BIRC5

Summary

BIRC5 (baculoviral IAP repeat containing 5, HGNC:593) is a protein-coding gene on chromosome 17q25.3, encoding Baculoviral IAP repeat-containing protein 5 (O15392). Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis. In precision oncology, BIRC5 NUCLEAR EXPRESSION confers sensitivity to Platinum Compound + Taxane Compound in Lung Non-small Cell Carcinoma (CIViC Level B); 1 further curated variant–drug associations are listed below. It is a common-essential gene (DepMap: required in 99.7% of cancer cell lines).

This gene is a member of the inhibitor of apoptosis (IAP) gene family, which encode negative regulatory proteins that prevent apoptotic cell death. IAP family members usually contain multiple baculovirus IAP repeat (BIR) domains, but this gene encodes proteins with only a single BIR domain. The encoded proteins also lack a C-terminus RING finger domain. Gene expression is high during fetal development and in most tumors, yet low in adult tissues. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 332 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 30 total — 1 likely-pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_001168

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:593
Approved symbol	BIRC5
Name	baculoviral IAP repeat containing 5
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	EPR-1, survivin
Ensembl gene	ENSG00000089685
Ensembl biotype	protein_coding
OMIM	603352
Entrez	332

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000301633, ENST00000350051, ENST00000374948, ENST00000586192, ENST00000587746, ENST00000589892, ENST00000590449, ENST00000590925, ENST00000591800, ENST00000592115, ENST00000592734, ENST00000917427

RefSeq mRNA: 3 — MANE Select: NM_001168 NM_001012270, NM_001012271, NM_001168

CCDS: CCDS11755, CCDS32751, CCDS32752

Canonical transcript exons

ENST00000350051 — 4 exons

Exon	Start	End
ENSE00001305879	78214253	78214427
ENSE00003498592	78214680	78214789
ENSE00003672851	78216664	78216781
ENSE00003848974	78223465	78225635

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 96.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 64.6074 / max 515.8674, expressed in 1538 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163043	55.1636	1519
163044	9.4438	1270

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	96.49	gold quality
ganglionic eminence	UBERON:0004023	93.54	gold quality
embryo	UBERON:0000922	93.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.95	gold quality
left testis	UBERON:0004533	87.59	gold quality
right testis	UBERON:0004534	87.19	gold quality
testis	UBERON:0000473	86.71	gold quality
mucosa of transverse colon	UBERON:0004991	86.30	gold quality
bone marrow	UBERON:0002371	86.28	gold quality
trabecular bone tissue	UBERON:0002483	85.60	gold quality
stromal cell of endometrium	CL:0002255	84.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.63	gold quality
bone element	UBERON:0001474	84.52	gold quality
bone marrow cell	CL:0002092	82.45	gold quality
thymus	UBERON:0002370	82.41	gold quality
tongue squamous epithelium	UBERON:0006919	81.91	silver quality
esophagus mucosa	UBERON:0002469	81.59	gold quality
lower esophagus mucosa	UBERON:0035834	80.67	gold quality
secondary oocyte	CL:0000655	80.18	gold quality
vermiform appendix	UBERON:0001154	79.57	gold quality
rectum	UBERON:0001052	78.63	gold quality
ileal mucosa	UBERON:0000331	78.19	gold quality
esophagus squamous epithelium	UBERON:0006920	76.58	gold quality
epithelium of esophagus	UBERON:0001976	76.31	gold quality
caecum	UBERON:0001153	76.16	gold quality
lymph node	UBERON:0000029	75.65	gold quality
adrenal tissue	UBERON:0018303	74.90	gold quality
squamous epithelium	UBERON:0006914	74.68	gold quality
oral cavity	UBERON:0000167	74.34	gold quality
gingival epithelium	UBERON:0001949	73.31	silver quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-MTAB-7051	yes	4309.11
E-GEOD-75140	yes	1210.20
E-MTAB-9435	yes	1004.08
E-GEOD-110499	yes	761.70
E-MTAB-10662	yes	759.52
E-ENAD-20	yes	675.25
E-MTAB-7249	yes	645.33
E-MTAB-7052	yes	374.16
E-MTAB-8530	yes	328.08
E-MTAB-9067	yes	298.22
E-MTAB-6678	yes	155.99
E-HCAD-1	yes	41.47
E-CURD-112	yes	39.35
E-HCAD-10	yes	39.04
E-HCAD-13	yes	25.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APC, BHLHE40, CTNNB1, CTNNBL1, DNMT1, E2F1, E2F2, E2F3, E2F4, EGR1, EHMT2, EP300, ESR1, ESR2, FHIT, FOXC1, FOXM1, FOXO1, FOXO3, GATA1, GATA3, GFI1, GTF3A, HDAC1, HIF1A, HLF, ILF3, IRF1, KLF4, KLF5, LEF1, MYBL2, MYC, MYCN, NFKB1, NFKB, NONO, NR4A1, PARP1, PAX1

miRNA regulators (miRDB)

52 targeting BIRC5, 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-4283	100.00	66.42	2097
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-218-5P	99.93	72.22	2103
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-6873-5P	98.45	66.14	1417

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Relative levels of expression of survivin mRNA and survivin protein increased after low- and high-dose CDDP treatment. Survivin mRNA was not detected in normal gastric mucosas. (PMID:11712083)
• data demonstrate a crucial role of PI3-kinase/Akt/NF-kappaB/survivin signaling in tubular morphogenesis of HCAEC triggered by hypoxic preconditioning. (PMID:11728454)
• Expression of survivin mRNA and protein in gastric cancer cell line (MKN-45) during cisplatin treatment (PMID:11773702)
• Survivin was expressed in all thymocyte subsets but its expression level was developmentally regulated. (PMID:11821157)
• expression associated with reduced survival and reduced apoptotic capacity in gliomas (PMID:11844831)
• Data demonstrate that the primary survivin pool in mitotic cells is associated with microtubules and participates in the assembly of a bipolar mitotic spindle. (PMID:11861764)
• expression of alternative survivin splice varients related to gastric tumor progression (PMID:11875736)
• The ratio of survivin to Fas in primary tumors may be used to predict the risk for recurrent disease in patients with neuroblastoma. (PMID:11877677)
• survivin may represent a novel neuroendocrine marker for chromaffin cell tumors, survivin does not appear to reliably distinguish benign from malignant pheochromocytomas/paragangliomas and thus does not identify patients at risk of recurrent disease (PMID:11888845)
• This nuclear shuttling protein is exported actively from the nucleus via the CRM1-dependent pathway. (PMID:11925104)
• Expression in primary glioblastomas. (PMID:12073047)
• survivin expression freqently seen in gastric cancer patients and first-degree relatives; co-expression with cyclooxygenase-2 suggests multiple pathways contributing to apoptosis inhibition in gastric cancer (PMID:12085263)
• expression of functionally different survivin splice variants suggests a role in the progression and clinical behavior of human renal cell carcinomas (PMID:12115583)
• Survivin expression was significantly associated with PCNA-labeling index, clinical stage, histological grade, clinical outcome, and survival rate in ovarian epithelial carcinomas. (PMID:12119561)
• Higher expression level of surviving mRNA in primary leukemic cells from acute leukemia patients may be one of the reasons that leukemic cells are insensitive to chemotherapy. (PMID:12133447)
• Survivin was not likely to be related with an inhibition of apoptosis or induction of telomerase but may have some role in gastric cancer extension. (PMID:12143224)
• comparative study of expression of survivin in primary and metastatic colonic adenocarcinomas (PMID:12168867)
• expression in laryngeal squamous cell carcinomas and its prognostic implications (PMID:12174930)
• studies define a novel p53-survivin signaling pathway activated by DNA damage that results in down-regulation of survivin, cell cycle arrest, and apoptosis (PMID:12235242)
• cellular studies and clinical data suggest a direct link between survivin expression and tumour cell susceptibility to taxol (PMID:12363043)
• survivin not only suppresses apoptosis but also accelerates cancer cell-proliferative activity and plays an important role in tumor progression in hepatocellular carcinoma (PMID:12374680)
• Reovirus-induced apoptosis involves reduction of cellular survivin levels (PMID:12388702)
• findings suggest that activated STAT3 signaling directly contributes to malignant progression of primary effusion lymphoma by preventing apoptosis, acting through the prosurvival protein survivin (PMID:12393476)
• These results indicate that survivin stimulates Aurora-B kinase activity and helps correctly target Aurora-B to its substrates during the cell cycle, thus providing a mechanism as to how survivin exerts its function in human cells. (PMID:12419797)
• Survivin may be actively involved in regulating cell viability during HIV-1 infection (PMID:12510154)
• Suppression of phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis. (PMID:12517802)
• the determination of nuclear survivin expression could be used to individualise therapeutic strategies in oesophageal squamous cell cancer in the future. (PMID:12556969)
• Survivin expression in astrocytic tumors varies with histologic malignancy and may play an important role in the oncogenesis and progression of astrocytic tumors (PMID:12569609)
• The level of survivin was decreased after thapsigargin treatment in hepatoma cell lines indicating that survivin plays an important role in endoplasmic reticulum stress-mediated apoptosis. (PMID:12609713)
• We conclude that the changes in the level of caspase-3 and survivin play an important role in the transformation from normal gastric mucosa to gastric cancer. (PMID:12643601)
• Survivin is an important inhibitor of apoptosis in colorectal cancer cell lines. (PMID:12654446)
• role in pathological conditions-REVIEW (PMID:12678716)
• Survivin is expressed in embryonic tissues as well as in the majority of human cancers, but is not expressed in most normal adult tissues. (PMID:12709681)
• Survivin-HBXIP complexes, but neither survivin nor HBXIP individually, bind pro-caspase-9, preventing its recruitment to Apaf1, and thereby selectively suppressing apoptosis. (PMID:12773388)
• survivin may play an important role in transition from intraductal papillary-mucinous tumor of the pancreas adenoma to carcinoma in situ (PMID:12794243)
• Data show that mammalian cells lacking survivin are unable to align their chromosomes, fail to recruit Aurora B to kinetochores and become polyploid at a very high frequency. (PMID:12805209)
• survivin is upregulated by oncogenic c-H-Ras in tumor cells (PMID:12833149)
• survivin plays an important role in the onset of gastric carcinoma and that high survivin expression is an early event of gastric carcinoma. (PMID:12854136)
• survivin has a role in the dedifferentiation of thyroid carcinoma (PMID:12883703)
• Expression of non-destructible beta catenin mutants increased survivin expression and protected against ultraviolet-B-induced apoptosis. (PMID:12885482)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	birc5a	ENSDARG00000075621
mus_musculus	Birc5	ENSMUSG00000017716
rattus_norvegicus	Birc5	ENSRNOG00000050819
drosophila_melanogaster	Diap2	FBGN0015247
caenorhabditis_elegans		WBGENE00000250

Paralogs (7): BIRC3 (ENSG00000023445), NLRC4 (ENSG00000091106), BIRC7 (ENSG00000101197), XIAP (ENSG00000101966), BIRC2 (ENSG00000110330), BIRC6 (ENSG00000115760), NAIP (ENSG00000249437)

Protein

Protein identifiers

Baculoviral IAP repeat-containing protein 5 — O15392 (reviewed: O15392)

Alternative names: Apoptosis inhibitor 4, Apoptosis inhibitor survivin

All UniProt accessions (6): O15392, A0A0B4J1S3, H3BLT4, K7ELG2, K7EMW2, K7EP76

UniProt curated annotations — full annotation on UniProt →

Function. Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis. Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis. Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules. Involved in the recruitment of CPC to centromeres during early mitosis via association with histone H3 phosphorylated at ‘Thr-3’ (H3pT3) during mitosis. The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. May counteract a default induction of apoptosis in G2/M phase. The acetylated form represses STAT3 transactivation of target gene promoters. May play a role in neoplasia. Inhibitor of CASP3 and CASP7. Essential for the maintenance of mitochondrial integrity and function. Isoform 2 and isoform 3 do not appear to play vital roles in mitosis. Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform.

Subunit / interactions. Monomer or homodimer. Exists as a homodimer in the apo state and as a monomer in the CPC-bound state. The monomer protects cells against apoptosis more efficiently than the dimer. Only the dimeric form is capable of enhancing tubulin stability in cells. When phosphorylated, interacts with LAMTOR5/HBXIP; the resulting complex binds pro-CASP9, as well as active CASP9, but much less efficiently. Component of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB or AURKC; in the complex forms a triple-helix bundle-based subcomplex with INCENP and CDCA8. Interacts with JTB. Interacts (via BIR domain) with histone H3 phosphorylated at ‘Thr-3’ (H3pT3). Interacts with EVI5. Interacts with GTP-bound RAN in both the S and M phases of the cell cycle. Interacts with USP9X. Interacts with tubulin. Interacts with BIRC2/c-IAP1. The acetylated form at Lys-129 interacts with STAT3. The monomeric form deacetylated at Lys-129 interacts with XPO1/CRM1. The monomeric form interacts with XIAP/BIRC4. Both the dimeric and monomeric form can interact with DIABLO/SMAC. Interacts with BIRC6/bruce. Interacts with FBXL7; this interaction facilitates the polyubiquitination and subsequent proteasomal degradation of BIRC5 by the SCF(FBXL7) E3 ubiquitin-protein ligase complex. (Microbial infection) Interacts with Epstein-Barr virus (EBV) EBNA1; this interaction is probably important for EBV episome maintenance in Burkitt’s lymphoma cells.

Subcellular location. Cytoplasm. Nucleus. Chromosome. Centromere. Cytoskeleton. Spindle. Kinetochore. Midbody.

Tissue specificity. Expressed only in fetal kidney and liver, and to lesser extent, lung and brain. Abundantly expressed in adenocarcinoma (lung, pancreas, colon, breast, and prostate) and in high-grade lymphomas. Also expressed in various renal cell carcinoma cell lines. Expressed in cochlea including the organ of Corti, the lateral wall, the interdental cells of the Limbus as well as in Schwann cells and cells of the cochlear nerve and the spiral ganglions (at protein level). Not expressed in cells of the inner and outer sulcus or the Reissner’s membrane (at protein level).

Post-translational modifications. Ubiquitinated by the Cul9-RING ubiquitin-protein ligase complex, leading to its degradation. Ubiquitination is required for centrosomal targeting. Deubiquitinated by USP35 or USP38; leading to stabilization. In vitro phosphorylation at Thr-117 by AURKB prevents interaction with INCENP and localization to mitotic chromosomes. Phosphorylation at Thr-48 by CK2 is critical for its mitotic and anti-apoptotic activities. Phosphorylation at Thr-34 by CDK15 is critical for its anti-apoptotic activity. Phosphorylation at Ser-20 by AURKC is critical for regulation of proper chromosome alignment and segregation, and possibly cytokinesis. Acetylation at Lys-129 by CBP results in its homodimerization, while deacetylation promotes the formation of monomers which heterodimerize with XPO1/CRM1 which facilitates its nuclear export. The acetylated form represses STAT3 transactivation. The dynamic equilibrium between its acetylation and deacetylation at Lys-129 determines its interaction with XPO1/CRM1, its subsequent subcellular localization, and its ability to inhibit STAT3 transactivation.

Domain organisation. The BIR repeat is necessary and sufficient for LAMTOR5 binding.

Induction. Up-regulated by COMP.

Similarity. Belongs to the IAP family.

Isoforms (7)

UniProt ID	Names	Canonical?
O15392-1	1, Alpha	yes
O15392-2	2, 2B, Beta
O15392-3	3, DeltaEx3
O15392-4	4, 3B
O15392-5	5, SI
O15392-6	6, 3 alpha
O15392-7	7, 2 alpha

RefSeq proteins (3): NP_001012270, NP_001012271, NP_001159* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001370	BIR_rpt	Repeat
IPR051190	Baculoviral_IAP	Family

Pfam: PF00653

UniProt features (65 total): mutagenesis site 22, modified residue 11, helix 7, splice variant 6, strand 5, binding site 4, sequence conflict 3, turn 3, chain 1, repeat 1, sequence variant 1, site 1

Structure

Experimental structures (PDB)

36 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2QFA	X-RAY DIFFRACTION	1.4
9TPI	X-RAY DIFFRACTION	1.8
6YIF	X-RAY DIFFRACTION	1.81
9TPH	X-RAY DIFFRACTION	2
3UEC	X-RAY DIFFRACTION	2.18
2RAW	X-RAY DIFFRACTION	2.4
3UIG	X-RAY DIFFRACTION	2.4
3UIH	X-RAY DIFFRACTION	2.4
8RUP	ELECTRON MICROSCOPY	2.42
3UEF	X-RAY DIFFRACTION	2.45
7LBO	X-RAY DIFFRACTION	2.5
6YIH	X-RAY DIFFRACTION	2.55
1F3H	X-RAY DIFFRACTION	2.58
3UEH	X-RAY DIFFRACTION	2.6
3UII	X-RAY DIFFRACTION	2.6
7LBP	X-RAY DIFFRACTION	2.6
4A0I	X-RAY DIFFRACTION	2.6
3UEE	X-RAY DIFFRACTION	2.61
7LBQ	X-RAY DIFFRACTION	2.69
3UED	X-RAY DIFFRACTION	2.7
3UEI	X-RAY DIFFRACTION	2.7
7LBK	X-RAY DIFFRACTION	2.7
3UIK	X-RAY DIFFRACTION	2.7
3UIJ	X-RAY DIFFRACTION	2.71
1E31	X-RAY DIFFRACTION	2.71
4A0N	X-RAY DIFFRACTION	2.74
3UEG	X-RAY DIFFRACTION	2.8
4A0J	X-RAY DIFFRACTION	2.8
9SI3	ELECTRON MICROSCOPY	2.83
9SJ5	ELECTRON MICROSCOPY	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15392-F1	95.07	0.91

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): 126 (interaction with fbxl7)

Ligand- & substrate-binding residues (4): 57; 60; 77; 84

Post-translational modifications (11): 48, 90, 110, 112, 115, 117, 121, 129, 20, 23, 34

Mutagenesis-validated functional residues (22):

Position	Phenotype
18	disrupts interaction with histone h3pt3, no effect on interaction with incenp.
23	increases ubiquitination and blocks dissociation from centromeres; when associated with r-62; r-78 and r-79.
25	disrupts interaction with histone h3pt3, no effect on interaction with incenp.
33	disrupts interaction with histone h3pt3, no effect on interaction with incenp.
34	loss of lamtor5 binding.
34	higher affinity for lamtor5 binding.
48	localizes normally during mitosis but cannot support cell proliferation. increased affinity for cdca8/borealin.
57	disrupts interaction with histone h3pt3, no effect on interaction with incenp.
62	increases ubiquitination and blocks dissociation from centromeres; when associated with r-23; r-78 and r-79.
65	almost abolishes ran-binding. does not disrupt binding to aurkb or cdca8. disrupts mitotic spindle assembly. does not di
67	disrupts interaction with histone h3pt3, no effect on interaction with incenp.
70	no change. loss of interaction with aurkb; when associated with a-71.
71	no change. loss of interaction with aurkb; when associated with a-70.
78	increases ubiquitination and blocks dissociation from centromeres; when associated with r-23; r-62 and r-79.
79	increases ubiquitination and blocks dissociation from centromeres; when associated with r-23; r-62 and r-78.
84	loss of cytoprotection.
90–91	loss of fbxl7 mediated polyubiquitination.
117	prevents phosphorylation by aurkb. still able to localize correctly but prevents interaction with incenp.
117	mimics phosphorylation. disrupts subcellular localization during mitosis and prevents interaction with incenp.
126	loss of fbxl7 binding.
129	mimics acetylation. localization primarily within the nucleus.
129	loss of acetylation. localization primarily within the cytoplasm.

Function

Pathways and Gene Ontology

Reactome pathways

34 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-4615885	SUMOylation of DNA replication proteins
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-6803205	TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain
R-HSA-68877	Mitotic Prometaphase
R-HSA-8951664	Neddylation
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-212436	Generic Transcription Pathway
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-392499	Metabolism of proteins
R-HSA-449147	Signaling by Interleukins
R-HSA-5633008	TP53 Regulates Transcription of Cell Death Genes
R-HSA-597592	Post-translational protein modification
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69618	Mitotic Spindle Checkpoint

MSigDB gene sets: 548 (showing top): GNF2_CKS1B, GOBP_MITOTIC_CYTOKINESIS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, HORIUCHI_WTAP_TARGETS_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, KANG_DOXORUBICIN_RESISTANCE_UP, GNF2_CENPF, SEMBA_FHIT_TARGETS_DN, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_CHROMOSOME_LOCALIZATION, GOBP_CELL_CYCLE_PHASE_TRANSITION

GO Biological Process (29): G2/M transition of mitotic cell cycle (GO:0000086), mitotic cell cycle (GO:0000278), mitotic cytokinesis (GO:0000281), apoptotic process (GO:0006915), mitotic spindle organization (GO:0007052), chromosome segregation (GO:0007059), mitotic spindle assembly checkpoint signaling (GO:0007094), sensory perception of sound (GO:0007605), positive regulation of cell population proliferation (GO:0008284), protein-containing complex localization (GO:0031503), positive regulation of exit from mitosis (GO:0031536), negative regulation of apoptotic process (GO:0043066), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of mitotic cell cycle (GO:0045931), chromosome localization (GO:0050000), mitotic spindle midzone assembly (GO:0051256), cell division (GO:0051301), positive regulation of mitotic cell cycle spindle assembly checkpoint (GO:0090267), mitotic spindle assembly (GO:0090307), positive regulation of mitotic sister chromatid separation (GO:1901970), positive regulation of attachment of mitotic spindle microtubules to kinetochore (GO:1902425), positive regulation of mitotic cytokinesis (GO:1903490), microtubule cytoskeleton organization (GO:0000226), meiosis I (GO:0007127), regulation of mitotic cell cycle (GO:0007346), regulation of apoptotic process (GO:0042981), negative regulation of neuron apoptotic process (GO:0043524), regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0061178), regulation of type B pancreatic cell proliferation (GO:0061469)

GO Molecular Function (15): cysteine-type endopeptidase inhibitor activity (GO:0004869), microtubule binding (GO:0008017), zinc ion binding (GO:0008270), tubulin binding (GO:0015631), enzyme binding (GO:0019899), small GTPase binding (GO:0031267), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), cysteine-type endopeptidase inhibitor activity involved in apoptotic process (GO:0043027), metal ion binding (GO:0046872), protein heterodimerization activity (GO:0046982), cobalt ion binding (GO:0050897), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (21): nuclear chromosome (GO:0000228), chromosome, centromeric region (GO:0000775), kinetochore (GO:0000776), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centriole (GO:0005814), cytosol (GO:0005829), microtubule (GO:0005874), spindle microtubule (GO:0005876), cytoplasmic microtubule (GO:0005881), microtubule cytoskeleton (GO:0015630), midbody (GO:0030496), interphase microtubule organizing center (GO:0031021), chromosome passenger complex (GO:0032133), protein-containing complex (GO:0032991), spindle midzone (GO:0051233), survivin complex (GO:1990713), chromosome (GO:0005694), spindle (GO:0005819), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Mitotic Prometaphase	2
M Phase	2
Post-translational protein modification	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
SUMO E3 ligases SUMOylate target proteins	1
RHO GTPase Effectors	1
Signaling by Interleukins	1
TP53 Regulates Transcription of Cell Death Genes	1
Immune System	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitotic cell cycle	5
cellular anatomical structure	5
intracellular membraneless organelle	4
mitotic nuclear division	3
protein binding	3
mitotic cell cycle process	2
transition metal ion binding	2
protein dimerization activity	2
nuclear lumen	2
microtubule organizing center	2
cytoplasm	2
microtubule cytoskeleton	2
spindle	2
microtubule	2
mitotic cell cycle phase transition	1
cell cycle G2/M phase transition	1
cell cycle	1
cytoskeleton-dependent cytokinesis	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
cell cycle process	1
negative regulation of mitotic metaphase/anaphase transition	1
spindle assembly checkpoint signaling	1
mitotic spindle checkpoint signaling	1
sensory perception of mechanical stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
macromolecule localization	1
regulation of exit from mitosis	1
exit from mitosis	1
positive regulation of mitotic cell cycle phase transition	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1

Protein interactions and networks

STRING

3746 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BIRC5	CDCA8	Q53HL2	997
BIRC5	AURKB	Q96GD4	997
BIRC5	INCENP	Q9NQS7	995
BIRC5	CCNB2	O95067	892
BIRC5	CDK1	P06493	890
BIRC5	CCNB1	P14635	885
BIRC5	AURKA	O14965	866
BIRC5	BUB1	O43683	866
BIRC5	XIAP	P98170	855
BIRC5	CENPE	Q02224	834
BIRC5	BUB1B	O60566	834
BIRC5	TOP2A	P11388	829
BIRC5	CENPF	P49454	826
BIRC5	BIRC7	Q96CA5	821
BIRC5	UBE2C	O00762	820

IntAct

171 interactions, top by confidence:

A	B	Type	Score
BIRC5	CDCA8	psi-mi:“MI:0407”(direct interaction)	0.960
CDCA8	BIRC5	psi-mi:“MI:0914”(association)	0.960
CDCA8	BIRC5	psi-mi:“MI:0915”(physical association)	0.960
CDCA8	BIRC5	psi-mi:“MI:0407”(direct interaction)	0.960
BIRC5	CDCA8	psi-mi:“MI:0915”(physical association)	0.960
BIRC5	CDCA8	psi-mi:“MI:0403”(colocalization)	0.960
BIRC5	CDCA8	psi-mi:“MI:2364”(proximity)	0.960
AURKB	BIRC5	psi-mi:“MI:0914”(association)	0.950
BIRC5	AURKB	psi-mi:“MI:0915”(physical association)	0.950
AURKB	BIRC5	psi-mi:“MI:0915”(physical association)	0.950
BIRC5	AURKB	psi-mi:“MI:0217”(phosphorylation reaction)	0.950
AURKB	BIRC5	psi-mi:“MI:2364”(proximity)	0.950
AURKB	BIRC5	psi-mi:“MI:0407”(direct interaction)	0.950
INCENP	BIRC5	psi-mi:“MI:0914”(association)	0.920

BioGRID (305): AIP (Affinity Capture-Western), BIRC5 (Affinity Capture-Western), BIRC5 (Affinity Capture-MS), BIRC5 (Reconstituted Complex), DIABLO (Reconstituted Complex), DIABLO (FRET), BIRC5 (Affinity Capture-Western), BIRC5 (Reconstituted Complex), BIRC5 (Reconstituted Complex), BIRC5 (Reconstituted Complex), RAN (Co-localization), RAN (Affinity Capture-Western), BIRC5 (Proximity Label-MS), CASP9 (Co-localization), BIRC5 (Affinity Capture-Western)

ESM2 similar proteins: A1A5G2, B3DLA6, E1BGQ2, E3SCZ8, O15392, O70201, O88597, O95453, P23727, P26450, P27986, P42694, P61798, P69341, Q13572, Q14457, Q4A1L4, Q4A1L5, Q5F407, Q5F480, Q5M939, Q5R685, Q5R878, Q5RAH9, Q5RC51, Q5ZIA0, Q5ZKS6, Q63787, Q6DC64, Q6DDJ3, Q6DFV5, Q6DJB3, Q6GP52, Q6GR37, Q6I6F4, Q6J1J1, Q6NRC7, Q6NYU2, Q7T0P6, Q80YV4

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

21 interactions.

A	Effect	B	Mechanism
TP53	down-regulates	BIRC5	binding
CDK1	up-regulates	BIRC5	phosphorylation
TP53	“down-regulates quantity by repression”	BIRC5	“transcriptional regulation”
BIRC5	up-regulates	XIAP	binding
AURKB	down-regulates	BIRC5	phosphorylation
BIRC5	down-regulates	DIABLO	binding
DIABLO	down-regulates	BIRC5	binding
FHIT	“down-regulates quantity by repression”	BIRC5	“transcriptional regulation”
PLK1	up-regulates	BIRC5	phosphorylation
STAT3	“up-regulates quantity by expression”	BIRC5	“transcriptional regulation”
“sepantronium bromide”	“down-regulates activity”	BIRC5	“chemical inhibition”
BIRC5	“form complex”	CPC	binding
CUL9	“down-regulates quantity”	BIRC5	ubiquitination
BIRC5	down-regulates	CASP3	binding
BIRC5	down-regulates	CASP9	binding
FBXL7	“down-regulates quantity by destabilization”	BIRC5	binding
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	BIRC5	polyubiquitination
E2F4	“down-regulates quantity by repression”	BIRC5	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	5	17.7×	4e-04
Resolution of Sister Chromatid Cohesion	6	15.7×	2e-04
EML4 and NUDC in mitotic spindle formation	5	14.1×	9e-04
Mitotic Prometaphase	6	12.6×	4e-04
RHO GTPases Activate Formins	5	11.8×	2e-03
Separation of Sister Chromatids	5	9.2×	4e-03
Cell Cycle, Mitotic	5	7.3×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitotic cell cycle	7	21.8×	6e-06
negative regulation of gene expression	5	8.0×	8e-03
cell division	7	7.5×	2e-03
negative regulation of apoptotic process	7	5.7×	5e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	19
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
146403	GRCh38/hg38 17q25.3(chr17:78225356-80099979)x1	Likely pathogenic

SpliceAI

1253 predictions. Top by Δscore:

Variant	Effect	Δscore
17:78214424:GCGG:G	donor_gain	1.0000
17:78214425:CGGG:C	donor_loss	1.0000
17:78214426:GGGTG:G	donor_loss	1.0000
17:78214427:GGTGA:G	donor_loss	1.0000
17:78214428:G:GA	donor_loss	1.0000
17:78214674:TTGCA:T	acceptor_loss	1.0000
17:78214676:GCAG:G	acceptor_loss	1.0000
17:78214678:A:AG	acceptor_gain	1.0000
17:78214678:AGAT:A	acceptor_gain	1.0000
17:78214679:G:GG	acceptor_gain	1.0000
17:78214679:GAT:G	acceptor_gain	1.0000
17:78214679:GATG:G	acceptor_gain	1.0000
17:78214785:CCCAT:C	donor_gain	1.0000
17:78214786:CCAT:C	donor_gain	1.0000
17:78214787:CAT:C	donor_gain	1.0000
17:78214788:AT:A	donor_gain	1.0000
17:78214788:ATG:A	donor_loss	1.0000
17:78214789:TGT:T	donor_loss	1.0000
17:78214790:G:GG	donor_gain	1.0000
17:78214791:T:G	donor_loss	1.0000
17:78216778:AATT:A	donor_gain	1.0000
17:78216782:G:GG	donor_gain	1.0000
17:78223462:CAG:C	acceptor_loss	1.0000
17:78223463:A:AC	acceptor_loss	1.0000
17:78223463:A:AG	acceptor_gain	1.0000
17:78223464:G:GG	acceptor_gain	1.0000
17:78214426:GG:G	donor_gain	0.9900
17:78214427:GG:G	donor_gain	0.9900
17:78214428:G:GG	donor_gain	0.9900
17:78214429:T:A	donor_loss	0.9900

AlphaMissense

953 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:78214767:T:A	W67R	1.000
17:78214767:T:C	W67R	1.000
17:78214769:G:C	W67C	1.000
17:78214769:G:T	W67C	1.000
17:78214768:G:C	W67S	0.999
17:78214389:T:A	W25R	0.998
17:78214389:T:C	W25R	0.998
17:78214391:G:C	W25C	0.998
17:78214391:G:T	W25C	0.998
17:78214693:G:A	G42D	0.998
17:78214696:T:C	F43S	0.998
17:78214737:T:C	C57R	0.998
17:78214768:G:T	W67L	0.998
17:78214746:T:C	C60R	0.997
17:78214759:T:C	L64P	0.997
17:78214786:C:A	P73H	0.997
17:78214681:T:C	M38T	0.996
17:78214692:G:C	G42R	0.996
17:78214693:G:T	G42V	0.996
17:78214748:C:G	C60W	0.996
17:78214764:G:C	G66R	0.996
17:78214767:T:G	W67G	0.996
17:78214368:C:A	R18S	0.995
17:78214395:T:C	F27L	0.995
17:78214397:C:A	F27L	0.995
17:78214397:C:G	F27L	0.995
17:78214695:T:C	F43L	0.995
17:78214697:C:A	F43L	0.995
17:78214697:C:G	F43L	0.995
17:78214737:T:A	C57S	0.995

dbSNP variants (sampled 300 via entrez): RS1000008750 (17:78216533 C>A,G,T), RS1000274575 (17:78221364 G>T), RS1000353713 (17:78215741 ATTC>A), RS1000691506 (17:78217062 T>A), RS1000964020 (17:78215365 C>A,T), RS1001078706 (17:78215199 C>T), RS1001124830 (17:78221332 G>A), RS1001193535 (17:78215838 G>A), RS1001260510 (17:78216280 A>G), RS1001304179 (17:78221117 G>A), RS1001406089 (17:78222096 G>A,C), RS1001428077 (17:78221894 G>A), RS1001514296 (17:78216168 G>A,C), RS1001564658 (17:78217419 A>C,G), RS1002813236 (17:78220808 C>A,G)

Disease associations

OMIM: gene MIM:603352 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002039_1	Blood trace element (Se levels)	5.000000e-06
GCST002127_11	Periodontitis (Mean PAL)	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5989 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,707 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL232201	BENZIODARONE	4	1,341
CHEMBL2105734	SEPANTRONIUM BROMIDE	2	366

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
BIRC5 NUCLEAR EXPRESSION	Platinum Compound + Taxane Compound	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID874
BIRC5 Overexpression	Trastuzumab	Her2-receptor Positive Breast Cancer	Resistance	CIViC B	EID1449

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9904341	BIRC5		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

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

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound III [PMID: 24080463]	Inhibition	4.6	pIC50

ChEMBL bioactivities

39 potent at pChembl≥5 of 41 total, top 39 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.55	IC50	2.8	nM	SEPANTRONIUM BROMIDE
8.52	IC50	3	nM	SEPANTRONIUM BROMIDE
8.36	IC50	4.4	nM	SEPANTRONIUM BROMIDE
8.10	IC50	7.9	nM	SEPANTRONIUM BROMIDE
8.05	IC50	8.9	nM	SEPANTRONIUM BROMIDE
7.86	IC50	13.9	nM	SEPANTRONIUM BROMIDE
7.47	Kd	34	nM	CHEMBL4793552
7.43	Kd	37	nM	CHEMBL234358
7.36	Kd	44	nM	CHEMBL234358
7.32	Kd	48	nM	CHEMBL233848
7.22	Kd	60	nM	CHEMBL272921
7.19	Kd	64	nM	CHEMBL234330
7.12	Kd	76	nM	CHEMBL234040
7.07	Kd	86	nM	CHEMBL232404
7.00	Kd	100	nM	CHEMBL234421
6.70	Kd	200	nM	CHEMBL234041
6.66	Kd	220	nM	CHEMBL396856
6.62	Kd	240	nM	CHEMBL4637348
6.58	Kd	260	nM	CHEMBL394046
6.36	Kd	440	nM	CHEMBL428195
6.31	Kd	490	nM	CHEMBL236619
6.29	Kd	510	nM	CHEMBL232402
6.28	Kd	530	nM	CHEMBL392286
6.28	Kd	520	nM	CHEMBL236620
6.21	Kd	620	nM	CHEMBL392285
6.16	Kd	700	nM	CHEMBL391681
6.16	Kd	700	nM	CHEMBL391106
6.10	Kd	800	nM	CHEMBL393124
6.09	Kd	810	nM	CHEMBL393124
6.06	Kd	880	nM	CHEMBL234608
5.93	Kd	1170	nM	CHEMBL236829
5.53	Kd	2980	nM	CHEMBL234852
5.37	Kd	4270	nM	CHEMBL4862376
5.30	Kd	5000	nM	CHEMBL391586
5.30	Kd	5000	nM	CHEMBL233218
5.24	Kd	5700	nM	CHEMBL391586
5.12	Kd	7560	nM	CHEMBL399196
5.10	Kd	8000	nM	BENZIODARONE
5.00	Kd	1e+04	nM	CHEMBL397092

PubChem BioAssay actives

41 with measured affinity, of 155 total; 33 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-(2-methoxyethyl)-2-methyl-3-(pyrazin-2-ylmethyl)benzo[f]benzimidazol-3-ium-4,9-dione bromide	2196883: Inhibition of survivin in Melphalan Resistant human RPMI-8226 cells assessed as reduction of cell growth incubated for 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay	ic50	0.0028	uM
N-[[5-chloro-3-[5-cyano-4-[2-iodo-5-(trifluoromethyl)phenyl]-6-oxo-1H-pyridin-2-yl]-2-hydroxyphenyl]methyl]-N-methyl-1-propylpiperidine-4-carboxamide	1685623: Binding affinity to recombinant full length N-terminal GST-tagged human survivin expressed in Escherichia coli BL21 incubated for 1 hr under shaking condition by fluorescence microplate reader assay	kd	0.0340	uM
N-[[5-chloro-3-[4-[2-chloro-5-(trifluoromethyl)phenyl]-5-cyano-6-oxo-1H-pyridin-2-yl]-2-hydroxyphenyl]methyl]-N-methyl-1-propylpiperidine-4-carboxamide	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.0370	uM
1-acetyl-N-[[5-chloro-3-[4-[2-chloro-5-(trifluoromethyl)phenyl]-5-cyano-6-oxo-1H-pyridin-2-yl]-2-hydroxyphenyl]methyl]piperidine-4-carboxamide	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.0480	uM
1-butanoyl-N-[[5-chloro-3-[4-[2-chloro-5-(trifluoromethyl)phenyl]-5-cyano-6-oxo-1H-pyridin-2-yl]-2-hydroxyphenyl]methyl]-N-methylpiperidine-4-carboxamide	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.0600	uM
N-[[5-chloro-3-[4-[2-chloro-5-(trifluoromethyl)phenyl]-5-cyano-6-oxo-1H-pyridin-2-yl]-2-hydroxyphenyl]methyl]-1-(2-methoxyacetyl)-N-methylpiperidine-4-carboxamide	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.0640	uM
N-[[5-chloro-3-[4-[2-chloro-5-(trifluoromethyl)phenyl]-5-cyano-6-oxo-1H-pyridin-2-yl]-2-hydroxyphenyl]methyl]-N-methyl-3-morpholin-4-ylpropanamide	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.0760	uM
1-acetyl-N-[[5-chloro-3-[4-[2-chloro-5-(trifluoromethyl)phenyl]-5-cyano-6-oxo-1H-pyridin-2-yl]-2-hydroxyphenyl]methyl]-N-methylpiperidine-4-carboxamide	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.0860	uM
N-[[5-chloro-3-[4-[2-chloro-5-(trifluoromethyl)phenyl]-5-cyano-6-oxo-1H-pyridin-2-yl]-2-hydroxyphenyl]methyl]-1-(cyclohexanecarbonyl)-N-methylpiperidine-4-carboxamide	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.1000	uM
N-[[5-chloro-3-[4-[2-chloro-5-(trifluoromethyl)phenyl]-5-cyano-6-oxo-1H-pyridin-2-yl]-2-hydroxyphenyl]methyl]-4-methoxy-N-methylcyclohexane-1-carboxamide	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.2000	uM
N-[[5-chloro-3-[4-[2-chloro-5-(trifluoromethyl)phenyl]-5-cyano-6-oxo-1H-pyridin-2-yl]-2-hydroxyphenyl]methyl]-N-methyl-1-pentylpiperidine-4-carboxamide	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.2200	uM
3-[5-[(E)-[[6-(2,3-dimethylanilino)-[1,2,5]oxadiazolo[3,4-b]pyrazin-5-yl]hydrazinylidene]methyl]furan-2-yl]benzoic acid	2025456: Binding affinity to Survivin (unknown origin) assessed as dissociation constant by fluorogenic assay	kd	0.2400	uM
tert-butyl 4-[[5-chloro-3-[4-[2-chloro-5-(trifluoromethyl)phenyl]-5-cyano-6-oxo-1H-pyridin-2-yl]-2-hydroxyphenyl]methyl-methylcarbamoyl]piperidine-1-carboxylate	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.2600	uM
N-[[5-chloro-3-[4-[2-chloro-5-(trifluoromethyl)phenyl]-5-cyano-6-oxo-1H-pyridin-2-yl]-2-hydroxyphenyl]methyl]-N-methyl-3-pyrrolidin-1-ylpropanamide	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.4400	uM
6-(5-bromo-2-hydroxyphenyl)-4-[2-chloro-5-(trifluoromethyl)phenyl]-2-oxo-1H-pyridine-3-carbonitrile	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.4900	uM
6-(5-cyclopentyl-2-hydroxyphenyl)-4-(2,5-dichlorophenyl)-2-oxo-1H-pyridine-3-carbonitrile	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.5100	uM
6-(5-chloro-2-hydroxyphenyl)-4-[2-chloro-5-(trifluoromethyl)phenyl]-2-oxo-1H-pyridine-3-carbonitrile	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.5200	uM
N-[[5-chloro-3-[4-[2-chloro-5-(trifluoromethyl)phenyl]-5-cyano-6-oxo-1H-pyridin-2-yl]-2-hydroxyphenyl]methyl]-N-methylpiperidine-4-carboxamide	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.5300	uM
N-[[5-chloro-3-[4-[2-chloro-5-(trifluoromethyl)phenyl]-5-cyano-6-oxo-1H-pyridin-2-yl]-2-hydroxyphenyl]methyl]-N-methylcyclohexanecarboxamide	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.6200	uM
4-(2,5-dichlorophenyl)-6-(2-hydroxy-5-phenylphenyl)-2-oxo-1H-pyridine-3-carbonitrile	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.7000	uM
6-(5-bromo-2-hydroxyphenyl)-4-(2,4-dimethylphenyl)-2-oxo-1H-pyridine-3-carbonitrile	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.7000	uM
6-(5-bromo-2-hydroxyphenyl)-4-(2,5-dichlorophenyl)-2-oxo-1H-pyridine-3-carbonitrile	437473: Inhibition of survivin	kd	0.8000	uM
N-[[5-chloro-3-[4-[2-chloro-5-(trifluoromethyl)phenyl]-5-cyano-6-oxo-1H-pyridin-2-yl]-2-hydroxyphenyl]methyl]cyclohexanecarboxamide	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	0.8800	uM
6-(5-bromo-2-hydroxyphenyl)-4-(2,5-dimethylphenyl)-2-oxo-1H-pyridine-3-carbonitrile	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	1.1700	uM
6-(5-cyclohexyl-2-hydroxyphenyl)-4-(2,5-dichlorophenyl)-2-oxo-1H-pyridine-3-carbonitrile	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	2.9800	uM
7-(piperidin-1-ylmethyl)-5-[[4-[4-(trifluoromethyl)phenyl]triazol-2-yl]methyl]quinolin-8-ol	1770548: Binding affinity to human survivin expressed in Escherichia coli BL21 assessed as dissociation constant measured by Surface plasmon resonance	kd	4.2700	uM
6-(5-bromo-2-hydroxyphenyl)-2-oxo-4-phenyl-1H-pyridine-3-carbonitrile	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	5.0000	uM
1-(4-chlorophenyl)indole	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	5.0000	uM
4-(2,5-dichlorophenyl)-6-[2-hydroxy-5-(2-methylpropyl)phenyl]-2-oxo-1H-pyridine-3-carbonitrile	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	7.5600	uM
(2-ethyl-1-benzofuran-3-yl)-(4-hydroxy-3,5-diiodophenyl)methanone	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	8.0000	uM
3-(3-bromophenyl)quinoline	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	10.0000	uM
3-[(2Z)-2-hydroxyimino-3-[4-[4-(trifluoromethoxy)phenyl]phenoxy]propyl]-5,5-dimethylimidazolidine-2,4-dione	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	10.0000	uM
N-(3-chlorophenyl)naphthalen-2-amine	295444: Binding affinity to human survivin expressed in Escherichia coli BL21 cells after 30 mins	kd	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	affects expression, increases response to substance, affects response to substance, decreases expression, affects cotreatment (+4 more)	35
Resveratrol	increases reaction, decreases reaction, affects cotreatment, decreases expression, increases expression	28
Cisplatin	increases expression, increases phosphorylation, increases reaction, decreases response to substance, affects cotreatment (+2 more)	19
Doxorubicin	increases response to substance, decreases expression, affects binding, increases reaction, affects cotreatment (+6 more)	19
bisphenol A	affects expression, decreases expression, increases expression, affects cotreatment	14
Fluorouracil	decreases response to substance, affects cotreatment, increases expression, decreases expression, decreases reaction (+2 more)	13
sodium arsenite	decreases reaction, increases expression, decreases expression, affects expression, increases activity (+1 more)	12
Curcumin	affects cotreatment, decreases expression, decreases reaction, increases expression	12
Quercetin	affects cotreatment, affects binding, increases expression, decreases expression, decreases reaction	12
Tretinoin	decreases expression, increases reaction, affects cotreatment	12
Paclitaxel	decreases response to substance, affects reaction, affects response to substance, decreases reaction, increases expression (+2 more)	12
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects cotreatment, decreases expression, decreases reaction, increases expression, increases reaction	9
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	affects cotreatment, decreases reaction, increases ubiquitination, decreases expression, increases degradation (+2 more)	8
Bortezomib	decreases expression, increases reaction, increases expression, affects cotreatment, increases cleavage	8
Estradiol	decreases reaction, increases expression, increases reaction, affects expression, decreases expression	8
Celecoxib	affects binding, decreases expression, increases expression, decreases reaction, increases activity	7
Sorafenib	affects cotreatment, decreases expression, decreases reaction, increases expression, decreases activity	7
Vorinostat	decreases phosphorylation, affects expression, decreases reaction, increases expression, affects cotreatment (+2 more)	7
(+)-JQ1 compound	decreases expression, increases reaction, decreases reaction, affects expression, affects cotreatment	6
Etoposide	decreases reaction, increases response to substance, affects cotreatment, decreases response to substance, increases expression (+1 more)	6
Niclosamide	increases expression, decreases expression, increases reaction, affects expression, decreases reaction	6
Sulindac	affects cotreatment, increases abundance, decreases expression, decreases reaction	6
alvocidib	affects cotreatment, decreases expression, decreases reaction, increases expression, increases phosphorylation (+1 more)	5
SB 203580	affects cotreatment, affects expression, affects reaction, decreases expression, decreases reaction (+1 more)	5
Acetylcysteine	decreases expression, decreases reaction	5
Benzo(a)pyrene	decreases expression, increases methylation, decreases reaction	5
Oxygen	increases expression, affects cotreatment, decreases expression, increases reaction, affects expression (+2 more)	5
Plant Extracts	affects cotreatment, decreases expression, decreases reaction, increases expression	5
methylselenic acid	affects cotreatment, decreases expression, affects binding, decreases reaction	4
deguelin	decreases reaction, increases expression, decreases expression	4

ChEMBL screening assays

65 unique, capped per target: 63 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1056061	Binding	Inhibition of survivin	Discovery of colon tumor cell growth inhibitory agents through a combinatorial approach. — Eur J Med Chem
CHEMBL4618209	Functional	In vivo inhibition of survivin in NSG mouse xenografted in human PC3 cells assessed as reduction in survivin expression at 100 mg/kg, po administered via gavage every other day for 10 times and measured post last dose by Western blot analys	Synthesis and Identification of a Novel Lead Targeting Survivin Dimerization for Proteasome-Dependent Degradation. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8UL	HEK293-Survivin	Transformed cell line	Female

Clinical trials (associated diseases)

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