BIRC6

Summary

BIRC6 (baculoviral IAP repeat containing 6, HGNC:13516) is a protein-coding gene on chromosome 2p22.3, encoding Dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6 (Q9NR09). Anti-apoptotic protein known as inhibitor of apoptosis (IAP) which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase. It is a selective cancer dependency (DepMap: 27.4% of cell lines).

This gene encodes a protein with a BIR (baculoviral inhibition of apoptosis protein repeat) domain and a UBCc (ubiquitin-conjugating enzyme E2, catalytic) domain. This protein inhibits apoptosis by facilitating the degradation of apoptotic proteins by ubiquitination.

Source: NCBI Gene 57448 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 742 total — 7 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 1
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 15 cancer types
• Cancer dependency (DepMap): dependent in 27.4% of screened cell lines
• MANE Select transcript: NM_016252

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13516
Approved symbol	BIRC6
Name	baculoviral IAP repeat containing 6
Location	2p22.3
Locus type	gene with protein product
Status	Approved
Aliases	BRUCE
Ensembl gene	ENSG00000115760
Ensembl biotype	protein_coding
OMIM	605638
Entrez	57448

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 retained_intron, 5 protein_coding, 1 nonsense_mediated_decay

ENST00000421745, ENST00000431454, ENST00000444173, ENST00000461788, ENST00000462504, ENST00000465130, ENST00000466527, ENST00000470250, ENST00000471232, ENST00000483194, ENST00000496555, ENST00000497023, ENST00000648282, ENST00000700518, ENST00000700519

RefSeq mRNA: 2 — MANE Select: NM_016252 NM_001378125, NM_016252

CCDS: CCDS33175

Canonical transcript exons

ENST00000421745 — 74 exons

Exon	Start	End
ENSE00000743520	32357023	32357486
ENSE00000743524	32377588	32377769
ENSE00000743528	32380153	32380290
ENSE00000743532	32388750	32388943
ENSE00000743537	32401163	32401385
ENSE00000743538	32401463	32401623
ENSE00000743539	32406499	32406557
ENSE00000743540	32414769	32416163
ENSE00000743541	32429146	32429295
ENSE00000743542	32430865	32431090
ENSE00000743543	32433644	32433804
ENSE00000743544	32435496	32435585
ENSE00000743545	32436053	32436184
ENSE00000743547	32441329	32441462
ENSE00000743551	32442324	32442455
ENSE00000743552	32443491	32443588
ENSE00000743556	32463194	32463381
ENSE00000743557	32464509	32464823
ENSE00000743558	32465065	32465164
ENSE00000743559	32467525	32467739
ENSE00000743560	32467903	32468111
ENSE00000743561	32468437	32468783
ENSE00000743563	32469395	32469614
ENSE00000743564	32470168	32470301
ENSE00000743565	32471014	32471124
ENSE00000743566	32473112	32473239
ENSE00000743567	32476213	32476344
ENSE00000743569	32477368	32477583
ENSE00000743570	32478635	32478818
ENSE00000743572	32479462	32479617
ENSE00000743574	32481320	32481453
ENSE00000743578	32485643	32485759
ENSE00000743580	32487647	32487801
ENSE00000743583	32488588	32488714
ENSE00000743585	32490041	32490151
ENSE00000743588	32491425	32491558
ENSE00000743591	32493540	32493667
ENSE00000743593	32499547	32500109
ENSE00000743595	32501713	32501888
ENSE00000743597	32502795	32502891
ENSE00000743604	32505005	32505205
ENSE00000743607	32507980	32508259
ENSE00000743610	32509738	32509994
ENSE00000743616	32512933	32513154
ENSE00000743619	32514990	32515770
ENSE00000743629	32524888	32525019
ENSE00000809493	32448795	32448928
ENSE00000809494	32482429	32482582
ENSE00001189810	32453808	32453942
ENSE00001504515	32518817	32518946
ENSE00001652421	32439508	32439686
ENSE00001846447	32617725	32618878
ENSE00003459762	32392039	32392150
ENSE00003460510	32611448	32611582
ENSE00003469795	32510526	32510634
ENSE00003475481	32442065	32442226
ENSE00003478034	32445521	32445668
ENSE00003494267	32599739	32599900
ENSE00003513036	32543241	32543541
ENSE00003527613	32547850	32548014
ENSE00003532910	32545643	32545860
ENSE00003553771	32603006	32603083
ENSE00003561761	32503042	32503236
ENSE00003562657	32597751	32597968
ENSE00003576196	32575156	32575366
ENSE00003621497	32607455	32607643
ENSE00003628338	32595034	32595144
ENSE00003645442	32395511	32395593
ENSE00003665324	32531355	32531551
ENSE00003674432	32518254	32518397
ENSE00003677966	32525464	32525628
ENSE00003681985	32593915	32594060
ENSE00003685003	32529651	32529824
ENSE00003686812	32549313	32549481

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.6838 / max 677.8579, expressed in 1820 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19641	39.5726	1818
19639	1.3789	735
19642	0.3738	161
19640	0.2830	118
202150	0.0754	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	98.48	gold quality
oviduct epithelium	UBERON:0004804	98.23	gold quality
calcaneal tendon	UBERON:0003701	97.90	gold quality
pancreatic ductal cell	CL:0002079	97.76	gold quality
adrenal tissue	UBERON:0018303	97.42	gold quality
ileal mucosa	UBERON:0000331	97.18	gold quality
tibialis anterior	UBERON:0001385	97.04	gold quality
bone marrow cell	CL:0002092	96.93	gold quality
colonic epithelium	UBERON:0000397	96.10	gold quality
corpus callosum	UBERON:0002336	95.83	gold quality
upper arm skin	UBERON:0004263	95.80	gold quality
cortical plate	UBERON:0005343	95.66	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.31	gold quality
cauda epididymis	UBERON:0004360	94.73	gold quality
colonic mucosa	UBERON:0000317	94.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.53	gold quality
left ventricle myocardium	UBERON:0006566	94.39	gold quality
seminal vesicle	UBERON:0000998	94.23	gold quality
tendon	UBERON:0000043	94.15	gold quality
ganglionic eminence	UBERON:0004023	94.04	gold quality
tonsil	UBERON:0002372	93.98	gold quality
sural nerve	UBERON:0015488	93.97	gold quality
ventricular zone	UBERON:0003053	93.95	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.86	gold quality
buccal mucosa cell	CL:0002336	93.83	gold quality
deltoid	UBERON:0001476	93.80	gold quality
skin of hip	UBERON:0001554	93.69	gold quality
jejunal mucosa	UBERON:0000399	93.65	gold quality
upper leg skin	UBERON:0004262	93.47	gold quality
corpus epididymis	UBERON:0004359	93.35	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.91
E-CURD-135	no	813.58
E-GEOD-100618	no	547.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

132 targeting BIRC6, 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-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-218-5P	99.93	72.22	2103

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 27.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Overexpression of Nrdp1 promotes ubiquitination and proteasomal degradation of BRUCE. (PMID:14765125)
• Apollon binds to, ubiquitinates and facilitates proteasomal degradation of SMAC and caspase-9, results suggesting that Apollon has an essential function in preventing SMAC-induced apoptosis (PMID:15300255)
• the ability of BRUCE to antagonize both the precursor and mature forms of Smac and caspase-9 is an important mechanism for the prevention of apoptosis under normal conditions (PMID:15507451)
• Study identifies BRUCE, a 528 kDa multifunctional protein, which processes ubiquitin-conjugating activity, as a major regulator of abscission; during cytokinesis, BRUCE moves from the vesicular system to the midbody ring. (PMID:18329369)
• p53 stabilisation and caspase-3 activation concur to determine the apoptotic response mediated by Apollon knockdown in breast cancer cells. (PMID:19223905)
• Gene knockdown of apollon inhibits cell proliferation, induces apoptosis, arrests cell cycle at S phase, and enhances the chemo-sensitivity of colorectal cancer Lovo cells to 5-FU, DDP and EPI. (PMID:21542283)
• Based on the data presented here we propose that BIRC6 protects the cancer stem cell fraction of colorectal tumors against oxaliplatin and cisplatin (PMID:21788403)
• Dowregulating Apollon with siRNA can enhance the chemosensitivity of hepatocellular carcinoma cells in vitro. (PMID:22027771)
• BIRC6 gene expression could be considered as an adverse risk factor in childhood acute leukemia (PMID:22085301)
• results indicated that Apollon plays a relevant role in melanoma resistance to apoptosis by antitumor agents that trigger the intrinsic or the extrinsic apoptosis pathways (PMID:22553342)
• Knockdown experiments were performed using BIRC6 lentiviral shRNA and phenotype responses were analyzed by Western blot and MTT-assays.Upon silencing of BIRC6 by shRNA, DIABLO protein levels increased and cells went into apoptosis. (PMID:22788920)
• Elevated expression of BIRC6 protein in non-small-cell lung cancers is associated with cancer recurrence and chemoresistance. (PMID:23287853)
• APPOLON to be a novel regulator of mitotic CYCLIN A degradation independent of SAC. (PMID:24302728)
• The expression of BIRC6 in the cytoplasm is associated with epithelial ovarian cancer (EOC) differentiation and may be a novel predictor for poor prognosis of EOC patients after curative resection. (PMID:24453032)
• The study demonstrates that the T allele of the rs2754511 in the BIRC6 gene plays a protective role in pseudoexfoliative glaucoma patients of the Pakistani population. (PMID:25118708)
• Humanin signaling pathway via htHNR/JAKs/STAT3 increased the expression levels of mRNA and protein of Apollon/Bruce, an unusual member of the inhibitors of apoptosis proteins (PMID:25138702)
• findings demonstrate that BIRC6 overexpression in hepatocellular carcinoma specimens is indicative of poor prognosis and that its interaction with p53 facilitates the degradation of p53 (PMID:25196217)
• BRUCE acts as a scaffold, bridging the ubiquitin-specific peptidase 8 (USP8) and BRIT1 in a complex to coordinate USP8-catalyzed deubiquitination of BRIT1. (PMID:25733871)
• BIRC6 overexpression is a predictor of poor prognosis in colorectal cancer and could be a potential target for colorectal cancer therapy. (PMID:25933218)
• Results show that in addition to the scaffolding function in complex formation, BRUCE has an E3 ligase function to promote BRIT1 deubiquitination by USP8 leading to accumulation of BRIT1 at DNA double-strand break. (PMID:26683461)
• Apollon gene silencing can induce apoptosis and growth impairment in HeLa cells. In this regard, apollon can be considered a candidate therapeutic target in HeLa cells as a positive human papillomavirus cancer cell line. (PMID:26748613)
• AVEN and BIRC6 are inhibited by combination therapy of miR-30e and proanthocyanidin in glioblastoma stem cells (PMID:27388765)
• Apollon expression is associated with the biological characteristics of esophageal squamous cell carcinoma (ESCC), and may be a valuable prognostic factor and a novel chemotherapeutic target for ESCC treatment. (PMID:27432467)
• Since specific expression of BRUCE protein was revealed in majority of gastric carcinoma tissues, BRUCE protein may be a useful therapeutic target for cancer therapy. (PMID:27614745)
• BRUCE protein was detected in 82% of tumors and tumor progression stage and invasion depth correlated significantly with BRUCE protein expression (PMID:27649954)
• BIRC6 targeting inhibited the growth of enzalutamide-resistant castration-resistant prostate cancer models and may represent a new option for clinical treatment of advanced, enzalutamide-resistant prostate cancer (PMID:27663589)
• Apollon role in the multidrug resistance of human chronic myelogenous leukemia cells (PMID:28358418)
• circBIRC6 and circCORO1C are functionally associated with the pluripotent state in undifferentiated human embryonic stem cells (PMID:29074849)
• Data indicate BRUCE/Apollon/Birc6, an inhibitor of apoptosis protein (IAP), as a new autophagy regulator. (PMID:29426817)
• Our study shows that BIRC6 is upregulated in prostate cancer and is associated with aggressive tumor progression. Moreover, elevated level of BIRC6 predicts poor prognosis for prostate cancer patients, and BIRC6 can regulate prostate cancer cell proliferation and apoptosis in vitro. (PMID:29429983)
• The miR-204 may play an anti-carcinogenic role in AML and function as a novel biomarker and therapeutic target for the treatment of this disease. (PMID:29764561)
• Circ-BIRC6 is upregulated in hepatocellular carcinoma tissues and is associated with poor prognosis of hepatocellular carcinoma patients, and promotes hepatocellular carcinoma progression by targeting the miR-3918/Bcl2 axis. (PMID:30931701)
• These findings demonstrate that UBA6 and BIRC6 negatively regulate autophagy by limiting the availability of LC3B. (PMID:31692446)
• MALAT1 knockdown inhibits prostate cancer progression by regulating miR-140/BIRC6 axis. (PMID:31935634)
• Besides the anti-apoptotic functions, recent discoveries have revealed that XIAP, survivin, and BRUCE also exhibit regulatory functions for autophagy in cells. As the role of autophagy in human diseases has already been discussed extensively in different reviews, this review will discuss the emerging autophagic role of XIAP, survivin, and BRUCE in cancer cells. (PMID:32019552)
• BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque. (PMID:33317170)
• Silencing circBIRC6 inhibits the proliferation, invasion, migration and epithelialmesenchymal transition of bladder cancer cells by targeting the miR4953p/XBP1 signaling axis. (PMID:34542161)
• BIRC6 modifies risk of invasive bacterial infection in Kenyan children. (PMID:35866869)
• Oral Squamous Cell Carcinoma: The Role of BIRC6 Serum Level. (PMID:36033570)
• Exploring the Role of the Inhibitor of Apoptosis BIRC6 in Breast Cancer: A Database Analysis. (PMID:36455174)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	birc6	ENSDARG00000074166
mus_musculus	Birc6	ENSMUSG00000024073
rattus_norvegicus	Birc6	ENSRNOG00000027191
drosophila_melanogaster	Bruce	FBGN0266717
caenorhabditis_elegans		WBGENE00006712

Paralogs (7): BIRC3 (ENSG00000023445), BIRC5 (ENSG00000089685), NLRC4 (ENSG00000091106), BIRC7 (ENSG00000101197), XIAP (ENSG00000101966), BIRC2 (ENSG00000110330), NAIP (ENSG00000249437)

Protein

Protein identifiers

Dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6 — Q9NR09 (reviewed: Q9NR09)

Alternative names: BIR repeat-containing ubiquitin-conjugating enzyme, Baculoviral IAP repeat-containing protein 6, Ubiquitin-conjugating BIR domain enzyme apollon

All UniProt accessions (6): Q9NR09, A0A3B3IUB9, A0A8V8TQB4, A0A8V8TR92, H7C094, H7C3P0

UniProt curated annotations — full annotation on UniProt →

Function. Anti-apoptotic protein known as inhibitor of apoptosis (IAP) which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase. Unlike most IAPs, does not contain a RING domain and it is not a RING-type E3 ligase. Instead acts as a dual E2/E3 enzyme that combines ubiquitin conjugating (E2) and ubiquitin ligase (E3) activities in a single polypeptide. Ubiquitination is mediated by a non-canonical E1 ubiquitin activating enzyme UBA6. Ubiquitinates CASP3, CASP7 and CASP9 and inhibits their caspase activity; also ubiquitinates their procaspases but to a weaker extent. Ubiquitinates pro-apoptotic factors DIABLO/SMAC and HTRA2. DIABLO/SMAC antagonizes the caspase inhibition activity of BIRC6 by competing for the same binding sites as the caspases. Ubiquitinates the autophagy protein MAP1LC3B; this activity is also inhibited by DIABLO/SMAC. Important regulator for the final stages of cytokinesis. Crucial for normal vesicle targeting to the site of abscission, but also for the integrity of the midbody and the midbody ring, and its striking ubiquitin modification.

Subunit / interactions. Homodimer; antiparallel. Interacts with RNF41. Interacts with DIABLO/SMAC, likely with higher affinity to SMAC dimer than SMAC monomer; this interaction blocks the substrate-binding site and inhibits the caspase inhibition activity of BIRC6. Interacts with KIF23/MKLP1, USP8/UBPY, BIRC5/survivin, MAP2K1/MEK1, RAB8A/RAB8, RAB11A/RAB11, PLK1, EXOC3/SEC6 and EXOC4/SEC8.

Subcellular location. Golgi apparatus. trans-Golgi network membrane. Endosome. Cytoplasm. Cytoskeleton. Spindle pole. Microtubule organizing center. Centrosome. Midbody. Midbody ring.

Tissue specificity. Expressed in brain cancer cells.

Post-translational modifications. Ubiquitinated; mediated by RNF41 E3 ligase and leads to proteasomal degradation, impairing inhibition of apoptosis. Deubiquitinated by USP8/UBPY. Autoubiquitinated; mediated by E1 ubiquitin activating enzyme UBA6. Proteolytically cleaved. Acts as substrate for CASP3, CASP6, CASP7, CASP9 and HTRA2.

Activity regulation. Inhibited by DIABLO/SMAC, which competes for the substrate-binding sites on BIRC6. BIRC6 inhibits caspases and protease by ubiquitination but BIRC6 itself is subjected to protease cleavage by CASP3, CASP6, CASP7, CASP9 and HTRA2 by protease cleavage.

Domain organisation. The BIR domain is essential for its anti-apoptotic function and is important for binding to DIABLO/SMAC and caspases.

Similarity. Belongs to the BIRC6 family.

RefSeq proteins (2): NP_001365054, NP_057336* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000608	UBC	Domain
IPR001370	BIR_rpt	Repeat
IPR016135	UBQ-conjugating_enzyme/RWD	Homologous_superfamily
IPR022103	BIRC6	Family

Pfam: PF00179, PF00653, PF12356

UniProt features (243 total): helix 97, strand 65, turn 25, mutagenesis site 12, modified residue 10, region of interest 9, repeat 8, compositionally biased region 7, binding site 4, domain 2, sequence conflict 2, chain 1, active site 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
8E2E	ELECTRON MICROSCOPY	1.98
3CEG	X-RAY DIFFRACTION	2.01
8E2D	ELECTRON MICROSCOPY	2.07
8E2H	ELECTRON MICROSCOPY	2.3
8E2F	ELECTRON MICROSCOPY	2.47
8E2G	ELECTRON MICROSCOPY	2.99
8ATO	ELECTRON MICROSCOPY	3
8E2I	ELECTRON MICROSCOPY	3.04
9QH5	ELECTRON MICROSCOPY	3.09
8E2K	ELECTRON MICROSCOPY	3.21
8ATM	ELECTRON MICROSCOPY	3.3
8ATU	ELECTRON MICROSCOPY	3.3
9QIV	ELECTRON MICROSCOPY	3.44
9QIM	ELECTRON MICROSCOPY	3.57
9QGW	ELECTRON MICROSCOPY	3.62
9QIP	ELECTRON MICROSCOPY	4.15
9QIO	ELECTRON MICROSCOPY	4.22
9QHI	ELECTRON MICROSCOPY	4.27
9QIA	ELECTRON MICROSCOPY	4.38
8AUK	ELECTRON MICROSCOPY	6.2
8ATX	ELECTRON MICROSCOPY	7
8AUW	ELECTRON MICROSCOPY	7.2

Predicted structure (AlphaFold)

No AlphaFold model available for Q9NR09 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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): 4666 (glycyl thioester intermediate)

Ligand- & substrate-binding residues (4): 328; 331; 348; 355

Post-translational modifications (10): 473, 480, 482, 581, 590, 1710, 2222, 2955, 3931, 4023

Mutagenesis-validated functional residues (12):

Position	Phenotype
328	impairs ubiquitination of casp3, casp7 and htra2 mutant ‘a-306’; when associated with s-331. abolishes interaction with
331	impairs ubiquitination of casp3, casp7 and htra2 mutant ‘a-306’; when associated with s-328. abolishes interaction with
342	abolishes interaction with casp3 and the caspase inhibition activity on casp3. impairs interaction with casp7 and abolis
342	fails to ubiquitinate n-degron peptide from htra2. impairs diablo/smac inhibition on the ubiquitination of map1lc3b by b
351	impairs interaction with casp3 and abolishes the caspase inhibition activity on casp3. impairs interaction with casp7 bu
1616–1666	slightly impairs interaction with diablo/smac. abolishes interaction with diablo/smac and impairs ubiquitination of diab
2228–2295	impairs diablo/smac inhibition on the ubiquitination of map1lc3b by birc6. enhances ubiquitination of diablo/smac. sever
3189–3193	impairs interaction with monomeric diablo/smac ’d-81’ mutant.
3189–3193	impairs interaction with casp7 and mildly impairs the caspase inhibition activity on casp7. impairs interaction with mon
3190–3193	no effect on diablo/smac inhibition on the ubiquitination of map1lc3b by birc6. no effect on ubiquitination of diablo/sm
4094–4145	impairs map1lc3b ubiquitination without disrupting htra2 ubiquitination.
4666	catalytically inactive; fails to autoubiquitinate in the presence of uba6.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9700645	ALK mutants bind TKIs
R-HSA-9725370	Signaling by ALK fusions and activated point mutants
R-HSA-1643685	Disease
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-9700206	Signaling by ALK in cancer

MSigDB gene sets: 180 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, ACTACCT_MIR196A_MIR196B, TGCACTT_MIR519C_MIR519B_MIR519A, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NEGATIVE_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_EMBRYONIC_PLACENTA_DEVELOPMENT, GOCC_TRANS_GOLGI_NETWORK, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_CYTOKINESIS, GOBP_REGULATION_OF_CELL_CYCLE

GO Biological Process (13): protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), cell population proliferation (GO:0008283), positive regulation of cell population proliferation (GO:0008284), protein ubiquitination (GO:0016567), regulation of cytokinesis (GO:0032465), regulation of cell population proliferation (GO:0042127), negative regulation of apoptotic process (GO:0043066), cell division (GO:0051301), labyrinthine layer development (GO:0060711), negative regulation of extrinsic apoptotic signaling pathway (GO:2001237), placenta development (GO:0001890), regulation of apoptotic process (GO:0042981)

GO Molecular Function (8): ubiquitin-protein transferase activity (GO:0004842), cysteine-type endopeptidase inhibitor activity (GO:0004869), metal ion binding (GO:0046872), ubiquitin conjugating enzyme activity (GO:0061631), protein binding (GO:0005515), transferase activity (GO:0016740), peptidase inhibitor activity (GO:0030414), ubiquitin protein ligase activity (GO:0061630)

GO Cellular Component (13): spindle pole (GO:0000922), nucleus (GO:0005634), endosome (GO:0005768), trans-Golgi network (GO:0005802), centrosome (GO:0005813), microtubule organizing center (GO:0005815), cytosol (GO:0005829), membrane (GO:0016020), midbody (GO:0030496), Flemming body (GO:0090543), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by ALK in cancer	2
Disease	1
Diseases of signal transduction by growth factor receptors and second messengers	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
cellular process	2
cell population proliferation	2
apoptotic process	2
ubiquitin-protein transferase activity	2
intracellular membrane-bounded organelle	2
endomembrane system	2
cytoplasm	2
phosphorylation	1
protein modification process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
protein modification by small protein conjugation	1
cytokinesis	1
regulation of cell cycle process	1
regulation of cell division	1
regulation of cellular process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
embryonic placenta development	1
anatomical structure development	1
extrinsic apoptotic signaling pathway	1
negative regulation of apoptotic signaling pathway	1
regulation of extrinsic apoptotic signaling pathway	1
animal organ development	1
regulation of programmed cell death	1
ubiquitin-like protein transferase activity	1
cysteine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
cation binding	1
ubiquitin-like protein conjugating enzyme activity	1
binding	1
catalytic activity	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
ubiquitin-like protein ligase activity	1

Protein interactions and networks

STRING

5290 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BIRC6	BIRC7	Q96CA5	917
BIRC6	RNF41	Q9H4P4	847
BIRC6	XIAP	P98170	832
BIRC6	CASP9	P55211	788
BIRC6	DIABLO	Q9NR28	764
BIRC6	USP8	P40818	722
BIRC6	KIF23	Q02241	718
BIRC6	HTRA2	O43464	688
BIRC6	CASP3	P42574	653
BIRC6	KCNJ11	Q14654	638
BIRC6	TTC27	Q6P3X3	566
BIRC6	DAD1	P46966	533
BIRC6	MYCBP2	O75592	514
BIRC6	NEURL4	Q96JN8	463
BIRC6	UBA6	A0AVT1	450

IntAct

202 interactions, top by confidence:

A	B	Type	Score
CAPN1	CAPNS1	psi-mi:“MI:0914”(association)	0.840
SNX6	SNX2	psi-mi:“MI:0914”(association)	0.800
CCDC22	VPS26C	psi-mi:“MI:0914”(association)	0.790
KRT31	HGS	psi-mi:“MI:0914”(association)	0.780
LDOC1	PEG10	psi-mi:“MI:0914”(association)	0.740
RPGR	NPHP4	psi-mi:“MI:2364”(proximity)	0.730
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TMEM266	KDM1A	psi-mi:“MI:0914”(association)	0.670
PLK1	EVI5	psi-mi:“MI:0914”(association)	0.660
AGRP	TK1	psi-mi:“MI:0914”(association)	0.640
VEGFD	ADAM9	psi-mi:“MI:0914”(association)	0.640
RALBP1	JUN	psi-mi:“MI:0914”(association)	0.640
BIRC6	PLK1	psi-mi:“MI:0403”(colocalization)	0.600
BIRC6	PLK1	psi-mi:“MI:0915”(physical association)	0.600
PLK1	BIRC6	psi-mi:“MI:0915”(physical association)	0.600
BIRC6	EXOC4	psi-mi:“MI:0403”(colocalization)	0.560
EXOC4	BIRC6	psi-mi:“MI:0915”(physical association)	0.560
BIRC6	EXOC4	psi-mi:“MI:0915”(physical association)	0.560
KIF23	BIRC6	psi-mi:“MI:0915”(physical association)	0.560
BIRC6	KIF23	psi-mi:“MI:0915”(physical association)	0.560
KIF23	BIRC6	psi-mi:“MI:0403”(colocalization)	0.560
NEURL4	APBB1	psi-mi:“MI:0914”(association)	0.530

BioGRID (413): BIRC6 (Biochemical Activity), DIABLO (Reconstituted Complex), BIRC6 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LFM6, A0A1B0GUA6, A0JMD2, A2VCZ5, A5WUT8, A6H5Y1, A6NKB5, B8JKP6, D3ZJ47, F1M5M3, F1MJR8, M0R5D6, O14513, O60284, P0CAX8, Q0P4S0, Q15468, Q1LV19, Q1RMQ5, Q4V7H1, Q5DU28, Q5DW34, Q5REU9, Q5SW75, Q5SWW4, Q5U4U4, Q5ZM13, Q60664, Q60988, Q6P9N1, Q6ZPK7, Q76I76, Q76I79, Q80TA9, Q80TY4, Q8BLN6, Q8BYM7, Q8IWB6, Q8JGS1, Q8K2J4

Diamond homologs: A1E2V0, A1L020, A1L3F4, A5D8Q0, A9JTP3, A9ULZ2, D3ZDI6, E3SCZ8, O08863, O10296, O10324, O14064, O15392, O62640, O70201, O88738, P40629, P41435, P41436, P41437, P41454, P47732, P98170, Q05AK5, Q0WPJ7, Q13489, Q13490, Q28ER3, Q28H51, Q50L39, Q557E7, Q5BKL8, Q5R881, Q5RAH9, Q60989, Q62210, Q69Z36, Q6I6F4, Q6J1J1, Q6NTT6

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
BIRC6	down-regulates	CASP3	binding
“Ub:E1 (UBA1 substrate)”	“up-regulates activity”	BIRC6	ubiquitination
“Ub:E1 (UBA6 substrate)”	“up-regulates activity”	BIRC6	ubiquitination

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 15 cancer types — ANSC, BLCA, BRCA, CCRCC, CHOL, COADREAD, DLBCLNOS, HCC, HNSC, LUAD, MGCT, MT…(+3 more).

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	2
Uncertain significance	527
Likely benign	53
Benign	47

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
219057	Single allele	Pathogenic
219060	Single allele	Pathogenic
219087	Single allele	Pathogenic
2684431	GRCh37/hg19 2p23.1-22.3(chr2:32083215-32684402)x1	Pathogenic
60108	GRCh38/hg38 2p23.1-22.3(chr2:31370181-32512769)x1	Pathogenic
625542	GRCh37/hg19 2p22.3(chr2:32339736-32875274)	Pathogenic
685336	GRCh37/hg19 2p23.1-22.3(chr2:31958977-33946495)x1	Pathogenic
545277	NC_000002.12:g.(?32528746)(32559427_?)del	Likely pathogenic
988099	NC_000002.11:g.(32289091_32312562)_(32958959_32999928)del	Likely pathogenic

SpliceAI

12305 predictions. Top by Δscore:

Variant	Effect	Δscore
2:32357484:GTG:G	donor_gain	1.0000
2:32357487:G:GA	donor_loss	1.0000
2:32357487:G:GG	donor_gain	1.0000
2:32357488:T:A	donor_loss	1.0000
2:32377586:A:AG	acceptor_gain	1.0000
2:32377587:G:GT	acceptor_gain	1.0000
2:32377587:GCT:G	acceptor_gain	1.0000
2:32377587:GCTA:G	acceptor_gain	1.0000
2:32377766:AGAG:A	donor_gain	1.0000
2:32377767:GAG:G	donor_gain	1.0000
2:32377767:GAGG:G	donor_gain	1.0000
2:32377768:AGGT:A	donor_loss	1.0000
2:32377769:GGTA:G	donor_loss	1.0000
2:32377770:G:C	donor_loss	1.0000
2:32377770:G:GG	donor_gain	1.0000
2:32377771:T:G	donor_loss	1.0000
2:32380286:CTAAG:C	donor_loss	1.0000
2:32380287:TAAG:T	donor_loss	1.0000
2:32380288:AAGG:A	donor_loss	1.0000
2:32380290:GGTAA:G	donor_loss	1.0000
2:32380291:G:C	donor_loss	1.0000
2:32380292:T:A	donor_loss	1.0000
2:32380918:A:G	donor_gain	1.0000
2:32380940:GAAAT:G	donor_gain	1.0000
2:32388747:CAGT:C	acceptor_loss	1.0000
2:32388748:A:AG	acceptor_gain	1.0000
2:32388748:AGT:A	acceptor_gain	1.0000
2:32388748:AGTG:A	acceptor_gain	1.0000
2:32388748:AGTGG:A	acceptor_gain	1.0000
2:32388749:G:GT	acceptor_gain	1.0000

AlphaMissense

31644 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:32377672:G:T	R137M	1.000
2:32380153:G:C	A170P	1.000
2:32380232:T:C	L196P	1.000
2:32388750:T:A	W216R	1.000
2:32388750:T:C	W216R	1.000
2:32388752:G:C	W216C	1.000
2:32388752:G:T	W216C	1.000
2:32388820:T:C	L239P	1.000
2:32392064:A:G	R289G	1.000
2:32392065:G:C	R289T	1.000
2:32392065:G:T	R289I	1.000
2:32392066:A:C	R289S	1.000
2:32392066:A:T	R289S	1.000
2:32392076:T:C	F293L	1.000
2:32392077:T:C	F293S	1.000
2:32392078:T:A	F293L	1.000
2:32392078:T:G	F293L	1.000
2:32392085:T:A	W296R	1.000
2:32392085:T:C	W296R	1.000
2:32392087:G:C	W296C	1.000
2:32392087:G:T	W296C	1.000
2:32392106:T:A	W303R	1.000
2:32392106:T:C	W303R	1.000
2:32392108:G:C	W303C	1.000
2:32392108:G:T	W303C	1.000
2:32392134:C:A	A312D	1.000
2:32392136:G:A	G313R	1.000
2:32392136:G:C	G313R	1.000
2:32392137:G:A	G313E	1.000
2:32392137:G:T	G313V	1.000

dbSNP variants (sampled 300 via entrez): RS1000012621 (2:32368546 CAAATAAAT>C,CAAAT,CAAATAAATAAAT), RS1000016902 (2:32616415 C>T), RS1000018059 (2:32542320 G>T), RS1000047407 (2:32472688 C>T), RS1000051893 (2:32446056 A>G), RS1000060026 (2:32512609 C>G), RS1000069122 (2:32616071 T>C), RS1000078141 (2:32616073 T>C), RS1000080083 (2:32518111 C>A,T), RS1000083990 (2:32581479 C>T), RS1000108017 (2:32457453 T>A,C,G), RS1000108864 (2:32463643 C>T), RS1000111404 (2:32593028 G>A), RS1000133135 (2:32512875 T>C), RS1000133515 (2:32551482 C>T)

Disease associations

OMIM: gene MIM:605638 | disease phenotypes: MIM:182601, MIM:181500

GenCC curated gene-disease

Mondo (4): hereditary spastic paraplegia 4 (MONDO:0008438), schizophrenia (MONDO:0005090), hereditary breast ovarian cancer syndrome (MONDO:0003582), autism spectrum disorder (MONDO:0005258)

Orphanet (4): Autosomal dominant spastic paraplegia type 4 (Orphanet:100985), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

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

HPO	Term
HP:0100753	Schizophrenia

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST006661_237	Male-pattern baldness	7.000000e-26
GCST006661_313	Male-pattern baldness	2.000000e-20
GCST006661_314	Male-pattern baldness	4.000000e-20
GCST007323_98	Risk-taking tendency (4-domain principal component model)	2.000000e-09
GCST007325_39	General risk tolerance (MTAG)	4.000000e-08
GCST007576_79	Chronotype	4.000000e-09
GCST008526_13	Coffee consumption	9.000000e-07
GCST010002_387	Refractive error	2.000000e-09
GCST90002404_14	Red cell distribution width	5.000000e-19

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement
EFO:0006781	coffee consumption measurement
EFO:0009188	Red cell distribution width

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
C536865	Spastic paraplegia 4, autosomal dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Inhibitors of apoptosis (IAP) protein family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects cotreatment, decreases expression, decreases response to substance	3
bisphenol A	decreases expression, decreases methylation	2
Benzo(a)pyrene	affects methylation, increases mutagenesis	2
Estradiol	increases expression	2
Fluorouracil	affects response to substance, decreases response to substance	2
Aflatoxin B1	increases methylation, decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
propylparaben	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression, increases abundance	1
tetrabromobisphenol A	increases expression	1
manganese chloride	decreases expression, increases abundance	1
aflatoxin B2	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
brevetoxin 2	increases expression	1
5-OH-BDE-47	decreases expression	1
6-OH-BDE-47	decreases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Caffeine	affects phosphorylation	1
Dieldrin	increases response to substance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SF21	HAP1 BIRC6 (-) 1	Cancer cell line	Male
CVCL_SF22	HAP1 BIRC6 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety