BAK1

Summary

BAK1 (BCL2 antagonist/killer 1, HGNC:949) is a protein-coding gene on chromosome 6p21.31, encoding Bcl-2 homologous antagonist/killer (Q16611). Plays a role in the mitochondrial apoptotic process. It is a selective cancer dependency (DepMap: 16.0% of cell lines).

The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein localizes to mitochondria, and functions to induce apoptosis. It interacts with and accelerates the opening of the mitochondrial voltage-dependent anion channel, which leads to a loss in membrane potential and the release of cytochrome c. This protein also interacts with the tumor suppressor P53 after exposure to cell stress.

Source: NCBI Gene 578 — RefSeq curated summary.

At a glance

• GWAS associations: 48
• Clinical variants (ClinVar): 36 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 16.0% of screened cell lines
• MANE Select transcript: NM_001188

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:949
Approved symbol	BAK1
Name	BCL2 antagonist/killer 1
Location	6p21.31
Locus type	gene with protein product
Status	Approved
Aliases	BCL2L7, BAK
Ensembl gene	ENSG00000030110
Ensembl biotype	protein_coding
OMIM	600516
Entrez	578

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 15 protein_coding

ENST00000374467, ENST00000442998, ENST00000886795, ENST00000886796, ENST00000886797, ENST00000886798, ENST00000886799, ENST00000886800, ENST00000938017, ENST00000938018, ENST00000938020, ENST00000963350, ENST00000963351, ENST00000963352, ENST00000963353

RefSeq mRNA: 1 — MANE Select: NM_001188 NM_001188

CCDS: CCDS4781

Canonical transcript exons

ENST00000374467 — 6 exons

Exon	Start	End
ENSE00000519515	33575793	33575928
ENSE00000741329	33575298	33575441
ENSE00000849371	33577535	33577635
ENSE00001915603	33572552	33573907
ENSE00001945899	33580025	33580276
ENSE00003531891	33574034	33574214

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 95.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.9060 / max 107.7886, expressed in 1803 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73171	12.8344	1801
73170	1.0717	705

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	95.46	gold quality
granulocyte	CL:0000094	92.52	gold quality
lower esophagus mucosa	UBERON:0035834	90.92	gold quality
transverse colon	UBERON:0001157	90.64	gold quality
left adrenal gland	UBERON:0001234	89.28	gold quality
left adrenal gland cortex	UBERON:0035825	89.13	gold quality
right adrenal gland	UBERON:0001233	88.84	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.70	gold quality
monocyte	CL:0000576	88.68	gold quality
apex of heart	UBERON:0002098	88.68	gold quality
duodenum	UBERON:0002114	88.62	gold quality
right adrenal gland cortex	UBERON:0035827	88.59	gold quality
leukocyte	CL:0000738	88.46	gold quality
rectum	UBERON:0001052	88.16	gold quality
esophagus mucosa	UBERON:0002469	88.16	gold quality
mononuclear cell	CL:0000842	88.09	gold quality
adrenal cortex	UBERON:0001235	87.90	gold quality
small intestine	UBERON:0002108	87.84	gold quality
ileal mucosa	UBERON:0000331	87.43	gold quality
spleen	UBERON:0002106	87.39	gold quality
adrenal gland	UBERON:0002369	87.01	gold quality
blood	UBERON:0000178	86.16	gold quality
heart left ventricle	UBERON:0002084	85.75	gold quality
esophagus	UBERON:0001043	85.55	gold quality
intestine	UBERON:0000160	85.31	gold quality
cardiac ventricle	UBERON:0002082	85.15	gold quality
body of stomach	UBERON:0001161	85.12	gold quality
colon	UBERON:0001155	85.11	gold quality
large intestine	UBERON:0000059	84.92	gold quality
stromal cell of endometrium	CL:0002255	84.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	549.54
E-GEOD-36552	yes	237.38
E-ANND-3	yes	4.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPG, CXXC1, DDIT3, ESR1, NFKB, NKX6-3, SP3, TP53, TP73, WT1, WWTR1, ZNF148

miRNA regulators (miRDB)

102 targeting BAK1, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6842-5P	99.80	67.54	1587

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 16.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Paracrine suppression of apoptosis by cytokine-stimulated neutrophils involves divergent regulation of NF-kappaB, Bcl-X(L), and Bak (PMID:11795669)
• analyzed expression in leiomyomas and myometrium from fertile and menopausal women (PMID:11867266)
• Bak mRNA and its protein were overexpressed in the intestinal lesions of coeliac disease patients (PMID:11908704)
• Bcl-2 family member Bfl-1/A1 sequesters truncated bid to inhibit is collaboration with pro-apoptotic Bak or Bax. (PMID:11929871)
• limits Adenovirus replication through apoptosis induction (PMID:11932420)
• calpain-mediated Bid cleavage and calpain-independent Bak modulation: two separate pathways in cisplatin-induced apoptosis (PMID:11940658)
• Erythrocyte survival is suppressed by a Bak-derived BH3 peptide that interacts with membrane-associated Bcl-X(L). (PMID:11964315)
• conformational changes of Bak are among the early steps in the induction of cell death (PMID:12176904)
• caspase 3-independent function of Bak in the TNF-alpha-induced apoptotic pathway (PMID:12297281)
• functional cooperation between Bax and Bak in cell hypoxia (PMID:12454021)
• Bax and Bak have roles in Bid-mediated apoptosis (PMID:12808108)
• suggestion that Bak is a regulatory molecule involved in IFNgamma-facilitated TRAIL-mediated apoptosis in thyroid cancer cells (PMID:14647456)
• Identification of a Bak homologue, Bak-like, that regulates apoptosis. (PMID:15003505)
• These results are consistent with a model in which p53 and Mcl1 have opposing effects on mitochondrial apoptosis by interacting with, and modulating the activity of, the death effector Bak. (PMID:15077116)
• both Bak and Bcl-2 were found to be increased in correlation with an immune marker (beta2-microglobulin) in white and gray matter and plaque compared with corresponding cortical regions (PMID:15124764)
• results suggest that Fas antigen stimulation not only activates caspase-8, but also a distinct signaling pathway involving protein kinase(s) to induce exposure of the N terminus of Bak protein (PMID:15159409)
• Myxoma virus M11L can interact with Bak independently of any involvement with Bax; conclude that M11L inhibits, in a species-independent fashion, apoptotic signals mediated by activation of Bak (PMID:15194786)
• Overexpression of the BAK gene can lead to apoptosis of gastric cancer cells in vitro, which does not appear to be dependent on p53 status. (PMID:15248898)
• Activation of Bak was inhibited in Chlamydia trachomatis infected Hela cells. (PMID:15322047)
• evaluated the expression of Bcl-2, Bax and Bak in patients with Graves Disease (GD); findings suggest that the differential expression of Bcl-2 family proteins in both thyrocytes and lymphoid follicles may be involved in the pathology of GD (PMID:15351796)
• establish distinct roles for Bax and Bak in linking the TRAIL death receptor pathway to the mitochondrial apoptosis signaling cascade and delineate a higher degree of specificity in signaling for cell death by multidomain Bcl-2 homologs (PMID:15467752)
• Results describe the expression of Bak and Bcl-2 in primary human breast cancers. (PMID:15478112)
• Expression may be useful for better characterising and predicting the prognosis of oral squamous cell carcinoma. (PMID:15638360)
• There may be a dominance expression of proapoptotic proteins in optic nerve axons in glaucoma. (PMID:15638362)
• VDAC-2 inhibits the Bak-mediated apoptotic response via Bax (PMID:15757910)
• Bak protein and its gene polymorphism may participate in the pathology and susceptibility of primary Sjogren’s syndrome (PMID:15846589)
• proteolytic activation of Bid and the subsequent induction of the mitochondrial apoptotic pathway through Bax/Bak is essential for apoptosis triggered by caspase-2 (PMID:16172118)
• may contribute to the higher level of constitutive apoptosis in cultures of cytotrophoblasts compared to syncytiotrophoblasts (PMID:16376985)
• activation of the c-Abl-PKCdelta-Rac1-p38 MAPK pathway in response to ionizing radiation signals conformational changes of Bak and Bax, resulting in mitochondrial activation-mediated apoptotic cell death in human non-small cell lung cancer cells (PMID:16410245)
• Helicobacter pylori vacuolating cytotoxin induces activation of the proapoptotic proteins Bax and Bak (PMID:16436379)
• Vaccinia virus F1L uses a specific, BH3-like domain to bind and inhibit Bak at the mitochondria. (PMID:16439990)
• Bak function was found to be regulated in two distinct steps by two SAP kinases, MEKK1 and JNK1 when human melanoma cells were treated with cisplatin, and the two-step regulation may be important for control of mitochondrial factor release and apoptosis. (PMID:16529740)
• Bcl-xL exerts an inhibitory effect over Bak via heterodimerization (PMID:16794010)
• p14(ARF) triggers apoptosis via a Bax/Bak-dependent pathway in p53-proficient cells. (PMID:16847458)
• In Bax(-/-)/Bak(-/-) cells a nonapoptotic pathway dependent on sustained autophagy commits the oxidatively damaged cells to death. (PMID:16874066)
• Mycobacterium leprae inhibits apoptosis in THP-1 cells by downregulation of Bak and upregulation of Mcl-1 gene expression. (PMID:16978419)
• inhibiting the fission machinery in Bax/Bak-mediated apoptosis, by down-regulating of Drp1 or hFis1, prevents the fragmentation of the mitochondrial network (PMID:17015472)
• in addition to interacting with the pro-apoptotic protein Bak, vaccinia F1L also functions to indirectly inhibit the activation of Bax, likely by interfering with the pro-apoptotic activity of BH3-only proteins such as BimL (PMID:17074758)
• Our results confirm that ultrasound induces apoptosis via a pathway that involves Bak, Bcl-2, and caspases, but not ROS. (PMID:17188240)
• GX15-070 induced apoptosis in vitro in MCL cell lines and primary cells from patients with MCL by releasing Bak from Mcl-1 and Bcl-X(L). (PMID:17227835)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bak1	ENSMUSG00000057789
rattus_norvegicus	Bak1	ENSRNOG00000000485
caenorhabditis_elegans		WBGENE00000423

Paralogs (8): BAX (ENSG00000087088), BCL2L2 (ENSG00000129473), BCL2L10 (ENSG00000137875), BCL2A1 (ENSG00000140379), MCL1 (ENSG00000143384), BCL2L1 (ENSG00000171552), BCL2 (ENSG00000171791), BOK (ENSG00000176720)

Protein

Protein identifiers

Bcl-2 homologous antagonist/killer — Q16611 (reviewed: Q16611)

Alternative names: Apoptosis regulator BAK, Bcl-2-like protein 7

All UniProt accessions (2): A0A0S2Z391, Q16611

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the mitochondrial apoptotic process. Upon arrival of cell death signals, promotes mitochondrial outer membrane (MOM) permeabilization by oligomerizing to form pores within the MOM. This releases apoptogenic factors into the cytosol, including cytochrome c, promoting the activation of caspase 9 which in turn processes and activates the effector caspases.

Subunit / interactions. Homodimer. Formation of the homodimer is zinc-dependent. Forms heterodimers with BCL2 and BCL2L1 isoform Bcl-X(L). Forms heterooligomers with BAX. Interacts with BCL2A1. Interacts with RTL10/BOP. Interacts with VDAC1. Interacts with GIMAP3/IAN4 and GIMAP5/IAN5. (Microbial infection) Interacts with vaccinia virus protein F1. (Microbial infection) Interacts with myxoma virus protein M11L. (Microbial infection) Interacts with Epstein-Barr virus protein BALF1. (Microbial infection) Interacts with adenovirus protein E1B 19K.

Subcellular location. Mitochondrion outer membrane.

Tissue specificity. Expressed in a wide variety of tissues, with highest levels in the heart and skeletal muscle.

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

Similarity. Belongs to the Bcl-2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16611-1	1	yes
Q16611-2	2

RefSeq proteins (1): NP_001179* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002475	Bcl2-like	Family
IPR020717	Bcl2_BH1_motif_CS	Conserved_site
IPR020726	Bcl2_BH2_motif_CS	Conserved_site
IPR020728	Bcl2_BH3_motif_CS	Conserved_site
IPR026298	Bcl-2_fam	Family
IPR036834	Bcl-2-like_sf	Homologous_superfamily
IPR046371	Bcl-2_BH1-3	Domain

Pfam: PF00452

UniProt features (30 total): helix 9, sequence variant 3, strand 3, short sequence motif 3, splice variant 2, turn 2, binding site 2, initiator methionine 1, chain 1, mutagenesis site 1, transmembrane region 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

55 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5VX1	X-RAY DIFFRACTION	1.22
8CZF	X-RAY DIFFRACTION	1.3
8CZH	X-RAY DIFFRACTION	1.3
2IMS	X-RAY DIFFRACTION	1.48
2IMT	X-RAY DIFFRACTION	1.49
9CPE	X-RAY DIFFRACTION	1.49
5FMI	X-RAY DIFFRACTION	1.49
7M5A	X-RAY DIFFRACTION	1.5
5VWY	X-RAY DIFFRACTION	1.55
5VX0	X-RAY DIFFRACTION	1.6
5VWZ	X-RAY DIFFRACTION	1.62
6UXQ	X-RAY DIFFRACTION	1.7
8IGC	X-RAY DIFFRACTION	1.7
9CPF	X-RAY DIFFRACTION	1.7
5FMK	X-RAY DIFFRACTION	1.73
6UXO	X-RAY DIFFRACTION	1.8
2JCN	X-RAY DIFFRACTION	1.8
6UXR	X-RAY DIFFRACTION	1.8
7M5B	X-RAY DIFFRACTION	1.85
9CPN	X-RAY DIFFRACTION	1.89
5VWV	X-RAY DIFFRACTION	1.9
8Y1Z	X-RAY DIFFRACTION	1.91
8CZG	X-RAY DIFFRACTION	1.99
8Y1Y	X-RAY DIFFRACTION	2.01
2XPX	X-RAY DIFFRACTION	2.05
8SRX	X-RAY DIFFRACTION	2.09
3I1H	X-RAY DIFFRACTION	2.2
8GSV	X-RAY DIFFRACTION	2.2
4U2V	X-RAY DIFFRACTION	2.3
4UF1	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16611-F1	81.82	0.35

Antibody-complex structures (SAbDab): 3 — 7LK4, 8UKY, 9CPH

Functional residue map

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

Ligand- & substrate-binding residues (2): 160; 164

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (1):

Position	Phenotype
164	strongly reduced zinc binding and homodimerization.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-111452	Activation and oligomerization of BAK protein
R-HSA-111457	Release of apoptotic factors from the mitochondria
R-HSA-5620971	Pyroptosis
R-HSA-109581	Apoptosis
R-HSA-109606	Intrinsic Pathway for Apoptosis
R-HSA-111471	Apoptotic factor-mediated response
R-HSA-5218859	Regulated Necrosis
R-HSA-5357801	Programmed Cell Death

MSigDB gene sets: 392 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_TRANSMEMBRANE_ELECTROCHEMICAL_GRADIENT, ELVIDGE_HYPOXIA_DN, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_B_CELL_HOMEOSTASIS, GOBP_IRE1_MEDIATED_UNFOLDED_PROTEIN_RESPONSE, GOBP_MYELOID_CELL_HOMEOSTASIS, MACLACHLAN_BRCA1_TARGETS_DN, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_B_CELL_ACTIVATION, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_LYMPHOCYTE_HOMEOSTASIS

GO Biological Process (59): B cell homeostasis (GO:0001782), B cell apoptotic process (GO:0001783), release of cytochrome c from mitochondria (GO:0001836), blood vessel remodeling (GO:0001974), myeloid cell homeostasis (GO:0002262), B cell negative selection (GO:0002352), apoptotic process (GO:0006915), mitochondrial fusion (GO:0008053), negative regulation of cell population proliferation (GO:0008285), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), response to xenobiotic stimulus (GO:0009410), response to fungus (GO:0009620), response to mycotoxin (GO:0010046), response to UV-C (GO:0010225), establishment or maintenance of transmembrane electrochemical gradient (GO:0010248), response to gamma radiation (GO:0010332), positive regulation of calcium ion transport into cytosol (GO:0010524), negative regulation of gene expression (GO:0010629), endocrine pancreas development (GO:0031018), animal organ regeneration (GO:0031100), positive regulation of protein-containing complex assembly (GO:0031334), endoplasmic reticulum calcium ion homeostasis (GO:0032469), negative regulation of endoplasmic reticulum calcium ion concentration (GO:0032471), cellular response to unfolded protein (GO:0034620), cellular response to UV (GO:0034644), limb morphogenesis (GO:0035108), response to hydrogen peroxide (GO:0042542), positive regulation of apoptotic process (GO:0043065), fibroblast apoptotic process (GO:0044346), response to ethanol (GO:0045471), positive regulation of proteolysis (GO:0045862), regulation of mitochondrial membrane permeability (GO:0046902), post-embryonic camera-type eye morphogenesis (GO:0048597), epithelial cell proliferation (GO:0050673), regulation of cell cycle (GO:0051726), regulation of mitochondrial membrane potential (GO:0051881), vagina development (GO:0060068), calcium ion transport into cytosol (GO:0060402), intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059), thymocyte apoptotic process (GO:0070242)

GO Molecular Function (12): channel activity (GO:0015267), porin activity (GO:0015288), heat shock protein binding (GO:0031072), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), transmembrane transporter binding (GO:0044325), protein-containing complex binding (GO:0044877), metal ion binding (GO:0046872), protein heterodimerization activity (GO:0046982), protein-folding chaperone binding (GO:0051087), BH domain binding (GO:0051400), protein binding (GO:0005515)

GO Cellular Component (10): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), pore complex (GO:0046930), Bcl-2 family protein complex (GO:0097136), BAK complex (GO:0097145), cytoplasm (GO:0005737), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Intrinsic Pathway for Apoptosis	2
Programmed Cell Death	2
Apoptotic factor-mediated response	1
Regulated Necrosis	1
Apoptosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	4
cytoplasm	3
cellular anatomical structure	3
apoptotic signaling pathway	2
protein dimerization activity	2
binding	2
intracellular membrane-bounded organelle	2
lymphocyte homeostasis	1
lymphocyte apoptotic process	1
apoptotic mitochondrial changes	1
tissue remodeling	1
immune system process	1
homeostasis of number of cells	1
B cell selection	1
programmed cell death	1
execution phase of apoptosis	1
mitochondrion organization	1
organelle fusion	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
DNA damage response	1
intrinsic apoptotic signaling pathway	1
response to chemical	1
response to other organism	1
response to toxic substance	1
response to UV	1
monoatomic ion transmembrane transport	1
response to ionizing radiation	1
positive regulation of cytosolic calcium ion concentration	1
regulation of calcium ion transport into cytosol	1
calcium ion transport into cytosol	1
positive regulation of calcium ion transmembrane transport	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
pancreas development	1
endocrine system development	1
anatomical structure development	1
regeneration	1

Protein interactions and networks

STRING

1964 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BAK1	BCL2	P10415	969
BAK1	BCL2L1	Q07817	950
BAK1	MCL1	Q07820	871
BAK1	TP53	P04637	867
BAK1	BAX	P55269	801
BAK1	BBC3	Q96PG8	770
BAK1	ERN1	O75460	758
BAK1	CYCS	P00001	752
BAK1	BCL2L11	O43521	722
BAK1	BCL2A1	Q16548	702
BAK1	BCL2L10	Q9HD36	675
BAK1	KCNJ6	P48051	666
BAK1	BID	P55957	656
BAK1	APAF1	O14727	654
BAK1	LHFPL5	Q8TAF8	635

IntAct

195 interactions, top by confidence:

A	B	Type	Score
BAX	BAX	psi-mi:“MI:0914”(association)	0.970
BAK1	MCL1	psi-mi:“MI:0915”(physical association)	0.960
MCL1	BAK1	psi-mi:“MI:0915”(physical association)	0.960
MCL1	BAK1	psi-mi:“MI:0914”(association)	0.960
BAK1	BCL2L1	psi-mi:“MI:2364”(proximity)	0.960
BAK1	BCL2L1	psi-mi:“MI:0915”(physical association)	0.960
BCL2L1	BAK1	psi-mi:“MI:0915”(physical association)	0.960

BioGRID (114): BCL2A1 (Two-hybrid), BCL2L2 (Two-hybrid), TP53 (Affinity Capture-Western), HERC1 (Co-localization), BAK1 (Protein-peptide), BAK1 (Protein-peptide), BAK1 (Affinity Capture-Western), MCL1 (Affinity Capture-Western), BAK1 (Affinity Capture-MS), BCL2L1 (Two-hybrid), BCL2L1 (Affinity Capture-Western), BAK1 (Affinity Capture-Western), BAK1 (Affinity Capture-Western), BAK1 (Affinity Capture-Western), BAK1 (Affinity Capture-Western)

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, O08734, O77737, P10415, P10417, P49950, P53563, P70345, Q00709, Q07440, Q07812, Q07813, Q07816, Q07817, Q07818, Q16548, Q16611, Q1RMX3, Q3C2I0, Q45T69, Q63690, Q64373, Q6R755, Q91827, Q91828, Q92843, Q9JJV8, P0C8H4, Q90343, Q90ZN1, P97287, Q7YRZ9, Q9Z1P3

SIGNOR signaling

26 interactions.

A	Effect	B	Mechanism
BAK1	up-regulates	BAK1	binding
BAK1	up-regulates	CYCS	relocalization
BID	up-regulates	BAK1	binding
BAK1	up-regulates	DIABLO	relocalization
BAK1	up-regulates	HTRA2	relocalization
TP53	up-regulates	BAK1	binding
SH3GLB1	up-regulates	BAK1
MCL1	down-regulates	BAK1	binding
BBC3	up-regulates	BAK1	binding
BCL2	down-regulates	BAK1	binding
BCL2L1	down-regulates	BAK1	binding
BCL2L2	down-regulates	BAK1	binding
BAK1	up-regulates	CYCS
BAK1	up-regulates	DIABLO
BAK1	up-regulates	HTRA2
BAK1	up-regulates	AIFM1	relocalization
BCL2L11	up-regulates	BAK1	binding
PTPN5	“up-regulates activity”	BAK1	dephosphorylation
WWTR1	“up-regulates quantity by expression”	BAK1	“transcriptional regulation”
BAK1	up-regulates	Apoptosis
BAK1	up-regulates	ENDOG

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 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
Intrinsic Pathway for Apoptosis	5	45.8×	1e-05
Apoptosis	5	26.2×	2e-04
Programmed Cell Death	5	22.9×	2e-04
Diseases of signal transduction by growth factor receptors and second messengers	5	8.9×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
release of cytochrome c from mitochondria	7	119.9×	5e-11
extrinsic apoptotic signaling pathway in absence of ligand	7	79.9×	6e-10
regulation of mitochondrial membrane potential	6	79.5×	1e-08
intrinsic apoptotic signaling pathway in response to DNA damage	7	55.3×	5e-09
ovarian follicle development	5	47.8×	5e-06
positive regulation of apoptotic process	12	16.6×	7e-10
negative regulation of neuron apoptotic process	5	13.5×	8e-04
negative regulation of apoptotic process	8	6.8×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3246015	NC_000006.11:g.(?33388042)(33679463_?)del	Pathogenic

SpliceAI

1184 predictions. Top by Δscore:

Variant	Effect	Δscore
6:33574026:ATACT:A	donor_loss	1.0000
6:33574028:ACT:A	donor_loss	1.0000
6:33574029:CTC:C	donor_loss	1.0000
6:33574030:TCA:T	donor_loss	1.0000
6:33574031:CA:C	donor_loss	1.0000
6:33574032:A:AC	donor_gain	1.0000
6:33574032:AC:A	donor_gain	1.0000
6:33574032:ACC:A	donor_gain	1.0000
6:33574033:C:CC	donor_gain	1.0000
6:33574033:CC:C	donor_gain	1.0000
6:33574033:CCC:C	donor_gain	1.0000
6:33574210:ACAGG:A	acceptor_gain	1.0000
6:33574211:CAGG:C	acceptor_gain	1.0000
6:33574211:CAGGC:C	acceptor_gain	1.0000
6:33574212:AGG:A	acceptor_gain	1.0000
6:33574213:GG:G	acceptor_gain	1.0000
6:33574213:GGC:G	acceptor_loss	1.0000
6:33574214:GC:G	acceptor_loss	1.0000
6:33574215:C:CC	acceptor_gain	1.0000
6:33574215:CTGTG:C	acceptor_loss	1.0000
6:33574216:T:A	acceptor_loss	1.0000
6:33574543:A:T	acceptor_gain	1.0000
6:33574545:C:CT	acceptor_gain	1.0000
6:33574546:A:T	acceptor_gain	1.0000
6:33575293:GGTAC:G	donor_loss	1.0000
6:33575294:GTAC:G	donor_loss	1.0000
6:33575295:TA:T	donor_loss	1.0000
6:33575296:A:AT	donor_loss	1.0000
6:33575297:C:CT	donor_loss	1.0000
6:33575324:A:AC	donor_gain	1.0000

AlphaMissense

1361 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:33574034:C:A	W177C	0.997
6:33574034:C:G	W177C	0.997
6:33574036:A:G	W177R	0.995
6:33574036:A:T	W177R	0.995
6:33575304:G:T	A115D	0.994
6:33574163:G:C	F134L	0.991
6:33574163:G:T	F134L	0.991
6:33574165:A:G	F134L	0.991
6:33575415:A:T	L78H	0.991
6:33574057:A:G	W170R	0.990
6:33574057:A:T	W170R	0.990
6:33575413:C:G	A79P	0.990
6:33574208:A:C	F119L	0.989
6:33574208:A:T	F119L	0.989
6:33574210:A:G	F119L	0.989
6:33575415:A:G	L78P	0.989
6:33575369:G:C	F93L	0.988
6:33575369:G:T	F93L	0.988
6:33575371:A:G	F93L	0.988
6:33574055:C:A	W170C	0.987
6:33574055:C:G	W170C	0.987
6:33574115:G:C	F150L	0.987
6:33574115:G:T	F150L	0.987
6:33574117:A:G	F150L	0.987
6:33575315:G:C	F111L	0.987
6:33575315:G:T	F111L	0.987
6:33575317:A:G	F111L	0.987
6:33575412:G:T	A79D	0.987
6:33574190:C:A	W125C	0.986
6:33574190:C:G	W125C	0.986

dbSNP variants (sampled 300 via entrez): RS1000219106 (6:33576888 C>A), RS1000239166 (6:33579599 C>G,T), RS1000317999 (6:33579881 T>C), RS1000541998 (6:33579483 A>G,T), RS1000760266 (6:33573200 G>A), RS1001191226 (6:33573496 T>C), RS1001783340 (6:33579414 T>A,C), RS1001933388 (6:33572776 C>G), RS1003054389 (6:33577914 G>A), RS1003500421 (6:33578270 C>T), RS1003795057 (6:33577771 T>C,G), RS1004002977 (6:33582250 A>G), RS1004616104 (6:33574295 C>G,T), RS1004729700 (6:33580255 C>A,T), RS1004828232 (6:33580080 G>T)

Disease associations

OMIM: gene MIM:600516 | disease phenotypes: MIM:612621

GenCC curated gene-disease

Mondo (1): intellectual disability, autosomal dominant 5 (MONDO:0012960)

Orphanet (1): SYNGAP1-related developmental and epileptic encephalopathy (Orphanet:544254)

HPO phenotypes

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

GWAS associations

48 associations (top):

Study	Trait	p-value
GCST000414_3	Testicular germ cell tumor	1.000000e-13
GCST000498_11	Hematological parameters	4.000000e-10
GCST000580_4	Platelet count	7.000000e-11
GCST001337_19	Platelet count	7.000000e-36
GCST001570_1	Chronic lymphocytic leukemia	9.000000e-16
GCST001762_743	Obesity-related traits	9.000000e-06
GCST001783_4	Platelet count	2.000000e-08
GCST001783_6	Platelet count	2.000000e-12
GCST002022_15	Testicular germ cell tumor	2.000000e-24
GCST002023_9	Testicular germ cell tumor	3.000000e-07
GCST002073_16	Chronic lymphocytic leukemia	5.000000e-08
GCST002186_5	Platelet count	6.000000e-08
GCST002299_11	Chronic lymphocytic leukemia	3.000000e-06
GCST002733_2	Platelet count	1.000000e-15
GCST003383_4	Platelet count	9.000000e-09
GCST003383_5	Platelet count	2.000000e-10
GCST004099_6	B-cell malignancies (chronic lymphocytic leukemia, Hodgkin lymphoma or multiple myeloma) (pleiotropy)	7.000000e-12
GCST004146_34	Chronic lymphocytic leukemia	6.000000e-16
GCST004521_251	Autism spectrum disorder or schizophrenia	6.000000e-12
GCST004521_75	Autism spectrum disorder or schizophrenia	8.000000e-10
GCST004600_126	Eosinophil percentage of white cells	3.000000e-17
GCST004603_20	Platelet count	1.000000e-144
GCST004606_139	Eosinophil count	1.000000e-17
GCST004607_137	Plateletcrit	3.000000e-171
GCST004623_21	Neutrophil percentage of granulocytes	3.000000e-15
GCST004624_97	Sum eosinophil basophil counts	1.000000e-18
GCST004635_14	Testicular germ cell tumor	4.000000e-37
GCST004713_23	Testicular germ cell tumor	3.000000e-34
GCST004748_121	Lung cancer	9.000000e-06
GCST005054_4	Platelet count	3.000000e-09

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0003939	energy intake
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007985	platelet crit
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0004340	body mass index
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0007984	platelet component distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567234	Mental Retardation, Autosomal Dominant 5 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL3137283 (PROTEIN-PROTEIN INTERACTION), CHEMBL3885516 (PROTEIN-PROTEIN INTERACTION), CHEMBL3885523 (PROTEIN COMPLEX), CHEMBL5169269 (PROTEIN-PROTEIN INTERACTION), CHEMBL5609 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,288 (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
CHEMBL376408	ABT 737	1	4,288

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

ChEMBL bioactivities

71 potent at pChembl≥5 of 102 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	IC50	10	nM	ABT 737
7.70	EC50	20	nM	ABT 737
7.24	IC50	57	nM	ABT 737
6.92	EC50	120	nM	CHEMBL2089293
6.92	Ki	120	nM	CHEMBL4160782
6.82	Ki	153	nM	CHEMBL5198484
6.80	EC50	160	nM	CHEMBL2089301
6.70	Ki	200	nM	GINKGOLIC ACID 13:0
6.70	IC50	200	nM	CHEMBL5182721
6.68	EC50	210	nM	CHEMBL2089302
6.66	EC50	220	nM	CHEMBL2089293
6.64	EC50	230	nM	CHEMBL2089300
6.64	IC50	230	nM	CHEMBL539481
6.60	Kd	250	nM	CHEMBL605114
6.57	IC50	270	nM	CHEMBL539481
6.55	IC50	280	nM	CHEMBL5203189
6.52	EC50	300	nM	CHEMBL2089294
6.52	Ki	300	nM	CHEMBL4589399
6.51	EC50	310	nM	CHEMBL2089295
6.51	IC50	310	nM	CHEMBL5182721
6.50	IC50	320	nM	CHEMBL5203189
6.50	IC50	320	nM	CHEMBL5182721
6.40	IC50	400	nM	CHEMBL539481
6.38	EC50	420	nM	CHEMBL2089288
6.32	EC50	480	nM	CHEMBL2089296
6.31	IC50	490	nM	CHEMBL539481
6.28	EC50	520	nM	CHEMBL2089303
6.25	EC50	560	nM	CHEMBL2089287
6.24	EC50	580	nM	CHEMBL2089288
6.21	IC50	620	nM	CHEMBL5182721
6.17	EC50	670	nM	CHEMBL2089290
6.17	EC50	670	nM	CHEMBL2089297
6.16	Ki	700	nM	CHEMBL5193670
6.14	IC50	730	nM	CHEMBL5203189
6.12	IC50	760	nM	CHEMBL5203189
5.99	EC50	1020	nM	CHEMBL2089285
5.96	EC50	1100	nM	CHEMBL2089298
5.92	Ki	1200	nM	CHEMBL4451281
5.83	EC50	1470	nM	CHEMBL2089286
5.82	IC50	1500	nM	CHEMBL5171545
5.75	Ki	1790	nM	CHEMBL4077940
5.71	EC50	1970	nM	CHEMBL2089299
5.68	EC50	2100	nM	CHEMBL2089291
5.68	IC50	2080	nM	CHEMBL5437551
5.64	Ki	2300	nM	CHEMBL3339154
5.64	Ki	2300	nM	CHEMBL5207317
5.58	EC50	2660	nM	CHEMBL2089292
5.58	Ki	2600	nM	CHEMBL4174120
5.58	Ki	2600	nM	MEIOGYNIN A
5.55	EC50	2810	nM	CHEMBL2089289

PubChem BioAssay actives

72 with measured affinity, of 149 total; 47 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	1504723: Inhibition of His-tagged Bcl-xL (unknown origin)/5-carboxyfluorescein-labeled Bak (unknown origin) protein protein interaction after 1 hr by fluorescence polarization assay	ki	0.0010	uM
1-[4-(4-chloro-3,5-dimethylphenoxy)phenyl]sulfonyl-3,4-dihydro-2H-quinoline-3-carboxylic acid	1858800: Binding affinity to Mcl-1/Bak (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.1200	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-(1-tricyclo[4.3.1.13,8]undecanylmethylsulfonyl)benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	0.1200	uM
(2R,4aR,5S,8aR)-5-[(E)-2-(4-carboxyphenyl)prop-1-enyl]-7-methyl-2-[2-(4-pyridin-3-yloxybenzoyl)oxyethyl]-2,5,8,8a-tetrahydro-1H-naphthalene-4a-carboxylic acid	1858800: Binding affinity to Mcl-1/Bak (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.1530	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[[3-(2-methylpropanoylamino)-1-adamantyl]methylsulfonyl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	0.1600	uM
2-hydroxy-6-tridecylbenzoic acid	1635028: Inhibition of His-tagged Bcl-xL/5-carboxyfluorescein-Bak (unknown origin) after 1 hr by fluorescence polarization assay	ki	0.2000	uM
5-hydroxy-2,3,7-trimethyl-N-(2-phenylpropyl)-6-[1,6,7-trihydroxy-5-(2-phenylpropylcarbamoyl)naphthalen-2-yl]naphthalene-1-carboxamide	1858790: Inhibition of Bfl-1/Bak (unknown origin)	ic50	0.2000	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[[3-(cyclopropanecarbonylamino)-1-adamantyl]methylsulfonyl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	0.2100	uM
N-[1-(4-chlorophenyl)ethyl]-6-[5-[1-(4-chlorophenyl)ethylcarbamoyl]-1,6,7-trihydroxy-3-methylnaphthalen-2-yl]-2,3,5-trihydroxy-7-methylnaphthalene-1-carboxamide	1858789: Inhibition of Mcl-1/Bak (unknown origin)	ic50	0.2300	uM
N-[(3-acetamido-1-adamantyl)methylsulfonyl]-4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	0.2300	uM
(2S)-2-[(5Z)-5-[[6-(2,3-dimethoxyphenyl)-3-pyridinyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid	1858802: Binding affinity to Mcl-1/Bak (unknown origin) assessed as dissociation constant by ITC method	kd	0.2500	uM
2,3,5-trihydroxy-7-methyl-N-(2-phenylpropyl)-6-[1,6,7-trihydroxy-3-methyl-5-[[(2S)-2-phenylpropyl]carbamoyl]naphthalen-2-yl]naphthalene-1-carboxamide	1858789: Inhibition of Mcl-1/Bak (unknown origin)	ic50	0.2800	uM
2-hydroxy-6-[(Z)-tridec-8-enyl]benzoic acid	1635028: Inhibition of His-tagged Bcl-xL/5-carboxyfluorescein-Bak (unknown origin) after 1 hr by fluorescence polarization assay	ki	0.3000	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[(3-hydroxy-1-adamantyl)methylsulfonyl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	0.3000	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[[3-(2-morpholin-4-ylethoxy)-1-adamantyl]methylsulfonyl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	0.3100	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[[(1R,2R,5R)-1,5,6,6-tetramethyl-2-bicyclo[3.1.1]heptanyl]methylsulfonyl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	0.4200	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[(3-fluoro-1-adamantyl)methylsulfonyl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	0.4800	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[[3-(2,2-dimethylpropanoylamino)-1-adamantyl]methylsulfonyl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	0.5200	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[[(1S,2S,5S)-1,5,6,6-tetramethyl-2-bicyclo[3.1.1]heptanyl]methylsulfonyl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	0.5600	uM
N-[(3-bromo-1-adamantyl)methylsulfonyl]-4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	0.6700	uM
N-(1-adamantylmethylsulfonyl)-4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	0.6700	uM
(2R,4aR,5S,8aR)-5-[(E)-2-(4-carboxyphenyl)prop-1-enyl]-7-methyl-2-[2-(4-phenoxybenzoyl)oxyethyl]-2,5,8,8a-tetrahydro-1H-naphthalene-4a-carboxylic acid	1858841: Binding affinity to human Bcl-xL/Bak (unkown origin) incubated for 1 hr by fluorescence polarization assay	ki	0.7000	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[[(1R)-7,7-dimethyl-2-oxo-1-bicyclo[2.2.1]heptanyl]methylsulfonyl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	1.0200	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[(3-methyl-1-adamantyl)methylsulfonyl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	1.1000	uM
2-hydroxy-6-undecylbenzoic acid	1635028: Inhibition of His-tagged Bcl-xL/5-carboxyfluorescein-Bak (unknown origin) after 1 hr by fluorescence polarization assay	ki	1.2000	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[[(1S)-7,7-dimethyl-2-oxo-1-bicyclo[2.2.1]heptanyl]methylsulfonyl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	1.4700	uM
azane;3-[4-[2-benzyl-4-[4-(carboxymethoxy)-2-(2-methylpropyl)phenyl]phenyl]-2-(2-methylpropyl)phenoxy]propanoic acid	1858797: Inhibition of Bcl-xL/Bak (unknown origin) by fluorescence polarization assay	ic50	1.5000	uM
4-[[5-[(4-amino-3-propan-2-yloxybenzoyl)amino]-6-propan-2-yloxypyridine-2-carbonyl]amino]-3-propan-2-yloxybenzoic acid	1858825: Binding affinity to Bak/Mcl-1 (unknown origin) protein protein interaction by fluorescence polarization assay	ki	1.7900	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[(3-phenyl-1-adamantyl)methylsulfonyl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	1.9700	uM
N-[3-nitro-4-(2-phenylsulfanylethylamino)phenyl]sulfonyl-4-(2-pyridin-2-ylethyl)benzamide	2030239: Inhibition of GST-tagged Bak (unknown origin)/ Bcl-Xl (unknown origin) protein-protein interaction by fluorescence polarization assay	ic50	2.0800	uM
N-(1-adamantylsulfamoyl)-4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	2.1000	uM
(2R,4aR,5S,8aR)-5-[(E)-2-(4-carboxycyclohexyl)prop-1-enyl]-7-methyl-2-[(2R)-6-methylhept-5-en-2-yl]-2,5,8,8a-tetrahydro-1H-naphthalene-4a-carboxylic acid	1166893: Inhibition of Bcl-xL/Bak (unknown origin) interaction	ki	2.3000	uM
(2S,4aS,5R,8aS)-5-[(E)-2-(4-carboxycyclohexyl)prop-1-enyl]-7-methyl-2-[(2R)-6-methylhept-5-en-2-yl]-2,5,8,8a-tetrahydro-1H-naphthalene-4a-carboxylic acid	1635028: Inhibition of His-tagged Bcl-xL/5-carboxyfluorescein-Bak (unknown origin) after 1 hr by fluorescence polarization assay	ki	2.6000	uM
(2R,4aR,5S,8aR)-5-[(E)-2-(4-carboxycyclohexyl)prop-1-enyl]-7-methyl-2-[(2S)-6-methylhept-5-en-2-yl]-2,5,8,8a-tetrahydro-1H-naphthalene-4a-carboxylic acid	1504723: Inhibition of His-tagged Bcl-xL (unknown origin)/5-carboxyfluorescein-labeled Bak (unknown origin) protein protein interaction after 1 hr by fluorescence polarization assay	ki	2.6000	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-(3-tricyclo[3.3.1.03,7]nonanylmethylsulfonyl)benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	2.6600	uM
N-[2-(1-adamantyl)ethylsulfonyl]-4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]benzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	2.8100	uM
6-(4-chloro-3,5-dimethylphenoxy)-2-phenylmethoxypyridine-3-carboxylic acid	1858800: Binding affinity to Mcl-1/Bak (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	2.9000	uM
2-hydroxy-6-[(Z)-undec-6-enyl]benzoic acid	1635028: Inhibition of His-tagged Bcl-xL/5-carboxyfluorescein-Bak (unknown origin) after 1 hr by fluorescence polarization assay	ki	3.2000	uM
(2R,4aR,5S,8aR)-5-[(E)-2-(4-carboxyphenyl)prop-1-enyl]-7-methyl-2-[(2R)-6-methylhept-5-en-2-yl]-2,5,8,8a-tetrahydro-1H-naphthalene-4a-carboxylic acid	1166893: Inhibition of Bcl-xL/Bak (unknown origin) interaction	ki	4.6000	uM
2,5-dihydroxy-3-methoxy-6-[(1R,6R)-4-(4-methylpent-3-enyl)-6-phenylcyclohex-3-ene-1-carbonyl]cyclohexa-2,5-diene-1,4-dione	1504723: Inhibition of His-tagged Bcl-xL (unknown origin)/5-carboxyfluorescein-labeled Bak (unknown origin) protein protein interaction after 1 hr by fluorescence polarization assay	ki	4.8000	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-ethylsulfonylbenzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	5.3100	uM
2-hydroxy-6-[(Z)-pentadec-10-enyl]benzoic acid	1635028: Inhibition of His-tagged Bcl-xL/5-carboxyfluorescein-Bak (unknown origin) after 1 hr by fluorescence polarization assay	ki	5.7000	uM
(2R,4aR,5S,8aR)-5-[(E)-2-(4-carboxyphenyl)prop-1-enyl]-7-methyl-2-[(2S)-6-methylhept-5-en-2-yl]-2,5,8,8a-tetrahydro-1H-naphthalene-4a-carboxylic acid	1166893: Inhibition of Bcl-xL/Bak (unknown origin) interaction	ki	7.5000	uM
1-[3-(4-chloro-3,5-dimethylphenoxy)propylsulfonyl]-3,4-dihydro-2H-quinoline-3-carboxylic acid	1858800: Binding affinity to Mcl-1/Bak (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	7.7700	uM
(2S)-2-[(5Z)-5-[[6-(3,4-dimethoxyphenyl)-3-pyridinyl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid	1858800: Binding affinity to Mcl-1/Bak (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	8.0000	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-methylsulfonylbenzamide	683531: Inhibition of Bcl2-BAK interaction after 1 hr by surface plasmon resonance assay	ec50	8.6200	uM
2-[(5Z)-5-[(4-bromophenyl)methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-methylbutanoic acid	1858801: Binding affinity to Bcl-xL/Bak (unknown origin) assessed as dissociation constant by ITC method	kd	8.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	increases reaction, increases activity, decreases activity, increases localization, affects folding (+5 more)	9
Cisplatin	increases response to substance, affects reaction, increases cleavage, affects cotreatment, decreases response to substance (+4 more)	9
Arsenic Trioxide	affects cotreatment, increases expression, decreases expression	7
Doxorubicin	decreases response to substance, increases response to substance, affects cotreatment, decreases reaction, increases activity (+2 more)	6
Tretinoin	increases expression, decreases expression, affects cotreatment	6
Paraquat	decreases reaction, increases expression, affects cotreatment, decreases expression, affects response to substance	5
bisphenol A	decreases reaction, increases expression, decreases expression, affects cotreatment, affects expression (+1 more)	4
Sorafenib	affects cotreatment, affects folding, decreases reaction, increases activity, increases expression (+2 more)	4
Vorinostat	affects activity, affects cotreatment, decreases expression, increases expression, increases reaction	4
Fluorouracil	increases expression, decreases reaction, increases response to substance	4
dioscin	increases expression	3
Curcumin	increases reaction, decreases expression, increases expression	3
Etoposide	decreases reaction, increases response to substance, affects expression, increases activity	3
Quercetin	increases expression	3
Paclitaxel	affects expression, increases expression, increases response to substance	3
picrasidine I	increases expression	2
diepoxybutane	increases expression	2
perfluorooctanoic acid	decreases expression, increases expression	2
ochratoxin A	affects cotreatment, decreases expression	2
diallyl trisulfide	increases activity, increases expression, decreases reaction	2
perfluorooctane sulfonic acid	affects binding, increases reaction, decreases expression	2
benzoylcarbonyl-valyl-aspartyl-valyl-alanyl-aspartyl-fluoromethyl ketone	affects folding, decreases reaction, increases activity	2
coronarin D	increases expression	2
Celecoxib	increases expression	2
Bortezomib	increases expression, affects cotreatment, affects reaction, increases activity, increases response to substance	2
Docetaxel	increases activity, increases reaction, affects folding, decreases reaction	2
Butyrates	increases expression, affects cotreatment, decreases expression	2
Melatonin	affects cotreatment, increases expression, decreases reaction	2
Methyl Methanesulfonate	decreases reaction, increases expression	2
Nickel	increases expression	2

ChEMBL screening assays

28 unique, capped per target: 27 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1251000	Binding	Inhibition of GST-tagged Bel-xl/FITC-conjugated Bak interaction by fluorescence polarisation assay	Synthesis and biological activities of new di- and trimeric quinoline derivatives. — Bioorg Med Chem
CHEMBL1007221	Functional	Activation of Bak in human HL60 cells assessed as oligomerization and conformational change at 80 uM after 8 hrs by immunostaining	Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress. — J Biol Chem

Cellosaurus cell lines

10 cell lines: 6 cancer cell line, 4 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B1KY	Abcam HeLa BAK1 KO	Cancer cell line	Female
CVCL_B7W5	Abcam Raji BAK1 KO	Cancer cell line	Male
CVCL_B9WN	Abcam THP-1 BAK1 KO	Cancer cell line	Male
CVCL_C6YP	Abcam PC-3 BAK1 KO	Cancer cell line	Male
CVCL_D6PL	BIHi250-A-2	Induced pluripotent stem cell	Female
CVCL_D6PM	BIHi250-A-1	Induced pluripotent stem cell	Female
CVCL_D6PN	BIHi005-A-15	Induced pluripotent stem cell	Male
CVCL_D6TW	BIHi005-A-17	Induced pluripotent stem cell	Male
CVCL_SE66	HAP1 BAK1 (-) 1	Cancer cell line	Male
CVCL_XL96	HAP1 BAK1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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