STK38L

Summary

STK38L (serine/threonine kinase 38 like, HGNC:17848) is a protein-coding gene on chromosome 12p11.23, encoding Serine/threonine-protein kinase 38-like (Q9Y2H1). Involved in the regulation of structural processes in differentiating and mature neuronal cells.

Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in intracellular signal transduction and negative regulation of autophagy. Acts upstream of or within protein phosphorylation. Located in cytosol.

Source: NCBI Gene 23012 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 50 total
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_015000

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17848
Approved symbol	STK38L
Name	serine/threonine kinase 38 like
Location	12p11.23
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0965, NDR2
Ensembl gene	ENSG00000211455
Ensembl biotype	protein_coding
OMIM	615836
Entrez	23012

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 17 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron

ENST00000389032, ENST00000407753, ENST00000434385, ENST00000536093, ENST00000539863, ENST00000540996, ENST00000541191, ENST00000543246, ENST00000543992, ENST00000544367, ENST00000544969, ENST00000545470, ENST00000546286, ENST00000891035, ENST00000891036, ENST00000891037, ENST00000891038, ENST00000891039, ENST00000891040, ENST00000891041, ENST00000931466, ENST00000931467, ENST00000960352, ENST00000960353

RefSeq mRNA: 1 — MANE Select: NM_015000 NM_015000

CCDS: CCDS31761

Canonical transcript exons

ENST00000389032 — 14 exons

Exon	Start	End
ENSE00001504706	27322328	27325959
ENSE00001504714	27312549	27312672
ENSE00002311736	27244286	27244332
ENSE00003496309	27315289	27315350
ENSE00003498906	27308339	27308461
ENSE00003514947	27297710	27297854
ENSE00003583024	27315015	27315117
ENSE00003585786	27319328	27319423
ENSE00003603611	27302137	27302188
ENSE00003644499	27317896	27318019
ENSE00003654917	27314504	27314658
ENSE00003690010	27317336	27317453
ENSE00003694586	27322143	27322234
ENSE00003786602	27309114	27309197

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 97.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.0805 / max 584.4135, expressed in 1754 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124831	21.7193	1754
124830	0.3323	135
124832	0.0289	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ascending aorta	UBERON:0001496	97.35	gold quality
thoracic aorta	UBERON:0001515	97.26	gold quality
aorta	UBERON:0000947	97.16	gold quality
popliteal artery	UBERON:0002250	97.14	gold quality
tibial artery	UBERON:0007610	97.13	gold quality
calcaneal tendon	UBERON:0003701	97.01	gold quality
right coronary artery	UBERON:0001625	96.50	gold quality
descending thoracic aorta	UBERON:0002345	95.79	gold quality
saphenous vein	UBERON:0007318	95.66	gold quality
left coronary artery	UBERON:0001626	95.48	gold quality
blood vessel layer	UBERON:0004797	94.71	gold quality
coronary artery	UBERON:0001621	94.69	gold quality
colonic epithelium	UBERON:0000397	94.43	gold quality
monocyte	CL:0000576	93.62	gold quality
lower esophagus	UBERON:0013473	93.52	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.52	gold quality
mononuclear cell	CL:0000842	93.41	gold quality
rectum	UBERON:0001052	93.18	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.14	gold quality
leukocyte	CL:0000738	92.98	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.74	gold quality
cauda epididymis	UBERON:0004360	92.58	gold quality
heart right ventricle	UBERON:0002080	92.52	gold quality
gall bladder	UBERON:0002110	92.43	gold quality
sigmoid colon	UBERON:0001159	92.38	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.36	gold quality
mucosa of stomach	UBERON:0001199	92.33	gold quality
right atrium auricular region	UBERON:0006631	92.29	gold quality
cardiac atrium	UBERON:0002081	91.95	gold quality
body of uterus	UBERON:0009853	91.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	no	2.76
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

262 targeting STK38L, 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-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
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-4692	100.00	67.32	2066
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34A-5P	99.99	71.21	1784

Literature-anchored findings (GeneRIF, showing 16)

• NDR1 and NDR2 serine-threonine kinases are regulated by mob proteins (PMID:15067004)
• The NDR1 and NDR2 kinases were incorporated into HIV-1 particles and were cleaved by the HIV-1 protease. (PMID:15582665)
• Activation of NDR2 is a multistep process involving phosphorylation of the hydrophobic motif site Thr444/2 by MST3, autophosphorylation of Ser281/2, and binding of MOB1A. (PMID:16314523)
• NDR2 is an upstream kinase of ARK5 that plays an essential role in tumor progression through ARK5 (PMID:16488889)
• findings identify NDR1/2 as novel proapoptotic kinases and key members of the RASSF1A/MST1 signaling cascade (PMID:19062280)
• These findings establish a novel MST3-NDR-p21 axis as an important regulator of G(1)/S progression of mammalian cells. (PMID:21262772)
• NDR2-mediated Rabin8 phosphorylation is crucial for ciliogenesis by triggering the switch in binding specificity of Rabin8 from PS to Sec15. (PMID:23435566)
• cyclin D1 has a role in promoting cell cycle progression by enhancing NDR1/2 kinase activity independent of Cdk4 (PMID:23897809)
• It was found that STK38L*I/D genotype had positive association with longevity in the ethnically homogeneous group of Tatars from the Republic of Bashkortostan, Russia. (PMID:28556638)
• This study shows that STK38L is co-amplified with oncogenic KRAS in pancreatic cancer cell lines, where it regulates LATS2 gene expression. (PMID:29108249)
• These results suggest that NDR2 may play important roles in IL-17-associated inflammation by promoting Smurf1-mediated MEKK2 ubiquitination and degradation. (PMID:30504095)
• Study identified rs10842893 as a novel independent SNP in the gene STK38L that was significantly associated with glioma risk in Chinese population, and furthermore confirmed previously reported associations of rs498872 and rs6010620 with glioma risk in European descent population and Chinese Han population. (PMID:30714141)
• NDR2 positively regulated an antiviral innate immune response in a kinase activity-independent manner. NDR2 interacts with RIG-I and promotes TRIM25-mediated RIG-I ubiquitination, which is required for downstream signaling activation and type I IFN production. (PMID:30775439)
• The results demonstrate that NDR2 is a reversible acetylated kinase regulated by SIRT1 and p300/CBP. (PMID:31427083)
• TRIM27 cooperates with STK38L to inhibit ULK1-mediated autophagy and promote tumorigenesis. (PMID:35670107)
• Hypoxia-induced activation of NDR2 underlies brain metastases from Non-Small Cell Lung Cancer. (PMID:38092743)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	stk38l	ENSDARG00000045482
mus_musculus	Stk38l	ENSMUSG00000001630
rattus_norvegicus	Stk38l	ENSRNOG00000001828
drosophila_melanogaster	trc	FBGN0003744
caenorhabditis_elegans		WBGENE00004727

Paralogs (1): STK38 (ENSG00000112079)

Protein

Protein identifiers

Serine/threonine-protein kinase 38-like — Q9Y2H1 (reviewed: Q9Y2H1)

Alternative names: NDR2 protein kinase, Nuclear Dbf2-related kinase 2

All UniProt accessions (8): Q9Y2H1, F5GY51, F5H0V1, F5H277, F5H5E6, F5H7Z3, H0YGN4, I3L0D0

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the regulation of structural processes in differentiating and mature neuronal cells.

Subunit / interactions. Homodimeric S100B binds two molecules of STK38L. Interacts with MICAL1; leading to inhibit the protein kinase activity by antagonizing activation by MST1/STK4. Interacts with MOB1 and MOB2.

Subcellular location. Cytoplasm. Cytoskeleton. Membrane.

Tissue specificity. Ubiquitously expressed with highest levels observed in the thymus.

Activity regulation. Activated by binding of S100B which releases autoinhibitory N-lobe interactions, enabling ATP to bind and the autophosphorylation of Ser-282. Thr-442 then undergoes calcium-dependent phosphorylation by STK24/MST3. Interactions between phosphorylated Thr-442 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 STK38L.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y2H1-1	1	yes
Q9Y2H1-2	2

RefSeq proteins (1): NP_055815* (*=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

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 (21 total): modified residue 4, mutagenesis site 4, splice variant 2, helix 2, domain 2, binding site 2, initiator methionine 1, chain 1, sequence variant 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5XQZ	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2H1-F1	85.15	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): 213 (proton acceptor)

Ligand- & substrate-binding residues (2): 96–104; 119

Post-translational modifications (4): 282, 442, 2, 75

Mutagenesis-validated functional residues (4):

Position	Phenotype
75	decreased kinase activity. reduced binding of s100b.
119	loss of autophosphorylation and kinase activity.
282	loss of autophosphorylation and kinase activity.
442	decreased kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 213 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, TGACCTY_ERR1_Q2, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, chr12p11, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY, SOX9_B1, GOBP_REGULATION_OF_CATABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, DOUGLAS_BMI1_TARGETS_DN, AACTTT_UNKNOWN, GOMF_ACTIN_BINDING, MODULE_95, GOBP_NEGATIVE_REGULATION_OF_CATABOLIC_PROCESS, MASSARWEH_TAMOXIFEN_RESISTANCE_UP

GO Biological Process (6): protein phosphorylation (GO:0006468), negative regulation of autophagy (GO:0010507), intracellular signal transduction (GO:0035556), regulation of cellular component organization (GO:0051128), negative regulation of metabolic process (GO:0009892), positive regulation of autophagy (GO:0010508)

GO Molecular Function (11): magnesium ion binding (GO:0000287), actin binding (GO:0003779), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (5): cytoplasm (GO:0005737), cytosol (GO:0005829), actin cytoskeleton (GO:0015629), membrane (GO:0016020), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
autophagy	2
regulation of autophagy	2
intracellular anatomical structure	2
protein kinase activity	2
phosphorylation	1
protein modification process	1
negative regulation of catabolic process	1
signal transduction	1
cellular component organization	1
regulation of cellular process	1
metabolic process	1
regulation of metabolic process	1
negative regulation of cellular process	1
positive regulation of catabolic process	1
metal ion binding	1
cytoskeletal protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cation binding	1
cytoplasm	1
cytoskeleton	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2098 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STK38L	NDRG2	Q9UN36	929
STK38L	NDRG3	Q9UGV2	922
STK38L	NDRG1	Q92597	894
STK38L	MOB1A	Q9H8S9	849
STK38L	MOB2	Q70IA6	791
STK38L	MOB1B	Q7L9L4	613
STK38L	SMCO2	A6NFE2	579
STK38L	RAB3IP	Q96QF0	554
STK38L	MICAL1	Q8TDZ2	531
STK38L	MOB3A	Q96BX8	505
STK38L	YWHAE	P29360	494
STK38L	CCDC91	Q7Z6B0	487
STK38L	ACTB	P02570	486
STK38L	SAV1	Q9H4B6	474
STK38L	MOB4	Q9Y3A3	458

IntAct

47 interactions, top by confidence:

A	B	Type	Score
STK38L	MOB2	psi-mi:“MI:0914”(association)	0.910
MOB2	STK38L	psi-mi:“MI:0915”(physical association)	0.910
MOB1A	STK38L	psi-mi:“MI:0915”(physical association)	0.900
MOB1B	LATS1	psi-mi:“MI:0914”(association)	0.840
CDC37	STK38L	psi-mi:“MI:0915”(physical association)	0.690
MOB1B	PPP6C	psi-mi:“MI:2364”(proximity)	0.480
MOB1A	PPP6C	psi-mi:“MI:2364”(proximity)	0.420
FMO2	STK38L	psi-mi:“MI:0915”(physical association)	0.400
STK38L	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
YWHAB	STK38L	psi-mi:“MI:0915”(physical association)	0.400
ARRB1		psi-mi:“MI:0914”(association)	0.350
STK38L		psi-mi:“MI:0914”(association)	0.350
STK38L	PRPH	psi-mi:“MI:0914”(association)	0.350
SLC25A25	METAP2	psi-mi:“MI:0914”(association)	0.350
DOK2	ARPC2	psi-mi:“MI:0914”(association)	0.350
CMBL	H2BC11	psi-mi:“MI:0914”(association)	0.350
PLK4	SF3B1	psi-mi:“MI:0914”(association)	0.350
STK38	VDR	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CTBP1	GSN	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
STK38L	PEX14	psi-mi:“MI:0914”(association)	0.350

BioGRID (119): MOB2 (Affinity Capture-MS), MOB1A (Affinity Capture-MS), LOC100419906 (Affinity Capture-MS), STK38L (Affinity Capture-MS), STK38L (Affinity Capture-MS), CDC37 (Affinity Capture-MS), MOB1A (Affinity Capture-MS), MOB1B (Affinity Capture-MS), MOB2 (Affinity Capture-MS), PRSS1 (Affinity Capture-MS), STK38L (Affinity Capture-MS), STK38L (Affinity Capture-Western), STK38L (Affinity Capture-MS), STK38L (Affinity Capture-MS), STK38L (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

6 interactions.

A	Effect	B	Mechanism
STK24	up-regulates	STK38L	phosphorylation
STK38L	up-regulates	STK38L	phosphorylation
STK38L	“up-regulates activity”	FLNA	phosphorylation
TRIM27	“up-regulates activity”	STK38L	ubiquitination
STK38L	“down-regulates quantity”	ULK1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2559 predictions. Top by Δscore:

Variant	Effect	Δscore
12:27297705:TTCA:T	acceptor_loss	1.0000
12:27297706:TCA:T	acceptor_loss	1.0000
12:27297707:CAGT:C	acceptor_loss	1.0000
12:27297708:A:AG	acceptor_gain	1.0000
12:27297708:A:G	acceptor_loss	1.0000
12:27297709:G:GT	acceptor_gain	1.0000
12:27297709:GT:G	acceptor_gain	1.0000
12:27297709:GTT:G	acceptor_gain	1.0000
12:27297709:GTTT:G	acceptor_gain	1.0000
12:27297709:GTTTC:G	acceptor_gain	1.0000
12:27297851:CCAG:C	donor_loss	1.0000
12:27297852:CAG:C	donor_loss	1.0000
12:27297853:AG:A	donor_loss	1.0000
12:27297854:GG:G	donor_loss	1.0000
12:27297855:GTAT:G	donor_loss	1.0000
12:27297856:T:G	donor_loss	1.0000
12:27302130:T:TA	acceptor_gain	1.0000
12:27302135:A:G	acceptor_gain	1.0000
12:27302185:AGAG:A	donor_loss	1.0000
12:27302187:AG:A	donor_loss	1.0000
12:27302188:GG:G	donor_loss	1.0000
12:27302189:GT:G	donor_loss	1.0000
12:27302190:T:G	donor_loss	1.0000
12:27308337:A:AG	acceptor_gain	1.0000
12:27308338:G:GG	acceptor_gain	1.0000
12:27308442:G:GT	donor_gain	1.0000
12:27309108:TTTTA:T	acceptor_loss	1.0000
12:27309109:TTTA:T	acceptor_loss	1.0000
12:27309110:TTAG:T	acceptor_loss	1.0000
12:27309111:TAG:T	acceptor_loss	1.0000

AlphaMissense

3094 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:27308352:G:C	R67P	1.000
12:27308391:T:C	L80P	1.000
12:27308397:G:C	R82T	1.000
12:27308397:G:T	R82M	1.000
12:27308398:G:C	R82S	1.000
12:27308398:G:T	R82S	1.000
12:27308420:T:C	F90L	1.000
12:27308421:T:C	F90S	1.000
12:27308422:T:A	F90L	1.000
12:27308422:T:G	F90L	1.000
12:27308439:T:A	I96K	1.000
12:27308441:G:A	G97R	1.000
12:27308441:G:C	G97R	1.000
12:27308442:G:A	G97E	1.000
12:27308442:G:T	G97V	1.000
12:27308447:G:A	G99R	1.000
12:27308447:G:C	G99R	1.000
12:27308448:G:A	G99E	1.000
12:27308448:G:C	G99A	1.000
12:27308448:G:T	G99V	1.000
12:27308453:T:A	F101I	1.000
12:27308453:T:C	F101L	1.000
12:27308453:T:G	F101V	1.000
12:27308454:T:C	F101S	1.000
12:27308454:T:G	F101C	1.000
12:27308455:T:A	F101L	1.000
12:27308455:T:G	F101L	1.000
12:27308456:G:A	G102R	1.000
12:27308456:G:C	G102R	1.000
12:27308457:G:A	G102E	1.000

dbSNP variants (sampled 300 via entrez): RS1000080899 (12:27311609 C>T), RS1000113203 (12:27297742 A>C), RS1000154974 (12:27277192 A>G), RS1000192380 (12:27252538 A>G), RS1000214178 (12:27247317 C>A,T), RS1000305129 (12:27278956 A>G), RS1000319015 (12:27246297 C>G,T), RS1000349635 (12:27319637 T>C), RS1000366930 (12:27282531 T>G), RS1000369964 (12:27246012 T>C), RS1000373240 (12:27313474 C>T), RS1000426937 (12:27313092 A>C), RS1000514392 (12:27283256 CTA>C), RS1000514962 (12:27245522 A>G), RS1000582453 (12:27319870 T>C)

Disease associations

OMIM: gene MIM:615836 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006630_34	Diastolic blood pressure	9.000000e-10
GCST007842_4	Glioma	2.000000e-12
GCST90002395_118	Mean platelet volume	3.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4851 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 92,011 (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
CHEMBL535	SUNITINIB	4	79,020
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL574737	UCN-01	2	2,217
CHEMBL607707	PELITINIB	2	6,340
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 — NDR family

Binding affinities (BindingDB)

3 measured of 3 human assays (3 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 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
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

24 potent at pChembl≥5 of 24 total, top 19 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.08	IC50	0.831	nM	STAUROSPORINE
8.84	IC50	1.45	nM	STAUROSPORINE
8.83	IC50	1.47	nM	STAUROSPORINE
7.55	Kd	28	nM	STAUROSPORINE
7.11	Kd	77	nM	STAUROSPORINE
6.43	Kd	370	nM	LESTAURTINIB
6.38	Kd	414	nM	UCN-01
6.24	Kd	580	nM	TAE-684
6.12	Kd	759	nM	CHEMBL4465866
6.01	Kd	970	nM	SUNITINIB
6.00	IC50	1000	nM	TP-030n
5.96	Kd	1100	nM	KW-2449
5.82	Kd	1500	nM	SUNITINIB
5.70	Kd	2000	nM	SU-014813
5.68	Kd	2100	nM	AST-487
5.67	Kd	2137	nM	K-252A
5.64	Kd	2300	nM	SP-600125
5.51	Kd	3100	nM	PELITINIB
5.16	Kd	6900	nM	TOZASERTIB

PubChem BioAssay actives

23 with measured affinity, of 431 total; 13 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	1715154: Inhibition of human STK38L using KKRNRRLSVA as substrate by [gamma-33P]-ATP assay	ic50	0.0008	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	507642: Binding affinity to NDR2	kd	0.3700	uM
(2S,3R,4R,6R,18S)-18-hydroxy-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	1425184: 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	0.4140	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	625092: Binding constant for NDR2 kinase domain	kd	0.5800	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-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-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526146: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged STK38L (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.7590	uM
Sunitinib	436025: Binding constant for NDR2 kinase domain	kd	0.9700	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625092: Binding constant for NDR2 kinase domain	kd	1.1000	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	436025: Binding constant for NDR2 kinase domain	kd	2.0000	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	625092: Binding constant for NDR2 kinase domain	kd	2.1000	uM
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-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-nonaene-16-carboxylate	1425184: 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	2.1370	uM
14,15-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(15),2,4,6,9(16),10,12-heptaen-8-one	256677: Average Binding Constant for STK38L; NA=Not Active at 10 uM	kd	2.3000	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	256677: Average Binding Constant for STK38L; NA=Not Active at 10 uM	kd	3.1000	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	625092: Binding constant for NDR2 kinase domain	kd	6.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	3
methylmercuric chloride	decreases expression	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Valproic Acid	affects expression, decreases methylation	2
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
myricetin	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	affects methylation	1
jinfukang	affects cotreatment, decreases expression	1
Dasatinib	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1

ChEMBL screening assays

201 unique, capped per target: 201 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1048292	Binding	Inhibition of NDR2 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

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2HQ	Abcam HeLa STK38L KO	Cancer cell line	Female
CVCL_TQ91	HAP1 STK38L (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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