BIRC7

Summary

BIRC7 (baculoviral IAP repeat containing 7, HGNC:13702) is a protein-coding gene on chromosome 20q13.33, encoding Baculoviral IAP repeat-containing protein 7 (Q96CA5). Apoptotic regulator capable of exerting proapoptotic and anti-apoptotic activities and plays crucial roles in apoptosis, cell proliferation, and cell cycle control. In precision oncology, BIRC7 Amplification is associated with resistance to Cisplatin in Colon Cancer (CIViC Level D).

This gene encodes a member of the inhibitor of apoptosis protein (IAP) family, and contains a single copy of a baculovirus IAP repeat (BIR) as well as a RING-type zinc finger domain. The BIR domain is essential for inhibitory activity and interacts with caspases, while the RING finger domain sometimes enhances antiapoptotic activity but does not inhibit apoptosis alone. Elevated levels of the encoded protein may be associated with cancer progression and play a role in chemotherapy sensitivity. Alternative splicing results in multiple transcript variants

Source: NCBI Gene 79444 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 52 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_139317

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13702
Approved symbol	BIRC7
Name	baculoviral IAP repeat containing 7
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	mliap, ML-IAP, KIAP, RNF50
Ensembl gene	ENSG00000101197
Ensembl biotype	protein_coding
OMIM	605737
Entrez	79444

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000217169, ENST00000342412, ENST00000395306

RefSeq mRNA: 2 — MANE Select: NM_139317 NM_022161, NM_139317

CCDS: CCDS13512, CCDS13513

Canonical transcript exons

ENST00000217169 — 7 exons

Exon	Start	End
ENSE00000663365	63238396	63238477
ENSE00000663366	63238569	63238614
ENSE00000856558	63237903	63238002
ENSE00000856559	63239162	63239233
ENSE00001174107	63239358	63239610
ENSE00001903310	63240256	63240495
ENSE00003844034	63235905	63236445

Expression profiles

Bgee: expression breadth ubiquitous, 109 present calls, max score 90.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0046 / max 96.1598, expressed in 174 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185794	0.8906	167
185793	0.0655	36
185795	0.0297	15
185796	0.0188	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	90.82	gold quality
tibial nerve	UBERON:0001323	88.60	gold quality
sural nerve	UBERON:0015488	88.41	gold quality
placenta	UBERON:0001987	77.40	gold quality
right adrenal gland cortex	UBERON:0035827	61.53	gold quality
right lung	UBERON:0002167	59.24	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	58.50	gold quality
skin of leg	UBERON:0001511	57.18	gold quality
zone of skin	UBERON:0000014	56.93	gold quality
skin of abdomen	UBERON:0001416	56.39	gold quality
lymph node	UBERON:0000029	56.04	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	54.34	gold quality
substantia nigra	UBERON:0002038	52.95	gold quality
metanephros cortex	UBERON:0010533	52.92	gold quality
spleen	UBERON:0002106	52.53	gold quality
cortex of kidney	UBERON:0001225	52.49	gold quality
ectocervix	UBERON:0012249	52.04	gold quality
apex of heart	UBERON:0002098	51.74	gold quality
right adrenal gland	UBERON:0001233	51.69	gold quality
subcutaneous adipose tissue	UBERON:0002190	51.69	gold quality
endocervix	UBERON:0000458	51.56	gold quality
upper lobe of left lung	UBERON:0008952	50.83	gold quality
temporal lobe	UBERON:0001871	50.76	gold quality
amygdala	UBERON:0001876	50.69	gold quality
adrenal gland	UBERON:0002369	50.41	gold quality
vermiform appendix	UBERON:0001154	50.38	gold quality
hypothalamus	UBERON:0001898	50.33	gold quality
uterine cervix	UBERON:0000002	49.87	gold quality
lung	UBERON:0002048	49.18	gold quality
granulocyte	CL:0000094	47.89	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	18.59
E-ANND-3	no	0.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, MITF, MYCN, TCF7L2

miRNA regulators (miRDB)

3 targeting BIRC7, 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-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-7113-5P	97.88	67.33	1735

Literature-anchored findings (GeneRIF, showing 40)

• SMAC negatively regulates the anti-apoptotic activity of melanoma inhibitor of apoptosis (ML-IAP). (PMID:11801603)
• alpha isoform of LIVIN, which is not expressed in normal bladder tissue, is expressed in a proportion of bladder carcinoma with a high risk of relapse (PMID:12488298)
• livin gene is susceptible to efficient and specific silencing by the siRNA technology (PMID:14614456)
• T cells in a large proportion of melanoma patients infiltrating the tumor or circulating in the peripheral blood specifically recognize ML-IAP-derived peptides (PMID:15009721)
• livin gene may play a role in NSCLC development and increased expression of livin mRNA may serve as a new target for lung cancer treatment as well as survivin (PMID:15541814)
• Like survivin, livin may act as a major cancer antigen in breast cancer patients (PMID:16026775)
• Livin beta isoform plays the key role for the antiapoptotic protection of HeLa cells by the livin gene. the Livin isoforms can strongly differ in their functional significance for the antiapoptotic resistance of tumor cells. (PMID:16437214)
• findings provide a novel function of Livin: it exhibits E3 ubiquitin ligase activity to degrade the pivotal apoptotic regulator Smac/DIABLO through the ubiquitin-proteasome pathway. (PMID:16729033)
• Livin cleavage in melanoma cells occurs in an Omi-independent fashion at residue 52 within its potential caspase substrate and suggests the involvement of a non-canonical caspase. (PMID:16806840)
• the BIRC7 gene might play a role in the development and aggression of non-Hodgkin’s lymphoma (PMID:16840203)
• Targeted inhibition of livin strongly sensitized NSCLC cells to different pro-apoptotic stimuli, such as UV-irradiation or the chemotherapeutic drug etoposide thus Livin is an important contributor to the apoptosis resistance of NSCLC cells. (PMID:16965834)
• The Livin expression is a novel prognostic marker in childhood ALL and thus needs to be incorporated into the patient stratification and treatment protocols. (PMID:16990595)
• Deguelin has great potential for chemosensitization of this protein and could represent a new therapeutic agent for treatment of breast cancer. (PMID:17035597)
• study demonstrates that only the first N-terminal glycine residue dictates the peri-nuclear distribution of tLivin; once it is properly localized, an intact RING domain enables pro-apoptotic function (PMID:17294084)
• Livin can contribute significantly to the apoptosis resistance of renal cell carcinoma cells. (PMID:17437058)
• Livin expression is detected in 59 (38.8%) of 152 renal cell carcinoma specimens but not any in normal samples. (PMID:17519534)
• High Livin expression is associated with osteosarcoma (PMID:17632732)
• Both Survivin and Livin were correlated to tumor recurrence and/or metastasis, and shorter survival. (PMID:17672950)
• Increased livin protein expression is associated with renal cell carcinoma (PMID:17968430)
• Silencing livin could significantly induce apoptosis, arrest cell cycle at the G0/G1 phase, and inhibit proliferation in LiBr cells (PMID:18031611)
• Livin beta moderately protects against NK cell killing whereas Livin alpha augments killing. Livin augments an extrinsic inhibitory signal rather than functioning as an independent inhibitory mechanism. (PMID:18034418)
• Livin is overexpressed in gastric carcinoma with a correlation to tumor differentiation and lymph node metastasis. (PMID:18210873)
• Livin expression may have a role in the development of bladder cancer (PMID:18278467)
• Overexpression of livin gene may play a synergic role in the pathogenesis of in acute non-lymphocytic leukemia and associates with complete remission. (PMID:18315896)
• MITF is a major transcriptional regulator of ML-IAP expression in melanomas. (PMID:18451137)
• The positive rate of Livin was higher in LSCC than that in normal soft palate tissue and the expression was significantly associated with lymph node metastasis. (PMID:18476630)
• Livin is implicated in testicular tumorigenesis and to be related to the histological testicular germ cell tumors subtype. (PMID:18515985)
• Livin may serve as a promising marker to identify the relapse risk in bladder cancer, and targeting Livin could offer a therapeutic benefit in apoptosis-inducing treatment. (PMID:18555709)
• Results showed that knockdown livin expression could inhibit cell growth and induce apoptosis in A549 and 103H non-small cell lung cancer cell lines. (PMID:18827979)
• Over-expression of livin and VEGF contributes to the pathogenesis of esophageal carcinoma. (PMID:18837095)
• review of the current understanding of the versatile roles of Livin in the apoptotic cascade [review] (PMID:19074843)
• Study demonstrates that alterations in the expression of IAP family members, including Survivin and Livin/ML-IAP, are frequent in hepatocellular carcinoma (HCC). (PMID:19397802)
• Livin plays a major role in tumorigenicity and that natural killer cells induce cleavage of Livin to its proapoptotic truncated protein that in turn inhibits tumor growth, shown here in transgenic NOD SCIID mice. (PMID:19549891)
• The expression and correlation of Livin and Smac/DIABLO vary in different stages and pathological types of gastric carcinoma. Overexpression of Livin is closely related to differentiation and metastases of gastric carcinoma. (PMID:19635196)
• The results suggest that livin may exert anti-apoptotic action on SPC-A1 by activating JNK1 signaling pathway and inhibiting caspase-3 activation. (PMID:19690982)
• MycN is required for livin expression and that livin may counteract the proapoptotic effects of MycNin neuroblastoma cells. (PMID:19724862)
• Inhibiting Livin and survivin expression with siRNA reduces colon cancer cell proliferation. (PMID:19806913)
• Livin is overexpressed in gastric carcinoma with a relationship to tumor differentiation and lymph node metastases (PMID:19914791)
• investigated the expression of three apoptosis related genes, BCL2L13, CASP8AP2, and Livin, as well as their prognostic significance, in a retrospective study of 90 pediatric ALL patients diagnosed between 1996 and 2007 in Taiwan (PMID:20109966)
• after Etoposide intervention glioblastoma stem-like cells showed a stronger resistance to apoptosis and death, and the anti-apoptotic gene livinbeta was related with the high survival rate (PMID:20388502)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	birc7	ENSDARG00000058082
mus_musculus	Birc7	ENSMUSG00000038840
rattus_norvegicus	Birc7	ENSRNOG00000043311
drosophila_melanogaster	Diap2	FBGN0015247
caenorhabditis_elegans		WBGENE00000250

Paralogs (7): BIRC3 (ENSG00000023445), BIRC5 (ENSG00000089685), NLRC4 (ENSG00000091106), XIAP (ENSG00000101966), BIRC2 (ENSG00000110330), BIRC6 (ENSG00000115760), NAIP (ENSG00000249437)

Protein

Protein identifiers

Baculoviral IAP repeat-containing protein 7 — Q96CA5 (reviewed: Q96CA5)

Alternative names: Kidney inhibitor of apoptosis protein, Livin, Melanoma inhibitor of apoptosis protein, RING finger protein 50, RING-type E3 ubiquitin transferase BIRC7

All UniProt accessions (2): Q96CA5, A8MTF4

UniProt curated annotations — full annotation on UniProt →

Function. Apoptotic regulator capable of exerting proapoptotic and anti-apoptotic activities and plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is mediated through the inhibition of CASP3, CASP7 and CASP9, as well as by its E3 ubiquitin-protein ligase activity. As it is a weak caspase inhibitor, its anti-apoptotic activity is thought to be due to its ability to ubiquitinate DIABLO/SMAC targeting it for degradation thereby promoting cell survival. May contribute to caspase inhibition, by blocking the ability of DIABLO/SMAC to disrupt XIAP/BIRC4-caspase interactions. Protects against apoptosis induced by TNF or by chemical agents such as adriamycin, etoposide or staurosporine. Suppression of apoptosis is mediated by activation of MAPK8/JNK1, and possibly also of MAPK9/JNK2. This activation depends on TAB1 and MAP3K7/TAK1. In vitro, inhibits CASP3 and proteolytic activation of pro-CASP9. Blocks staurosporine-induced apoptosis. Promotes natural killer (NK) cell-mediated killing. Blocks etoposide-induced apoptosis. Protects against natural killer (NK) cell-mediated killing.

Subunit / interactions. Binds to CASP9. Interaction with DIABLO/SMAC via the BIR domain disrupts binding to CASP9 and apoptotic suppressor activity. Interacts with TAB1. In vitro, interacts with CASP3 and CASP7 via its BIR domain.

Subcellular location. Nucleus. Cytoplasm. Golgi apparatus.

Tissue specificity. Isoform 1 and isoform 2 are expressed at very low levels or not detectable in most adult tissues. Detected in adult heart, placenta, lung, lymph node, spleen and ovary, and in several carcinoma cell lines. Isoform 2 is detected in fetal kidney, heart and spleen, and at lower levels in adult brain, skeletal muscle and peripheral blood leukocytes.

Post-translational modifications. Autoubiquitinated and undergoes proteasome-mediated degradation. The truncated protein (tLivin) not only loses its anti-apoptotic effect but also acquires a pro-apoptotic effect.

Domain organisation. The RING domain is essential for autoubiquitination.

Similarity. Belongs to the IAP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96CA5-1	2, Livin alpha	yes
Q96CA5-2	1, Livin beta

RefSeq proteins (2): NP_071444, NP_647478* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001370	BIR_rpt	Repeat
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR050784	IAP	Family

Pfam: PF00653, PF13920

UniProt features (40 total): helix 9, strand 7, turn 6, binding site 4, mutagenesis site 4, chain 2, region of interest 2, site 1, splice variant 1, sequence variant 1, repeat 1, zinc finger region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
2I3H	X-RAY DIFFRACTION	1.62
3GT9	X-RAY DIFFRACTION	1.7
3GTA	X-RAY DIFFRACTION	1.7
3UW5	X-RAY DIFFRACTION	1.71
1TW6	X-RAY DIFFRACTION	1.71
3F7H	X-RAY DIFFRACTION	1.8
3F7I	X-RAY DIFFRACTION	1.9
4AUQ	X-RAY DIFFRACTION	2.18
1OXN	X-RAY DIFFRACTION	2.2
1OXQ	X-RAY DIFFRACTION	2.3
2I3I	X-RAY DIFFRACTION	2.3
3F7G	X-RAY DIFFRACTION	2.3
1OY7	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CA5-F1	72.40	0.49

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): 52–53 (cleavage; by casp3 and casp7)

Ligand- & substrate-binding residues (4): 151; 124; 127; 144

Mutagenesis-validated functional residues (4):

Position	Phenotype
87–88	no change in smac interaction and anti-apoptotic activity.
120	abolishes inhibition of caspases, smac binding and anti-apoptotic activity.
124	abolishes inhibition of caspases and anti-apoptotic activity.
138	abolishes inhibition of caspases, smac binding and anti-apoptotic activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9824594	Regulation of MITF-M-dependent genes involved in apoptosis
R-HSA-1266738	Developmental Biology
R-HSA-9730414	MITF-M-regulated melanocyte development
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 99 (showing top): GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TUMOR_NECROSIS_FACTOR_MEDIATED_SIGNALING_PATHWAY, GOCC_MICROTUBULE_ORGANIZING_CENTER, ONKEN_UVEAL_MELANOMA_UP, GOBP_JNK_CASCADE, GOBP_REGULATION_OF_CELL_CYCLE, GOCC_CENTROSOME, GOBP_TUMOR_NECROSIS_FACTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_CYTOKINE_STIMULUS, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (12): lens development in camera-type eye (GO:0002088), apoptotic process (GO:0006915), negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), protein ubiquitination (GO:0016567), positive regulation of protein ubiquitination (GO:0031398), regulation of cell population proliferation (GO:0042127), regulation of apoptotic process (GO:0042981), negative regulation of apoptotic process (GO:0043066), positive regulation of JNK cascade (GO:0046330), regulation of cell cycle (GO:0051726), regulation of natural killer cell apoptotic process (GO:0070247), regulation of intracellular signal transduction (GO:1902531)

GO Molecular Function (10): ubiquitin-protein transferase activity (GO:0004842), cysteine-type endopeptidase inhibitor activity (GO:0004869), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), cysteine-type endopeptidase inhibitor activity involved in apoptotic process (GO:0043027), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), peptidase inhibitor activity (GO:0030414), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
MITF-M-dependent gene expression	1
Developmental Biology	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of cellular process	2
apoptotic process	2
intracellular membrane-bounded organelle	2
cytoplasm	2
camera-type eye development	1
anatomical structure development	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
negative regulation of cytokine-mediated signaling pathway	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
protein modification by small protein conjugation	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
cell population proliferation	1
regulation of programmed cell death	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
JNK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	1
cell cycle	1
regulation of lymphocyte apoptotic process	1
natural killer cell apoptotic process	1
regulation of signal transduction	1
intracellular signal transduction	1
ubiquitin-like protein transferase activity	1
cysteine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
transition metal ion binding	1
protein binding	1
cysteine-type endopeptidase regulator activity involved in apoptotic process	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
enzyme inhibitor activity	1

Protein interactions and networks

STRING

1408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BIRC7	CASP9	P55211	917
BIRC7	BIRC6	Q9NR09	917
BIRC7	DIABLO	Q9NR28	883
BIRC7	CASP7	P55210	872
BIRC7	BIRC5	O15392	821
BIRC7	CASP3	P42574	752
BIRC7	RNF4	P78317	749
BIRC7	KCNJ11	Q14654	724
BIRC7	UBE2D2	P51669	715
BIRC7	TNFRSF10B	O14763	635
BIRC7	CYCS	P00001	618
BIRC7	TNFRSF10A	O00220	597
BIRC7	TNFRSF21	O75509	593
BIRC7	UBE2D1	P51668	578
BIRC7	CASP6	P55212	544

IntAct

125 interactions, top by confidence:

A	B	Type	Score
BIRC7	CASP9	psi-mi:“MI:0915”(physical association)	0.920
CASP9	BIRC7	psi-mi:“MI:0915”(physical association)	0.920
BIRC7	BIRC2	psi-mi:“MI:0915”(physical association)	0.800
BIRC2	BIRC7	psi-mi:“MI:0915”(physical association)	0.800
DDX6	BIRC7	psi-mi:“MI:0915”(physical association)	0.780
BIRC7	DDX6	psi-mi:“MI:0915”(physical association)	0.780
BIRC7	POLR1C	psi-mi:“MI:0915”(physical association)	0.720
POLR1C	BIRC7	psi-mi:“MI:0915”(physical association)	0.720
BIRC7	DIABLO	psi-mi:“MI:0915”(physical association)	0.690
DIABLO	BIRC7	psi-mi:“MI:0915”(physical association)	0.690

BioGRID (108): DIABLO (Biochemical Activity), UBE2D2 (Reconstituted Complex), BIRC7 (Affinity Capture-Western), BIRC7 (Two-hybrid), BIRC7 (Two-hybrid), BIRC7 (Two-hybrid), BIRC7 (Two-hybrid), BIRC7 (Two-hybrid), BIRC7 (Two-hybrid), FAM124B (Two-hybrid), BIRC7 (Biochemical Activity), DIABLO (Biochemical Activity), BIRC7 (Reconstituted Complex), PCNT (Affinity Capture-MS), BIRC2 (Affinity Capture-MS)

ESM2 similar proteins: A1E2V0, A2AWP0, A6QPT6, A9JTP3, A9ULZ2, B1WBS3, O08863, O14771, O15037, O43918, O94966, P05433, P48778, P51617, Q08DD7, Q0P5G1, Q13077, Q15477, Q2LGB3, Q3TD16, Q3UJD6, Q499Z3, Q4R3B7, Q4R6Y5, Q5RA67, Q5XIS1, Q62210, Q62406, Q6AXX1, Q6J1Y9, Q75NR7, Q80U38, Q80VL3, Q811H0, Q8BHW9, Q8CFK6, Q8JHV9, Q8K330, Q8R2S1, Q8TE77

Diamond homologs: A2AWP0, A5D8Q0, A9JTP3, A9ULZ2, D3ZDI6, O14064, O62640, O88738, P41437, Q05AK5, Q13075, Q24307, Q28H51, Q5BKL8, Q5E9J6, Q5NVC7, Q60989, Q68LP1, Q6AYH3, Q6GNY1, Q6R7D0, Q6R7I2, Q6TEM9, Q804S5, Q80SY4, Q86YT6, Q8JGN5, Q8JHV9, Q8R516, Q8WY64, Q969K3, Q96AX9, Q96CA5, Q96P09, Q99KR6, Q9JIB3, Q9JIB6, Q9LY87, Q9NR09, Q9QUK4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
BIRC7	down-regulates	DIABLO	binding
Ub:E2	“up-regulates activity”	BIRC7	ubiquitination

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

BIRC7 encodes the protein Livin which is a member of the inhibitor of apoptosis protein (IAP) family. Livin consists of a single baculoviral IAP repeat domain (BIR) and a RING domian at the C-terminus. The protein inhibits apoptosis by inhibiting proteolytic activation of capsases. Overexpression of Livin has been observed in a variety of cancers including lung, colon, and prostate compared to most normal adult tissues and has been proposed as a putative therapeutic target.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1059 predictions. Top by Δscore:

Variant	Effect	Δscore
20:63236444:AGG:A	donor_loss	1.0000
20:63236447:T:G	donor_loss	0.9900
20:63238675:GCCAC:G	donor_gain	0.9900
20:63238708:G:GT	donor_gain	0.9900
20:63238710:A:T	donor_gain	0.9900
20:63238983:G:GT	donor_gain	0.9900
20:63240251:TCTA:T	acceptor_loss	0.9900
20:63240252:CTAG:C	acceptor_loss	0.9900
20:63240253:TAGG:T	acceptor_loss	0.9900
20:63238565:CCA:C	acceptor_loss	0.9800
20:63238566:CAG:C	acceptor_loss	0.9800
20:63238567:A:AG	acceptor_gain	0.9800
20:63238567:AGGAC:A	acceptor_loss	0.9800
20:63238568:G:GA	acceptor_gain	0.9800
20:63238568:G:GT	acceptor_loss	0.9800
20:63238612:CCGGT:C	donor_loss	0.9800
20:63238615:G:GG	donor_gain	0.9800
20:63238615:GT:G	donor_loss	0.9800
20:63238616:T:TC	donor_loss	0.9800
20:63238721:C:T	donor_gain	0.9800
20:63239905:A:T	donor_gain	0.9800
20:63238731:G:GT	donor_gain	0.9700
20:63237938:G:A	acceptor_gain	0.9600
20:63238617:G:GG	donor_loss	0.9600
20:63238709:G:T	donor_gain	0.9600
20:63239607:CCAGG:C	donor_loss	0.9600
20:63239608:CAGGT:C	donor_loss	0.9600
20:63239609:AGG:A	donor_loss	0.9600
20:63239610:GGTG:G	donor_loss	0.9600
20:63239611:G:A	donor_loss	0.9600

AlphaMissense

1916 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:63237995:T:C	F148L	0.993
20:63237997:C:A	F148L	0.993
20:63237997:C:G	F148L	0.993
20:63237955:G:C	W134C	0.992
20:63237955:G:T	W134C	0.992
20:63236376:T:C	F94L	0.991
20:63236378:C:A	F94L	0.991
20:63236378:C:G	F94L	0.991
20:63239594:T:C	F296L	0.990
20:63239596:C:A	F296L	0.990
20:63239596:C:G	F296L	0.990
20:63238403:T:C	F153L	0.989
20:63238405:C:A	F153L	0.989
20:63238405:C:G	F153L	0.989
20:63236436:T:C	F114L	0.987
20:63236438:C:A	F114L	0.987
20:63236438:C:G	F114L	0.987
20:63236434:T:C	F113S	0.986
20:63239496:T:A	V263D	0.985
20:63237985:T:A	H144Q	0.984
20:63237985:T:G	H144Q	0.984
20:63236431:G:A	G112D	0.983
20:63236433:T:C	F113L	0.983
20:63236435:C:A	F113L	0.983
20:63236435:C:G	F113L	0.983
20:63237923:T:C	C124R	0.983
20:63237987:C:A	A145D	0.983
20:63236364:C:A	R90S	0.982
20:63237953:T:A	W134R	0.982
20:63237953:T:C	W134R	0.982

dbSNP variants (sampled 300 via entrez): RS1000983705 (20:63236753 A>C), RS1001016581 (20:63236554 G>C), RS1002416215 (20:63240304 C>T), RS1002419651 (20:63240655 C>A,G,T), RS1002435177 (20:63236127 C>T), RS1003032969 (20:63240532 A>C), RS1003129295 (20:63237379 T>G), RS1003162884 (20:63234966 T>G), RS1003846298 (20:63237812 C>T), RS1003874234 (20:63237090 G>A), RS1003908885 (20:63236854 G>A), RS1005120595 (20:63237206 C>G), RS1005551713 (20:63236096 C>T), RS1005583062 (20:63235816 G>A), RS1005837976 (20:63235327 T>C)

Disease associations

OMIM: gene MIM:605737 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075127 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,571 (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
CHEMBL2431768	LCL-161	2	1,365
CHEMBL3039522	BIRINAPANT	2	925
CHEMBL2063869	GDC-0152	1	281

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items; also 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
BIRC7 Amplification	Cisplatin	Colon Cancer	Resistance	CIViC D	EID661

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

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

Ligand	Action	Affinity	Parameter
GDC-0152	Antagonist	7.85	pKi

ChEMBL bioactivities

17 potent at pChembl≥5 of 30 total, top 17 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Kd	1	nM	BIRINAPANT
8.05	IC50	9	nM	LCL-161
7.96	IC50	11	nM	CHEMBL5174454
7.85	Kd	14	nM	GDC-0152
7.82	IC50	15	nM	LCL-161
7.70	IC50	20	nM	CHEMBL5186855
7.46	IC50	35	nM	CHEMBL5181541
7.37	IC50	43	nM	CHEMBL5174454
7.30	IC50	50	nM	CHEMBL5175233
6.73	Ki	185	nM	CHEMBL5174454
6.56	IC50	278	nM	CHEMBL5195146
6.55	IC50	280	nM	CHEMBL5193194
6.54	IC50	291	nM	CHEMBL5195146
6.50	IC50	319	nM	CHEMBL5191180
6.32	IC50	482	nM	CHEMBL5170823
6.25	IC50	556	nM	CHEMBL5203019
6.06	IC50	866	nM	CHEMBL5169527

PubChem BioAssay actives

48 with measured affinity, of 97 total; 43 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
(2S)-N-[(2S)-1-[(2R,4S)-2-[[6-fluoro-2-[6-fluoro-3-[[(2R,4S)-4-hydroxy-1-[(2S)-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]pyrrolidin-2-yl]methyl]-1H-indol-2-yl]-1H-indol-3-yl]methyl]-4-hydroxypyrrolidin-1-yl]-1-oxobutan-2-yl]-2-(methylamino)propanamide	1553576: Binding affinity to ML-IAP-BIR domain (unknown origin)	kd	0.0010	uM
(2S)-N-[(1S)-1-cyclohexyl-2-[(2S)-2-[4-(4-fluorobenzoyl)-1,3-thiazol-2-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide	1847716: Antagonist activity at N-terminal His-tagged wild type ML-IAP BIR domain (63 to 179 residues) (unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay	ic50	0.0090	uM
3-[[(2S)-3-[(2S)-2-[[(1R)-2,3-dihydro-1H-inden-1-yl]carbamoyl]pyrrolidin-1-yl]-2-[[(2S)-2-(methylamino)propanoyl]amino]-3-oxopropyl]carbamoyl]-4-methoxybenzenesulfonyl fluoride	1847720: Antagonist activity at N-terminal His-tagged wild type ML-IAP BIR domain (63 to 179 residues)(unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate preincubated for 2 hrs with protein followed by substrate addition measured after 2 hrs by DELFIA assay	ic50	0.0110	uM
(2S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-(4-phenylthiadiazol-5-yl)pyrrolidine-2-carboxamide	1553576: Binding affinity to ML-IAP-BIR domain (unknown origin)	kd	0.0140	uM
(2S)-N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-1-[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carboxamide	1847716: Antagonist activity at N-terminal His-tagged wild type ML-IAP BIR domain (63 to 179 residues) (unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay	ic50	0.0200	uM
4-[[(2S)-3-[(2S)-2-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-[[(2S)-2-(methylamino)propanoyl]amino]-3-oxopropyl]carbamoyl]-2-methoxybenzenesulfonyl fluoride	1847716: Antagonist activity at N-terminal His-tagged wild type ML-IAP BIR domain (63 to 179 residues) (unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay	ic50	0.0350	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]-4-fluoronaphthalene-1-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	0.0380	uM
(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoic acid	1797623: Fluorescence Polarization Affinity Measurements. from Article 10.1021/cb600276q: “Design, synthesis, and biological activity of a potent Smac mimetic that sensitizes cancer cells to apoptosis by antagonizing IAPs.”	ki	0.0400	uM
(2S)-1-[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-3-methylbutanoyl]-N-(2,2-diphenylethyl)pyrrolidine-2-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	0.0430	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]naphthalene-1-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	0.0460	uM
3-[[(2S)-3-[(2S)-2-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-[[(2S)-2-(methylamino)propanoyl]amino]-3-oxopropyl]carbamoyl]-4-methoxybenzenesulfonyl fluoride	1847716: Antagonist activity at N-terminal His-tagged wild type ML-IAP BIR domain (63 to 179 residues) (unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay	ic50	0.0500	uM
(3R,6S,9aR)-2,2-dimethyl-6-[[(2S)-2-(methylamino)propanoyl]amino]-N-(5-methyl-2-phenylpyrazol-3-yl)-5-oxo-3,6,7,8,9,9a-hexahydro-[1,3]thiazolo[3,2-a]azepine-3-carboxamide	1797623: Fluorescence Polarization Affinity Measurements. from Article 10.1021/cb600276q: “Design, synthesis, and biological activity of a potent Smac mimetic that sensitizes cancer cells to apoptosis by antagonizing IAPs.”	ki	0.0500	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]-4-methylnaphthalene-1-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	0.0630	uM
(2S)-N-[(2S)-1-[(3aR,6S,6aS)-6-[(2,2-diphenylacetyl)amino]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]-2-(methylamino)propanamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	0.0820	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]naphthalene-2-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	0.0910	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]-1-benzofuran-5-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	0.1000	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]-1-benzothiophene-3-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	0.1100	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]-2-methoxynaphthalene-1-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	0.1100	uM
(3R,6S,9aS)-2,2-dimethyl-6-[[(2S)-2-(methylamino)propanoyl]amino]-N-(5-methyl-2-phenylpyrazol-3-yl)-5-oxo-3,6,7,8,9,9a-hexahydro-[1,3]thiazolo[3,2-a]azepine-3-carboxamide	1797623: Fluorescence Polarization Affinity Measurements. from Article 10.1021/cb600276q: “Design, synthesis, and biological activity of a potent Smac mimetic that sensitizes cancer cells to apoptosis by antagonizing IAPs.”	ki	0.1900	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]-2H-benzotriazole-5-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	0.2600	uM
3-[[(2S)-3-[(2S)-2-[[(1R)-2,3-dihydro-1H-inden-1-yl]carbamoyl]pyrrolidin-1-yl]-2-[[(2S)-2-(methylamino)propanoyl]amino]-3-oxopropyl]carbamoyl]-4-methoxybenzenesulfonic acid	1847716: Antagonist activity at N-terminal His-tagged wild type ML-IAP BIR domain (63 to 179 residues) (unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay	ic50	0.2780	uM
3-[[(2S)-3-[(3S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]-3,4-dihydro-1H-isoquinolin-2-yl]-2-[[(2S)-2-(methylamino)propanoyl]amino]-3-oxopropyl]carbamoyl]-4-methoxybenzenesulfonyl fluoride	1847716: Antagonist activity at N-terminal His-tagged wild type ML-IAP BIR domain (63 to 179 residues) (unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay	ic50	0.2800	uM
(3R,6S,9aR)-6-[[(2S)-2-(methylamino)propanoyl]amino]-N-(5-methyl-2-phenylpyrazol-3-yl)-5-oxo-3,6,7,8,9,9a-hexahydro-2H-[1,3]thiazolo[3,2-a]azepine-3-carboxamide	1797623: Fluorescence Polarization Affinity Measurements. from Article 10.1021/cb600276q: “Design, synthesis, and biological activity of a potent Smac mimetic that sensitizes cancer cells to apoptosis by antagonizing IAPs.”	ki	0.2800	uM
(2S)-N-[(2S)-1-[(2S)-2-[[(2,2-diphenylacetyl)amino]methyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]-2-(methylamino)propanamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	0.2900	uM
3-[[(2S)-3-[(2S)-2-[[(1R)-4-fluoro-2,3-dihydro-1H-inden-1-yl]carbamoyl]pyrrolidin-1-yl]-2-[[(2S)-2-(methylamino)propanoyl]amino]-3-oxopropyl]carbamoyl]-4-methoxybenzenesulfonyl fluoride	1847716: Antagonist activity at N-terminal His-tagged wild type ML-IAP BIR domain (63 to 179 residues) (unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay	ic50	0.3190	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]-1-benzofuran-3-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	0.4400	uM
3-[[(2S)-3-[(3S)-3-[[(1R)-2,3-dihydro-1H-inden-1-yl]carbamoyl]-3,4-dihydro-1H-isoquinolin-2-yl]-2-[[(2S)-2-(methylamino)propanoyl]amino]-3-oxopropyl]carbamoyl]-4-methoxybenzenesulfonyl fluoride	1847716: Antagonist activity at N-terminal His-tagged wild type ML-IAP BIR domain (63 to 179 residues) (unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay	ic50	0.4820	uM
(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-3-methylpentanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]pentanedioic acid	1797623: Fluorescence Polarization Affinity Measurements. from Article 10.1021/cb600276q: “Design, synthesis, and biological activity of a potent Smac mimetic that sensitizes cancer cells to apoptosis by antagonizing IAPs.”	ki	0.5000	uM
3-[[(2S)-3-[(2S)-2-[[(1R)-2,3-dihydro-1H-inden-1-yl]carbamoyl]piperidin-1-yl]-2-[[(2S)-2-(methylamino)propanoyl]amino]-3-oxopropyl]carbamoyl]-4-methoxybenzenesulfonyl fluoride	1847716: Antagonist activity at N-terminal His-tagged wild type ML-IAP BIR domain (63 to 179 residues) (unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay	ic50	0.5560	uM
(2S)-N-[(2S)-1-[(3aR,6S,6aS)-6-[[(4-fluorophenyl)-methylcarbamoyl]amino]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]-2-(methylamino)propanamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	0.7400	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]-2,3-dihydro-1-benzofuran-5-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	0.7800	uM
N-[[(2S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]pyrrolidin-2-yl]methyl]naphthalene-1-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	0.7800	uM
3-[[(2S)-3-[(2S)-2-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]piperidin-1-yl]-2-[[(2S)-2-(methylamino)propanoyl]amino]-3-oxopropyl]carbamoyl]-4-methoxybenzenesulfonyl fluoride	1847716: Antagonist activity at N-terminal His-tagged wild type ML-IAP BIR domain (63 to 179 residues) (unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay	ic50	0.8660	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]benzamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	1.0000	uM
(2S)-N-[(2S)-1-[(3aR,6S,6aS)-6-[[methyl(phenyl)carbamoyl]amino]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]-2-(methylamino)propanamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	1.1000	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]-1,3-benzodioxole-5-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	1.3000	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]-2,3-dihydro-1-benzofuran-3-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	1.5000	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]quinoline-8-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	1.7000	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]-3H-benzimidazole-5-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	1.7000	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]-2,1,3-benzoxadiazole-5-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	1.8000	uM
N-[(3aR,6S,6aS)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-6-yl]-2,3-dihydroindole-1-carboxamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	1.9000	uM
(3R,6S,9aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-N-(5-methyl-2-phenylpyrazol-3-yl)-5-oxo-3,6,7,8,9,9a-hexahydro-2H-[1,3]thiazolo[3,2-a]azepine-3-carboxamide	1797623: Fluorescence Polarization Affinity Measurements. from Article 10.1021/cb600276q: “Design, synthesis, and biological activity of a potent Smac mimetic that sensitizes cancer cells to apoptosis by antagonizing IAPs.”	ki	4.1900	uM
(2S)-N-[(2S)-1-[(3aR,6S,6aS)-6-[[methyl(pyridin-2-yl)carbamoyl]amino]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrol-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]-2-(methylamino)propanamide	1798849: Fluorescence Polarization Affinity Measurements from Article 10.1021/jm801450c: “Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.”	ki	5.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	decreases reaction, decreases expression, increases reaction, affects cotreatment, increases expression (+1 more)	3
Curcumin	affects cotreatment, increases expression	2
Estradiol	decreases expression, increases expression	2
FR900359	decreases phosphorylation	1
bisphenol A	decreases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
deoxyshikonin	decreases expression	1
jinfukang	increases expression	1
Bortezomib	decreases expression, increases reaction	1
Resveratrol	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cholera Toxin	increases expression	1
Doxorubicin	increases expression	1
Etoposide	decreases response to substance	1
Fluorouracil	decreases response to substance	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Plant Extracts	increases expression	1
Polychlorinated Biphenyls	affects expression	1
Silicon Dioxide	increases expression	1
Testosterone	decreases expression	1
Valproic Acid	increases methylation	1
Vinblastine	decreases response to substance	1
2,4-Dichlorophenoxyacetic Acid	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Crocidolite	affects expression	1
Particulate Matter	increases expression, increases abundance	1

ChEMBL screening assays

14 unique, capped per target: 13 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1111551	Functional	Antagonist activity at ML-IAP MLXBIR3SG domain by fluorescence polarization assay	Antagonists of inhibitor of apoptosis proteins based on thiazole amide isosteres. — Bioorg Med Chem Lett
CHEMBL2066538	Binding	Binding affinity to ML-IAP BIR domain after 30 mins by fluorescence polarization-based competition assay	Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152). — J Med Chem

Clinical trials (associated diseases)

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