INTS3

Summary

INTS3 (integrator complex subunit 3, HGNC:26153) is a protein-coding gene on chromosome 1q21.3, encoding Integrator complex subunit 3 (Q68E01). Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

The protein encoded by this gene can form a complex with human single-strand DNA binding proteins 1 or 2 (hSSB1 and hSSB2) and other proteins to mediate genome stability and the DNA damage response. The encoded protein is also part of a multiprotein complex that interacts with the C-terminal domain of RNA polymerase II large subunit to help regulate processing of U1 and U2 small nuclear RNAs.

Source: NCBI Gene 65123 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 113 total
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_023015

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26153
Approved symbol	INTS3
Name	integrator complex subunit 3
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21919, INT3, SOSS-A
Ensembl gene	ENSG00000143624
Ensembl biotype	protein_coding
OMIM	611347
Entrez	65123

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 10 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay

ENST00000318967, ENST00000368669, ENST00000368670, ENST00000435409, ENST00000476843, ENST00000480659, ENST00000481797, ENST00000491790, ENST00000503133, ENST00000512605, ENST00000624515, ENST00000906150, ENST00000906151, ENST00000906152, ENST00000925886, ENST00000958124, ENST00000958125, ENST00000958126

RefSeq mRNA: 2 — MANE Select: NM_023015 NM_001324475, NM_023015

CCDS: CCDS1052

Canonical transcript exons

ENST00000318967 — 30 exons

Exon	Start	End
ENSE00003467355	153741285	153741368
ENSE00003470239	153761570	153761676
ENSE00003475506	153768893	153768961
ENSE00003477754	153760827	153760918
ENSE00003478191	153772925	153773081
ENSE00003488348	153754642	153754739
ENSE00003515720	153764118	153764221
ENSE00003523770	153771796	153771963
ENSE00003526087	153751095	153751239
ENSE00003529751	153770685	153770733
ENSE00003536875	153764944	153765063
ENSE00003539254	153740651	153740734
ENSE00003568700	153773193	153774808
ENSE00003572910	153728050	153728784
ENSE00003576218	153763832	153763886
ENSE00003582801	153772639	153772711
ENSE00003589677	153770198	153770311
ENSE00003589809	153760311	153760390
ENSE00003590456	153752279	153752408
ENSE00003598294	153767674	153767827
ENSE00003601858	153748689	153748755
ENSE00003630777	153764690	153764734
ENSE00003636203	153747279	153747363
ENSE00003638090	153759526	153759613
ENSE00003673584	153772340	153772440
ENSE00003680192	153757572	153757763
ENSE00003684766	153763233	153763362
ENSE00003685887	153746957	153747070
ENSE00003686708	153762728	153762847
ENSE00003693601	153769769	153769844

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.7284 / max 200.9506, expressed in 1818 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5435	32.7284	1818

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.20	gold quality
pituitary gland	UBERON:0000007	96.97	gold quality
right ovary	UBERON:0002118	96.66	gold quality
left ovary	UBERON:0002119	96.62	gold quality
adenohypophysis	UBERON:0002196	96.36	gold quality
endocervix	UBERON:0000458	96.29	gold quality
ovary	UBERON:0000992	96.21	gold quality
body of uterus	UBERON:0009853	95.91	gold quality
fallopian tube	UBERON:0003889	95.90	gold quality
metanephros cortex	UBERON:0010533	95.85	gold quality
right adrenal gland	UBERON:0001233	95.81	gold quality
right adrenal gland cortex	UBERON:0035827	95.68	gold quality
ascending aorta	UBERON:0001496	95.67	gold quality
myometrium	UBERON:0001296	95.65	gold quality
thoracic aorta	UBERON:0001515	95.60	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.53	gold quality
right testis	UBERON:0004534	95.46	gold quality
right lobe of thyroid gland	UBERON:0001119	95.43	gold quality
fundus of stomach	UBERON:0001160	95.40	gold quality
lower esophagus	UBERON:0013473	95.34	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.34	gold quality
tibial nerve	UBERON:0001323	95.32	gold quality
left testis	UBERON:0004533	95.32	gold quality
sural nerve	UBERON:0015488	95.27	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.23	gold quality
mucosa of stomach	UBERON:0001199	95.09	gold quality
descending thoracic aorta	UBERON:0002345	95.07	gold quality
right coronary artery	UBERON:0001625	95.06	gold quality
left uterine tube	UBERON:0001303	94.93	gold quality
apex of heart	UBERON:0002098	94.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.00
E-MTAB-7303	no	224.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting INTS3, 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-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-4784	99.15	67.41	1733

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• INTS3 is part of an ssDNA-binding heterotrimeric complex, SOSS which is involved in the maintenance of genome stability. (PMID:19683501)
• INT3 plays a key role in the DNA damage response (PMID:19759019)
• INTS3 controls the hSSB1-mediated DNA damage response. (PMID:19786574)
• In response to the DNA damage response, INTS3-hSSB1-INTS6 complex relocates to the DNA damage sites. (PMID:23986477)
• INTS3, but not C9ORF80, affects the nucleic acid-binding ability of hNABP1 and hNABP2, indicating that INTS3 might regulate hNABP1/hNABP2 biological function, while the role of C9ORF80 remains unknown. (PMID:29150435)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ints3	ENSDARG00000016811
mus_musculus	Ints3	ENSMUSG00000027933
rattus_norvegicus	Ints3	ENSRNOG00000015153
drosophila_melanogaster	IntS3	FBGN0262117
caenorhabditis_elegans	ints-3	WBGENE00022360

Protein

Protein identifiers

Integrator complex subunit 3 — Q68E01 (reviewed: Q68E01)

Alternative names: SOSS complex subunit A, Sensor of single-strand DNA complex subunit A

All UniProt accessions (4): Q68E01, A0A096LNW8, A0A096LPB9, H0Y8Z1

UniProt curated annotations — full annotation on UniProt →

Function. Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes. The integrator complex provides a quality checkpoint during transcription elongation by driving premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: the complex terminates transcription by (1) catalyzing dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, (2) degrading the exiting nascent RNA transcript via endonuclease activity and (3) promoting the release of Pol II from bound DNA. The integrator complex is also involved in terminating the synthesis of non-coding Pol II transcripts, such as enhancer RNAs (eRNAs), small nuclear RNAs (snRNAs), telomerase RNAs and long non-coding RNAs (lncRNAs). Within the integrator complex, INTS3 is involved in the post-termination step: INTS3 binds INTS7 in the open conformation of integrator complex and prevents the rebinding of Pol II to the integrator after termination cycle. Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the integrator complex. Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint. The SOSS complex associates with single-stranded DNA at DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. The SOSS complex is required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ATM-dependent signaling pathways. In the SOSS complex, it is required for the assembly of the complex and for stabilization of the complex at DNA damage sites.

Subunit / interactions. Component of the Integrator complex, composed of core subunits INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L, INTS12, INTS13, INTS14 and INTS15. The core complex associates with protein phosphatase 2A subunits PPP2CA and PPP2R1A, to form the Integrator-PP2A (INTAC) complex. Component of the SOSS complex, composed of SOSS-B (SOSS-B1/NABP2 or SOSS-B2/NABP1), SOSS-A/INTS3 and SOSS-C/INIP. SOSS complexes containing SOSS-B1/NABP2 are more abundant than complexes containing SOSS-B2/NABP1. Interacts with SOSS-B1/NABP2, SOSS-B2/NABP1 and SOSS-C/INIP; the interaction is direct. Interacts with NBN/NBS1.

Subcellular location. Nucleus. Cytoplasm.

Similarity. Belongs to the Integrator subunit 3 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q68E01-1	1	yes
Q68E01-2	2
Q68E01-3	3
Q68E01-4	4

RefSeq proteins (2): NP_001311404, NP_075391* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019333	INTS3_N	Domain
IPR045334	INTS3	Family
IPR056518	HEAT_Ints3_C	Domain

Pfam: PF10189, PF24566

UniProt features (99 total): helix 60, sequence conflict 10, turn 10, strand 8, splice variant 4, modified residue 4, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4OWT	X-RAY DIFFRACTION	2
4OWW	X-RAY DIFFRACTION	2.3
4OWX	X-RAY DIFFRACTION	2.3
7BV7	X-RAY DIFFRACTION	2.4
8HPP	X-RAY DIFFRACTION	3
6WLG	X-RAY DIFFRACTION	3.11
8RBZ	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q68E01-F1	84.01	0.69

Functional residue map

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

Post-translational modifications (4): 1, 502, 537, 995

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 172 (showing top): GOBP_RESPONSE_TO_IONIZING_RADIATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MITOTIC_G2_M_TRANSITION_CHECKPOINT, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_RNA_SURVEILLANCE, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GATA3_01, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, DACOSTA_UV_RESPONSE_VIA_ERCC3_TTD_DN, KMCATNNWGGA_UNKNOWN, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_DNA_DAMAGE_RESPONSE

GO Biological Process (8): double-strand break repair via homologous recombination (GO:0000724), DNA repair (GO:0006281), DNA damage response (GO:0006974), response to ionizing radiation (GO:0010212), snRNA processing (GO:0016180), regulation of transcription elongation by RNA polymerase II (GO:0034243), mitotic G2/M transition checkpoint (GO:0044818), RNA polymerase II transcription initiation surveillance (GO:0160240)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), integrator complex (GO:0032039), site of double-strand break (GO:0035861), SOSS complex (GO:0070876), INTAC complex (GO:0160232)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear protein-containing complex	3
cellular anatomical structure	2
recombinational repair	1
double-strand break repair	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
response to radiation	1
RNA processing	1
snRNA metabolic process	1
transcription elongation by RNA polymerase II	1
regulation of DNA-templated transcription elongation	1
mitotic cell cycle checkpoint signaling	1
negative regulation of G2/M transition of mitotic cell cycle	1
transcription initiation at RNA polymerase II promoter	1
nuclear RNA surveillance	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
site of DNA damage	1
integrator complex	1

Protein interactions and networks

STRING

714 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INTS3	INIP	Q9NRY2	999
INTS3	INTS6	Q9UL03	934
INTS3	NABP2	Q9BQ15	894
INTS3	INTS4	Q96HW7	890
INTS3	INTS1	Q8N201	883
INTS3	INTS11	Q5TA45	872
INTS3	INTS9	Q9NV88	861
INTS3	NABP1	Q96AH0	843
INTS3	SSBP1	Q04837	837
INTS3	SSBP2	P81877	825
INTS3	RPAP2	Q8IXW5	813
INTS3	RPAP3	Q9H6T3	810
INTS3	RPAP1	Q9BWH6	810
INTS3	INTS5	Q6P9B9	795
INTS3	GPN1	Q9HCN4	776

IntAct

124 interactions, top by confidence:

A	B	Type	Score
LSM3	LSM1	psi-mi:“MI:0914”(association)	0.950
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2R1A	STRN	psi-mi:“MI:2364”(proximity)	0.880
NABP2	INTS3	psi-mi:“MI:0914”(association)	0.810
INTS3	NABP2	psi-mi:“MI:0915”(physical association)	0.810
INTS3	NABP2	psi-mi:“MI:0407”(direct interaction)	0.810
NABP2	INTS3	psi-mi:“MI:0915”(physical association)	0.810
BLM	RPA2	psi-mi:“MI:0914”(association)	0.640
FAM174A	GAK	psi-mi:“MI:0914”(association)	0.640
INIP	INTS3	psi-mi:“MI:0914”(association)	0.630
INTS3	INIP	psi-mi:“MI:0915”(physical association)	0.630
INTS3	INIP	psi-mi:“MI:0407”(direct interaction)	0.630
INTS3	NABP1	psi-mi:“MI:0914”(association)	0.620
NABP1	INTS3	psi-mi:“MI:0914”(association)	0.620
INTS3	NABP1	psi-mi:“MI:0915”(physical association)	0.620
INTS3	NABP1	psi-mi:“MI:0407”(direct interaction)	0.620
ZBTB14	INTS3	psi-mi:“MI:0915”(physical association)	0.560
INTS3	ZBTB14	psi-mi:“MI:0915”(physical association)	0.560
NABP2	BLM	psi-mi:“MI:0914”(association)	0.540
POLR2I	SUPT5H	psi-mi:“MI:0914”(association)	0.530
POLR2J	SUPT5H	psi-mi:“MI:0914”(association)	0.530
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530

BioGRID (234): INTS3 (Two-hybrid), INTS3 (Affinity Capture-Western), INTS3 (Affinity Capture-MS), INTS3 (Affinity Capture-MS), INTS3 (Affinity Capture-MS), INTS3 (Affinity Capture-MS), INTS3 (Affinity Capture-MS), INTS3 (Affinity Capture-MS), INTS3 (Affinity Capture-MS), INTS3 (Affinity Capture-MS), INIP (Co-fractionation), INTS1 (Co-fractionation), INTS3 (Co-fractionation), INTS3 (Affinity Capture-MS), INTS3 (Affinity Capture-MS)

ESM2 similar proteins: A0A4X1TB62, A4VCH4, G3V7Q0, O14795, O35841, O43237, O70585, P23116, P48553, Q0P5J8, Q14152, Q15542, Q1JU68, Q3TLI0, Q3UHE1, Q4R5P6, Q5R660, Q5R7S4, Q5R7U7, Q5RE09, Q5RE70, Q5VSL9, Q5XI83, Q658Y4, Q68E01, Q6IQ26, Q6PAL8, Q6PDL0, Q6TEP1, Q6WKZ8, Q7SYD9, Q7TPD0, Q8BIK4, Q8BWQ6, Q8C079, Q8C092, Q8C9H6, Q8CBY8, Q8IWV8, Q8K400

Diamond homologs: B3N449, B4IMI7, B4ISV0, B4JPR2, B4KJ11, B4LQY8, B4NP05, Q1LXC9, Q55EZ4, Q5RE70, Q68E01, Q7PLS8, Q7PRB8, Q7TPD0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
INTS3	“form complex”	“Integrator complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 143 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
FGFR2 mutant receptor activation	8	62.8×	1e-11
Signaling by FGFR2 IIIa TM	8	49.6×	8e-11
Abortive elongation of HIV-1 transcript in the absence of Tat	9	46.1×	1e-11
Pausing and recovery of Tat-mediated HIV elongation	10	38.0×	8e-12
Tat-mediated HIV elongation arrest and recovery	10	38.0×	8e-12
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	9	37.8×	6e-11
Signaling by FGFR2	9	37.8×	6e-11
RNA Pol II CTD phosphorylation and interaction with CE	9	37.8×	6e-11

GO biological processes:

GO term	Partners	Fold	FDR
RNA polymerase II transcription initiation surveillance	6	41.2×	4e-06
regulation of transcription elongation by RNA polymerase II	5	31.1×	1e-04
double-strand break repair via homologous recombination	8	9.7×	4e-04
transcription by RNA polymerase II	11	6.0×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4246 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153740639:A:AG	acceptor_gain	1.0000
1:153740640:C:G	acceptor_gain	1.0000
1:153740647:CCA:C	acceptor_loss	1.0000
1:153740649:A:AG	acceptor_gain	1.0000
1:153740650:G:GG	acceptor_gain	1.0000
1:153740650:G:GT	acceptor_loss	1.0000
1:153740650:GA:G	acceptor_gain	1.0000
1:153740650:GAGA:G	acceptor_gain	1.0000
1:153740650:GAGAT:G	acceptor_gain	1.0000
1:153740731:GTAT:G	donor_gain	1.0000
1:153740734:TGTAA:T	donor_loss	1.0000
1:153740735:G:GG	donor_gain	1.0000
1:153740736:T:G	donor_loss	1.0000
1:153741276:A:AG	acceptor_gain	1.0000
1:153741277:C:G	acceptor_gain	1.0000
1:153741278:A:AG	acceptor_gain	1.0000
1:153741281:CCA:C	acceptor_loss	1.0000
1:153741283:A:AG	acceptor_gain	1.0000
1:153741283:AG:A	acceptor_gain	1.0000
1:153741284:G:GC	acceptor_loss	1.0000
1:153741284:G:GG	acceptor_gain	1.0000
1:153741284:GG:G	acceptor_gain	1.0000
1:153741284:GGT:G	acceptor_gain	1.0000
1:153741284:GGTGT:G	acceptor_gain	1.0000
1:153741365:GAAG:G	donor_gain	1.0000
1:153741366:AAGGT:A	donor_loss	1.0000
1:153741368:GGT:G	donor_loss	1.0000
1:153741369:G:C	donor_loss	1.0000
1:153741369:G:GG	donor_gain	1.0000
1:153741370:T:G	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008695 (1:153732049 A>C), RS1000025650 (1:153746561 C>T), RS1000027583 (1:153765175 G>T), RS1000052095 (1:153751760 C>A,G), RS1000160439 (1:153731708 C>A,G,T), RS1000193671 (1:153733093 G>A), RS1000246417 (1:153739653 G>A), RS1000318910 (1:153726401 T>C), RS1000348217 (1:153753506 G>A), RS1000412485 (1:153733451 T>C), RS1000414649 (1:153772609 C>T), RS1000481501 (1:153745371 G>A), RS1000527771 (1:153734688 G>A), RS1000548707 (1:153736763 T>TC), RS1000550832 (1:153774982 G>A,C)

Disease associations

OMIM: gene MIM:611347 | disease phenotypes:

GenCC curated gene-disease

Mondo (3): prostate cancer (MONDO:0008315), myoepithelial tumor (MONDO:0002380), breast ductal adenocarcinoma (MONDO:0005590)

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

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST010137_3	Cooked vegetable consumption	3.000000e-09
GCST010696_22	Cortical thickness (min-P)	4.000000e-10
GCST010697_50	Cortical surface area (min-P)	1.000000e-12
GCST010698_81	Subcortical volume (min-P)	1.000000e-23
GCST010699_7	Brain morphology (min-P)	1.000000e-10
GCST010700_11	Cortical thickness (MOSTest)	4.000000e-13
GCST010701_73	Cortical surface area (MOSTest)	4.000000e-09
GCST010702_45	Subcortical volume (MOSTest)	4.000000e-10
GCST010703_276	Brain morphology (MOSTest)	2.000000e-15
GCST012216_1	Vegetable consumption	1.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D009208	Myoepithelioma	C04.557.435.585
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)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
cobaltous chloride	decreases expression	2
Arsenic	increases abundance, increases expression, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Aflatoxin B1	increases methylation	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
chromium hexavalent ion	increases abundance, decreases expression	1
CPG-oligonucleotide	decreases expression	1
pyrachlostrobin	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, affects expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Dronabinol	increases expression	1
Thiram	decreases expression	1

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