ULK4

Summary

ULK4 (unc-51 like kinase 4, HGNC:15784) is a protein-coding gene on chromosome 3p22.1, encoding Serine/threonine-protein kinase ULK4 (Q96C45). May be involved in the remodeling of cytoskeletal components, such as alpha-tubulin, and in this way regulates neurite branching and elongation, as well as cell motility.

This gene encodes a member of the unc-51-like serine/threonine kinase (STK) family. Members of this protein family play a role in neuronal growth and endocytosis. The encoded protein is likely involved in neurite branching, neurite elongation and neuronal migration. Genome-wide association studies (GWAS) indicate an association of variations in this gene with blood pressure and hypertension. Sequence variations in this gene may also be be associated with psychiatric disorders, including schizophrenia and bipolar disorder. Pseudogenes associated with this gene have been identified and are located on chromosome 15.

Source: NCBI Gene 54986 — RefSeq curated summary.

At a glance

• Gene–disease (curated): prostate cancer (Limited, GenCC)
• GWAS associations: 56
• Clinical variants (ClinVar): 278 total — 3 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_017886

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15784
Approved symbol	ULK4
Name	unc-51 like kinase 4
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20574, REC01035, FAM7C1
Ensembl gene	ENSG00000168038
Ensembl biotype	protein_coding
OMIM	617010
Entrez	54986

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 5 protein_coding, 5 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000301831, ENST00000414606, ENST00000420927, ENST00000431379, ENST00000453224, ENST00000459802, ENST00000460406, ENST00000460978, ENST00000481226, ENST00000484323, ENST00000489118, ENST00000497684, ENST00000889811, ENST00000951851

RefSeq mRNA: 3 — MANE Select: NM_017886 NM_001322500, NM_001322501, NM_017886

CCDS: CCDS43071

Canonical transcript exons

ENST00000301831 — 37 exons

Exon	Start	End
ENSE00000597930	41919717	41919818
ENSE00000764004	41915977	41916052
ENSE00000825771	41898432	41898492
ENSE00000825772	41900725	41900829
ENSE00000825773	41907845	41907941
ENSE00000825779	41918457	41918540
ENSE00001119577	41566025	41566130
ENSE00001119579	41615669	41615717
ENSE00001119580	41663607	41663699
ENSE00001156453	41681508	41681652
ENSE00001166376	41398079	41398264
ENSE00001166381	41455497	41455595
ENSE00001166386	41463087	41463253
ENSE00001223199	41681753	41681804
ENSE00001223211	41705057	41705151
ENSE00001223220	41705254	41705305
ENSE00001223228	41715237	41715293
ENSE00001223233	41715447	41715568
ENSE00001223241	41717728	41717861
ENSE00001223251	41754361	41754488
ENSE00001536951	41789661	41789843
ENSE00001536953	41800132	41800293
ENSE00001713680	41883874	41883952
ENSE00001726594	41896822	41897003
ENSE00001772607	41895518	41895564
ENSE00001905956	41962016	41962103
ENSE00001942273	41246599	41246992
ENSE00003485501	41911317	41911386
ENSE00003514049	41912807	41912899
ENSE00003516805	41819423	41819506
ENSE00003538346	41954622	41954807
ENSE00003540652	41938098	41938197
ENSE00003602336	41249489	41249574
ENSE00003613757	41911541	41911659
ENSE00003652144	41935801	41935940
ENSE00003669435	41931844	41932006
ENSE00003681008	41835864	41835971

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 94.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.3535 / max 116.7331, expressed in 1672 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41773	6.8085	1648
41769	0.6957	206
41774	0.4291	185
41768	0.3592	60
41767	0.0360	26
41770	0.0250	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	94.38	gold quality
secondary oocyte	CL:0000655	92.48	gold quality
buccal mucosa cell	CL:0002336	92.48	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.28	gold quality
sperm	CL:0000019	90.57	gold quality
bronchial epithelial cell	CL:0002328	90.26	gold quality
calcaneal tendon	UBERON:0003701	89.36	gold quality
caput epididymis	UBERON:0004358	88.95	gold quality
bronchus	UBERON:0002185	88.88	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.16	gold quality
oocyte	CL:0000023	87.21	gold quality
left testis	UBERON:0004533	86.66	gold quality
right testis	UBERON:0004534	86.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.68	gold quality
testis	UBERON:0000473	85.54	gold quality
bone marrow cell	CL:0002092	84.68	gold quality
right uterine tube	UBERON:0001302	83.67	gold quality
oviduct epithelium	UBERON:0004804	83.66	gold quality
myocardium	UBERON:0002349	82.78	gold quality
endocervix	UBERON:0000458	82.15	gold quality
cardiac atrium	UBERON:0002081	81.42	gold quality
right atrium auricular region	UBERON:0006631	81.16	gold quality
cauda epididymis	UBERON:0004360	81.00	gold quality
corpus epididymis	UBERON:0004359	80.31	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.18	gold quality
monocyte	CL:0000576	79.61	gold quality
adult organism	UBERON:0007023	79.52	gold quality
leukocyte	CL:0000738	79.15	gold quality
fallopian tube	UBERON:0003889	78.45	gold quality
ectocervix	UBERON:0012249	78.43	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	139.78
E-CURD-119	yes	52.85
E-MTAB-6678	yes	28.56
E-ANND-3	yes	9.64
E-MTAB-6379	no	187.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting ULK4, 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-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-5702	96.68	68.21	958
HSA-MIR-6734-5P	95.70	65.56	950

Literature-anchored findings (GeneRIF, showing 8)

• First identified as an ULK family kinase and predicted to be catalytically inactive. (PMID:12471243)
• Single-nucleotide polymorphism rs1052501 in ULK4 gene is associated with monoclonal gammopathy of undetermined significance and multiple myeloma (PMID:22945773)
• Our findings indicate that ULK4 is a rare susceptibility gene for schizophrenia. (PMID:24284070)
• results indicate that genetic variations in LRP1 and ULK4 contribute to risk for presenting with an acute aortic dissection (PMID:27569546)
• High-Resolution Structure and Inhibition of the Schizophrenia-Linked Pseudokinase ULK4. (PMID:31841327)
• Nucleotide Binding, Evolutionary Insights, and Interaction Partners of the Pseudokinase Unc-51-like Kinase 4. (PMID:32814032)
• Regional heritability mapping identifies several novel loci (STAT4, ULK4, and KCNH5) for primary biliary cholangitis in the Japanese population. (PMID:33833419)
• Association of Unc-51-like Kinase 4 (ULK4) with the reactivity of the extended reward system in response to conditioned stimuli. (PMID:39185807)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ulk4	ENSDARG00000004176
mus_musculus	Ulk4	ENSMUSG00000040936
rattus_norvegicus	Ulk4	ENSRNOG00000019271

Paralogs (1): STK36 (ENSG00000163482)

Protein

Protein identifiers

Serine/threonine-protein kinase ULK4 — Q96C45 (reviewed: Q96C45)

Alternative names: Unc-51-like kinase 4

All UniProt accessions (3): A0A0C4DG77, C9JVZ3, Q96C45

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the remodeling of cytoskeletal components, such as alpha-tubulin, and in this way regulates neurite branching and elongation, as well as cell motility.

Tissue specificity. Expressed in the brain, mainly in postmitotic neurons, including GABAergic neurons, but not in astrocytes (at protein level).

Disease relevance. Various anomalies in ULK4 gene have been reported for several cases of schizophrenia, schizophrenia plus bipolar disorder and autism. ULK4 gene has been proposed to be a rare susceptibility risk factor for a range of psychiatric diseases including schizophrenia.

Domain organisation. The protein kinase domain is predicted to be catalytically inactive.

Induction. Up-regulated during neuronal differentiation of neuroblastoma cells treated with all-trans or 9-cis retinoic acid.

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

RefSeq proteins (3): NP_001309429, NP_001309430, NP_060356* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR045906	ULK4	Family
IPR056981	HEAT_ULK4_RUNKEL	Domain

Pfam: PF00069, PF23606

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 (55 total): sequence variant 15, helix 15, strand 8, repeat 5, sequence conflict 4, compositionally biased region 2, turn 2, region of interest 2, chain 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6U5L	X-RAY DIFFRACTION	1.75
6TSZ	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96C45-F1	82.59	0.48

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 111 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_JNK_CASCADE, GOBP_REGULATION_OF_NEURON_MIGRATION, chr3p22, GOBP_NEURON_MIGRATION, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, GOBP_REGULATION_OF_NEURON_PROJECTION_DEVELOPMENT, GOBP_CELL_PROJECTION_ORGANIZATION, ZHENG_BOUND_BY_FOXP3, SCGGAAGY_ELK1_02, MGGAAGTG_GABP_B, GOMF_PROTEIN_KINASE_ACTIVITY

GO Biological Process (9): microtubule cytoskeleton organization (GO:0000226), regulation of neuron projection development (GO:0010975), protein kinase C deactivation (GO:0042313), regulation of MAPK cascade (GO:0043408), regulation of JNK cascade (GO:0046328), regulation of p38MAPK cascade (GO:1900744), regulation of neuron migration (GO:2001222), protein phosphorylation (GO:0006468), regulation of signal transduction (GO:0009966)

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 (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of MAPK cascade	2
protein kinase activity	2
cytoskeleton organization	1
microtubule-based process	1
neuron projection development	1
regulation of plasma membrane bounded cell projection organization	1
regulation of G protein-coupled receptor signaling pathway	1
MAPK cascade	1
regulation of intracellular signal transduction	1
JNK cascade	1
p38MAPK cascade	1
neuron migration	1
regulation of cell migration	1
phosphorylation	1
protein modification process	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	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

Protein interactions and networks

STRING

958 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ULK4	TRAK1	Q9UPV9	567
ULK4	CHRFAM7A	Q494W8	564
ULK4	CSPP1	Q1MSJ5	561
ULK4	HAUS8	Q9BT25	517
ULK4	PLEKHA7	Q6IQ23	505
ULK4	DRC11	Q86XH1	502
ULK4	STK36	Q9NRP7	483
ULK4	SQSTM1	Q13501	480
ULK4	CABCOCO1	Q8IVU9	477
ULK4	CDCA7L	Q96GN5	465
ULK4	CCDC149	Q6ZUS6	461
ULK4	JHY	Q6NUN7	459
ULK4	PEAK1	Q9H792	456
ULK4	CCP110	O43303	453
ULK4	PLCD3	Q8N3E9	445

IntAct

10 interactions, top by confidence:

A	B	Type	Score
ULK4	STK36	psi-mi:“MI:0915”(physical association)	0.630
STK36	ULK4	psi-mi:“MI:0915”(physical association)	0.630
ULK4	ANKRD40	psi-mi:“MI:0915”(physical association)	0.590
ULK4	RPL7A	psi-mi:“MI:0915”(physical association)	0.400
YWHAQ	ULK4	psi-mi:“MI:0915”(physical association)	0.370
ULK4	NDUFA4	psi-mi:“MI:0914”(association)	0.350
DISC1	ULK4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): ANKRD40 (Affinity Capture-MS), ULK4 (Affinity Capture-RNA), ULK4 (Protein-RNA), ULK4 (Proximity Label-MS), ANKRD40 (Affinity Capture-MS), NDUFA4 (Affinity Capture-MS), ZW10 (Affinity Capture-MS), UBL4A (Affinity Capture-MS), BAG6 (Affinity Capture-MS), SQSTM1 (Affinity Capture-MS), FKBP8 (Affinity Capture-MS), ATAD3B (Affinity Capture-MS), ERC1 (Affinity Capture-MS), RHOT2 (Affinity Capture-MS), MTR (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JEB6, A0JM56, B0DOB4, B0FXQ5, B1ANS9, B4F7L9, B4GQJ7, B5DHW4, B7FF06, B7FF07, B7FF08, B7FF09, B7FF12, C5IAW9, F1LW30, F1P4W9, O08747, O95185, P0DM40, Q008S8, Q18264, Q32NR9, Q3V0B4, Q402B2, Q4G0P3, Q5R4M2, Q5T0N1, Q5XI14, Q6AXU1, Q6DCF6, Q6NRS1, Q6P2C0, Q6P5D8, Q6UXZ4, Q6ZTR5, Q6ZU64, Q761X5, Q7T2Z5, Q80W93, Q86YR7

Diamond homologs: D3ZHP7, G4N7X0, O15021, O22042, O70293, P0C8M8, P11801, P28178, P32298, P34101, P38070, P43250, P97711, Q0V7M1, Q1LUA6, Q2QAV0, Q2QYY8, Q2RBR1, Q39030, Q3U3Q1, Q3V129, Q40541, Q43531, Q4V7Q6, Q54PK9, Q5R4M2, Q5RAJ5, Q5ZJH6, Q69ZM6, Q6AVM3, Q6FN53, Q6PHR2, Q6RET6, Q75DK7, Q869W6, Q8C1R0, Q8RWL2, Q91YA2, Q96C45, Q9NRP7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	184
Likely benign	33
Benign	19

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
545296	NC_000003.12:g.(?41609544)(41811095_?)del	Likely pathogenic
545297	NC_000003.12:g.(?41760954)(41858293_?)del	Likely pathogenic
545298	NC_000003.12:g.(?41803875)(41849829_?)del	Likely pathogenic

SpliceAI

8493 predictions. Top by Δscore:

Variant	Effect	Δscore
3:41249488:CCCA:C	donor_gain	1.0000
3:41249571:TGAT:T	acceptor_gain	1.0000
3:41249572:GATC:G	acceptor_loss	1.0000
3:41249574:TC:T	acceptor_loss	1.0000
3:41249575:C:CC	acceptor_gain	1.0000
3:41249584:C:CT	acceptor_gain	1.0000
3:41398071:GAACT:G	donor_loss	1.0000
3:41398072:AACT:A	donor_loss	1.0000
3:41398073:ACTCA:A	donor_loss	1.0000
3:41398074:CT:C	donor_loss	1.0000
3:41398075:T:TA	donor_loss	1.0000
3:41398076:C:CG	donor_loss	1.0000
3:41398077:A:AC	donor_gain	1.0000
3:41398077:ACC:A	donor_loss	1.0000
3:41398078:C:CC	donor_gain	1.0000
3:41398078:CCATT:C	donor_gain	1.0000
3:41398260:GGAAG:G	acceptor_gain	1.0000
3:41398261:GAAG:G	acceptor_gain	1.0000
3:41398262:AAGC:A	acceptor_loss	1.0000
3:41398263:AGCTG:A	acceptor_loss	1.0000
3:41398265:C:CC	acceptor_gain	1.0000
3:41398265:CT:C	acceptor_loss	1.0000
3:41455494:TACC:T	donor_loss	1.0000
3:41455495:A:AC	donor_gain	1.0000
3:41455495:A:T	donor_loss	1.0000
3:41455496:C:CC	donor_gain	1.0000
3:41455591:TGGGC:T	acceptor_gain	1.0000
3:41455594:GC:G	acceptor_gain	1.0000
3:41455594:GCC:G	acceptor_loss	1.0000
3:41455595:CC:C	acceptor_gain	1.0000

AlphaMissense

8333 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:41938146:A:G	W64R	0.998
3:41938146:A:T	W64R	0.998
3:41954695:C:G	R22P	0.997
3:41681633:G:C	S951R	0.995
3:41681633:G:T	S951R	0.995
3:41681635:T:G	S951R	0.995
3:41938122:A:G	W72R	0.995
3:41938122:A:T	W72R	0.995
3:41954668:G:T	A31D	0.995
3:41954669:C:G	A31P	0.995
3:41954698:C:T	G21E	0.994
3:41954699:C:A	G21W	0.994
3:41954699:C:G	G21R	0.994
3:41954699:C:T	G21R	0.994
3:41954700:T:A	K20N	0.993
3:41954700:T:G	K20N	0.993
3:41715533:G:T	R831S	0.991
3:41800185:A:G	W653R	0.991
3:41800185:A:T	W653R	0.991
3:41919753:A:G	W203R	0.991
3:41919753:A:T	W203R	0.991
3:41954705:A:C	Y19D	0.991
3:41663652:A:G	L1009P	0.990
3:41663655:G:T	A1008D	0.990
3:41938118:A:G	L73P	0.990
3:41938124:A:G	L71P	0.990
3:41954625:G:C	N45K	0.990
3:41954625:G:T	N45K	0.990
3:41938102:G:C	C78W	0.989
3:41938193:C:G	R48P	0.989

dbSNP variants (sampled 300 via entrez): RS1000000307 (3:41535361 C>T), RS1000002155 (3:41790951 C>T), RS1000005660 (3:41698037 T>C), RS1000010012 (3:41736951 T>A), RS1000015892 (3:41723183 T>G), RS1000018149 (3:41655270 C>A,G,T), RS1000020961 (3:41376176 G>C,T), RS1000023338 (3:41335415 A>G), RS1000025643 (3:41292207 A>G), RS1000027222 (3:41953396 C>G,T), RS1000030729 (3:41247413 C>G), RS1000037829 (3:41834798 C>T), RS1000039444 (3:41587158 T>C), RS1000042049 (3:41909827 A>G), RS1000051745 (3:41552267 C>A,G,T)

Disease associations

OMIM: gene MIM:617010 | disease phenotypes: MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
prostate cancer	Limited	Autosomal dominant

Mondo (2): schizophrenia (MONDO:0005090), prostate cancer (MONDO:0008315)

Orphanet (1): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

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

HPO	Term
HP:0100753	Schizophrenia

GWAS associations

56 associations (top):

Study	Trait	p-value
GCST000396_4	Diastolic blood pressure	3.000000e-09
GCST001235_13	Blood pressure	8.000000e-07
GCST001331_2	Multiple myeloma	2.000000e-08
GCST002143_3	Blood pressure	5.000000e-13
GCST002921_4	Multiple myeloma	5.000000e-07
GCST002922_4	Multiple myeloma and monoclonal gammopathy	3.000000e-08
GCST003264_1379	Post bronchodilator FEV1/FVC ratio	1.000000e-06
GCST003264_1392	Post bronchodilator FEV1/FVC ratio	1.000000e-07
GCST003264_196	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST003264_761	Post bronchodilator FEV1/FVC ratio	2.000000e-07
GCST003854_4	Gut microbiota (functional units)	1.000000e-08
GCST004028_2	Immunoglobulin light chain (AL) amyloidosis	3.000000e-06
GCST004099_3	B-cell malignancies (chronic lymphocytic leukemia, Hodgkin lymphoma or multiple myeloma) (pleiotropy)	8.000000e-12
GCST004386_1	Diastolic blood pressure	2.000000e-09
GCST004386_3	Diastolic blood pressure	5.000000e-12
GCST004388_2	Blood pressure traits (multi-trait analysis)	1.000000e-10
GCST004388_3	Blood pressure traits (multi-trait analysis)	1.000000e-11
GCST004756_5	Alcohol dependence	6.000000e-06
GCST004775_18	Pulse pressure	6.000000e-10
GCST004777_1	Diastolic blood pressure	7.000000e-11
GCST006020_18	Diastolic blood pressure	3.000000e-09
GCST006166_19	Diastolic blood pressure x alcohol consumption interaction (2df test)	6.000000e-26
GCST006166_53	Diastolic blood pressure x alcohol consumption interaction (2df test)	6.000000e-22
GCST006168_16	Pulse pressure x alcohol consumption interaction (2df test)	9.000000e-38
GCST006168_41	Pulse pressure x alcohol consumption interaction (2df test)	2.000000e-32
GCST006169_23	Diastolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	4.000000e-18
GCST006169_7	Diastolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	3.000000e-10
GCST006171_16	Pulse pressure x alcohol consumption (light vs heavy) interaction (2df test)	2.000000e-13
GCST006258_25	Diastolic blood pressure	4.000000e-12
GCST007094_133	Diastolic blood pressure	1.000000e-26

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0004713	FEV/FVC ratio
EFO:0007874	gut microbiome measurement
EFO:0006335	systolic blood pressure
EFO:0004329	alcohol drinking
EFO:0004509	hemoglobin measurement
EFO:0004530	triglyceride measurement
EFO:0008343	sex interaction measurement
EFO:0004348	hematocrit
EFO:0004305	erythrocyte count

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: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, affects methylation, decreases expression	3
sodium arsenite	decreases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	affects methylation, decreases methylation	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	increases expression	1
afimoxifene	decreases response to substance	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	affects methylation	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Irinotecan	decreases expression	1
Sunitinib	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Lead	increases expression	1
Manganese	decreases expression, increases abundance	1
Methapyrilene	affects methylation	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Progesterone	increases expression	1
Smoke	increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TW37	HAP1 ULK4 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

600 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