ULK2

Summary

ULK2 (unc-51 like autophagy activating kinase 2, HGNC:13480) is a protein-coding gene on chromosome 17p11.2, encoding Serine/threonine-protein kinase ULK2 (Q8IYT8). Serine/threonine-protein kinase involved in autophagy in response to starvation.

This gene encodes a protein that is similar to a serine/threonine kinase in C. elegans which is involved in axonal elongation. The structure of this protein is similar to the C. elegans protein in that both proteins have an N-terminal kinase domain, a central proline/serine rich (PS) domain, and a C-terminal (C) domain. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternatively spliced transcript variants encoding the same protein have been identified.

Source: NCBI Gene 9706 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 184 total — 1 likely-pathogenic
• Druggable target: yes — 19 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014683

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13480
Approved symbol	ULK2
Name	unc-51 like autophagy activating kinase 2
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0623, Unc51.2, ATG1B
Ensembl gene	ENSG00000083290
Ensembl biotype	protein_coding
OMIM	608650
Entrez	9706

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000361658, ENST00000395544, ENST00000570983, ENST00000571137, ENST00000571177, ENST00000571454, ENST00000574732, ENST00000574854, ENST00000575432, ENST00000580118, ENST00000580130, ENST00000909802, ENST00000909803, ENST00000945213, ENST00000945214

RefSeq mRNA: 2 — MANE Select: NM_014683 NM_001142610, NM_014683

CCDS: CCDS11213

Canonical transcript exons

ENST00000395544 — 27 exons

Exon	Start	End
ENSE00001052923	19865736	19865828
ENSE00001052940	19864803	19864844
ENSE00001104056	19785937	19786086
ENSE00001104057	19780472	19780629
ENSE00001104068	19777581	19777716
ENSE00001104085	19780986	19781104
ENSE00001155001	19796095	19796282
ENSE00001155007	19797396	19797682
ENSE00001415890	19867328	19867936
ENSE00001805712	19770830	19776407
ENSE00003480920	19810378	19810438
ENSE00003481929	19838501	19838583
ENSE00003531992	19799495	19799575
ENSE00003536112	19825094	19825182
ENSE00003560929	19849742	19849774
ENSE00003564351	19816749	19816920
ENSE00003566622	19841489	19841547
ENSE00003575016	19826139	19826186
ENSE00003596782	19843121	19843222
ENSE00003597765	19795622	19795725
ENSE00003604454	19801777	19801922
ENSE00003608353	19783697	19783905
ENSE00003609657	19845304	19845377
ENSE00003657937	19804693	19804830
ENSE00003659058	19846737	19846910
ENSE00003692586	19849369	19849405
ENSE00003786007	19781889	19782067

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 94.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.8862 / max 92.0482, expressed in 1584 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164897	3.9415	1431
164895	1.3758	771
164892	0.3645	184
164896	0.3540	155
164891	0.3341	137
164893	0.3226	168
208089	0.1057	33
164894	0.0881	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	94.60	gold quality
ganglionic eminence	UBERON:0004023	92.78	gold quality
ventricular zone	UBERON:0003053	92.67	gold quality
corpus callosum	UBERON:0002336	92.28	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.05	gold quality
spinal cord	UBERON:0002240	90.66	gold quality
sperm	CL:0000019	90.28	gold quality
male germ cell	CL:0000015	89.96	gold quality
right testis	UBERON:0004534	89.94	gold quality
prefrontal cortex	UBERON:0000451	89.85	gold quality
secondary oocyte	CL:0000655	89.84	gold quality
left testis	UBERON:0004533	89.79	gold quality
testis	UBERON:0000473	89.74	gold quality
orbitofrontal cortex	UBERON:0004167	87.88	gold quality
stromal cell of endometrium	CL:0002255	87.86	gold quality
oocyte	CL:0000023	87.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.49	gold quality
CA1 field of hippocampus	UBERON:0003881	87.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.21	gold quality
sural nerve	UBERON:0015488	87.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.12	gold quality
frontal cortex	UBERON:0001870	86.76	gold quality
subthalamic nucleus	UBERON:0001906	86.50	gold quality
calcaneal tendon	UBERON:0003701	86.42	gold quality
neocortex	UBERON:0001950	86.25	gold quality
inferior vagus X ganglion	UBERON:0005363	86.00	gold quality
entorhinal cortex	UBERON:0002728	85.95	gold quality
hair follicle	UBERON:0002073	85.69	silver quality
cerebral cortex	UBERON:0000956	85.62	gold quality
substantia nigra	UBERON:0002038	85.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

291 targeting ULK2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
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-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882

Literature-anchored findings (GeneRIF, showing 23)

• First identification and naming of ULK2 as an ortholog of mouse ULK2. (PMID:12471243)
• The ULK-Atg13-FIP200 complexes are direct targets of mTOR and important regulators of autophagy in response to mTOR signaling. (PMID:19225151)
• In response to DNA damage, ULK1 and ULK2 are upregulated by p53. The upregulation of ULK1 (ULK2)/ATG13 complex by p53 is necessary for the sustained autophagy activity induced by DNA damage. (PMID:21475306)
• Glioblastoma and glioma cell lines had low levels of ULK2 transcripts. ULK2 promoter methylation and transcript levels showed significant negative correlation. (PMID:24923441)
• a novel signaling pathway identified whereby starvation-induced activation of ULK leads to phosphorylation of endogenous DENND3, with subsequent activation of Rab12 and initiation of membrane trafficking events required for autophagy (PMID:25925668)
• Kapbeta2 interacts with ULK2 through ULK2’s putative PY-NLS motif, and facilitates transport from the cytoplasm to the nucleus, depending on its Ser1027 residue phosphorylation by PKA, thereby reducing autophagic activity. (PMID:26052940)
• miR-26b was down-regulated in LNCaP, DU145, C4-2 and PC-3 cells compared to the two normal prostate cells RWPE-1 and WPMY-1 except DU145 cells. This inversely correlates with ULK2 level in the same cell lines. (PMID:26920049)
• Knockdown of ULK2 expression significantly induced autophagy, EMT, and cell migration in lung cancer cell line. (PMID:27062295)
• ULK1/2 function as a bifurcate-signaling node that sustains glucose metabolic fluxes besides initiation of autophagy in response to nutritional deprivation. (PMID:27153534)
• The serine/threonine kinase ULK2 binds to and phosphorylates CARMA2sh. (PMID:28230860)
• MiRNA-26b may play a key role in cell growth and death of laryngeal carcinoma through ULK2 and the PTEN/AKT pathway. (PMID:28713931)
• The data presented here provide structural models and chemical starting points for the development of ULK1/2 dual inhibitors with improved selectivity for future exploitation of autophagy inhibition. (PMID:30782972)
• Copper is an essential regulator of the autophagic kinases ULK1/ULK2 to drive lung adenocarcinoma. (PMID:32203415)
• ULK complex organization in autophagy by a C-shaped FIP200 N-terminal domain dimer. (PMID:32516362)
• Long noncoding RNA growth arrestspecific 5 (GAS5) acts as a tumor suppressor by promoting autophagy in breast cancer. (PMID:32705220)
• Coxsackievirus infection induces a non-canonical autophagy independent of the ULK and PI3K complexes. (PMID:33149253)
• Methylation silencing of ULK2 via epithelial-mesenchymal transition causes transformation to poorly differentiated gastric cancers. (PMID:34554345)
• PKClambda/iota inhibition activates an ULK2-mediated interferon response to repress tumorigenesis. (PMID:34560002)
• CircARHGAP12 Triggers Mesenchymal Stromal Cell Autophagy to Facilitate its Effect on Repairing Diabetic Wounds by Sponging miR-301b-3p/ATG16L1 and miR-301b-3p/ULK2. (PMID:34933019)
• Association between Unc-51-like autophagy activating kinase 2 gene polymorphisms and schizophrenia in the Korean population. (PMID:35119028)
• An ULK1/2-PXN mechanotransduction pathway suppresses breast cancer cell migration. (PMID:37846507)
• ULK2 Is a Key Pro-Autophagy Protein That Contributes to the High Chemoresistance and Disease Relapse in FLT3-Mutated Acute Myeloid Leukemia. (PMID:38203816)
• Inhibition of ULK1/2 and KRAS[G12C] controls tumor growth in preclinical models of lung cancer. (PMID:39213022)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ulk2	ENSDARG00000097205
mus_musculus	Ulk2	ENSMUSG00000004798
rattus_norvegicus	Ulk2	ENSRNOG00000002763
drosophila_melanogaster	Atg1	FBGN0260945
caenorhabditis_elegans		WBGENE00006786

Paralogs (2): ULK3 (ENSG00000140474), ULK1 (ENSG00000177169)

Protein

Protein identifiers

Serine/threonine-protein kinase ULK2 — Q8IYT8 (reviewed: Q8IYT8)

Alternative names: Unc-51-like kinase 2

All UniProt accessions (4): Q8IYT8, K7EIU2, K7EKK9, K7EP89

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and a negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK, also acts as a negative regulator of AMPK through phosphorylation of the AMPK subunits PRKAA1, PRKAB2 and PRKAG1. May phosphorylate ATG13/KIAA0652, FRS2, FRS3 and RPTOR; however such data need additional evidences. Not involved in ammonia-induced autophagy or in autophagic response of cerebellar granule neurons (CGN) to low potassium concentration. Plays a role early in neuronal differentiation and is required for granule cell axon formation: may govern axon formation via Ras-like GTPase signaling and through regulation of the Rab5-mediated endocytic pathways within developing axons.

Subunit / interactions. Interacts with SYNGAP1. Component of a complex consisting of ATG13/KIAA0652, ULK1 and RB1CC1/FIP200. Interacts (via C-terminus) with ATG13/KIAA0652. Associates with the mammalian target of rapamycin complex 1 (mTORC1) through an interaction with RPTOR.

Subcellular location. Cytoplasmic vesicle membrane.

Post-translational modifications. Autophosphorylated. In response to nutrient limitation, probably phosphorylated and activated by AMPK, leading to activate autophagy.

Domain organisation. The CTD-like region mediates membrane-binding and incorporation into large protein complexes.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily.

RefSeq proteins (2): NP_001136082, NP_055498* (*=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
IPR016237	Ser/Thr_kin_STPK_Ulk-1/2	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR022708	Atg1-like_tMIT	Domain
IPR045269	Atg1-like	Family
IPR048941	ATG1-like_MIT2	Domain

Pfam: PF00069, PF12063, PF21127

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 (52 total): helix 13, strand 9, sequence variant 7, region of interest 6, compositionally biased region 4, modified residue 3, turn 3, binding site 2, chain 1, domain 1, active site 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6QAV	X-RAY DIFFRACTION	2.05
6QAU	X-RAY DIFFRACTION	2.48
6YID	X-RAY DIFFRACTION	2.7
6QAT	X-RAY DIFFRACTION	2.77

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYT8-F1	60.32	0.30

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): 131 (proton acceptor)

Ligand- & substrate-binding residues (2): 15–23; 39

Post-translational modifications (3): 430, 771, 780

Mutagenesis-validated functional residues (1):

Position	Phenotype
39	decreased kinase activity and decreased autophosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 343 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GCM_MAP4K4, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_COLLATERAL_SPROUTING, GCM_PTPRD, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_VACUOLE_ORGANIZATION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (18): autophagosome assembly (GO:0000045), mitophagy (GO:0000423), autophagy (GO:0006914), signal transduction (GO:0007165), axon guidance (GO:0007411), intracellular protein localization (GO:0008104), regulation of autophagy (GO:0010506), piecemeal microautophagy of the nucleus (GO:0034727), response to starvation (GO:0042594), protein autophosphorylation (GO:0046777), collateral sprouting (GO:0048668), negative regulation of collateral sprouting (GO:0048671), axon extension (GO:0048675), reticulophagy (GO:0061709), somatic sensory system development (GO:0160038), protein phosphorylation (GO:0006468), nervous system development (GO:0007399), axonogenesis (GO:0007409)

GO Molecular Function (8): 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)

GO Cellular Component (8): phagophore assembly site (GO:0000407), cytoplasm (GO:0005737), autophagosome (GO:0005776), cytosol (GO:0005829), cytoplasmic vesicle membrane (GO:0030659), phagophore assembly site membrane (GO:0034045), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
axonogenesis	3
cytoplasm	3
macroautophagy	2
protein kinase activity	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
autophagy of mitochondrion	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
neuron projection guidance	1
macromolecule localization	1
autophagy	1
regulation of catabolic process	1
microautophagy	1
nucleophagy	1
nucleus disassembly	1
response to stress	1
response to nutrient levels	1
protein phosphorylation	1
developmental cell growth	1
developmental growth involved in morphogenesis	1
negative regulation of cell growth	1
negative regulation of developmental growth	1
collateral sprouting	1
regulation of collateral sprouting	1
negative regulation of axonogenesis	1
neuron projection extension	1
sensory system development	1

Protein interactions and networks

STRING

1398 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ULK2	RB1CC1	Q8TDY2	997
ULK2	ATG101	Q9BSB4	997
ULK2	ATG13	O75143	997
ULK2	ULK1	O75385	964
ULK2	BECN1	Q14457	920
ULK2	PIK3C3	Q8NEB9	857
ULK2	SYNGAP1	Q96PV0	847
ULK2	F5GZY7	F5GZY7	831
ULK2	GABARAPL2	P60520	809
ULK2	ATG14	Q6ZNE5	805
ULK2	ATG5	Q9H1Y0	794
ULK2	ATG12	O94817	794
ULK2	ATG7	O95352	792
ULK2	PIK3R4	Q99570	773
ULK2	ATG3	Q9NT62	767

IntAct

26 interactions, top by confidence:

A	B	Type	Score
ATG101	ATG13	psi-mi:“MI:0914”(association)	0.950
ATG13	ULK1	psi-mi:“MI:2364”(proximity)	0.940
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
GABARAPL1	ULK2	psi-mi:“MI:0915”(physical association)	0.400
GABARAPL2	ULK2	psi-mi:“MI:0915”(physical association)	0.400
GABARAP	ULK2	psi-mi:“MI:0915”(physical association)	0.400
ULK2	MAP1LC3B	psi-mi:“MI:0915”(physical association)	0.400
ZNF32	ULK2	psi-mi:“MI:0915”(physical association)	0.370
ULK2	LNX1	psi-mi:“MI:0915”(physical association)	0.370
DIXDC1	ULK2	psi-mi:“MI:0915”(physical association)	0.370
P		psi-mi:“MI:0914”(association)	0.350
ULK2	PRKAB2	psi-mi:“MI:0914”(association)	0.350
WIPI2	VTN	psi-mi:“MI:0914”(association)	0.350
ULK2	ULK2	psi-mi:“MI:0914”(association)	0.350
ATG101	EMC8	psi-mi:“MI:0914”(association)	0.350
RB1CC1	TRAPPC13	psi-mi:“MI:2364”(proximity)	0.270
ULK2	UBR5	psi-mi:“MI:2364”(proximity)	0.270
IRF1	ULK2	psi-mi:“MI:0915”(physical association)	0.000
ULK2	LUC7L2	psi-mi:“MI:0915”(physical association)	0.000
ULK2	SETDB1	psi-mi:“MI:0915”(physical association)	0.000
ULK2	NASP	psi-mi:“MI:0915”(physical association)	0.000
ULK2	POLA2	psi-mi:“MI:0915”(physical association)	0.000
ULK2	EEF1B2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (32): ULK2 (Phenotypic Enhancement), SYNGAP1 (Reconstituted Complex), ATG14 (Biochemical Activity), ULK2 (Affinity Capture-MS), ULK2 (Protein-RNA), TNPO1 (Affinity Capture-Western), ULK2 (Affinity Capture-Western), TNPO1 (Reconstituted Complex), RPTOR (Affinity Capture-Western), ULK2 (Affinity Capture-Western), POLA2 (Two-hybrid), NASP (Two-hybrid), LUC7L2 (Two-hybrid), SETDB1 (Two-hybrid), ULK2 (Affinity Capture-Western)

ESM2 similar proteins: A0A8I3PDQ1, A0M8S4, A0M8T5, A5GFW5, B6RSP1, B9EJA2, D4A039, E9Q0S6, O00750, O35177, Q00PJ1, Q07DV1, Q07DW4, Q07DX4, Q07DY4, Q07E15, Q07E28, Q07E41, Q08EC4, Q09YG9, Q09YI1, Q09YK4, Q09YM8, Q108T9, Q14511, Q155Q3, Q2IBA2, Q2IBB2, Q2IBD4, Q2IBE6, Q2IBF7, Q2QL82, Q2QLA2, Q2QLB3, Q2QLF8, Q2QLG9, Q2VUH7, Q3UIL6, Q5JV73, Q61140

Diamond homologs: A1CHL6, A1CX69, A2QIL5, A6RYB8, A6ZU07, A7F0W2, A7KAL2, A7TIZ4, A8WYE4, B2DD29, D3ZHP7, D3ZML2, F4I1N8, F4IRW0, F4JBP3, I1RNG8, J4W0G2, O08678, O08679, O42844, O70405, O75385, O94547, P0CP70, P0CP71, P25323, P27448, P32562, P53104, P87248, P92937, Q03141, Q05512, Q0CLX3, Q0JI49, Q0UY20, Q10LQ2, Q19469, Q1DN93, Q23023

SIGNOR signaling

18 interactions.

A	Effect	B	Mechanism
ULK2	down-regulates	PRKAA2	phosphorylation
ULK2	down-regulates	PRKAB1	phosphorylation
ULK2	down-regulates	PRKAG3	phosphorylation
MTOR	down-regulates	ULK2	phosphorylation
ATG13	up-regulates	ULK2	binding
ULK2	up-regulates	ATG13	phosphorylation
ULK2	down-regulates	AMPK	phosphorylation
ULK2	“up-regulates activity”	DENND3	phosphorylation
ULK2	“down-regulates activity”	ENO1	phosphorylation
ULK2	“down-regulates activity”	FBP1	phosphorylation
ULK2	“up-regulates activity”	HK1	phosphorylation
ULK2	“down-regulates activity”	PFKM	phosphorylation
ULK2	“up-regulates activity”	RB1CC1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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
Macroautophagy	10	60.7×	1e-14

GO biological processes:

GO term	Partners	Fold	FDR
autophagosome assembly	9	80.9×	1e-13
mitophagy	6	76.3×	1e-08
negative regulation of cell population proliferation	5	8.4×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	134
Likely benign	8
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
402174	NM_014683.4(ULK2):c.1733A>G (p.His578Arg)	Likely pathogenic

SpliceAI

5442 predictions. Top by Δscore:

Variant	Effect	Δscore
17:19777574:AACTT:A	donor_loss	1.0000
17:19777575:ACTTA:A	donor_loss	1.0000
17:19777577:TTACA:T	donor_loss	1.0000
17:19777578:TA:T	donor_loss	1.0000
17:19777579:A:AC	donor_gain	1.0000
17:19777579:ACAT:A	donor_loss	1.0000
17:19777580:C:CG	donor_gain	1.0000
17:19777580:CA:C	donor_gain	1.0000
17:19777580:CAT:C	donor_gain	1.0000
17:19777580:CATT:C	donor_gain	1.0000
17:19777580:CATTT:C	donor_gain	1.0000
17:19777628:AGG:A	donor_gain	1.0000
17:19777724:C:CT	acceptor_gain	1.0000
17:19777724:C:T	acceptor_gain	1.0000
17:19777725:A:T	acceptor_gain	1.0000
17:19777729:A:T	acceptor_gain	1.0000
17:19780466:GGTTA:G	donor_loss	1.0000
17:19780471:C:CT	donor_loss	1.0000
17:19780625:GACAA:G	acceptor_gain	1.0000
17:19780626:ACAA:A	acceptor_gain	1.0000
17:19780627:CAA:C	acceptor_gain	1.0000
17:19780627:CAAC:C	acceptor_gain	1.0000
17:19780628:AA:A	acceptor_gain	1.0000
17:19780628:AAC:A	acceptor_loss	1.0000
17:19780629:ACT:A	acceptor_loss	1.0000
17:19780630:C:CC	acceptor_gain	1.0000
17:19780630:CTGA:C	acceptor_loss	1.0000
17:19780980:CCATA:C	donor_loss	1.0000
17:19780981:CATA:C	donor_loss	1.0000
17:19780983:TA:T	donor_loss	1.0000

AlphaMissense

6775 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:19838511:T:A	R259S	1.000
17:19838511:T:G	R259S	1.000
17:19838533:A:G	L252P	1.000
17:19843147:A:G	C207R	1.000
17:19843164:C:T	G201E	1.000
17:19843165:C:G	G201R	1.000
17:19843165:C:T	G201R	1.000
17:19843169:G:C	S199R	1.000
17:19843169:G:T	S199R	1.000
17:19843171:T:G	S199R	1.000
17:19843172:C:A	W198C	1.000
17:19843172:C:G	W198C	1.000
17:19843174:A:G	W198R	1.000
17:19843174:A:T	W198R	1.000
17:19843180:C:A	D196Y	1.000
17:19843180:C:G	D196H	1.000
17:19843182:G:T	A195D	1.000
17:19843212:A:T	V185D	1.000
17:19843218:G:T	P183H	1.000
17:19845305:A:T	M181K	1.000
17:19845309:A:G	Y180H	1.000
17:19845320:C:A	G176V	1.000
17:19845320:C:T	G176E	1.000
17:19845321:C:G	G176R	1.000
17:19845321:C:T	G176R	1.000
17:19845322:A:C	C175W	1.000
17:19845323:C:T	C175Y	1.000
17:19845324:A:G	C175R	1.000
17:19845326:A:G	L174P	1.000
17:19845335:G:T	A171D	1.000

dbSNP variants (sampled 300 via entrez): RS1000071911 (17:19818806 T>C), RS1000081043 (17:19770519 C>A), RS1000101515 (17:19813690 T>C), RS1000169062 (17:19827053 G>C), RS1000174069 (17:19837307 G>C), RS1000206657 (17:19837626 A>C,G), RS1000284346 (17:19770755 T>C), RS1000360170 (17:19861381 T>C), RS1000389965 (17:19799399 A>G), RS1000422772 (17:19799768 A>G), RS1000445649 (17:19776273 G>A), RS1000456926 (17:19775845 T>A), RS1000511285 (17:19839039 A>G), RS1000522219 (17:19845700 A>G), RS1000560789 (17:19856699 G>A)

Disease associations

OMIM: gene MIM:608650 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5435 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

19 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 185,636 (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
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL3904602	LEROCICLIB	3	1,012
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL1738757	REBASTINIB	2	1,478
CHEMBL475251	R-406	2	762
CHEMBL6068018	INLEXISERTIB	2	13
CHEMBL1908394	GSK-461364	1	1,093
CHEMBL1908397	KW-2449	1	622
CHEMBL494089	GSK-690693	1	2,061
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 — Unc-51-like kinase (ULK) family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
SBP-7455	Inhibition	5.94	pIC50

ChEMBL bioactivities

84 potent at pChembl≥5 of 85 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.10	Kd	0.79	nM	STAUROSPORINE
8.96	IC50	1.1	nM	CHEMBL3605057
8.96	IC50	1.1	nM	CHEMBL4516990
8.96	IC50	1.1	nM	CHEMBL5266681
8.76	IC50	1.72	nM	STAUROSPORINE
8.74	Kd	1.8	nM	TAE-684
8.70	EC50	1.995	nM	CHEMBL5570377
8.59	IC50	2.6	nM	CHEMBL5280560
8.59	IC50	2.6	nM	CHEMBL5568152
8.57	IC50	2.67	nM	STAUROSPORINE
8.44	IC50	3.66	nM	STAUROSPORINE
8.26	Kd	5.5	nM	LEROCICLIB
8.05	IC50	9	nM	INLEXISERTIB
7.96	IC50	11	nM	CHEMBL4128069
7.89	IC50	13	nM	CHEMBL3605055
7.89	Kd	13	nM	SUNITINIB
7.72	Kd	19	nM	R-406
7.52	Kd	30	nM	CHEMBL4465866
7.52	IC50	30	nM	CHEMBL5269042
7.52	IC50	30	nM	CHEMBL4744680
7.46	Kd	35	nM	CHEMBL4554938
7.42	IC50	38	nM	CHEMBL4127042
7.42	IC50	38	nM	CHEMBL3605057
7.42	IC50	38	nM	CHEMBL5288376
7.40	IC50	39.81	nM	CHEMBL6175168
7.38	IC50	41.5	nM	CHEMBL4554938
7.27	Kd	54	nM	DOVITINIB
7.22	Kd	60	nM	LESTAURTINIB
7.21	Kd	61	nM	CHEMBL4576489
7.19	Kd	65	nM	SU-014813
7.10	Kd	79	nM	FEDRATINIB
6.94	IC50	114	nM	STAUROSPORINE
6.89	Kd	130	nM	KW-2449
6.72	Kd	190	nM	RUXOLITINIB
6.70	IC50	200	nM	CHEMBL3603853
6.67	IC50	212	nM	CHEMBL4128069
6.64	IC50	230	nM	CHEMBL3605057
6.51	IC50	310	nM	BX-795
6.50	IC50	320	nM	REBASTINIB
6.44	IC50	360	nM	CHEMBL3605056
6.44	Kd	360	nM	AST-487
6.42	Kd	380	nM	NINTEDANIB
6.35	Kd	450	nM	CHEMBL1908395
6.35	Kd	450	nM	BOSUTINIB
6.33	Kd	470	nM	ALVOCIDIB
6.32	IC50	476	nM	CHEMBL4779423
6.16	IC50	695	nM	CHEMBL4795918
6.15	IC50	711	nM	CHEMBL4128069
6.15	IC50	714	nM	CHEMBL4746440
6.15	IC50	703	nM	CHEMBL4741912

PubChem BioAssay actives

73 with measured affinity, of 585 total; 49 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	625085: Binding constant for ULK2 kinase domain	kd	0.0008	uM
N-[3-[[5-cyclopropyl-2-[3-(morpholin-4-ylmethyl)anilino]pyrimidin-4-yl]amino]propyl]cyclopropanecarboxamide	1946673: Inhibition of ULK2 (unknown origin)	ic50	0.0011	uM
N-[3-[[5-cyclopropyl-2-[3-(morpholin-4-ylmethyl)anilino]pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide	1494458: Inhibition of GST-tagged ULK2 (unknown origin)	ic50	0.0011	uM
N-[3-[[5-cyclopropyl-2-[(2-methyl-3,4-dihydro-1H-isoquinolin-6-yl)amino]pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide	1512693: Inhibition of ULK2 (unknown origin) after 5 mins in presence of gamma-[32]P-ATP by immunoblot analysis	ic50	0.0011	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	625085: Binding constant for ULK2 kinase domain	kd	0.0018	uM
4-[2-(1,2,3,6-tetrahydropyridin-5-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	2101114: Binding affinity to human ULK2 assessed as target engagement by cell-based NanoBRET assay	ec50	0.0020	uM
4-[5-[4-(2-piperidin-1-ylethoxy)phenyl]-1,2-dihydropyrazolo[1,5-a]pyrimidin-2-yl]-N-[(2S)-1,1,1-trifluoro-3-methylbutan-2-yl]thiophene-2-carboxamide	1946673: Inhibition of ULK2 (unknown origin)	ic50	0.0026	uM
4-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-N-[(2S)-1,1,1-trifluoro-3-methylbutan-2-yl]thiophene-2-carboxamide	2156561: Inhibition of human ULK2	ic50	0.0026	uM
4-[[5-(4-propan-2-ylpiperazin-1-yl)-2-pyridinyl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1’-cyclohexane]-10-one	1609452: Binding affinity to ULK2 (unknown origin)	kd	0.0055	uM
2-[5-bromo-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]oxy-N-methylbenzamide	1512689: Inhibition of ULK2 (unknown origin)	ic50	0.0110	uM
Sunitinib	508127: Binding affinity to ULK2	kd	0.0130	uM
2-N-(3H-benzimidazol-5-yl)-4-N-(5-cyclobutyl-1H-pyrazol-3-yl)quinazoline-2,4-diamine	1241331: Inhibition of SUMO-tagged ULK2 (unknown origin) kinase domain expressed in KRX cells using [32P]-gamma-ATP and myelin basic protein substrate incubated for 7 mins	ic50	0.0130	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	625085: Binding constant for ULK2 kinase domain	kd	0.0190	uM
N-[(1S)-1-cyclopropyl-2,2,2-trifluoroethyl]-4-[6-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	2074073: Inhibition of human ULK2 by discoverX kinome scan assay	ic50	0.0300	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	1526164: Binding affinity to recombinant N-terminal His-FLAG-GST-tagged ULK2 (unknown origin) (1 to 478 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0300	uM
N-[(1S)-1-cyclopropyl-2,2,2-trifluoroethyl]-4-[5-(4-fluorophenyl)-1,2-dihydropyrazolo[1,5-a]pyrimidin-2-yl]thiophene-2-carboxamide	1946673: Inhibition of ULK2 (unknown origin)	ic50	0.0300	uM
4-[(2,9-dimethyl-8-oxo-6-thia-2,9,12,14-tetrazatricyclo[8.4.0.03,7]tetradeca-1(14),3(7),4,10,12-pentaen-13-yl)amino]benzenesulfonamide	2189162: Binding affinity to ULK2 (unknown origin) assessed as dissociation constant	kd	0.0350	uM
N’-[3-[[5-cyclopropyl-2-[(2-methyl-3,4-dihydro-1H-isoquinolin-6-yl)amino]pyrimidin-4-yl]amino]propyl]cyclobutanecarboximidamide	1494458: Inhibition of GST-tagged ULK2 (unknown origin)	ic50	0.0380	uM
N-[3-[[5-cyclopropyl-2-[(2-methyl-3,4-dihydro-1H-isoquinolin-6-yl)amino]pyrimidin-4-yl]amino]propyl]cyclopropanecarboxamide	1946673: Inhibition of ULK2 (unknown origin)	ic50	0.0380	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	625085: Binding constant for ULK2 kinase domain	kd	0.0540	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	508127: Binding affinity to ULK2	kd	0.0600	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]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526164: Binding affinity to recombinant N-terminal His-FLAG-GST-tagged ULK2 (unknown origin) (1 to 478 residues) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0610	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	625085: Binding constant for ULK2 kinase domain	kd	0.0650	uM
Fedratinib	625085: Binding constant for ULK2 kinase domain	kd	0.0790	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625085: Binding constant for ULK2 kinase domain	kd	0.1300	uM
Ruxolitinib	625085: Binding constant for ULK2 kinase domain	kd	0.1900	uM
N-[3-[[4-[3-(cyclopropanecarbonylamino)propylamino]-5-iodopyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide	1241331: Inhibition of SUMO-tagged ULK2 (unknown origin) kinase domain expressed in KRX cells using [32P]-gamma-ATP and myelin basic protein substrate incubated for 7 mins	ic50	0.2000	uM
N-[3-[[5-iodo-4-[3-(thiophene-2-carbonylamino)propylamino]pyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide	1241331: Inhibition of SUMO-tagged ULK2 (unknown origin) kinase domain expressed in KRX cells using [32P]-gamma-ATP and myelin basic protein substrate incubated for 7 mins	ic50	0.3100	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	2168265: Inhibition of human wild type ULK2 using Casein as substrate preincubated for 2 hrs followed by ATP addition and measured every 2 mins for 2.5 hrs by spectrophotometric analysis	ic50	0.3200	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	625085: Binding constant for ULK2 kinase domain	kd	0.3600	uM
N-[3-[[4-(3-aminopropylamino)-5-iodopyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide	1241331: Inhibition of SUMO-tagged ULK2 (unknown origin) kinase domain expressed in KRX cells using [32P]-gamma-ATP and myelin basic protein substrate incubated for 7 mins	ic50	0.3600	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625085: Binding constant for ULK2 kinase domain	kd	0.3800	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625085: Binding constant for ULK2 kinase domain	kd	0.4500	uM
Bosutinib	625085: Binding constant for ULK2 kinase domain	kd	0.4500	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	625085: Binding constant for ULK2 kinase domain	kd	0.4700	uM
4-N-cyclopropyl-2-N-(3,4-dimethoxyphenyl)-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682984: Inhibition of recombinant human ULK2 (1 to 478 residues) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.4760	uM
4-N-cyclopropyl-2-N-(5-methoxy-3-pyridinyl)-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682984: Inhibition of recombinant human ULK2 (1 to 478 residues) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.6950	uM
2-N-(3H-benzimidazol-5-yl)-4-N-cyclopropyl-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682986: Inhibition of ULK2 (unknown origin) expressed in HEK293T cells incubated for 2 hrs by NanoBRET assay	ic50	0.7030	uM
4-N-cyclopropyl-2-N-quinolin-6-yl-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682984: Inhibition of recombinant human ULK2 (1 to 478 residues) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.7140	uM
2-N-(1,3-benzoxazol-6-yl)-4-N-cyclopropyl-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682984: Inhibition of recombinant human ULK2 (1 to 478 residues) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	1.1930	uM
2-N-(4-aminophenyl)-4-N-cyclopropyl-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682984: Inhibition of recombinant human ULK2 (1 to 478 residues) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	1.3290	uM
5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	625085: Binding constant for ULK2 kinase domain	kd	1.4000	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	625085: Binding constant for ULK2 kinase domain	kd	1.5000	uM
Crizotinib	625085: Binding constant for ULK2 kinase domain	kd	1.6000	uM
4-[[[2-[3-(morpholin-4-ylmethyl)anilino]pyrimidin-4-yl]amino]methyl]benzenesulfonamide	1823802: Inhibition of recombinant human ULK2 (1to 306 residues) using casein as substrate incubated for 40 mins in presence of [gamma-33P-ATP] by radiometric scintillation assay	ic50	1.7420	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	625085: Binding constant for ULK2 kinase domain	kd	2.3000	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	625085: Binding constant for ULK2 kinase domain	kd	4.9000	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625085: Binding constant for ULK2 kinase domain	kd	6.0000	uM
Axitinib	625085: Binding constant for ULK2 kinase domain	kd	9.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
mercuric bromide	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
trovafloxacin	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
Pioglitazone	increases expression	1
Zoledronic Acid	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Metformin	increases expression	1
Nickel	decreases expression	1
Silicon Dioxide	decreases expression	1
Testosterone	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	increases expression	1
Uranium	affects expression	1
Cyclosporine	increases expression	1
Topotecan	affects response to substance	1

ChEMBL screening assays

188 unique, capped per target: 188 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1059395	Binding	Inhibition of ULK2 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

10 cell lines: 9 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C2VS	HeLa S3 penta KO-ULK1/ULK2 DKO	Cancer cell line	Female
CVCL_C2VT	HeLa S3 penta KO-TBK1/ULK1/ULK2 TKO	Cancer cell line	Female
CVCL_C9DW	HeLa S3 penta KO-ULK1/ULK2 DKO-AZI2/TBKBP1 DKO	Cancer cell line	Female
CVCL_D8D9	Ubigene A-549 ULK2 KO	Cancer cell line	Male
CVCL_D8XZ	Ubigene HCT 116 ULK2 KO	Cancer cell line	Male
CVCL_D9VG	Ubigene HEK293 ULK2 KO	Transformed cell line	Female
CVCL_E0SK	Ubigene HeLa ULK2 KO	Cancer cell line	Female
CVCL_E1DZ	Ubigene U2OS ULK2 KO	Cancer cell line	Female
CVCL_TW32	HAP1 ULK2 (-) 1	Cancer cell line	Male
CVCL_TW33	HAP1 ULK2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer