BIK

Summary

BIK (BCL2 interacting killer, HGNC:1051) is a protein-coding gene on chromosome 22q13.2, encoding Bcl-2-interacting killer (Q13323). Accelerates programmed cell death.

The protein encoded by this gene shares a critical BH3 domain with other death-promoting proteins, such as BID, BAK, BAD and BAX, that is required for its pro-apoptotic activity, and for interaction with anti-apoptotic members of the BCL2 family, and viral survival-promoting proteins. Since the activity of this protein is suppressed in the presence of survival-promoting proteins, it is suggested as a likely target for anti-apoptotic proteins.

Source: NCBI Gene 638 — RefSeq curated summary.

At a glance

• Gene–disease (curated): prostate cancer (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 36 total — 1 pathogenic
• MANE Select transcript: NM_001197

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1051
Approved symbol	BIK
Name	BCL2 interacting killer
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Aliases	NBK
Ensembl gene	ENSG00000100290
Ensembl biotype	protein_coding
OMIM	603392
Entrez	638

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000216115, ENST00000910665, ENST00000910667, ENST00000910669, ENST00000918051, ENST00000918052, ENST00000956707

RefSeq mRNA: 1 — MANE Select: NM_001197 NM_001197

CCDS: CCDS14044

Canonical transcript exons

ENST00000216115 — 5 exons

Exon	Start	End
ENSE00000656749	43127697	43127795
ENSE00000656750	43128496	43128625
ENSE00000880611	43124016	43124183
ENSE00000880612	43129213	43129712
ENSE00001044574	43110750	43110803

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 93.50.

FANTOM5 (CAGE): breadth broad, TPM avg 7.0010 / max 375.1817, expressed in 801 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192589	7.0010	801

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nasal cavity epithelium	UBERON:0005384	93.50	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.74	gold quality
palpebral conjunctiva	UBERON:0001812	89.34	gold quality
mucosa of transverse colon	UBERON:0004991	89.13	gold quality
nasal cavity mucosa	UBERON:0001826	89.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.76	gold quality
epithelium of bronchus	UBERON:0002031	87.60	gold quality
bronchus	UBERON:0002185	86.81	gold quality
bronchial epithelial cell	CL:0002328	86.60	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.74	gold quality
colonic mucosa	UBERON:0000317	84.48	gold quality
cervix squamous epithelium	UBERON:0006922	83.15	silver quality
buccal mucosa cell	CL:0002336	83.04	silver quality
minor salivary gland	UBERON:0001830	82.81	gold quality
mucosa of paranasal sinus	UBERON:0005030	82.67	gold quality
lower esophagus mucosa	UBERON:0035834	81.93	gold quality
mouth mucosa	UBERON:0003729	81.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.05	gold quality
saliva-secreting gland	UBERON:0001044	80.25	gold quality
esophagus mucosa	UBERON:0002469	79.29	gold quality
type B pancreatic cell	CL:0000169	78.38	gold quality
olfactory bulb	UBERON:0002264	77.90	gold quality
prostate gland	UBERON:0002367	77.52	gold quality
epithelium of esophagus	UBERON:0001976	77.47	silver quality
epithelium of nasopharynx	UBERON:0001951	77.41	silver quality
trachea	UBERON:0003126	77.27	gold quality
epithelial cell of pancreas	CL:0000083	76.20	silver quality
squamous epithelium	UBERON:0006914	76.14	silver quality
esophagus squamous epithelium	UBERON:0006920	75.56	silver quality
epithelium of mammary gland	UBERON:0003244	75.55	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	1784.51
E-MTAB-9388	yes	10.88
E-ANND-3	yes	9.94
E-CURD-114	yes	7.67
E-MTAB-8410	yes	4.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CD27, CD40, CTBP2, CTNNB1, FUBP1, GRHL3, KLF3, TP53, TP73, ZGPAT

miRNA regulators (miRDB)

25 targeting BIK, 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-12136	99.98	72.81	5713
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-936	98.87	70.51	1124
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-6731-3P	98.61	67.86	749
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-7112-3P	97.67	68.77	948
HSA-MIR-4712-5P	97.24	67.79	775
HSA-MIR-770-5P	97.24	68.10	758
HSA-MIR-548AD-3P	94.39	66.04	350

Literature-anchored findings (GeneRIF, showing 40)

• Systemic tumor suppression by the proapoptotic gene bik. (PMID:11782349)
• The results identify BIK as an initiator of cytochrome c release from mitochondria operating from a location at the ER. (PMID:11884414)
• NBK mediates apoptosis entirely by BAX-dependent mitochondrial pathway. (PMID:12853473)
• Several sequence alterations of the BIK gene have been identified in peripheral B-cell lymphomas which may have a role in disease pathogenesis. (PMID:12874789)
• Bik is induced in MCF-7 cells in the absence of estrogen signaling and plays a critical role in the antiestrogen-provoked breast cancer cell apoptosis. (PMID:14983013)
• degraded in Chlamydia trachomatis-infected cells. (PMID:15731089)
• Bik and Bim have roles in bortezomib sensitization of cells to killing by death receptor ligand TRAIL (PMID:15767553)
• Data show that BIK activates recruitment of DRP1 to the surface of the endoplasmic reticulum in intact cells, resulting in mitochondrial fragmentation but little release of cytochrome c to the cytosol. (PMID:15791210)
• Endogenous cellular BIK, therefore, regulates a BAX,BAK-dependent ER pathway that contributes to mitochondrial apoptosis (PMID:15809295)
• Bik/NBK accumulation was caused by stabilization of the protein from degradation and was associated with bortezomib cytotoxicity and apoptosis induction. (PMID:15824729)
• Bik does not have a definitive role in development and progression of sporadic breast neoplasms in Mexican females (PMID:16060964)
• E2Fs transactivate bik by a p53-independent mechanism. (PMID:17027756)
• Results suggest that expression of BIK in human breast cancer cells is regulated at the mRNA level by a mechanism involving a nontranscriptional activity of p53 and by proteasomal degradation of BIK protein. (PMID:17047080)
• The activation of caspase-9 and depolarization of mitochondrial membrane potential were induced by BIK, which were decreased concomitant with caspase-12 silenced. (PMID:17574210)
• Genes encoding KU70, MGST1 and BIK show age-related mRNA expression levels in hematopoietic stem cells. (PMID:17714764)
• The depletion of ER Ca2+ stores rather than the elevation of cytosolic Ca2+ or the extracellular Ca2+ entry contributed to Bik-induced Hep3B cells apoptosis. (PMID:18299962)
• BIK might not play a major role in the susceptibility of schizophrenia in Japanese population. (PMID:19632297)
• BIK is mainly localized in the ER & induces apoptosis through the mitochondrial pathway. It is involved in mature B cell selection. It a pro-apoptotic tumor suppressor in several human tissues. Review. (PMID:19641504)
• genetic polymorphism in patients with ataxia telangiectasia is associated with the disease progression (PMID:19898928)
• Bik has a role in both, apoptosis induction and sensitivity to oxidative stress in myeloma cells. (PMID:21063407)
• GRP78 can decrease BCL-2 sequestration by BIK at the endoplasmic reticulum (PMID:21622563)
• Data show that association of study-wide significance (P < 8.2 x 10(-5)) was identified for single-nucleotide polymorphisms (SNP) in TP53, LIG1, and BIK. (PMID:22139380)
• Data indicate that methylation-induced transcriptional silencing of the BIK (bcl2-interacting killer) pro-apoptotic gene may occur in multiple myeloma (MM), which might serve as a predictor of the development of relapsed/refractory MM. (PMID:22288719)
• Src tyrosine kinase inhibits apoptosis through the Erk1/2- dependent degradation of the death accelerator Bik. (PMID:22388352)
• BIK/NBK gene expression may have important clinical implications and provide predictive, prognostic or therapeutic marker in breast cancer patients (PMID:22855140)
• A previously undescribed indirect epigenetic regulation of BIK in FA-C lymphoblasts is mediated by DeltaNp73, an isoform of p73 lacking its transactivation domain that activates BIK through a proximal element in its promoter. (PMID:22873408)
• Data suggest BIK expression in tumor cells is not subject to direct regulation by MAP kinase signaling; BIK expression appears to be cell-cycle-dependent and increases in G1 cell-cycle arrest which results from inhibition of MAP kinase signaling. (PMID:24527759)
• Authors show that human herpesvirus 4 EBNA2 represses BIK in B-cell lymphoma-derived cell lines and that this host-virus interaction can inhibit the proapoptotic effect of transforming growth factor beta1. (PMID:24554662)
• BikDDA, a novel mutant of Bik, showed a prolonged half-life and enhanced pro-apoptotic ability in triple-negative breast cancer cells compared with BikDD. (PMID:24637719)
• Findings identify novel cross talk between autophagy and apoptosis, wherein targeting SQSTM1/p62 converts cytoprotective autophagy to an inefficient form due to cargo loading failure, leading to NBK/Bik accumulation, which triggers apoptosis. (PMID:25002530)
• HCV RNA replication and release were significantly suppressed in BIK-depleted cells and over-expression of the RNA-dependent RNA polymerase, NS5B, was able to induce BIK expression (PMID:25463603)
• our data demonstrated that suppression of BIK in ER-positive MCF-7 cells prevents the cytotoxic effect of TAM and favors a more aggressive phenotype, due to the molecular change of different pathways (PMID:25861752)
• These studies suggest a link between Bik-mediated caspase activation and cleavage of viral proteins. (PMID:26437021)
• Suggest complex mechanism of tumor promotion in Bik high breast tumors. (PMID:27120789)
• Data suggest that the ERalpha-H19-BIK signaling axis plays an important role in promoting breast cancer cell chemoresistance. (PMID:27845892)
• the results revealed the autophagy modulator TMEM74 interrelates with apoptosis inducer BIK and inhibits its function. (PMID:28412412)
• The current studies demonstrate that the proinflammatory IL-13 induces Bcl-2 in airway epithelial cells. Because IL-13 also induces the proapoptotic Bik, targeted blocking of Bcl-2 function switches IL-13 into a cell death inducer. (PMID:28784260)
• BIK significantly contributes to DNA damage-induced mitochondrial apoptosis in HCT-116 wt cells upstream of the second peak of ROS production, BAX and BAK activation, cytochrome c release and caspase activation. (PMID:28796811)
• study reveals that different cellular stresses regulate BIK ubiquitination by ASB11 in opposing directions, which determines whether or not cells survive, and that blocking BIK degradation has the potential to be used as an anti-cancer strategy. (PMID:31387940)
• BIK knockdown mimicked, while overexpression reversed the protective effects of miR-1306-5p against OGD/R induced injury (PMID:31460837)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bik	ENSMUSG00000016758
rattus_norvegicus	Bik	ENSRNOG00000010359

Protein

Protein identifiers

Bcl-2-interacting killer — Q13323 (reviewed: Q13323)

Alternative names: Apoptosis inducer NBK, BIP1, BP4

All UniProt accessions (1): Q13323

UniProt curated annotations — full annotation on UniProt →

Function. Accelerates programmed cell death. Association to the apoptosis repressors Bcl-X(L), BHRF1, Bcl-2 or its adenovirus homolog E1B 19k protein suppresses this death-promoting activity. Does not interact with BAX.

Subunit / interactions. Interacts with RHBDL4/RHBDD1. Interacts with BCL2L10/BCL-B.

Subcellular location. Endomembrane system. Mitochondrion membrane.

Post-translational modifications. Proteolytically cleaved by RHBDL4/RHBDD1. RHBDL4/RHBDD1-induced cleavage is a necessary step prior its degradation by the proteosome-dependent mechanism. Ubiquitinated by the ECS(ASB11) complex in response to endoplasmic reticulum stress, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome.

Domain organisation. Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family.

RefSeq proteins (1): NP_001188* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020728	Bcl2_BH3_motif_CS	Conserved_site
IPR024579	Bcl2-int_killer	Family

Pfam: PF12201

UniProt features (9 total): sequence variant 3, chain 1, transmembrane region 1, region of interest 1, short sequence motif 1, site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13323-F1	62.38	0.00

Functional residue map

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

Catalytic / active sites (1): 153–154 (cleavage; by rhbdl4/rhbdd1)

Mutagenesis-validated functional residues (1):

Position	Phenotype
153–154	inhibits rhbdl4/rhbdd1-induced cleavage.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 191 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, HARRIS_HYPOXIA, MODULE_169, PEREZ_TP63_TARGETS, SATO_SILENCED_BY_DEACETYLATION_IN_PANCREATIC_CANCER, FOXO4_01, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_RELEASE_OF_CYTOCHROME_C_FROM_MITOCHONDRIA, PUJANA_CHEK2_PCC_NETWORK, MODULE_118, GOBP_REGULATION_OF_MITOCHONDRION_ORGANIZATION, MODULE_120, MUELLER_PLURINET

GO Biological Process (6): apoptotic process (GO:0006915), male gonad development (GO:0008584), apoptotic mitochondrial changes (GO:0008637), positive regulation of protein-containing complex assembly (GO:0031334), regulation of apoptotic process (GO:0042981), positive regulation of release of cytochrome c from mitochondria (GO:0090200)

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

GO Cellular Component (5): endomembrane system (GO:0012505), mitochondrial membrane (GO:0031966), Bcl-2 family protein complex (GO:0097136), mitochondrion (GO:0005739), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	2
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
gonad development	1
development of primary male sexual characteristics	1
mitochondrion organization	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
regulation of programmed cell death	1
release of cytochrome c from mitochondria	1
positive regulation of organelle organization	1
regulation of release of cytochrome c from mitochondria	1
binding	1
vacuole	1
plasma membrane	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1
protein-containing complex	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

724 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BIK	BCL2	P10415	995
BIK	BCL2L1	Q07817	987
BIK	HRK	O00198	968
BIK	BMF	Q96LC9	950
BIK	MCL1	Q07820	920
BIK	BCL2L11	O43521	893
BIK	BCL2L2-PABPN1	Q92843	861
BIK	PMAIP1	Q13794	853
BIK	BCL2A1	Q16548	831
BIK	BOK	Q9UMX3	721
BIK	APAF1	O14727	698
BIK	FIS1	Q9Y3D6	697
BIK	CASP9	P55211	678
BIK	RTL10	Q7L3V2	669
BIK	PEX11A	O75192	666

IntAct

349 interactions, top by confidence:

A	B	Type	Score
BIK	BCL2L2	psi-mi:“MI:0407”(direct interaction)	0.930
BIK	BCL2L2	psi-mi:“MI:0915”(physical association)	0.930
BCL2L2	BIK	psi-mi:“MI:0915”(physical association)	0.930
BIK	BCL2L1	psi-mi:“MI:0407”(direct interaction)	0.910
BCL2L1	BIK	psi-mi:“MI:0915”(physical association)	0.910
BIK	BCL2L1	psi-mi:“MI:0915”(physical association)	0.910
BCL2	BIK	psi-mi:“MI:0407”(direct interaction)	0.860
BCL2	BIK	psi-mi:“MI:0915”(physical association)	0.860
FATE1	BIK	psi-mi:“MI:0915”(physical association)	0.830
BIK	BCL2A1	psi-mi:“MI:0915”(physical association)	0.780
BCL2A1	BIK	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (165): BIK (Protein-peptide), BIK (Two-hybrid), BIK (Two-hybrid), FATE1 (Two-hybrid), BIK (Protein-peptide), BIK (Protein-peptide), BIK (Protein-peptide), BIK (Protein-peptide), BIK (Two-hybrid), BIK (Two-hybrid), FATE1 (Two-hybrid), BIK (Protein-peptide), BIK (Protein-peptide), BIK (Protein-peptide), BIK (Protein-peptide)

ESM2 similar proteins: A8E1G1, B8NI18, F5HEF2, F5HGN8, F5HIC6, O36368, O95424, P03256, P04486, P05729, P06492, P09047, P09301, P0C6J0, P0C6U7, P0C6X6, P0DJX0, P10580, P12418, P12535, P16726, P21698, P22656, P24414, P24635, P25073, P25214, P28938, P28991, P52511, P52512, P68335, P68336, P83978, P89430, Q00028, Q00106, Q00335, Q13323, Q2GF15

Diamond homologs: O70337, Q13323

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
FUBP1	“down-regulates quantity by repression”	BIK	“transcriptional regulation”
BIK	down-regulates	BCL2L1	binding
CD27	“down-regulates quantity by repression”	BIK	“transcriptional regulation”
CD40	“up-regulates quantity by expression”	BIK	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 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.

GO biological processes:

GO term	Partners	Fold	FDR
release of cytochrome c from mitochondria	6	52.0×	4e-07
extrinsic apoptotic signaling pathway in absence of ligand	7	40.5×	2e-07
intrinsic apoptotic signaling pathway in response to DNA damage	7	28.0×	1e-06
positive regulation of apoptotic process	8	5.6×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	23
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
997811	Single allele	Pathogenic

SpliceAI

1077 predictions. Top by Δscore:

Variant	Effect	Δscore
22:43113911:G:GT	donor_gain	1.0000
22:43124014:A:AG	acceptor_gain	1.0000
22:43124015:G:GG	acceptor_gain	1.0000
22:43124015:GA:G	acceptor_gain	1.0000
22:43124015:GAGGA:G	acceptor_gain	1.0000
22:43124179:GGCAG:G	donor_gain	1.0000
22:43124180:GCAG:G	donor_gain	1.0000
22:43124180:GCAGG:G	donor_gain	1.0000
22:43124184:G:GA	donor_loss	1.0000
22:43124184:G:GG	donor_gain	1.0000
22:43127692:TGCAG:T	acceptor_loss	1.0000
22:43127693:GCAGT:G	acceptor_loss	1.0000
22:43127694:CA:C	acceptor_loss	1.0000
22:43127695:A:AC	acceptor_loss	1.0000
22:43127695:A:AG	acceptor_gain	1.0000
22:43127695:AGT:A	acceptor_gain	1.0000
22:43127696:G:GA	acceptor_gain	1.0000
22:43127696:GT:G	acceptor_gain	1.0000
22:43127696:GTG:G	acceptor_gain	1.0000
22:43127696:GTGAC:G	acceptor_gain	1.0000
22:43127794:AG:A	donor_loss	1.0000
22:43127795:GG:G	donor_loss	1.0000
22:43127796:G:GA	donor_loss	1.0000
22:43127797:T:A	donor_loss	1.0000
22:43128487:T:TA	acceptor_gain	1.0000
22:43128491:TATA:T	acceptor_loss	1.0000
22:43128492:A:AG	acceptor_gain	1.0000
22:43128492:ATAGC:A	acceptor_loss	1.0000
22:43128493:T:G	acceptor_gain	1.0000
22:43128494:A:AG	acceptor_gain	1.0000

AlphaMissense

1046 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:43127717:T:C	L61P	0.969
22:43127732:A:T	D66V	0.958
22:43127740:G:C	D69H	0.958
22:43127726:T:A	I64N	0.955
22:43127731:G:C	D66H	0.953
22:43127739:G:A	M68I	0.951
22:43127739:G:C	M68I	0.951
22:43127739:G:T	M68I	0.951
22:43127732:A:C	D66A	0.950
22:43127717:T:A	L61Q	0.949
22:43127728:G:T	G65W	0.945
22:43127729:G:A	G65E	0.942
22:43127719:G:C	A62P	0.938
22:43127738:T:C	M68T	0.934
22:43127720:C:A	A62D	0.930
22:43127717:T:G	L61R	0.928
22:43127741:A:T	D69V	0.924
22:43127733:C:A	D66E	0.920
22:43127733:C:G	D66E	0.920
22:43127732:A:G	D66G	0.919
22:43127728:G:A	G65R	0.918
22:43127728:G:C	G65R	0.918
22:43127726:T:G	I64S	0.910
22:43127731:G:T	D66Y	0.901
22:43127738:T:G	M68R	0.901
22:43127740:G:T	D69Y	0.895
22:43127741:A:G	D69G	0.894
22:43127741:A:C	D69A	0.883
22:43127794:A:C	S87R	0.883
22:43128496:C:A	S87R	0.883

dbSNP variants (sampled 300 via entrez): RS1000009171 (22:43119847 A>G), RS1000221934 (22:43125354 C>A,T), RS1000266240 (22:43126398 G>C), RS1000312350 (22:43114744 C>G,T), RS1000573929 (22:43125492 G>C), RS1000577690 (22:43117313 CTTTT>C,CT,CTT,CTTT,CTTTTT), RS1000633674 (22:43112128 G>A), RS1000650625 (22:43122263 G>A), RS1000662017 (22:43122615 C>T), RS1000868284 (22:43127430 C>A,T), RS1001062482 (22:43114330 T>C,G), RS1001066820 (22:43121024 A>C), RS1001530910 (22:43118188 A>G), RS1001685950 (22:43118442 G>A), RS1001981686 (22:43118484 G>A,C,T)

Disease associations

OMIM: gene MIM:603392 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
prostate cancer	Limited	Autosomal dominant

Mondo (2): intellectual disability (MONDO:0001071), prostate cancer (MONDO:0008315)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001147_9	Prostate cancer	6.000000e-06
GCST001370_51	Prostate cancer (SNP x SNP interaction)	2.000000e-06
GCST002890_6	Prostate cancer	1.000000e-16

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
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

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, affects cotreatment, decreases expression, increases expression	8
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	6
Tetrachlorodibenzodioxin	decreases expression, affects cotreatment, increases expression	4
Valproic Acid	affects expression, increases expression	4
Cisplatin	affects expression, affects localization, increases expression, decreases reaction	3
Doxorubicin	increases response to substance, decreases expression, increases expression	3
Hydrogen Peroxide	decreases reaction, increases expression, affects expression, affects localization	3
Aflatoxin B1	affects expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Bortezomib	increases response to substance, increases activity, increases expression	2
Decitabine	affects cotreatment, increases expression, decreases expression, decreases reaction, increases reaction	2
Leflunomide	increases expression	2
Acetaminophen	increases expression	2
Paraquat	increases expression, affects cotreatment	2
Silicon Dioxide	increases expression	2
Smoke	decreases expression, decreases reaction	2
Cadmium Chloride	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
sanguinarine	affects cotreatment, increases expression	1
bis(tri-n-butyltin)oxide	decreases expression	1
propylparaben	increases expression	1
VX-agent	increases expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
afimoxifene	increases expression	1
butyraldehyde	increases expression	1

Clinical trials (associated diseases)

497 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