BCL2L2

Summary

BCL2L2 (BCL2 like 2, HGNC:995) is a protein-coding gene on chromosome 14q11.2, encoding Bcl-2-like protein 2 (Q92843). Promotes cell survival.

This gene encodes a member of the BCL-2 protein family. The proteins of this family form hetero- or homodimers and act as anti- and pro-apoptotic regulators. Expression of this gene in cells has been shown to contribute to reduced cell apoptosis under cytotoxic conditions. Studies of the related gene in mice indicated a role in the survival of NGF- and BDNF-dependent neurons. Mutation and knockout studies of the mouse gene demonstrated an essential role in adult spermatogenesis. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream PABPN1 (poly(A) binding protein, nuclear 1) gene.

Source: NCBI Gene 599 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 13 total
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004050

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:995
Approved symbol	BCL2L2
Name	BCL2 like 2
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0271, BCL-W, PPP1R51
Ensembl gene	ENSG00000129473
Ensembl biotype	protein_coding
OMIM	601931
Entrez	599

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 nonsense_mediated_decay

ENST00000250405, ENST00000553824, ENST00000554635, ENST00000556100, ENST00000556599, ENST00000557236, ENST00000557579, ENST00000678311, ENST00000679000, ENST00000679219, ENST00000879294, ENST00000879295

RefSeq mRNA: 2 — MANE Select: NM_004050 NM_001199839, NM_004050

CCDS: CCDS9591

Canonical transcript exons

ENST00000250405 — 4 exons

Exon	Start	End
ENSE00001031652	23308816	23311751
ENSE00002456772	23306833	23306894
ENSE00003658124	23307192	23307279
ENSE00004474378	23307760	23308199

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 97.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.7165 / max 244.0114, expressed in 1768 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138887	29.7165	1768

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	97.25	gold quality
prefrontal cortex	UBERON:0000451	97.06	gold quality
spinal cord	UBERON:0002240	96.77	gold quality
lower esophagus	UBERON:0013473	96.61	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.61	gold quality
amygdala	UBERON:0001876	96.54	gold quality
right frontal lobe	UBERON:0002810	96.52	gold quality
postcentral gyrus	UBERON:0002581	96.51	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.49	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.49	gold quality
cingulate cortex	UBERON:0003027	96.46	gold quality
orbitofrontal cortex	UBERON:0004167	96.46	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.43	gold quality
anterior cingulate cortex	UBERON:0009835	96.41	gold quality
frontal cortex	UBERON:0001870	96.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.36	gold quality
hypothalamus	UBERON:0001898	96.28	gold quality
substantia nigra	UBERON:0002038	96.25	gold quality
parietal lobe	UBERON:0001872	96.19	gold quality
pons	UBERON:0000988	96.15	gold quality
midbrain	UBERON:0001891	96.12	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.90	gold quality
neocortex	UBERON:0001950	95.73	gold quality
putamen	UBERON:0001874	95.72	gold quality
dorsal plus ventral thalamus	UBERON:0001897	95.57	gold quality
superior frontal gyrus	UBERON:0002661	95.56	gold quality
superior vestibular nucleus	UBERON:0007227	95.53	gold quality
substantia nigra pars compacta	UBERON:0001965	95.44	gold quality
subthalamic nucleus	UBERON:0001906	95.42	gold quality
Ammon’s horn	UBERON:0001954	95.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, FOXO1, IRF1, NFKB, TCF7L2

miRNA regulators (miRDB)

113 targeting BCL2L2, 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-4481	100.00	66.42	1669
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 40)

• although the cytosolic domain of BCL-w exhibits an overall structure similar to that of BCL-xL and BCL-2, the unique organization of its C-terminal helix may modulate BCL-w interactions with pro-apoptotic binding partners (PMID:12651847)
• structure of reveals a role for the C-terminal residues in modulating biological activity (PMID:12660157)
• Bcl-w may play an important protective role in neurons in the Alzheimer disease brain and this aspect could be therapeutically harnessed to afford neuroprotection (PMID:15147516)
• Peptide = to BH3 region of proapoptotic protein BID, bound in cleft of antiapoptotic protein BCL-w.Binding induced major conformational rearrangements in both peptide & protein components & led to displacement & unfolding of BCL-w C-terminal alpha-helix. (PMID:16475813)
• overexpressed BCL2L2, through amplification or other mechanisms, promotes the growth of a non-smalll cell lung caner cell line. (PMID:17459056)
• Bcl-w is a direct target of miR-122 that functions as an endogenous apoptosis regulator in these human hepatocellular carcinoma -derived cell lines. (PMID:18692484)
• both uPA and MMP-2 contribute to Bcl-w-induced invasion via the stimulation of the FAK-dependent migratory pathway. (PMID:19097687)
• BCL-W may function as a downstream effector of inappropriate WNT/beta-catenin signalling. (PMID:19124064)
• Results show that the folate-induced DNA methylation limits proliferation and increases the sensitivity to temozolomide-induced apoptosis in glioma cells through methylation of PDGF-B, MGMT, survivin, and bcl-w genes. (PMID:19451595)
• over-expression of miR-133B increased apoptosis in response to gemcitabine and reduced MCL-1 and BCL2L2 expression. (PMID:19654003)
• our results provide evidence that miR-335 might function as a metastasis suppressor in gastric cancer by targeting SP1 directly and indirectly through the Bcl-w-induced phosphoinositide 3-kinase-Akt-Sp1 pathway (PMID:21822301)
• miR-195 could improve the drug sensitivity at least in part by targeting Bcl-w to increase cell apoptosis in hepatocellular carcinoma cells. (PMID:21947305)
• The alpha4-alpha5 hinge region is required for dimerization of BCL-W, and functioning of both pro- and antiapoptotic BCL-2 proteins. (PMID:22000515)
• Data show that ABT-737, a small molecule inhibitor of Bcl-2, Bcl-X(L), and Bcl-w, significantly induced apoptosis in HTLV-1 infected T-cell lines as well as in fresh adult T-cell leukemia/lymphoma (ATLL) cells. (PMID:22138435)
• By using human cancer cells and mouse embryonic fibroblasts, the study shows that BCL-W functions in the mitochondria to increase the levels of reactive oxygen species (ROS), which subsequently stimulates the invasion-promoting signaling pathway. (PMID:22570867)
• Bcl-w protein plays a significant role in the carcinogenesis of human small intestinal adenocarcinoma. Down-regulation of Bcl-w protein in HuTu-80 cells makes them susceptible to 5-Fu. (PMID:22780970)
• These findings indicate that miR-29c-mediated BCL2L2 suppression is involved in influenza virus-induced cell death in A549 cells. (PMID:22850539)
• Expression of miR-214 reduces cell survival, induces apoptosis and enhances sensitivity to cisplatin through directly inhibiting Bcl2l2 expression. (PMID:23337879)
• we describe that the specific knockdown of Bcl-xL, but not that of Bcl-2, Bcl-w or Mcl-1, renders cells sensitive to TNFalpha-induced apoptosis. (PMID:23369735)
• over-expression of miR-195 sensitized resistant cells to DOX and enhanced cell apoptosis activity, all of which can be partly rescued by BCL2L2 siRNA and cDNA expression (PMID:23526568)
• MiR-335 lacks of expression brings about the abnormal accumulation of Bcl-w. (PMID:23708561)
• High expression of Bcl-w was associated with mesenchymal changes and invading populations in the glioblastoma multiforme; Bcl-w functions as a positive regulator of invasion by enhancing mesenchymal traits of glioblastoma multiforme, consequently contributing to malignancy. (PMID:23826359)
• Bcl-w-induced Sp1 activation is a potential marker for aggressiveness of glioblastoma multiforme. (PMID:24552705)
• A structural basis for a conserved binding mechanism between p53DBD and the anti-apoptotic Bcl-2 family proteins. (PMID:24646834)
• Crystal structure of human BCL-W in complex with different DARPins is virtually identical to the ligand-free conformation of its closest relative BCL-XL. (PMID:24747052)
• HDMF inhibits Bcl-w-induced neurosphere formation and the expression of glioma stem cell markers, such as Musashi, Sox-2 and c-myc. (PMID:24946210)
• The crystal structures of BCL-W and BCL-XL, along with cellular, studies reveal critical features of the BH3 domains of pro-survival proteins that distinguish them functionally from their pro-apoptotic counterparts. (PMID:25371206)
• these results indicate that miR-335 acts as a novel tumor suppressor to regulate ccRCC cell proliferation and invasion through downregulation of BCL-W expression. (PMID:25846734)
• miR-15a acts as a tumor suppressor in NSCLC by directly targeting BCL2L2 and may serve as a potential diagnostic biomarker and therapeutic target for NSCLC. (PMID:25874488)
• Data show that BCL2-like 2 protein (BCL2L2) is a direct target of micrRNA miR-29b. (PMID:26155940)
• Genetic and pharmacological inhibition of BCL-W and BCL-XL causes directed elimination of senescent cells. (PMID:27048913)
• we conclude that BER treatment reduces cisplatin resistance of gastric cancer cells by modulating the miR-203/Bcl-w apoptotic axis. BER may be a novel agent to enhance chemotherapeutic responses in cisplatin-resistant gastric cancer patients (PMID:27142767)
• BCL-W contributes to the threshold of anti-apoptotic activity during mitosis (PMID:27231850)
• overexpression of miR-15a in the FaDu cells was associated with significantly decreased BCL2L2 and BCL2 expression and a significant increase in the apoptosis rate. The opposite results were observed in HPV-positive HSCC, where downregulation of miR-15a suppressed apoptosis (PMID:27573302)
• BCL2L2 was the virtual target of miR-133b, and we found a negative regulatory relationship between miR-133b and BCL2L2. MiR-133b and BCL2L2 interfered with the viability and apoptosis of cells. (PMID:27802259)
• Our comprehensive analysis indicates B-cell lymphomas commonly select for BCLW overexpression in combination with or instead of other antiapoptotic BCL2 family members. (PMID:28855351)
• HOTAIR up-regulates Bcl-w to enhance cell proliferation through sequestering miR-206 in breast cancer (PMID:29222472)
• the present study demonstrates that miR-422a may serve as a tumor suppressor in osteosarcoma via inhibiting BCL2L2 and KRAS translation both in vitro and in vivo Therefore, miR-422a could be developed as a novel therapeutic target in osteosarcoma. (PMID:29358307)
• Data found that Bcl-w promotes epithelial-mesenchymal transition by increasing respiratory complex-I activity and reactive oxygen species (ROS) levels. (PMID:29596889)
• Upregulation of miR-335-5p expression enhanced the cisplatin sensitivity of ovarian cancer cells through suppressing BCL2L2, suggesting the potential of miR-335-5p/BCL2L2 axis as a therapeutic target for the cisplatin resistance of patients with ovarian cancer. (PMID:30019389)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bcl2l2	ENSMUSG00000089682
rattus_norvegicus	Bcl2l2	ENSRNOG00000015732

Paralogs (8): BAK1 (ENSG00000030110), BAX (ENSG00000087088), BCL2L10 (ENSG00000137875), BCL2A1 (ENSG00000140379), MCL1 (ENSG00000143384), BCL2L1 (ENSG00000171552), BCL2 (ENSG00000171791), BOK (ENSG00000176720)

Protein

Protein identifiers

Bcl-2-like protein 2 — Q92843 (reviewed: Q92843)

Alternative names: Apoptosis regulator Bcl-W

All UniProt accessions (6): Q92843, G3V3B7, G3V3G8, G3V4B7, G3V5A9, H0YJC7

UniProt curated annotations — full annotation on UniProt →

Function. Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX.

Subunit / interactions. Interacts with HIF3A (via C-terminus domain). Interacts with BOP.

Subcellular location. Mitochondrion membrane.

Tissue specificity. Expressed (at protein level) in a wide range of tissues with highest levels in brain, spinal cord, testis, pancreas, heart, spleen and mammary glands. Moderate levels found in thymus, ovary and small intestine. Not detected in salivary gland, muscle or liver. Also expressed in cell lines of myeloid, fibroblast and epithelial origin. Not detected in most lymphoid cell lines.

Domain organisation. The BH4 motif seems to be involved in the anti-apoptotic function. The BH1 and BH2 motifs form a hydrophobic groove which acts as a docking site for the BH3 domain of some pro-apoptotic proteins. The C-terminal residues of BCL2L2 fold into the BH3-binding cleft and modulate pro-survival activity by regulating ligand access. When BH3 domain-containing proteins bind, they displace the C-terminus, allowing its insertion into the membrane and neutralizing the pro-survival activity of BCL2L2.

Miscellaneous. Based on a readthrough transcript which may produce a BCL2L2-PABPN1 fusion protein.

Similarity. Belongs to the Bcl-2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92843-1	1	yes
Q92843-2	3, BCL2L2-PABPN1

RefSeq proteins (2): NP_001186768, NP_004041* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002475	Bcl2-like	Family
IPR003093	Bcl2_BH4	Domain
IPR013280	Apop_reg_BclW	Family
IPR020717	Bcl2_BH1_motif_CS	Conserved_site
IPR020726	Bcl2_BH2_motif_CS	Conserved_site
IPR020731	Bcl2_BH4_motif_CS	Conserved_site
IPR026298	Bcl-2_fam	Family
IPR036834	Bcl-2-like_sf	Homologous_superfamily
IPR046371	Bcl-2_BH1-3	Domain

Pfam: PF00452, PF02180

UniProt features (27 total): helix 9, modified residue 5, turn 4, short sequence motif 3, strand 2, initiator methionine 1, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4CIM	X-RAY DIFFRACTION	1.5
2Y6W	X-RAY DIFFRACTION	2
1MK3	SOLUTION NMR
1O0L	SOLUTION NMR
1ZY3	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92843-F1	82.27	0.43

Functional residue map

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

Post-translational modifications (5): 177, 262, 286, 290, 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 252 (showing top): GGGACCA_MIR133A_MIR133B, TAATAAT_MIR126, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGCACTT_MIR519C_MIR519B_MIR519A, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, AP4_Q6, GOBP_MALE_GAMETE_GENERATION, CAGCTG_AP4_Q5

GO Biological Process (11): release of cytochrome c from mitochondria (GO:0001836), spermatogenesis (GO:0007283), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), regulation of apoptotic process (GO:0042981), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), Sertoli cell proliferation (GO:0060011), extrinsic apoptotic signaling pathway in absence of ligand (GO:0097192), developmental process involved in reproduction (GO:0003006), apoptotic process (GO:0006915), transmembrane transport (GO:0055085)

GO Molecular Function (4): channel activity (GO:0015267), identical protein binding (GO:0042802), disordered domain specific binding (GO:0097718), protein binding (GO:0005515)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), Bcl-2 family protein complex (GO:0097136), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	3
apoptotic signaling pathway	2
regulation of apoptotic process	2
cytoplasm	2
cellular anatomical structure	2
apoptotic mitochondrial changes	1
developmental process involved in reproduction	1
male gamete generation	1
DNA damage response	1
intrinsic apoptotic signaling pathway	1
regulation of programmed cell death	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
male gonad development	1
epithelial cell proliferation	1
signal transduction in absence of ligand	1
extrinsic apoptotic signaling pathway	1
reproductive process	1
developmental process	1
programmed cell death	1
execution phase of apoptosis	1
transport	1
cellular process	1
passive transmembrane transporter activity	1
protein binding	1
protein domain specific binding	1
binding	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
protein-containing complex	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1

Protein interactions and networks

STRING

1117 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCL2L2	BCL2L11	O43521	998
BCL2L2	PMAIP1	Q13794	996
BCL2L2	BMF	Q96LC9	993
BCL2L2	BECN1	Q14457	976
BCL2L2	MCL1	Q07820	975
BCL2L2	HRK	O00198	968
BCL2L2	BCL2L10	Q9HD36	880
BCL2L2	BIK	Q13323	861
BCL2L2	BCL2L1	Q07817	841
BCL2L2	RTL10	Q7L3V2	822
BCL2L2	CYCS	P00001	797
BCL2L2	BCL2	P10415	756
BCL2L2	CASP9	P55211	743
BCL2L2	BBC3	Q96PG8	739
BCL2L2	CASP3	P42574	696

IntAct

261 interactions, top by confidence:

A	B	Type	Score
BCL2L11	BCL2L2	psi-mi:“MI:0407”(direct interaction)	0.930
BIK	BCL2L2	psi-mi:“MI:0407”(direct interaction)	0.930
BIK	BCL2L2	psi-mi:“MI:0915”(physical association)	0.930
BCL2L2	BIK	psi-mi:“MI:0915”(physical association)	0.930
BCL2L11	BCL2L2	psi-mi:“MI:0915”(physical association)	0.930
BAX	BCL2L2	psi-mi:“MI:0915”(physical association)	0.820
BCL2L2	BID	psi-mi:“MI:0407”(direct interaction)	0.810
KASH5	BCL2L2	psi-mi:“MI:0915”(physical association)	0.790
BCL2L2	KASH5	psi-mi:“MI:0915”(physical association)	0.790
BBC3	BCL2L2	psi-mi:“MI:0407”(direct interaction)	0.780
BCL2L2	BAD	psi-mi:“MI:0407”(direct interaction)	0.770
BCL2L2	BAD	psi-mi:“MI:0915”(physical association)	0.770
BCL2L2	BAK1	psi-mi:“MI:0915”(physical association)	0.720
FATE1	BCL2L2	psi-mi:“MI:0915”(physical association)	0.720
BCL2L2	BMF	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (123): BCL2L2 (Two-hybrid), BIK (Two-hybrid), TCF4 (Two-hybrid), FATE1 (Two-hybrid), BMF (Two-hybrid), CCDC155 (Two-hybrid), BID (Protein-peptide), BCL2L11 (Protein-peptide), BAD (Protein-peptide), BIK (Protein-peptide), BCL2L2 (Affinity Capture-Western), BCL2L2 (Affinity Capture-MS), BCL2L2 (Affinity Capture-MS), BCL2L2 (Affinity Capture-MS), BCL2L2 (Proximity Label-MS)

ESM2 similar proteins: A0JMW6, A1L2I9, A1L3G9, A7Z033, B9X187, E7FE40, F1QB30, F1QYC4, O02703, O08734, O77737, P53563, P70345, P70444, Q07440, Q07812, Q07813, Q07816, Q07817, Q08ED0, Q0II48, Q16548, Q16611, Q1M161, Q1RMX3, Q28EH9, Q28FG4, Q45T69, Q568Z0, Q5TBC7, Q63690, Q64373, Q6DC66, Q6GMB1, Q6ZTN6, Q7T381, Q8BXV2, Q8JGM8, Q8K1H7, Q8N4U5

Diamond homologs: O02703, O02718, O77737, P10415, P10417, P49950, P53563, P70345, Q00709, Q07812, Q07813, Q07816, Q07817, Q07820, Q1RMX3, Q45T69, Q63690, Q64373, Q6R755, Q7YRZ9, Q90343, Q91827, Q92843, Q9JJV8, O08734, Q07440, Q07818, Q16548, Q16611, Q3C2I0, Q91828, P0C8H4, P0C8H5, P0C8H6, P42485, Q07819, Q90ZN1, P97287, Q8HYS5, Q99M66

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
BAD	down-regulates	BCL2L2	binding
BBC3	down-regulates	BCL2L2	binding
BCL2L11	down-regulates	BCL2L2	binding
ABT-737	down-regulates	BCL2L2	“chemical inhibition”
BCL2L2	down-regulates	BAK1	binding
BCL2L2	down-regulates	BAX	binding
4-[4-[[2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohexenyl]methyl]-1-piperazinyl]-N-[4-[[(2R)-4-(4-morpholinyl)-1-(phenylthio)butan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide	down-regulates	BCL2L2	“chemical inhibition”
“Obatoclax mesylate”	“down-regulates activity”	BCL2L2	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 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
Activation of BH3-only proteins	6	96.1×	1e-09
Intrinsic Pathway for Apoptosis	8	75.6×	1e-11
Apoptosis	8	43.3×	8e-10
Programmed Cell Death	8	37.8×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of release of cytochrome c from mitochondria	8	127.7×	3e-13
release of cytochrome c from mitochondria	5	73.1×	6e-07
positive regulation of protein-containing complex assembly	7	49.1×	2e-08
intrinsic apoptotic signaling pathway in response to DNA damage	5	33.8×	3e-05
positive regulation of apoptotic process	8	9.5×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1253 predictions. Top by Δscore:

Variant	Effect	Δscore
14:23301323:C:CA	donor_gain	0.9900
14:23302154:GCCTA:G	donor_loss	0.9900
14:23302155:CCTAC:C	donor_loss	0.9900
14:23302156:CTACC:C	donor_loss	0.9900
14:23302157:TAC:T	donor_loss	0.9900
14:23302158:A:AT	donor_loss	0.9900
14:23302159:C:CG	donor_loss	0.9900
14:23306890:GACCC:G	donor_gain	0.9900
14:23306895:G:GG	donor_gain	0.9900
14:23307278:GG:G	donor_gain	0.9900
14:23307279:GG:G	donor_gain	0.9900
14:23299537:CCCTT:C	acceptor_gain	0.9800
14:23299538:CCTTC:C	acceptor_gain	0.9800
14:23299539:CTT:C	acceptor_gain	0.9800
14:23299572:A:C	acceptor_gain	0.9800
14:23301409:T:A	donor_gain	0.9800
14:23307186:TTCCA:T	acceptor_loss	0.9800
14:23307187:TCCA:T	acceptor_loss	0.9800
14:23307190:A:AG	acceptor_gain	0.9800
14:23307190:AG:A	acceptor_gain	0.9800
14:23307190:AGGG:A	acceptor_loss	0.9800
14:23307191:G:A	acceptor_loss	0.9800
14:23307191:G:GA	acceptor_loss	0.9800
14:23307191:G:GG	acceptor_gain	0.9800
14:23307191:GG:G	acceptor_gain	0.9800
14:23307275:GCTGG:G	donor_gain	0.9800
14:23307276:CTGGG:C	donor_loss	0.9800
14:23307279:GGTG:G	donor_loss	0.9800
14:23307280:G:GG	donor_gain	0.9800
14:23307280:G:T	donor_loss	0.9800

AlphaMissense

1230 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:23307936:T:C	F57L	0.999
14:23307938:C:A	F57L	0.999
14:23307938:C:G	F57L	0.999
14:23308046:G:C	W93C	0.999
14:23308046:G:T	W93C	0.999
14:23308199:G:C	W144C	0.999
14:23308199:G:T	W144C	0.999
14:23308003:T:C	F79S	0.998
14:23308823:T:C	F147S	0.998
14:23308924:G:A	G181R	0.998
14:23308924:G:C	G181R	0.998
14:23307924:T:C	F53L	0.997
14:23307926:C:A	F53L	0.997
14:23307926:C:G	F53L	0.997
14:23307948:T:C	F61L	0.997
14:23307950:C:A	F61L	0.997
14:23307950:C:G	F61L	0.997
14:23308071:T:C	F102L	0.997
14:23308073:T:A	F102L	0.997
14:23308073:T:G	F102L	0.997
14:23308074:G:T	G103W	0.997
14:23308075:G:A	G103E	0.997
14:23308197:T:A	W144R	0.997
14:23308197:T:C	W144R	0.997
14:23308822:T:C	F147L	0.997
14:23308823:T:G	F147C	0.997
14:23308824:C:A	F147L	0.997
14:23308824:C:G	F147L	0.997
14:23308925:G:A	G181E	0.997
14:23307817:T:C	F17S	0.996

dbSNP variants (sampled 300 via entrez): RS1000038650 (14:23309658 T>C), RS1000946613 (14:23310177 C>A,T), RS1001383421 (14:23309267 C>T), RS1002085630 (14:23304872 T>G), RS1002153518 (14:23306513 A>G), RS1002373263 (14:23311275 C>A,G,T), RS1002769277 (14:23307864 C>T), RS1003293333 (14:23307554 T>A), RS1003454773 (14:23310762 C>G,T), RS1003531483 (14:23306042 TG>T), RS1003889174 (14:23309290 G>C,T), RS1004193768 (14:23311564 T>A), RS1004343723 (14:23305358 T>C), RS1005524830 (14:23309583 C>T), RS1005710310 (14:23305675 G>A)

Disease associations

OMIM: gene MIM:601931 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST008163_213	Height	3.000000e-07
GCST008163_368	Height	4.000000e-09
GCST012227_601	Hip circumference adjusted for BMI	5.000000e-12
GCST90020028_1234	Hip circumference adjusted for BMI	4.000000e-08
GCST90020028_1235	Hip circumference adjusted for BMI	5.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4677 (SINGLE PROTEIN), CHEMBL5169271 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 58,159 (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
CHEMBL3137309	VENETOCLAX	4	9,389
CHEMBL408194	OBATOCLAX	3	2,914
CHEMBL443684	NAVITOCLAX	3	4,791
CHEMBL51483	GOSSYPOL	3	13,973
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL376408	ABT 737	1	4,288

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — B-cell lymphoma 2 (Bcl-2) protein family

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
ABT-737	Antagonist	9.0	pKi
venetoclax	Antagonist	6.61	pKi

Binding affinities (BindingDB)

133 measured of 136 human assays (137 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
4-(4-{[2-(4-chlorophenyl)phenyl]methyl}piperazin-1-yl)-N-[(4-{[(2R)-4-(dimethylamino)-1-(phenylsulfanyl)butan-2-yl]amino}-3-nitrobenzene)sulfonyl]benzamide	IC50	14 nM
2,5-bis(chloranyl)-3-(4-methylpiperazin-1-yl)-6-(2-piperidin-1-yl-1,3-thiazol-5-yl)cyclohexa-2,5-diene-1,4-dione	EC50	160 nM
2-chloranyl-3-[[4-(diethylamino)phenyl]amino]naphthalene-1,4-dione	EC50	170 nM
2,5-bis(chloranyl)-3-[2-(dimethylamino)-1,3-thiazol-5-yl]-6-pyrrolidin-1-yl-cyclohexa-2,5-diene-1,4-dione	EC50	210 nM
4-[2-[(6,7-dimethoxy-2-sulfanylidene-1H-quinazolin-4-yl)amino]ethyl]benzenesulfonamide	EC50	540 nM
4-[[4-(2-methyl-3-imidazo[1,2-a]pyrimidinyl)-2-thiazolyl]amino]phenol;hydrobromide	EC50	670 nM
(5Z)-5-{[4-(dimethylamino)phenyl]imino}-1-(3-hydroxypropyl)-4-methyl-2,6-dioxo-1,2,5,6-tetrahydropyridine-3-carbonitrile	EC50	760 nM
(m-anisylideneamino)-([1,2,4]triazolo[3,4-a]phthalazin-6-yl)amine	EC50	980 nM
MLS000571745	EC50	980 nM
1-(3-chlorophenyl)-3-(2-pyridin-3-ylpyrimidin-4-yl)urea	EC50	1110 nM
6-(3,4-Dimethoxy-phenyl)-3-furan-2-yl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine	EC50	1210 nM
2-[[2-amino-1-(3-ethoxypropyl)pyrrolo[3,2-b]quinoxaline-3-carbonyl]amino]-4,5,6,7-tetrahydrobenzothiophene-3-carboxylic acid methyl ester	EC50	1280 nM
2-(2-bromo-6-methoxy-4-{[(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)amino]methyl}phenoxy)-N-(tert-butyl)acetamide	EC50	1470 nM
4-(4-carbethoxyanilino)quinazoline-2-carboxylic acid ethyl ester	EC50	1510 nM
5-[4-(dimethylamino)phenyl]imino-1-(2-hydroxyethyl)-2,6-diketo-4-methyl-nicotinonitrile	EC50	1630 nM
6-methyl-2-(1-naphthalenyl)-5-benzotriazolamine	EC50	1750 nM
MLS000537607	EC50	1800 nM
(4E)-4-[[[4-(2-furanyl)-2-(2-methoxyethylimino)-3-thiazolyl]amino]methylidene]-2,3-dihydroxy-1-cyclohexa-2,5-dienone	EC50	1810 nM
(1,1-diketo-1,2-benzothiazol-3-yl)-methyl-[[(E)-3-phenylprop-2-enylidene]amino]amine	EC50	1940 nM
2-[[2-amino-1-(3-methoxypropyl)pyrrolo[3,2-b]quinoxaline-3-carbonyl]amino]-4,5,6,7-tetrahydrobenzothiophene-3-carboxylic acid methyl ester	EC50	1950 nM
2-(8-(2-(Benzothiazol-2-yl)hydrazono)-5,6,7,8-tetrahydronaphthalen-2-yl)thiazole-4-carboxylic acid (Compound 4)	IC50	2000 nM
6-Methoxy-1,3-dimethyl-1H-benzo[de]cinnoline	EC50	2010 nM
2-[[(5Z)-5-[(4-methoxyphenyl)methylidene]-4-oxo-2-thiazolyl]thio]acetic acid ethyl ester	EC50	2060 nM
4-(3-ethoxypropylamino)-6,7-dimethoxy-1H-quinazoline-2-thione	EC50	2200 nM
1,2,3-trimethyl-2,3-dihydro-1H-perimidine	EC50	2260 nM
(1,1-diketo-1,2-benzothiazol-3-yl)-methyl-(4-pyridylmethyleneamino)amine	EC50	2440 nM
4-[(2-benzoxybenzyl)amino]phenol	EC50	2980 nM
(E)-1-(4-methylphenyl)-3-[5-(4-methylphenyl)-2-furanyl]-2-propen-1-one	EC50	3080 nM
4-(2,3-dihydro-1H-perimidin-2-yl)-2,6-dimethoxy-phenol	EC50	3250 nM
4-amino-6,7-dimethoxy-3-(2-phenylethyl)-2-quinazolinethione	EC50	3340 nM
MLS000392298	EC50	3490 nM
MLS000685782	EC50	3530 nM
4-[(2-ethoxybenzyl)amino]phenol	EC50	3630 nM
6,7-dimethoxy-4-(3-methoxypropylamino)-1H-quinazoline-2-thione	EC50	3680 nM
(3-chloro-4,5-dimethoxy-benzyl)-(4-pyrrolidinophenyl)amine	EC50	3720 nM
6,7-dimethoxy-4-(2-methoxyethylamino)-1H-quinazoline-2-thione	EC50	3860 nM
MLS001013472	EC50	4000 nM
MLS000080844	EC50	4050 nM
5-[(6-Bromo-2-hydroxy-naphthalen-1-ylmethylene)-amino]-1,3-dihydro-benzoimidazol-2-one	EC50	4150 nM
MLS000392290	EC50	4380 nM
(2Z)-2-(5-fluoranyl-2-oxidanylidene-indol-3-yl)-2-(4-methyl-3H-1,3-thiazol-2-ylidene)ethanenitrile	EC50	4560 nM
6,7-dimethoxy-4-(2-oxolanylmethylamino)-1H-quinazoline-2-thione	EC50	4620 nM
MLS000530834	EC50	4650 nM
(4E)-2,3-dihydroxy-4-[[2-(2-morpholin-4-ylsulfonyl-4-nitrophenyl)hydrazinyl]methylidene]cyclohexa-2,5-dien-1-one	EC50	4660 nM
MLS000390291	EC50	4670 nM
4-N,4-N-diethyl-1-N-(4-morpholin-4-ylquinazolin-2-yl)benzene-1,4-diamine	EC50	4710 nM
MLS000530401	EC50	4760 nM
(4E)-2,3-dihydroxy-4-[[(2-methylimino-4-thiophen-2-yl-1,3-thiazol-3-yl)amino]methylidene]cyclohexa-2,5-dien-1-one	EC50	5050 nM
(2E,5E)-2,5-bis(4-hydroxy-3,5-dimethoxy-benzylidene)cyclopentanone	EC50	5130 nM
3-[[[(E)-(2,3-dihydroxy-4-keto-cyclohexa-2,5-dien-1-ylidene)methyl]amino]carbamoyl]-N,N-diethyl-benzenesulfonamide	EC50	5130 nM

ChEMBL bioactivities

55 potent at pChembl≥5 of 86 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	Ki	2	nM	CHEMBL5712050
8.40	Ki	4	nM	CHEMBL3793424
8.10	Ki	8	nM	A-1155463
7.72	Ki	19	nM	A-1155463
7.68	Ki	21	nM	NAVITOCLAX
7.68	Ki	21	nM	CHEMBL1916194
7.40	IC50	40	nM	ABT 737
7.31	Ki	49	nM	CHEMBL221854
7.26	Ki	55	nM	CHEMBL1916191
7.23	Ki	59	nM	CHEMBL1916193
7.21	Kd	62	nM	CHEMBL3287301
7.20	Ki	63	nM	CHEMBL1916190
7.18	IC50	66	nM	ABT 737
7.16	IC50	70	nM	NAVITOCLAX
6.77	Ki	170	nM	CHEMBL1916192
6.61	Ki	245	nM	VENETOCLAX
6.61	Ki	245	nM	NAVITOCLAX
6.61	IC50	245	nM	CHEMBL1689141
6.56	IC50	275	nM	CHEMBL1689145
6.54	Ki	285	nM	ABT 737
6.36	IC50	440	nM	CHEMBL1689139
6.34	Kd	459	nM	CHEMBL192571
6.27	IC50	540	nM	CHEMBL1689143
6.07	Ki	852	nM	A-1211212
6.00	IC50	1000	nM	CHEMBL4592905
6.00	Ki	1000	nM	OBATOCLAX
5.89	Ki	1300	nM	CHEMBL404899
5.87	Ki	1360	nM	CHEMBL3265297
5.80	Ki	1580	nM	CHEMBL3265299
5.72	Ki	1920	nM	CHEMBL3265294
5.70	IC50	2020	nM	GAMBOGIC ACID
5.68	Ki	2100	nM	APOGOSSYPOL
5.66	Ki	2190	nM	CHEMBL3265295
5.66	Ki	2200	nM	CHEMBL270646
5.66	IC50	2210	nM	CHEMBL5207007
5.64	Ki	2300	nM	CHEMBL406312
5.63	IC50	2330	nM	EPIGALOCATECHIN GALLATE
5.40	IC50	4010	nM	CHEMBL4473013
5.36	Ki	4410	nM	CHEMBL3265296
5.36	IC50	4370	nM	CHEMBL4474764
5.34	IC50	4570	nM	CHEMBL5193844
5.30	IC50	5000	nM	CHEMBL2398263
5.30	IC50	5000	nM	CHEMBL2398260
5.16	Ki	6980	nM	CHEMBL242340
5.15	Ki	7010	nM	OBATOCLAX
5.11	Kd	7800	nM	CHEMBL3287293
5.09	Ki	8190	nM	CHEMBL1331211
5.09	IC50	8090	nM	CHEMBL205750
5.09	Ki	8190	nM	CHEMBL3265291
5.03	Ki	9430	nM	CHEMBL521253

PubChem BioAssay actives

61 with measured affinity, of 142 total; 46 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
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide	1483464: Inhibition of Bcl-w (unknown origin)	ki	0.0010	uM
N-[3-[chloro(difluoro)methyl]sulfonyl-4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]phenyl]sulfonyl-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]benzamide	2187835: Binding affinity to BCL-W (unknown origin) assessed as dissociation constant incubated for 1 hrs by TR-FRET assay	ki	0.0020	uM
3-[1-(1-adamantylmethyl)-5-methylpyrazol-4-yl]-6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinolin-2-yl]pyridine-2-carboxylic acid	2187835: Binding affinity to BCL-W (unknown origin) assessed as dissociation constant incubated for 1 hrs by TR-FRET assay	ki	0.0040	uM
2-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinolin-2-yl]-5-[3-[4-[3-(dimethylamino)prop-1-ynyl]-2-fluorophenoxy]propyl]-1,3-thiazole-4-carboxylic acid	2187835: Binding affinity to BCL-W (unknown origin) assessed as dissociation constant incubated for 1 hrs by TR-FRET assay	ki	0.0080	uM
4-[4-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide	2187835: Binding affinity to BCL-W (unknown origin) assessed as dissociation constant incubated for 1 hrs by TR-FRET assay	ki	0.0210	uM
N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonyl-4-[(2R)-2-propan-2-yl-4-[[2-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]benzamide	628490: Displacement of BODIPY-Bak conjugated peptide from GST-tagged human wild type Bcl-W expressed in Escherichia coli BL21 cells at 10 uM after 3 hrs by fluorescence polarization competition assay	ki	0.0210	uM
N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonyl-4-[4-[[2-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]benzamide	628490: Displacement of BODIPY-Bak conjugated peptide from GST-tagged human wild type Bcl-W expressed in Escherichia coli BL21 cells at 10 uM after 3 hrs by fluorescence polarization competition assay	ki	0.0490	uM
N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonyl-4-[(3R)-3-methyl-4-[[2-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]benzamide	628490: Displacement of BODIPY-Bak conjugated peptide from GST-tagged human wild type Bcl-W expressed in Escherichia coli BL21 cells at 10 uM after 3 hrs by fluorescence polarization competition assay	ki	0.0550	uM
N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonyl-4-[(2S)-2-propan-2-yl-4-[[2-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]benzamide	628490: Displacement of BODIPY-Bak conjugated peptide from GST-tagged human wild type Bcl-W expressed in Escherichia coli BL21 cells at 10 uM after 3 hrs by fluorescence polarization competition assay	ki	0.0590	uM
2-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinolin-2-yl]-5-(3-phenoxypropyl)-1,3-thiazole-4-carboxylic acid	1156102: Binding affinity to Bcl-w (unknown origin) by surface plasmon resonance assay	kd	0.0620	uM
N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonyl-4-[(3S)-3-methyl-4-[[2-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]benzamide	628490: Displacement of BODIPY-Bak conjugated peptide from GST-tagged human wild type Bcl-W expressed in Escherichia coli BL21 cells at 10 uM after 3 hrs by fluorescence polarization competition assay	ki	0.0630	uM
N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonyl-4-[3,5-dimethyl-4-[[2-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]benzamide	628490: Displacement of BODIPY-Bak conjugated peptide from GST-tagged human wild type Bcl-W expressed in Escherichia coli BL21 cells at 10 uM after 3 hrs by fluorescence polarization competition assay	ki	0.1700	uM
Venetoclax	1483478: Binding affinity to Bcl-w (unknown origin) by TR-FRET assay	ki	0.2450	uM
N-[7-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]quinazolin-4-yl]-4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)benzenesulfonamide	587011: Displacement of wild type mBimBH3 from human Bcl-w by solution competition assay	ic50	0.2450	uM
N-[7-[4-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]quinazolin-4-yl]-4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)benzenesulfonamide	587011: Displacement of wild type mBimBH3 from human Bcl-w by solution competition assay	ic50	0.2750	uM
N-[7-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]quinazolin-4-yl]-4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrobenzenesulfonamide	587011: Displacement of wild type mBimBH3 from human Bcl-w by solution competition assay	ic50	0.4400	uM
N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonyl-4-(4,4-dimethylpiperidin-1-yl)benzamide	260143: Binding affinity to Bclw	kd	0.4590	uM
N-[7-[4-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]quinazolin-4-yl]-4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrobenzenesulfonamide	587011: Displacement of wild type mBimBH3 from human Bcl-w by solution competition assay	ic50	0.5400	uM
4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[(4-methoxycyclohexyl)methylamino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2187835: Binding affinity to BCL-W (unknown origin) assessed as dissociation constant incubated for 1 hrs by TR-FRET assay	ki	0.8520	uM
(2Z)-2-[(5Z)-5-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-4-methoxypyrrol-2-ylidene]indole	330736: Inhibition of BH3 peptide binding to human recombinant BCL-w by fluorescence polarization assay	ki	1.0000	uM
4-(4-fluorophenyl)-N-[4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide	1610201: Inhibition of recombinant human N-terminal 6xHis-tagged Bcl-w (M1 to R171) expressed in Escherichia coli using HyLite Fluor 647-labeled Bim peptide as substrate incubated for 120 to 180 mins by TR-FRET assay	ic50	1.0000	uM
(2S)-2-[(5Z)-5-[[4-[2-[4-[(Z)-[3-[(1S)-1-carboxy-2-phenylethyl]-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl]phenoxy]ethoxy]phenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid	316742: Inhibition of Bak peptide binding to human recombinant Bcl-w	ki	1.3000	uM
2-[4-[[4-(4-chlorophenyl)phenyl]sulfonylamino]-1-hydroxynaphthalen-2-yl]sulfanylacetic acid	1140885: Displacement of Flu-BID/FAM-BID from His-tagged BCLW (1 to 155) (unknown origin) expressed in Escherichia coli BL21(DE3) after 3 hrs by fluorescence polarization assay	ki	1.3600	uM
2-[1-hydroxy-4-[(4-phenoxyphenyl)sulfonylamino]naphthalen-2-yl]sulfanylacetic acid	1140885: Displacement of Flu-BID/FAM-BID from His-tagged BCLW (1 to 155) (unknown origin) expressed in Escherichia coli BL21(DE3) after 3 hrs by fluorescence polarization assay	ki	1.5800	uM
2-[1-hydroxy-4-[(4-phenylphenyl)sulfonylamino]naphthalen-2-yl]sulfanylacetic acid	1140885: Displacement of Flu-BID/FAM-BID from His-tagged BCLW (1 to 155) (unknown origin) expressed in Escherichia coli BL21(DE3) after 3 hrs by fluorescence polarization assay	ki	1.9200	uM
(Z)-4-[(1S,2S,8R,17S,19R)-12-hydroxy-8,21,21-trimethyl-5-(3-methylbut-2-enyl)-8-(4-methylpent-3-enyl)-14,18-dioxo-3,7,20-trioxahexacyclo[15.4.1.02,15.02,19.04,13.06,11]docosa-4(13),5,9,11,15-pentaen-19-yl]-2-methylbut-2-enoic acid	1938344: Displacement of fluorescein tagged BID BH3 peptide from GST-tagged recombinant Bcl-W (unknown origin) by fluorescence polarization-based competitive binding assay	ic50	2.0200	uM
3-methyl-5-propan-2-yl-2-(1,6,7-trihydroxy-3-methyl-5-propan-2-ylnaphthalen-2-yl)naphthalene-1,6,7-triol	1599456: Inhibition of Bcl-w (unknown origin)	ki	2.1000	uM
2-[1-hydroxy-4-[(3-phenylphenyl)sulfonylamino]naphthalen-2-yl]sulfanylacetic acid	1140885: Displacement of Flu-BID/FAM-BID from His-tagged BCLW (1 to 155) (unknown origin) expressed in Escherichia coli BL21(DE3) after 3 hrs by fluorescence polarization assay	ki	2.1900	uM
(2S)-2-[(5Z)-5-[[4-[2-[2-[4-[(Z)-[3-[(1S)-1-carboxy-2-phenylethyl]-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl]phenoxy]ethoxy]ethoxy]phenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid	316742: Inhibition of Bak peptide binding to human recombinant Bcl-w	ki	2.2000	uM
[4-[(4,9-dioxo-3a,9a-dihydrobenzo[f][1,3]benzothiazol-2-yl)amino]phenyl] (2S)-2-(methoxycarbonylamino)-4-methylsulfanylbutanoate	1858794: Inhibition of Bcl-W/Bid (unknown origin) by fluorescence polarization assay	ic50	2.2100	uM
(2S)-2-[(5Z)-5-[[4-[[4-[(Z)-[3-[(1S)-1-carboxy-2-phenylethyl]-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl]phenoxy]methoxy]phenyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid	316742: Inhibition of Bak peptide binding to human recombinant Bcl-w	ki	2.3000	uM
[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	1858783: Inhibition of Bcl-W/Bid (unknown origin)	ic50	2.3300	uM
5-fluoro-2-[4-[[4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylcarbamoyl]phenyl]benzenesulfonyl fluoride	1610201: Inhibition of recombinant human N-terminal 6xHis-tagged Bcl-w (M1 to R171) expressed in Escherichia coli using HyLite Fluor 647-labeled Bim peptide as substrate incubated for 120 to 180 mins by TR-FRET assay	ic50	4.0100	uM
5-[3-[4-(aminomethyl)phenoxy]propyl]-2-[(8E)-8-(1,3-benzothiazol-2-ylhydrazinylidene)-6,7-dihydro-5H-naphthalen-2-yl]-1,3-thiazole-4-carboxylic acid	1800239: SPR Directy Binding Assay (Biacore 4000) from Article 10.1038/nchembio.1246: “Structure-guided design of a selective BCL-X(L) inhibitor.”	ic50	4.1000	uM
2-(4-fluorophenyl)-5-[[4-[[(2R)-4-[methyl(prop-2-ynyl)amino]-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylcarbamoyl]benzenesulfonyl fluoride	1610201: Inhibition of recombinant human N-terminal 6xHis-tagged Bcl-w (M1 to R171) expressed in Escherichia coli using HyLite Fluor 647-labeled Bim peptide as substrate incubated for 120 to 180 mins by TR-FRET assay	ic50	4.3700	uM
2-[1-hydroxy-4-[(2-phenylphenyl)sulfonylamino]naphthalen-2-yl]sulfanylacetic acid	1140885: Displacement of Flu-BID/FAM-BID from His-tagged BCLW (1 to 155) (unknown origin) expressed in Escherichia coli BL21(DE3) after 3 hrs by fluorescence polarization assay	ki	4.4100	uM
[(1S,2R,5S,6S,9R)-2-butyl-6-[(3-formamido-2-hydroxybenzoyl)amino]-5,9-dimethyl-3,7-dioxocyclononyl] 3-methylbutanoate	1858834: Inhibition of Bcl-W(unknown origin)/ human Bid by fluorescence polarization assay	ic50	4.5700	uM
2-[(8Z)-8-(1,3-benzothiazol-2-ylhydrazinylidene)-6,7-dihydro-5H-naphthalen-2-yl]-1,3-thiazole-4-carboxylic acid	756756: Binding affinity to Bcl-w (unknown origin) by surface plasmon resonance assay	ic50	5.0000	uM
4-[(8Z)-8-(1,3-benzothiazol-2-ylhydrazinylidene)-6,7-dihydro-5H-naphthalen-2-yl]pyridine-2-carboxylic acid	756756: Binding affinity to Bcl-w (unknown origin) by surface plasmon resonance assay	ic50	5.0000	uM
2-[(8E)-8-(1,3-benzothiazol-2-ylhydrazinylidene)-6,7-dihydro-5H-naphthalen-2-yl]-1,3-thiazole-4-carboxylic acid	1800239: SPR Directy Binding Assay (Biacore 4000) from Article 10.1038/nchembio.1246: “Structure-guided design of a selective BCL-X(L) inhibitor.”	ic50	5.3000	uM
(2S)-4-methyl-2-[(5Z)-4-oxo-5-[phenyl-(4-phenylphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]pentanoic acid	293613: Displacement of Flu-Bak peptide from recombinant antiapoptotic Bcl-w protein by fluorescence polarization assay	ki	6.9800	uM
2-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinolin-2-yl]-1,3-thiazole-4-carboxylic acid	1156102: Binding affinity to Bcl-w (unknown origin) by surface plasmon resonance assay	kd	7.8000	uM
5-butyl-1-[2-(2-methoxyphenyl)ethyl]-4-(2-phenoxyphenyl)imidazole	261994: Inhibition of Bclw by FP assay	ic50	8.0900	uM
2-[4-[(3-bromophenyl)sulfonylamino]-1-hydroxynaphthalen-2-yl]sulfanylacetic acid	1858823: Binding affinity to Bcl-W/Bid (unknown origin) by fluorescence polarization assay	ki	8.1900	uM
2-[4-[(4-bromophenyl)sulfonylamino]-1-hydroxynaphthalen-2-yl]sulfanylacetic acid	1140885: Displacement of Flu-BID/FAM-BID from His-tagged BCLW (1 to 155) (unknown origin) expressed in Escherichia coli BL21(DE3) after 3 hrs by fluorescence polarization assay	ki	8.1900	uM
N-[2-[4-(1-adamantylamino)-3-nitroanilino]-2-oxoethyl]-N-methyl-4-phenylbenzamide	340022: Inhibition of 5-carboxyfluorescein-labeled Flu-Bak-BH3 peptide binding to Bcl-w by fluorescence polarization assay	ki	9.4300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression, decreases expression, affects cotreatment	5
Resveratrol	increases expression, affects cotreatment, decreases expression, decreases reaction	3
Atrazine	affects cotreatment, increases expression, decreases expression	2
Curcumin	affects cotreatment, affects expression, increases expression	2
Estradiol	increases expression, decreases reaction	2
Valproic Acid	affects expression, increases methylation	2
triphenyl phosphate	affects expression	1
propylparaben	increases expression	1
geraniol	decreases expression	1
arsenite	decreases reaction, increases expression, decreases expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
salvin	affects cotreatment, decreases expression, decreases reaction	1
tetrathiomolybdate	increases expression	1
sodium chromate(VI)	decreases expression	1
usnic acid	increases expression	1
deguelin	decreases expression	1
K 7174	increases expression	1
pinostrobin	decreases expression	1
WP 744	decreases expression	1
dihydromyricetin	decreases expression	1
2’-benzoyloxycinnamaldehyde	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
jinfukang	increases expression	1
PF 3758309	increases expression	1
picoxystrobin	decreases expression	1
Bortezomib	increases expression	1
Erlotinib Hydrochloride	increases expression, decreases reaction, increases response to substance	1

ChEMBL screening assays

41 unique, capped per target: 41 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1693159	Binding	Displacement of wild type mBimBH3 from human Bcl-w by solution competition assay	Quinazoline sulfonamides as dual binders of the proteins B-cell lymphoma 2 and B-cell lymphoma extra long with potent proapoptotic cell-based activity. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1L5	Abcam HeLa BCL2L2 KO	Cancer cell line	Female
CVCL_SE95	HAP1 BCL2L2 (-) 1	Cancer cell line	Male
CVCL_SE96	HAP1 BCL2L2 (-) 2	Cancer cell line	Male
CVCL_SE97	HAP1 BCL2L2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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