IBTK

Summary

IBTK (inhibitor of Bruton tyrosine kinase, HGNC:17853) is a protein-coding gene on chromosome 6q14.1, encoding Inhibitor of Bruton tyrosine kinase (Q9P2D0). Acts as an inhibitor of BTK tyrosine kinase activity, thereby playing a role in B-cell development.

Bruton tyrosine kinase (BTK) is a protein tyrosine kinase that is expressed in B cells, macrophages, and neutrophils. The protein encoded by this gene binds to BTK and downregulates BTK’s kinase activity. In addition, the encoded protein disrupts BTK-mediated calcium mobilization and negatively regulates the activation of nuclear factor-kappa-B-driven transcription. This gene has a pseudogene on chromosome 18. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 25998 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 161 total
• MANE Select transcript: NM_015525

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17853
Approved symbol	IBTK
Name	inhibitor of Bruton tyrosine kinase
Location	6q14.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP564B116, BTBD26
Ensembl gene	ENSG00000005700
Ensembl biotype	protein_coding
OMIM	606457
Entrez	25998

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 19 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000306270, ENST00000369751, ENST00000445419, ENST00000471036, ENST00000503400, ENST00000503631, ENST00000505222, ENST00000508381, ENST00000510291, ENST00000610980, ENST00000870342, ENST00000870343, ENST00000870344, ENST00000870345, ENST00000928502, ENST00000928503, ENST00000928504, ENST00000928505, ENST00000928506, ENST00000945770, ENST00000945771, ENST00000945772, ENST00000945773, ENST00000945774, ENST00000945775

RefSeq mRNA: 2 — MANE Select: NM_015525 NM_001300906, NM_015525

CCDS: CCDS34490, CCDS75486

Canonical transcript exons

ENST00000306270 — 29 exons

Exon	Start	End
ENSE00002051719	82169987	82171556
ENSE00003466153	82216076	82216250
ENSE00003469029	82214227	82214829
ENSE00003476655	82227192	82227302
ENSE00003484504	82234159	82234255
ENSE00003487273	82181879	82182028
ENSE00003498506	82223440	82223620
ENSE00003504751	82204857	82204958
ENSE00003511535	82240166	82240843
ENSE00003532859	82210814	82210910
ENSE00003537574	82220590	82220713
ENSE00003544759	82173367	82173438
ENSE00003556033	82191073	82191216
ENSE00003569663	82196298	82196446
ENSE00003584563	82201422	82201482
ENSE00003588719	82202528	82202645
ENSE00003592981	82224068	82224185
ENSE00003603101	82212707	82212793
ENSE00003612408	82191787	82191879
ENSE00003627540	82194479	82194642
ENSE00003634505	82200587	82200708
ENSE00003635626	82172380	82172512
ENSE00003638237	82211490	82211572
ENSE00003653149	82225477	82225647
ENSE00003659999	82231718	82231842
ENSE00003661204	82200141	82200253
ENSE00003666370	82217960	82218137
ENSE00003693344	82211367	82211404
ENSE00003851011	82247562	82247744

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 96.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.5128 / max 348.8699, expressed in 1813 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74540	41.5128	1813

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	96.28	gold quality
islet of Langerhans	UBERON:0000006	93.60	gold quality
calcaneal tendon	UBERON:0003701	93.56	gold quality
corpus callosum	UBERON:0002336	93.05	gold quality
liver	UBERON:0002107	92.65	gold quality
right lobe of liver	UBERON:0001114	92.58	gold quality
pancreas	UBERON:0001264	92.05	gold quality
body of pancreas	UBERON:0001150	91.89	gold quality
right adrenal gland cortex	UBERON:0035827	91.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.66	gold quality
adrenal gland	UBERON:0002369	91.62	gold quality
endometrium	UBERON:0001295	91.50	gold quality
left adrenal gland	UBERON:0001234	91.30	gold quality
right adrenal gland	UBERON:0001233	91.26	gold quality
left adrenal gland cortex	UBERON:0035825	91.23	gold quality
rectum	UBERON:0001052	90.76	gold quality
skeletal muscle tissue	UBERON:0001134	90.51	gold quality
tonsil	UBERON:0002372	90.28	gold quality
skeletal muscle organ	UBERON:0014892	90.16	gold quality
muscle of leg	UBERON:0001383	90.15	gold quality
gastrocnemius	UBERON:0001388	89.80	gold quality
stromal cell of endometrium	CL:0002255	89.74	gold quality
muscle tissue	UBERON:0002385	89.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.02	gold quality
saliva-secreting gland	UBERON:0001044	88.93	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.93	gold quality
cortical plate	UBERON:0005343	88.40	gold quality
colonic epithelium	UBERON:0000397	88.27	gold quality
cerebellar cortex	UBERON:0002129	88.20	gold quality
cerebellar hemisphere	UBERON:0002245	88.18	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

81 targeting IBTK, 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-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
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-8485	100.00	77.57	4731
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-450B-5P	99.92	71.48	3175

Literature-anchored findings (GeneRIF, showing 10)

• Identification of three IBTKalpha, IBTKbeta and IBTKgamma mRNAs, whose transcription is driven by two distinct promoter regions. (PMID:18596081)
• The IBTK gene encodes the proteins IBtk-alpha, beta and gamma that regulate the B cell receptor signalling through Bruton’s tyrosine kinase, which promotes B cell survival and differentiation. (PMID:19782003)
• three novel (Ala347fsX55, I355T, and Thr324fsX24) mutations in Bruton’s tyrosine kinase in patients with X-linked agammaglobulinemia (PMID:20721470)
• A novel pathway of Btk regulation via protein kinase C phosphorylation of IBtkgamma. (PMID:21482705)
• Depletion of IBTKalpha by short hairpin RNA reduced viability of cultured cells coincident with increased caspase 3/7 cleavage, suggesting that IBTKalpha is a key regulator in determining cell fate during the UPR. (PMID:24648495)
• CRL3(IBTK) is a novel ubiquitin ligase with regulatory roles in cellular pathways, such as the Pdcd4-dependent translation of mRNAs (PMID:25882842)
• The results indicate that IBTKa differently modulates gene expression and RNA splicing in HeLa and K562 cells, demonstrating a novel biological role of this protein. (PMID:27827994)
• Data suggest that IBTKalpha is (a) localized in hepatocytes in endoplasmic reticulum (ER), (b) associates with specific proteins (LC3b, SEC16A, SEC31A), and (c) plays role in autophagy. Progression of nonalcoholic fatty liver disease is associated with changes in liver: (a) up-regulation of expression of IBTKalpha, (b) unfolded protein response, (c) ER stress, and (d) inhibition of autophagy. (PMID:28710282)
• RNA interference of Inhibitor of brutons tyrosine kinase-isoform alpha up regulated the expression of pro-apoptotic genes, including TNF, CRADD, CASP7, BNIP3 and BIRC3 and is a novel marker of CLL progression promoting cell growth and resistance to apoptosis. (PMID:29317636)
• IBtkalpha Activates the beta-Catenin-Dependent Transcription of MYC through Ubiquitylation and Proteasomal Degradation of GSK3beta in Cancerous B Cells. (PMID:35216159)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ibtk	ENSDARG00000074424
mus_musculus	Ibtk	ENSMUSG00000035941
rattus_norvegicus	Ibtk	ENSRNOG00000027728
drosophila_melanogaster	CG8060	FBGN0034113

Protein

Protein identifiers

Inhibitor of Bruton tyrosine kinase — Q9P2D0 (reviewed: Q9P2D0)

All UniProt accessions (5): Q9P2D0, D6R9F4, E7EPI0, E9PDR5, H0Y9N7

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an inhibitor of BTK tyrosine kinase activity, thereby playing a role in B-cell development. Down-regulates BTK kinase activity, leading to interference with BTK-mediated calcium mobilization and NF-kappa-B-driven transcription.

Subunit / interactions. Interacts with the PH domain of BTK. Isoform 2 does not interact with BTK.

Subcellular location. Cytoplasm. Membrane Nucleus.

Tissue specificity. Expressed in DeFew, HEK293T, HeLa and in Jurkat, MC3 and NB4 lymphoid cells (at protein level). Isoform 1 is the predominant isoform expressed in all examined tissues and cell lines. Highly expressed in hemopoietic tissues (fetal liver, spleen, lymph node, thymus, peripheral blood leukocytes and bone marrow). Weakly or not expressed in other tissues.

Miscellaneous. Due to a partial intron retention. Due to a partial intron retention.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9P2D0-1	1, IBtk-alpha	yes
Q9P2D0-2	2, IBtk-beta
Q9P2D0-3	3, IBtk-gamma

RefSeq proteins (2): NP_001287835, NP_056340* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR000408	Reg_chr_condens	Repeat
IPR002110	Ankyrin_rpt	Repeat
IPR009091	RCC1/BLIP-II	Homologous_superfamily
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR051625	Signaling_Regulatory_Domain	Family

Pfam: PF00415, PF00651, PF12796

UniProt features (33 total): modified residue 11, repeat 6, splice variant 4, sequence conflict 3, region of interest 2, compositionally biased region 2, sequence variant 2, domain 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2D0-F1	71.00	0.41

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 (11): 990, 1004, 1030, 1033, 1039, 1045, 1054, 1083, 1111, 1113, 1116

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 177 (showing top): PID_BCR_5PATHWAY, GOBP_REGULATION_OF_PHOSPHORYLATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_MAINTENANCE_OF_LOCATION, GAZDA_DIAMOND_BLACKFAN_ANEMIA_PROGENITOR_DN, GOBP_NEGATIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_NEGATIVE_REGULATION_OF_PHOSPHORYLATION, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, CHANDRAN_METASTASIS_UP, GOBP_TRANSMEMBRANE_TRANSPORT

GO Biological Process (2): negative regulation of protein phosphorylation (GO:0001933), release of sequestered calcium ion into cytosol (GO:0051209)

GO Molecular Function (3): protein kinase binding (GO:0019901), protein tyrosine kinase inhibitor activity (GO:0030292), protein binding (GO:0005515)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), membrane (GO:0016020), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of protein phosphorylation	1
protein phosphorylation	1
negative regulation of protein modification process	1
negative regulation of phosphorylation	1
intercellular transport	1
calcium ion transmembrane import into cytosol	1
kinase binding	1
protein tyrosine kinase activity	1
protein kinase inhibitor activity	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1068 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IBTK	BTK	Q06187	867
IBTK	IRAK1BP1	Q5VVH5	528
IBTK	TMEM248	Q9NWD8	507
IBTK	PLEK2	Q9NYT0	479
IBTK	PLEK	P08567	476
IBTK	CUL3	Q13618	450
IBTK	ANKRD9	Q96BM1	450
IBTK	ZNF469	Q96JG9	448
IBTK	AKT1	P31749	447
IBTK	LRRK1	Q38SD2	447
IBTK	DNAJC17	Q9NVM6	443
IBTK	GLT8D2	Q9H1C3	429
IBTK	TENT5A	Q96IP4	426
IBTK	LCN12	Q6JVE5	421
IBTK	SRC	P12931	418

IntAct

58 interactions, top by confidence:

A	B	Type	Score
EIF4A1	EIF4G3	psi-mi:“MI:0914”(association)	0.800
CUL3	ENC1	psi-mi:“MI:0914”(association)	0.640
N	RBM47	psi-mi:“MI:0914”(association)	0.530
CUL3	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
EIF4A1	EIF3D	psi-mi:“MI:0914”(association)	0.530
POP7	RPP40	psi-mi:“MI:0914”(association)	0.530
RPP25L	RPP40	psi-mi:“MI:0914”(association)	0.530
IBTK	BTK	psi-mi:“MI:0915”(physical association)	0.460
BTK	IBTK	psi-mi:“MI:0403”(colocalization)	0.460
LAMTOR3	IBTK	psi-mi:“MI:0915”(physical association)	0.370
IBTK	PPP1CA	psi-mi:“MI:0915”(physical association)	0.370
Rrbp1	PIPSL	psi-mi:“MI:0914”(association)	0.350
NOP56	C12orf43	psi-mi:“MI:0914”(association)	0.350
IBTK	POP7	psi-mi:“MI:0914”(association)	0.350
Eif3e	RPSA	psi-mi:“MI:0914”(association)	0.350
Sars1	PARP10	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
rep	TBKBP1	psi-mi:“MI:0914”(association)	0.350
N	RBM47	psi-mi:“MI:0914”(association)	0.350
EIF4A1	EIF3F	psi-mi:“MI:0914”(association)	0.350
FKBP5	IFT56	psi-mi:“MI:0914”(association)	0.350
PTGES3	KIFBP	psi-mi:“MI:0914”(association)	0.350
EIF4A1	CASC3	psi-mi:“MI:0914”(association)	0.350
RPP25L	GTPBP1	psi-mi:“MI:0914”(association)	0.350
ODF2	DDX3X	psi-mi:“MI:2364”(proximity)	0.270
RPGRIP1L	ILVBL	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (181): IBTK (Synthetic Lethality), IBTK (Affinity Capture-Western), CUL3 (Affinity Capture-Western), RBX1 (Affinity Capture-Western), IBTK (Affinity Capture-MS), CAND1 (Affinity Capture-MS), COPS2 (Affinity Capture-MS), COPS4 (Affinity Capture-MS), UBA1 (Affinity Capture-MS), CUL3 (Affinity Capture-MS), UBC (Affinity Capture-MS), COPS3 (Affinity Capture-MS), PDCD4 (Affinity Capture-MS), IBTK (Reconstituted Complex), IBTK (Proximity Label-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: A0JMG1, A1YEX3, B0WWP2, B3DIV9, B3M9V8, B3NDN0, B4GRJ2, B4HIK1, B4J045, B4L0G9, B4LIG6, B4MXW3, B4PD06, B4QLQ2, B7U179, D3Z8N4, D4A2K4, E0CZ16, E7F6F9, F1LZF0, F1MBP6, O14682, O22286, O35709, O43791, O81432, O95198, P0DMR5, P0DMR6, P24278, P28575, P34568, P58544, P58545, Q08DK3, Q08DS0, Q0D2A9, Q0IHH9, Q0VCW1, Q16RL8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKCB	down-regulates	IBTK	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
Translation initiation complex formation	6	26.6×	7e-06
Ribosomal scanning and start codon recognition	6	26.6×	7e-06
Loss of Nlp from mitotic centrosomes	5	18.4×	2e-04
Loss of proteins required for interphase microtubule organization from the centrosome	5	18.4×	2e-04
Anchoring of the basal body to the plasma membrane	7	18.4×	7e-06
AURKA Activation by TPX2	5	17.7×	3e-04
Recruitment of mitotic centrosome proteins and complexes	5	15.8×	4e-04
Regulation of PLK1 Activity at G2/M Transition	5	14.8×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
translational initiation	6	34.7×	8e-06
non-motile cilium assembly	5	23.4×	2e-04
negative regulation of translation	6	19.0×	1e-04
intracellular protein localization	6	10.1×	1e-03
cilium assembly	6	7.1×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	121
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

4603 predictions. Top by Δscore:

Variant	Effect	Δscore
6:82172375:TTTA:T	donor_loss	1.0000
6:82172376:TTAC:T	donor_loss	1.0000
6:82172377:TAC:T	donor_loss	1.0000
6:82172508:AGGGA:A	acceptor_gain	1.0000
6:82172509:GGGA:G	acceptor_gain	1.0000
6:82172510:GGA:G	acceptor_gain	1.0000
6:82172511:GA:G	acceptor_gain	1.0000
6:82172513:C:CC	acceptor_gain	1.0000
6:82173365:A:AC	donor_gain	1.0000
6:82173366:C:CC	donor_gain	1.0000
6:82181873:TATTA:T	donor_loss	1.0000
6:82181875:TTACC:T	donor_loss	1.0000
6:82181876:TA:T	donor_loss	1.0000
6:82182025:TGCC:T	acceptor_gain	1.0000
6:82182026:GCC:G	acceptor_gain	1.0000
6:82182026:GCCCT:G	acceptor_loss	1.0000
6:82182027:CC:C	acceptor_gain	1.0000
6:82182027:CCC:C	acceptor_gain	1.0000
6:82182028:CC:C	acceptor_gain	1.0000
6:82182029:C:CC	acceptor_gain	1.0000
6:82182029:CTG:C	acceptor_loss	1.0000
6:82182030:T:A	acceptor_loss	1.0000
6:82191217:C:CC	acceptor_gain	1.0000
6:82191785:AC:A	donor_gain	1.0000
6:82191786:CC:C	donor_gain	1.0000
6:82194475:CTA:C	donor_loss	1.0000
6:82194477:A:AC	donor_gain	1.0000
6:82194478:C:CA	donor_loss	1.0000
6:82194478:C:CC	donor_gain	1.0000
6:82196308:T:C	donor_gain	1.0000

AlphaMissense

8938 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:82227241:C:T	G202D	0.999
6:82227217:C:T	G210E	0.998
6:82227281:A:G	S189P	0.998
6:82231794:C:T	G156D	0.998
6:82227218:C:G	G210R	0.997
6:82227218:C:T	G210R	0.997
6:82227241:C:A	G202V	0.997
6:82227253:A:T	V198D	0.997
6:82227285:A:C	F187L	0.997
6:82227285:A:T	F187L	0.997
6:82227287:A:G	F187L	0.997
6:82231822:A:G	W147R	0.997
6:82231822:A:T	W147R	0.997
6:82240243:C:G	D82H	0.997
6:82240328:C:A	R53S	0.997
6:82240328:C:G	R53S	0.997
6:82240342:C:G	D49H	0.997
6:82171445:A:G	W1348R	0.996
6:82171445:A:T	W1348R	0.996
6:82225541:C:T	G254D	0.996
6:82225599:C:G	A235P	0.996
6:82225643:G:T	P220H	0.996
6:82227242:C:G	G202R	0.996
6:82231795:C:G	G156R	0.996
6:82231797:A:G	L155P	0.996
6:82231811:A:C	N150K	0.996
6:82231811:A:T	N150K	0.996
6:82231819:C:G	G148R	0.996
6:82240228:A:G	W87R	0.996
6:82240228:A:T	W87R	0.996

dbSNP variants (sampled 300 via entrez): RS1000037774 (6:82239450 C>A,T), RS1000161653 (6:82226902 G>A), RS1000167036 (6:82246300 G>A), RS1000208716 (6:82201318 G>A), RS1000253660 (6:82249348 G>C), RS1000339159 (6:82207596 C>G,T), RS1000370225 (6:82207870 T>C), RS1000431503 (6:82239269 A>G), RS1000478727 (6:82215022 C>A), RS1000501524 (6:82214016 C>A,T), RS1000555463 (6:82221395 G>A), RS1000587032 (6:82201026 A>C), RS1000597401 (6:82206158 G>A), RS1000700748 (6:82199345 T>C), RS1000731529 (6:82199876 C>CCTAT)

Disease associations

OMIM: gene MIM:606457 | 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

8 associations (top):

Study	Trait	p-value
GCST001806_7	Corneal structure	1.000000e-12
GCST005170_29	Intraocular pressure	9.000000e-18
GCST005580_220	Intraocular pressure	3.000000e-20
GCST005580_31	Intraocular pressure	2.000000e-13
GCST006366_4	Central corneal thickness	8.000000e-08
GCST009414_6	Central corneal thickness	5.000000e-09
GCST010866_115	Coronary artery disease	2.000000e-09
GCST011390_3	Corneal resistance factor	6.000000e-28

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004345	corneal topography
EFO:0004695	intraocular pressure measurement
EFO:0005213	central corneal thickness
EFO:0010067	corneal resistance factor

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)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Cyclosporine	increases expression	3
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects expression	1
titanium dioxide	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
calfactant	affects cotreatment, increases expression	1
K 7174	increases expression	1
bisphenol S	affects cotreatment, increases methylation	1
Bortezomib	increases expression	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression, affects cotreatment	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SR91	HAP1 IBTK (-) 1	Cancer cell line	Male
CVCL_SR92	HAP1 IBTK (-) 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