OLA1

Summary

OLA1 (Obg like ATPase 1, HGNC:28833) is a protein-coding gene on chromosome 2q31.1, encoding Obg-like ATPase 1 (Q9NTK5). Hydrolyzes ATP, and can also hydrolyze GTP with lower efficiency.

This gene encodes a member of the GTPase protein family. The encoded protein interacts with breast cancer-associated gene 1 (BRCA1) and BRCA1-associated RING domain protein (BARD1), and is involved in centrosome regulation. Overexpression of this gene has been observed in multiple types of cancer and may be associated with poor survival. Pseudogenes of this gene have been defined on chromosomes 17 and 22.

Source: NCBI Gene 29789 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 61 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_013341

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28833
Approved symbol	OLA1
Name	Obg like ATPase 1
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	PTD004
Ensembl gene	ENSG00000138430
Ensembl biotype	protein_coding
OMIM	611175
Entrez	29789

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000284719, ENST00000344357, ENST00000392560, ENST00000409546, ENST00000427472, ENST00000428402, ENST00000429575, ENST00000462000, ENST00000497760, ENST00000882906, ENST00000882907, ENST00000882908, ENST00000939498, ENST00000939499, ENST00000961742, ENST00000961743

RefSeq mRNA: 3 — MANE Select: NM_013341 NM_001011708, NM_001328688, NM_013341

CCDS: CCDS2255, CCDS42779

Canonical transcript exons

ENST00000284719 — 11 exons

Exon	Start	End
ENSE00001284553	174072447	174075527
ENSE00001411681	174248452	174248532
ENSE00003506997	174229308	174229451
ENSE00003546489	174223033	174223160
ENSE00003546597	174078968	174079090
ENSE00003602074	174081924	174082064
ENSE00003615649	174141825	174142000
ENSE00003619452	174123180	174123277
ENSE00003667928	174081152	174081248
ENSE00003680255	174123595	174123675
ENSE00003755994	174246715	174246815

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 80.4734 / max 1307.4279, expressed in 1824 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31856	48.8218	1820
31855	17.4359	1778
31857	14.2157	1792

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	99.24	gold quality
endothelial cell	CL:0000115	98.72	gold quality
ganglionic eminence	UBERON:0004023	98.65	gold quality
cortical plate	UBERON:0005343	98.65	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.64	gold quality
tongue squamous epithelium	UBERON:0006919	98.31	gold quality
pons	UBERON:0000988	98.20	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.02	gold quality
gingival epithelium	UBERON:0001949	97.99	gold quality
gingiva	UBERON:0001828	97.98	gold quality
embryo	UBERON:0000922	97.94	gold quality
mammary duct	UBERON:0001765	97.88	gold quality
parotid gland	UBERON:0001831	97.81	gold quality
entorhinal cortex	UBERON:0002728	97.77	gold quality
squamous epithelium	UBERON:0006914	97.77	gold quality
ventricular zone	UBERON:0003053	97.68	gold quality
prefrontal cortex	UBERON:0000451	97.67	gold quality
mammalian vulva	UBERON:0000997	97.66	gold quality
biceps brachii	UBERON:0001507	97.65	gold quality
hair follicle	UBERON:0002073	97.62	gold quality
epithelium of mammary gland	UBERON:0003244	97.61	gold quality
parietal lobe	UBERON:0001872	97.54	gold quality
substantia nigra pars compacta	UBERON:0001965	97.49	gold quality
oral cavity	UBERON:0000167	97.48	gold quality
orbitofrontal cortex	UBERON:0004167	97.46	gold quality
tongue	UBERON:0001723	97.45	gold quality
superior vestibular nucleus	UBERON:0007227	97.45	gold quality
postcentral gyrus	UBERON:0002581	97.44	gold quality
superior frontal gyrus	UBERON:0002661	97.42	gold quality
skin of hip	UBERON:0001554	97.41	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8207	yes	309.08
E-MTAB-10042	yes	13.42
E-ANND-3	yes	9.73
E-MTAB-6379	no	697.26
E-HCAD-5	no	14.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

110 targeting OLA1, 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-3134	100.00	66.43	777
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317

Literature-anchored findings (GeneRIF, showing 20)

• Results indicate that Gbp45/OLA1 plays important roles in cell proliferation and death related to mitochondrial function. (PMID:18536999)
• OLA1 suppresses the antioxidant response through nontranscriptional mechanisms. (PMID:19706404)
• knockdown of OLA1 inhibits breast cancer cell migration and invasion through a mechanism that involves the modulation of intracellular ROS levels (PMID:19882753)
• DOC45 is a novel ATPase that is linked to cellular stress response and tumorigenesis, and may also serve as a valuable tumor marker. (PMID:20053727)
• Downregulation of OLA1 in mammalian cells by either RNAi or targeted gene disruption results in reduced steady-state levels of HSP70, impaired HSP70 induction by heat, and functionally, increased cellular sensitivity to heat shock. (PMID:23412384)
• OLA1 plays an important role in centrosome regulation together with BRCA1. (PMID:24289923)
• OLA1 plays an important negative role in cell adhesion and spreading, in part through the regulation of FAK expression and cofilin phosphorylation, and manipulation of OLA1 may lead to significant changes in cell adhesion and the associated phenotypes. (PMID:24486488)
• Our work suggests that OLA1 is a novel translational GTPase and plays a suppressive role in translation and cell survival, as well as cancer growth and progression. (PMID:26283179)
• OLA1 contributes to epithelial-mesenchymal transition by modulating the GSK3beta/Snail/E-cadherin signaling, and its overexpression is associated with clinical progression and poor survival in lung cancer patients. (PMID:26863455)
• No germline mutations were found in the OLA1 gene in in patients with BRCA1/2 mutation-negative suspected hereditary breast and ovarian cancer. (PMID:27271530)
• these data reveal that the OLA1-BARD1 interaction is important for the regulation of centrosome number. Regulation of centrosome number by BRCA1/BARD1 together with OLA1 is important for the genome integrity to prevent tumor development. (PMID:29858377)
• It explores the various functional roles of hOLA1 in mammalian cells during stress response and cancer progression, and of YchF in bacterial cells. (PMID:30742486)
• We conclude that decreased OLA1 expression accounts for SOD2 downregulation in persistent pulmonary hypertension of the newborn. (PMID:31476900)
• Obg-like ATPase 1 (OLA1) overexpression predicts poor prognosis and promotes tumor progression by regulating P21/CDK2 in hepatocellular carcinoma. (PMID:32045367)
• HIV p17 enhances T cell proliferation by suppressing autophagy through the p17-OLA1-GSK3beta axis under nutrient starvation. (PMID:32790080)
• Obg-like ATPase 1 inhibited oral carcinoma cell metastasis through TGFbeta/SMAD2 axis in vitro. (PMID:32928102)
• N6-methyladenosine reader IMP2 stabilizes the ZFAS1/OLA1 axis and activates the Warburg effect: implication in colorectal cancer. (PMID:34743750)
• OLA1 promotes colorectal cancer tumorigenesis by activation of HIF1alpha/CA9 axis. (PMID:35440019)
• OLA1 Phosphorylation Governs the Mitochondrial Bioenergetic Function of Pulmonary Vascular Cells. (PMID:36481055)
• Clinicopathological significance of Obg-like ATPase 1 and its association with Snail in gastric cancer. (PMID:37306352)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ola1	ENSMUSG00000027108
rattus_norvegicus	Ola1	ENSRNOG00000019047
drosophila_melanogaster	CG1354	FBGN0030151
caenorhabditis_elegans	ola-1	WBGENE00012344

Protein

Protein identifiers

Obg-like ATPase 1 — Q9NTK5 (reviewed: Q9NTK5)

Alternative names: DNA damage-regulated overexpressed in cancer 45, GTP-binding protein 9

All UniProt accessions (4): Q9NTK5, C9JCJ9, C9JTK6, J3KQ32

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes ATP, and can also hydrolyze GTP with lower efficiency. Has lower affinity for GTP.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Tissue specificity. Expressed in all tissues tested but its expression is more abundant in testis, liver, lung, and brain. Overexpressed in several malignancies, including cancers of the colon, rectum, ovary, lung, stomach, and uterus.

Induction. Strongly down-regulated by DNA damage-inducing agents.

Similarity. Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family. YchF/OLA1 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NTK5-1	1	yes
Q9NTK5-2	2
Q9NTK5-3	3

RefSeq proteins (3): NP_001011708, NP_001315617, NP_037473* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004095	TGS	Domain
IPR004396	ATPase_YchF/OLA1	Family
IPR006073	GTP-bd	Domain
IPR012675	Beta-grasp_dom_sf	Homologous_superfamily
IPR012676	TGS-like	Homologous_superfamily
IPR013029	YchF_C	Domain
IPR023192	TGS-like_dom_sf	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR031167	G_OBG	Domain
IPR041706	YchF_N	Domain

Pfam: PF01926, PF06071

UniProt features (50 total): helix 17, strand 13, sequence conflict 4, binding site 4, splice variant 3, mutagenesis site 3, domain 2, chain 1, sequence variant 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2OHF	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NTK5-F1	88.82	0.77

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 32–37; 36; 56; 231

Post-translational modifications (1): 294

Mutagenesis-validated functional residues (3):

Position	Phenotype
127	loss of atp-binding.
230	loss of atp-binding.
231–233	retention of atp-binding specificity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation

MSigDB gene sets: 184 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GGTGTGT_MIR329, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, PATIL_LIVER_CANCER, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, LIAO_METASTASIS, GGCAGTG_MIR3243P

GO Biological Process (1): ATP metabolic process (GO:0046034)

GO Molecular Function (10): ATP binding (GO:0005524), GTP binding (GO:0005525), ATP hydrolysis activity (GO:0016887), ribosomal large subunit binding (GO:0043023), cadherin binding (GO:0045296), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787), ribosome binding (GO:0043022)

GO Cellular Component (9): extracellular region (GO:0005576), nucleolus (GO:0005730), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), membrane (GO:0016020), platelet alpha granule lumen (GO:0031093), extracellular exosome (GO:0070062), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
purine ribonucleoside triphosphate binding	2
purine ribonucleotide metabolic process	1
purine ribonucleoside triphosphate metabolic process	1
adenyl ribonucleotide binding	1
guanyl ribonucleotide binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
ribosome binding	1
cell adhesion molecule binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
ribonucleoprotein complex binding	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
cytoplasm	1
platelet alpha granule	1
secretory granule lumen	1
extracellular vesicle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3238 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OLA1	BARD1	Q99728	914
OLA1	BRCA1	P38398	735
OLA1	HSPA4	P34932	576
OLA1	TARS3	A2RTX5	510
OLA1	TARS1	P26639	506
OLA1	EIF5AL1	Q6IS14	506
OLA1	TARS2	Q9BW92	491
OLA1	EIF5A	P10159	489
OLA1	GTPBP8	Q8N3Z3	482
OLA1	GTPBP6	O43824	447
OLA1	TUFM	P49411	433
OLA1	GTPBP3	Q969Y2	431
OLA1	LENG8	Q96PV6	431
OLA1	ATXN7L3B	Q96GX2	411
OLA1	ADIPOR1	Q96A54	409

IntAct

77 interactions, top by confidence:

A	B	Type	Score
TP53	CUL7	psi-mi:“MI:0914”(association)	0.930
gag	SEPSECS	psi-mi:“MI:0914”(association)	0.560
gag	EEF1E1	psi-mi:“MI:0914”(association)	0.560
gag	OLA1	psi-mi:“MI:0915”(physical association)	0.560
PRPF31	SSB	psi-mi:“MI:0914”(association)	0.510
gag	SDCBP	psi-mi:“MI:0914”(association)	0.460
PA	OLA1	psi-mi:“MI:0915”(physical association)	0.370
OLA1		psi-mi:“MI:0915”(physical association)	0.370
HSCB	OLA1	psi-mi:“MI:0915”(physical association)	0.370
OLA1	PCNA	psi-mi:“MI:0915”(physical association)	0.370
JUN		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
HMGA1	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
	IPO5	psi-mi:“MI:0914”(association)	0.350
SHOC2	PNP	psi-mi:“MI:0914”(association)	0.350
	TIMM8A	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
rep	NVL	psi-mi:“MI:0914”(association)	0.350
TIFAB	DDX3X	psi-mi:“MI:0914”(association)	0.350
SOX2	SEC16A	psi-mi:“MI:0914”(association)	0.350
PRKCZ	PGRMC1	psi-mi:“MI:0914”(association)	0.350
NEK7	SUPT5H	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
SAR1B	UBA6	psi-mi:“MI:0914”(association)	0.350

BioGRID (192): OLA1 (Affinity Capture-MS), OLA1 (Affinity Capture-MS), BCAP31 (Co-fractionation), OLA1 (Co-fractionation), OLA1 (Co-fractionation), PHB (Co-fractionation), TUBB (Co-fractionation), OLA1 (Affinity Capture-MS), OLA1 (Proximity Label-MS), OLA1 (Affinity Capture-MS), OLA1 (Affinity Capture-MS), OLA1 (Proximity Label-MS), PRPF31 (Affinity Capture-MS), OLA1 (Affinity Capture-MS), OLA1 (Affinity Capture-MS)

ESM2 similar proteins: A0JPJ7, A3GHT9, A5DK38, A6RLH0, A6UV44, A7A0X4, A7TFN8, A8WTI8, B0DSK4, B3LT39, B5VN01, B6K286, B8BBN7, O13998, O14078, P09604, P0ABU2, P0ABU3, P0ABU4, P25039, P38219, P38746, P43690, P44681, P47270, P75088, P91917, Q2HJ33, Q54HP3, Q5R821, Q5ZM25, Q66JG0, Q6BPD3, Q6CRY5, Q6FUQ6, Q6LXI2, Q6Z1J6, Q75CZ5, Q7SH14, Q7VMI2

Diamond homologs: A0JPJ7, A1KAD0, A2C050, A3DBS5, A4SVA3, A5CDM6, A5IKX2, A5UZ80, A5VD74, A6LJZ0, A6TQJ6, A6UDV6, A7HJZ8, A7NRU6, A8F063, A8F2Y3, A8F478, A8GQ55, A8GTZ9, A8GUG0, A8MHK8, A9BK05, A9BP68, A9IMA6, A9KMF5, A9M061, B0BVJ1, B0K414, B0KAB8, B0S3Z4, B1LA53, B1X0M2, B1XT35, B2A6B7, B2JHD7, B3CQ33, B7IGK8, B7JVH9, B7KIC1, B8BBN7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 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
ESR-mediated signaling	6	10.8×	6e-03
mRNA Splicing - Major Pathway	11	8.5×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	5	17.9×	3e-03
cellular response to xenobiotic stimulus	5	14.9×	4e-03
mRNA splicing, via spliceosome	9	10.2×	2e-04
regulation of gene expression	7	7.2×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2580 predictions. Top by Δscore:

Variant	Effect	Δscore
2:174075523:GCAGC:G	acceptor_gain	1.0000
2:174075524:CAGC:C	acceptor_gain	1.0000
2:174075524:CAGCC:C	acceptor_gain	1.0000
2:174075525:AGC:A	acceptor_gain	1.0000
2:174075526:GC:G	acceptor_gain	1.0000
2:174075526:GCCTG:G	acceptor_loss	1.0000
2:174075527:CC:C	acceptor_gain	1.0000
2:174075527:CCTG:C	acceptor_loss	1.0000
2:174075528:C:CC	acceptor_gain	1.0000
2:174075535:C:CT	acceptor_gain	1.0000
2:174075536:A:T	acceptor_gain	1.0000
2:174078962:CTTTA:C	donor_loss	1.0000
2:174078963:TTTA:T	donor_loss	1.0000
2:174078964:TTA:T	donor_loss	1.0000
2:174078965:TA:T	donor_loss	1.0000
2:174078966:A:C	donor_loss	1.0000
2:174078967:CCTTG:C	donor_loss	1.0000
2:174079087:CTTT:C	acceptor_gain	1.0000
2:174079091:C:CC	acceptor_gain	1.0000
2:174079092:T:C	acceptor_gain	1.0000
2:174079093:T:C	acceptor_gain	1.0000
2:174079093:T:TC	acceptor_gain	1.0000
2:174081249:C:CC	acceptor_gain	1.0000
2:174081921:AAC:A	donor_gain	1.0000
2:174081922:A:C	donor_gain	1.0000
2:174081942:T:TA	donor_gain	1.0000
2:174082060:TCAAC:T	acceptor_gain	1.0000
2:174082061:CAAC:C	acceptor_gain	1.0000
2:174082061:CAACC:C	acceptor_gain	1.0000
2:174082063:ACC:A	acceptor_loss	1.0000

AlphaMissense

2652 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:174075456:A:C	F387L	1.000
2:174075456:A:T	F387L	1.000
2:174075458:A:G	F387L	1.000
2:174075487:A:T	V377D	1.000
2:174079031:G:C	F342L	1.000
2:174079031:G:T	F342L	1.000
2:174079033:A:G	F342L	1.000
2:174079052:G:C	H335Q	1.000
2:174079052:G:T	H335Q	1.000
2:174079054:G:C	H335D	1.000
2:174079065:G:T	A331E	1.000
2:174081163:A:G	W319R	1.000
2:174081163:A:T	W319R	1.000
2:174223076:A:C	F110L	1.000
2:174223076:A:T	F110L	1.000
2:174223078:A:G	F110L	1.000
2:174223123:C:G	G95R	1.000
2:174223125:G:T	A94D	1.000
2:174229391:G:C	F54L	1.000
2:174229391:G:T	F54L	1.000
2:174229393:A:G	F54L	1.000
2:174229449:T:A	K35I	1.000
2:174075461:T:C	K386E	0.999
2:174075498:T:A	R373S	0.999
2:174075498:T:G	R373S	0.999
2:174075502:C:T	G372D	0.999
2:174075503:C:A	G372C	0.999
2:174075503:C:G	G372R	0.999
2:174078968:C:A	K363N	0.999
2:174078968:C:G	K363N	0.999

dbSNP variants (sampled 300 via entrez): RS1000047476 (2:174188152 T>C), RS1000057129 (2:174203794 G>A), RS1000077388 (2:174194765 G>A,C), RS1000110448 (2:174142333 TCTAAA>T), RS1000125354 (2:174240897 T>C,G), RS1000149060 (2:174170157 C>T), RS1000182080 (2:174169760 G>A), RS1000208749 (2:174215880 A>C), RS1000263597 (2:174208515 T>C), RS1000338276 (2:174202410 C>T), RS1000349873 (2:174149155 C>A,G), RS1000351632 (2:174195691 T>C), RS1000352086 (2:174073641 C>A,G,T), RS1000354570 (2:174241493 G>A), RS1000361059 (2:174107315 C>A,T)

Disease associations

OMIM: gene MIM:611175 | 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

13 associations (top):

Study	Trait	p-value
GCST005173_20	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	2.000000e-06
GCST005174_4	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	8.000000e-06
GCST005748_11	Digit length ratio (right hand)	9.000000e-12
GCST005749_16	Digit length ratio (left hand)	1.000000e-15
GCST005749_23	Digit length ratio (left hand)	2.000000e-14
GCST005750_3	Digit length ratio	2.000000e-15
GCST005830_39	Hand grip strength	3.000000e-08
GCST006268_240	Reaction time	4.000000e-08
GCST006268_502	Reaction time	2.000000e-10
GCST006268_503	Reaction time	5.000000e-09
GCST006585_346	Blood protein levels	9.000000e-15
GCST006628_47	Systolic blood pressure	6.000000e-10
GCST007327_29	Smoking status (ever vs never smokers)	3.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0004841	digit length ratio
EFO:0006941	grip strength measurement
EFO:0008393	reaction time measurement
EFO:0006335	systolic blood pressure
EFO:0004318	smoking behavior

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): CHEMBL4105704 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,789 (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
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL1908397	KW-2449	1	622

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	Kd	3	nM	KW-2449
8.15	Kd	7	nM	CRENOLANIB

PubChem BioAssay actives

2 with measured affinity, of 189 total; 2 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
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	1425096: 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	0.0030	uM
1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine	1425096: 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	0.0070	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	4
trichostatin A	affects cotreatment, decreases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
bisphenol S	decreases methylation, increases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases metabolic processing	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	decreases expression, increases expression	1
methylmercuric chloride	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
butyraldehyde	increases expression	1
quinoline	decreases expression	1
pentanal	increases expression	1
calfactant	affects cotreatment, increases expression	1
K 7174	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
LDN 193189	increases expression, affects cotreatment	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
bisphenol AF	increases expression	1
Decitabine	decreases expression, affects reaction	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Benztropine	increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991809	Binding	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 ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8RT	Ubigene HCT 116 OLA1 KO	Cancer cell line	Male
CVCL_E0JH	Ubigene HeLa OLA1 KO	Cancer cell line	Female
CVCL_E0X6	Ubigene L-02 OLA1 KO	Cancer cell line	Female
CVCL_E0XH	Ubigene LoVo OLA1 KO	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