1.000
6:36496741:A:G	F413L	1.000
6:36496748:G:C	F410L	1.000
6:36496748:G:T	F410L	1.000
6:36496749:A:C	F410C	1.000
6:36496749:A:G	F410S	1.000
6:36496750:A:G	F410L	1.000
6:36497851:T:A	R367S	1.000
6:36497851:T:G	R367S	1.000
6:36497852:C:G	R367T	1.000
6:36498473:G:C	F322L	1.000
6:36498473:G:T	F322L	1.000
6:36498474:A:G	F322S	1.000
6:36498475:A:G	F322L	1.000
6:36498475:A:T	F322I	1.000
6:36498477:G:T	P321H	1.000
6:36498486:C:A	G318V	1.000
6:36498486:C:T	G318D	1.000
6:36499873:C:G	G318R	1.000
6:36499878:A:G	L316P	1.000
6:36499883:C:A	E314D	1.000
6:36499883:C:G	E314D	1.000
6:36499884:T:A	E314V	1.000
6:36499884:T:G	E314A	1.000
6:36499899:C:T	G309E	1.000
6:36499900:C:A	G309W	1.000

dbSNP variants (sampled 300 via entrez): RS1000047316 (6:36495032 A>G), RS1000076522 (6:36549372 T>C), RS1000090681 (6:36500620 C>T), RS1000122125 (6:36541190 G>A), RS1000183339 (6:36500312 T>C), RS1000232525 (6:36547577 G>A,T), RS1000239190 (6:36531307 C>T), RS1000288928 (6:36507009 G>A), RS1000355256 (6:36513032 A>C,T), RS1000387859 (6:36512830 T>G), RS1000407521 (6:36543106 C>T), RS1000494336 (6:36541603 T>C), RS1000512192 (6:36538686 G>A,T), RS1000519068 (6:36498778 A>G), RS1000529364 (6:36495923 G>A)

Disease associations

OMIM: gene MIM:606964 | disease phenotypes: MIM:600057

GenCC curated gene-disease

Mondo (2): bladder exstrophy-epispadias-cloacal exstrophy complex (MONDO:0700039), dilated cardiomyopathy (MONDO:0005021)

Orphanet (2): Classic bladder exstrophy (Orphanet:93930), Dilated cardiomyopathy (Orphanet:217604)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001644	Dilated cardiomyopathy

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004526_1	Subclinical trait of interstitial lung disease (basilar percentage of high attenuation areas on CT scan)	4.000000e-08
GCST009724_5	Vertical cup-disc ratio (multi-trait analysis)	8.000000e-13
GCST90002395_445	Mean platelet volume	3.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007627	airway imaging measurement
EFO:0006939	cup-to-disc ratio measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075155 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

9 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 89,545 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL535	SUNITINIB	4	79,020
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL4303241	BAY-1161909	2	47
CHEMBL475251	R-406	2	762
CHEMBL1908397	KW-2449	1	622
CHEMBL3128043	PF-03758309	1	233

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — NDR family

ChEMBL bioactivities

16 potent at pChembl≥5 of 18 total, top 14 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.23	IC50	0.584	nM	STAUROSPORINE
9.20	IC50	0.628	nM	STAUROSPORINE
8.16	IC50	6.87	nM	STAUROSPORINE
7.25	Kd	56	nM	STAUROSPORINE
7.12	Kd	75	nM	PF-03758309
6.66	Kd	220	nM	LESTAURTINIB
6.41	Kd	390	nM	KW-2449
6.39	Kd	410	nM	SUNITINIB
6.36	Kd	440	nM	TAE-684
6.18	Kd	660	nM	DOVITINIB
6.16	Kd	700	nM	SU-014813
6.00	IC50	1000	nM	TP-030n
5.24	Kd	5800	nM	FEDRATINIB
5.03	Kd	9400	nM	R-406

PubChem BioAssay actives

15 with measured affinity, of 426 total; 10 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	1531895: Inhibition of human STK38 using KKRNRRLSVA as substrate by [gamma-33P]-ATP assay	ic50	0.0006	uM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	1425183: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0750	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	507641: Binding affinity to NDR1	kd	0.2200	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625067: Binding constant for NDR1 kinase domain	kd	0.3900	uM
Sunitinib	507641: Binding affinity to NDR1	kd	0.4100	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	625067: Binding constant for NDR1 kinase domain	kd	0.4400	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	625067: Binding constant for NDR1 kinase domain	kd	0.6600	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	625067: Binding constant for NDR1 kinase domain	kd	0.7000	uM
Fedratinib	625067: Binding constant for NDR1 kinase domain	kd	5.8000	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	625067: Binding constant for NDR1 kinase domain	kd	9.4000	uM

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, affects expression	7
sodium arsenite	decreases expression, increases abundance	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants, Occupational	affects expression, decreases expression	2
Estradiol	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Irinotecan	increases expression	1
Temozolomide	increases expression	1
Fulvestrant	increases methylation	1
Vorinostat	affects cotreatment, decreases expression	1
Leflunomide	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Azacitidine	decreases expression	1
Benzo(a)pyrene	affects methylation	1

ChEMBL screening assays

153 unique, capped per target: 153 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1116729	Binding	Inhibition of NDR1 at 5 uM	Structure-activity relationship study of EphB3 receptor tyrosine kinase inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TQ90	HAP1 STK38 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00629018	PHASE2	COMPLETED	Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096	PHASE2	COMPLETED	Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy
NCT00765518	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
NCT00847964	PHASE2	COMPLETED	Safety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery
NCT01020968	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy
NCT01302171	PHASE2	COMPLETED	Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy
NCT01350310	PHASE2	COMPLETED	Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy
NCT02133911	PHASE2	COMPLETED	A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy
NCT03071653	PHASE2	SUSPENDED	Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study
NCT03572660	PHASE2	ACTIVE_NOT_RECRUITING	Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM
NCT03775070	PHASE2	COMPLETED	Simvastatin Therapy in Patients With Dilated Cardiomyopathy.
NCT04405804	PHASE2	UNKNOWN	Early Administration of Ivabradine in Children With Heart Failure
NCT05410873	PHASE2	COMPLETED	Examining the Effects of Mitochondrial Oxidative Stress in DCM
NCT06632834	PHASE2	RECRUITING	Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation
NCT00585546	PHASE1	TERMINATED	Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure
NCT02293603	PHASE1	UNKNOWN	Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC)
NCT03062956	PHASE1	COMPLETED	A Single Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of MYK-491
NCT03129568	PHASE1	COMPLETED	Transcoronary Infusion of Cardiac Progenitor Cells in Pediatric Dilated Cardiomyopathy
NCT04982081	PHASE1	UNKNOWN	Treating Congestive HF With hiPSC-CMs Through Endocardial Injection
NCT06381466	PHASE1	TERMINATED	A Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral AZD0233 Compared With Placebo in Healthy Adult Participants.
NCT06464588	PHASE1	RECRUITING	A Phase 1 Open-Label Study of the Safety of Intravenous Allogeneic Neonatal Mesenchymal Cells (nMSCs) in Young Adult (1A) and Pediatric (1B) Patients With Dilated Cardiomyopathy (DCM)
NCT06902896	PHASE1	COMPLETED	Safety and Efficacy of FAP iCDC in End-stage Dilated Cardiomyopathy
NCT07137338	PHASE1	RECRUITING	A Phase 1 AAV Gene Therapy Trial Evaluating Safety and Preliminary Efficacy of RP-A701 in Subjects With BAG3 Dilated Cardiomyopathy
NCT07241104	PHASE1	RECRUITING	A Study of AZD4063 in PLN R14del Dilated Cardiomyopathy