BAX

Summary

BAX (BCL2 associated X, apoptosis regulator, HGNC:959) is a protein-coding gene on chromosome 19q13.33, encoding Apoptosis regulator BAX (Q07812). Plays a role in the mitochondrial apoptotic process.

The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. The association and the ratio of BAX to BCL2 also determines survival or death of a cell following an apoptotic stimulus. This protein is reported to interact with, and increase the opening of, the mitochondrial voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the release of cytochrome c. The expression of this gene is regulated by the tumor suppressor P53 and has been shown to be involved in P53-mediated apoptosis. Multiple alternatively spliced transcript variants, which encode different isoforms, have been reported for this gene.

Source: NCBI Gene 581 — RefSeq curated summary.

At a glance

• Gene–disease (curated): leukemia, acute lymphocytic, susceptibility to, 1 (Limited, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 54 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 10
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_138761

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:959
Approved symbol	BAX
Name	BCL2 associated X, apoptosis regulator
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	BCL2L4
Ensembl gene	ENSG00000087088
Ensembl biotype	protein_coding
OMIM	600040
Entrez	581

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000293288, ENST00000345358, ENST00000354470, ENST00000356483, ENST00000415969, ENST00000502487, ENST00000503726, ENST00000506183, ENST00000513217, ENST00000513545, ENST00000515540, ENST00000539787, ENST00000880100

RefSeq mRNA: 8 — MANE Select: NM_138761 NM_001291428, NM_001291429, NM_001291430, NM_001291431, NM_004324, NM_138761, NM_138763, NM_138764

CCDS: CCDS12742, CCDS12743, CCDS12744, CCDS12745, CCDS77327

Canonical transcript exons

ENST00000345358 — 6 exons

Exon	Start	End
ENSE00000853382	48955548	48955599
ENSE00001558844	48954875	48954962
ENSE00001636776	48961532	48961798
ENSE00003478529	48955687	48955833
ENSE00003686930	48960810	48960914
ENSE00003731885	48956198	48956333

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 98.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 55.0126 / max 277.8262, expressed in 1822 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176887	51.4151	1822
176886	1.7927	1141
176885	1.5993	905
176888	0.2055	105

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.83	gold quality
stromal cell of endometrium	CL:0002255	98.46	gold quality
granulocyte	CL:0000094	98.36	gold quality
monocyte	CL:0000576	97.84	gold quality
gall bladder	UBERON:0002110	96.79	gold quality
leukocyte	CL:0000738	96.78	gold quality
mononuclear cell	CL:0000842	96.70	gold quality
right lung	UBERON:0002167	96.44	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.36	gold quality
rectum	UBERON:0001052	96.33	gold quality
upper lobe of left lung	UBERON:0008952	96.27	gold quality
spleen	UBERON:0002106	96.05	gold quality
transverse colon	UBERON:0001157	96.04	gold quality
ascending aorta	UBERON:0001496	95.91	gold quality
thoracic aorta	UBERON:0001515	95.88	gold quality
right adrenal gland cortex	UBERON:0035827	95.48	gold quality
ectocervix	UBERON:0012249	95.37	gold quality
right coronary artery	UBERON:0001625	95.30	gold quality
endocervix	UBERON:0000458	95.23	gold quality
ventricular zone	UBERON:0003053	95.13	gold quality
right adrenal gland	UBERON:0001233	95.02	gold quality
descending thoracic aorta	UBERON:0002345	94.97	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.94	silver quality
lower esophagus mucosa	UBERON:0035834	94.85	gold quality
ganglionic eminence	UBERON:0004023	94.78	gold quality
body of stomach	UBERON:0001161	94.72	gold quality
left adrenal gland	UBERON:0001234	94.71	gold quality
cortical plate	UBERON:0005343	94.71	gold quality
left uterine tube	UBERON:0001303	94.67	gold quality
right lobe of thyroid gland	UBERON:0001119	94.66	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.21
E-CURD-88	yes	4.30
E-HCAD-6	no	224.01
E-GEOD-99795	no	46.91

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
PMAIP1	Repression

Upstream regulators (CollecTRI, top): AATF, ABL1, AHR, AP1, ATF3, ATM, CTCF, DMAP1, E2F1, E2F2, EGR1, ELK1, ELL, ERCC2, ESR1, ETS1, ETV4, FOXA2, FOXO1, GFI1, GRHL3, HBP1, HIF1A, HMGA1, HMGB2, ID3, ING1, ING4, IRF8, JUNB, MEOX2, MLLT10, MLLT3, MYC, MYCN, MYCT1, NFKB1, NFKB, NKX3-1, NR3C1

miRNA regulators (miRDB)

8 targeting BAX, 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-766-5P	99.47	67.91	2225
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-5590-5P	98.81	68.78	969
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-4640-3P	94.58	63.02	263
HSA-MIR-6798-3P	94.55	68.78	325

Literature-anchored findings (GeneRIF, showing 40)

• Gamma-radiation-induced apoptosis of leukemia cells was associated with activation of multiple caspases and bax up-regulation as determined by RNase protection assays. TLCK prevented bax up-regulation as a result of its inhibitory effect on p53 function. (PMID:10437917)
• expression is related to apoptosis in thymus (PMID:11642719)
• an elevated bcl-2/bax ratio in rectal carcinoma tissue specimens suggests increased tumor resistance to adjuvant radiotherapy (PMID:11759059)
• Bax-dependent release of Smac/DIABLO from mitochondria mediates death receptor-mediated apoptosis (PMID:11782443)
• Sanguinarine-treated K562 human cells showed a significant increase in expression of the pro-apoptotic Bax protein in apoptosis. (PMID:11787859)
• BAX expression in Hodgkin and Reed-Sternberg cells of Hodgkin’s disease: correlation with clinical outcome (PMID:11839668)
• Protein kinase A RIalpha antisense inhibition of PC3M prostate cancer cell growth: Bcl-2 hyperphosphorylation, Bax up-regulation, and Bad-hypophosphorylation (PMID:11839683)
• The phosphatidylinositol 3-kinase (PI3K)-Akt pathway suppresses Bax translocation to mitochondria (PMID:11842081)
• conserved intronic response element mediates direct p53-dependent transcriptional activation of bax gene (PMID:11850816)
• Curcumin induces apoptosis in human breast cancer cells through p53-dependent Bax induction. (PMID:11852106)
• analyzed expression in leiomyomas and myometrium from fertile and menopausal women (PMID:11867266)
• the expression of apoptosis-regulating proteins BAX in patients with Burkitt’s lymphoma, expression of pro-apoptotic proteins could provide BL cells ability to undergo apoptosis after chemotherapy. (PMID:11869962)
• Results show that Bax is essential for death receptor-mediated apoptosis in cancer cells; it is also involved in mitochondrial changes and downstream caspase activation. (PMID:11875499)
• Bax induction triggers apoptosis by initiating caspase activation not mediated by mitochondrial cytochrome c release and mitochondrial membrane potential change in K562 cells (PMID:11894116)
• Bcl-2 expression was not related with any pathological parameters: size, nuclear grade and stage or prognosis in renal cell carcinmoma (PMID:11899739)
• mediation of Ca2+ mobilization promotes cytochrome c release during apoptosis (PMID:11909872)
• Expression of apoptotic regulators and their significance in cervical cancer (PMID:11911971)
• BAX is required for TRAIL/Apo2L-induced apoptosis of colorectal cancers: synergism with sulindac-mediated inhibition of Bcl-x(L). (PMID:11912124)
• data suggest that oxidation of extracellular matrix proteins may enhance human mesangial cell apoptosis via a mechanism that appears to involve enhanced expression of Bax and caspase activation (PMID:11922616)
• 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)
• Peg3/Pw1 is a mediator between p53 and Bax in DNA damage-induced neuronal death (PMID:11943780)
• expression of apoptosis-regulating proteins p53, Bcl-2, and Bax in primary resected esophageal squamous cell carcinoma (PMID:11949842)
• disrupted p53/BAX pathway is associated with a poor clinical outcome in UICC III tumors (PMID:11992551)
• Identification of novel isoforms of the BH3 domain protein Bim which directly activate Bax to trigger apoptosis. (PMID:11997495)
• activation during apoptosis due to oxidative stress in cells expressing wild-type and mutant cystic fibrosis transmembrane conductance regulator (PMID:12023951)
• high Bax expression associated with apoptosis in renal cell carcinoma (PMID:12025227)
• Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells (PMID:12032841)
• Defective Bax activation in Hodgkin B-cell lines confers resistance to staurosporine-induced apoptosis (PMID:12058280)
• Studies of the mechanism of CD40-mediated apoptosis of human Burkitt lymphoma cell lines revealed an increase in bax messenger RNA with a subsequent increase in Bax protein in the mitochondria. (PMID:12070030)
• BAX translocation and conformation changes are necessary for TRAIL-induced apoptosis. (PMID:12082629)
• Inactivation of p21WAF1 sensitizes cells to apoptosis via an increase of both p14ARF and p53 levels and an alteration of this protein and Bcl-2 ratio (PMID:12151395)
• Bcl-2 proto-oncogene proteins are expressed in Meissner corpuscles and may play a role in resistance to apoptosis. (PMID:12165421)
• A mitochondrial matrix targeting signal can override the inhibition of import of Bax in the absence of apoptotic stimulus. Truncated variants of Bax cause apoptosis when targeted to mitochondria by cytochrome c release from an ectopic environment. (PMID:12169275)
• conformational changes of Bax are among the early steps in the induction of cell death (PMID:12176904)
• Retinoids cause apoptosis in pancreatic cancer cells via activation of RAR-gamma and altered expression of Bcl-2/Bax. (PMID:12189556)
• Bax oligomerization in mitochondrial membranes requires tBid (caspase-8-cleaved Bid) and a mitochondrial protein (PMID:12193163)
• During endothelial cell apoptosis, Bax protein was upregulated in HUVECs stimulated with TNF-alpha alone or in combination with IFN-gamma. (PMID:12214154)
• the role of nitric oxide and death regulatory genes, bcl-2 and bax, in human endometria apoptosis (PMID:12215338)
• Differential rates of frameshift alterations in four repeat sequences of hereditary nonpolyposis colorectal cancer tumors.These repeats consisted of (A)10 in the TGF beta RII, (G)8 in the BAX, (A)8 in the CASP1, and (CCA)7 in the APP genes. (PMID:12215842)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	baxa	ENSDARG00000020623
danio_rerio	baxb	ENSDARG00000030881
danio_rerio		ENSDARG00000089129
mus_musculus	Bax	ENSMUSG00000003873
rattus_norvegicus	Bax	ENSRNOG00000020876
caenorhabditis_elegans		WBGENE00000423

Paralogs (8): BAK1 (ENSG00000030110), BCL2L2 (ENSG00000129473), BCL2L10 (ENSG00000137875), BCL2A1 (ENSG00000140379), MCL1 (ENSG00000143384), BCL2L1 (ENSG00000171552), BCL2 (ENSG00000171791), BOK (ENSG00000176720)

Protein

Protein identifiers

Apoptosis regulator BAX — Q07812 (reviewed: Q07812)

Alternative names: Bcl-2-like protein 4

All UniProt accessions (3): Q07812, H0YA56, I6LPK7

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the mitochondrial apoptotic process. Under normal conditions, BAX is largely cytosolic via constant retrotranslocation from mitochondria to the cytosol mediated by BCL2L1/Bcl-xL, which avoids accumulation of toxic BAX levels at the mitochondrial outer membrane (MOM). Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis. Promotes activation of CASP3, and thereby apoptosis.

Subunit / interactions. Homodimer. Forms higher oligomers under stress conditions. Forms heterooligomers with BAK. Interacts with BCL2L11. Interaction with BCL2L11 promotes BAX oligomerization and association with mitochondrial membranes, with subsequent release of cytochrome c. Forms heterodimers with BCL2, BCL2L1 isoform Bcl-X(L), BCL2L2, MCL1 and A1. Interacts with SH3GLB1. Interacts with humanin; forms fibers with humanin which results in BAX conformational changes and sequestering of BAX into the fibers, preventing BAX activation. Interacts with SFN and YWHAZ; the interaction occurs in the cytoplasm. Under stress conditions, JNK-mediated phosphorylation of SFN and YWHAZ, releases BAX to mitochondria. Interacts with RNF144B, which regulates the ubiquitin-dependent stability of BAX. Interacts with CLU under stress conditions that cause a conformation change leading to BAX oligomerization and association with mitochondria. Does not interact with CLU in unstressed cells. Interacts with FAIM2/LFG2. Interacts with RTL10/BOP. Interacts (via a C-terminal 33 residues) with NOL3 (via CARD domain); inhibits BAX activation and translocation and consequently cytochrome c release from mitochondria. Interacts with GIMAP3/IAN4 and GIMAP5/IAN5; this interaction is increased, when cells initiate apoptosis upon IL2 withdrawal. Interacts with IRF3; the interaction is direct, increases upon Sendai virus infection and mediates the formation of the apoptosis complex TOMM70:HSP90AA1:IRF3:BAX. Interacts with MOAP1, facilitating BAX-dependent mitochondrial outer membrane permeabilization and apoptosis. Interacts with BCL2L10/BCL-B. Interacts with non-acetylated XRCC6/Ku70; this interaction leads to BAX sequestration in the cytosol, away from the mitochondria, preventing BAX-mediated apoptosis. Interacts with BCL2A1 and BCL2L1 isoform Bcl-X(L). (Microbial infection) Interacts with adenovirus E1B 19K protein; this interaction blocks BAX oligomerization. (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein vMIA/UL37. (Microbial infection) Interacts with enterovirus protein 2B; this interaction activates BAX-induced apoptosis.

Subcellular location. Mitochondrion outer membrane. Cytoplasm. Nucleus Cytoplasm Cytoplasm Cytoplasm.

Tissue specificity. Expressed in a wide variety of tissues. Isoform Psi is found in glial tumors. Isoform Alpha is expressed in spleen, breast, ovary, testis, colon and brain, and at low levels in skin and lung. Isoform Sigma is expressed in spleen, breast, ovary, testis, lung, colon, brain and at low levels in skin. Isoform Alpha and isoform Sigma are expressed in pro-myelocytic leukemia, histiocytic lymphoma, Burkitt’s lymphoma, T-cell lymphoma, lymphoblastic leukemia, breast adenocarcinoma, ovary adenocarcinoma, prostate carcinoma, prostate adenocarcinoma, lung carcinoma, epidermoid carcinoma, small cell lung carcinoma and colon adenocarcinoma cell lines.

Post-translational modifications. Ubiquitinated in the absence of XRCC6/Ku70. Ubiquitination promotes protein degradation. Ubiquitinated on Lys-128 and Lys-190. ‘Lys-63’-linked polyubiquitin chains on Lys-128 are removed by USP12.

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 (8)

UniProt ID	Names	Canonical?
Q07812-1	Alpha	yes
Q07812-2	Beta
Q07812-3	Gamma
Q07812-4	Delta
Q07812-5	Epsilon
Q07812-6	Zeta
Q07812-7	Psi
Q07812-8	Sigma

RefSeq proteins (8): NP_001278357, NP_001278358, NP_001278359, NP_001278360, NP_004315, NP_620116, NP_620118, NP_620119 (=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 (45 total): helix 10, splice variant 8, mutagenesis site 8, sequence variant 4, turn 4, short sequence motif 3, strand 3, cross-link 2, chain 1, transmembrane region 1, modified residue 1

Structure

Experimental structures (PDB)

37 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4ZIE	X-RAY DIFFRACTION	1.8
5W60	X-RAY DIFFRACTION	1.8
4S0O	X-RAY DIFFRACTION	1.9
5W5Z	X-RAY DIFFRACTION	2
6EB6	X-RAY DIFFRACTION	2.02
8SRX	X-RAY DIFFRACTION	2.09
8G1T	X-RAY DIFFRACTION	2.09
6TRR	X-RAY DIFFRACTION	2.12
4ZII	X-RAY DIFFRACTION	2.19
4ZIG	X-RAY DIFFRACTION	2.2
8SPF	X-RAY DIFFRACTION	2.2
4BD2	X-RAY DIFFRACTION	2.21
7ADT	X-RAY DIFFRACTION	2.21
4BD8	X-RAY DIFFRACTION	2.22
8SVK	X-RAY DIFFRACTION	2.25
2G5B	X-RAY DIFFRACTION	2.3
5W61	X-RAY DIFFRACTION	2.3
8SPE	X-RAY DIFFRACTION	2.3
8SPZ	X-RAY DIFFRACTION	2.4
8SRY	X-RAY DIFFRACTION	2.4
4ZIF	X-RAY DIFFRACTION	2.4
3PK1	X-RAY DIFFRACTION	2.49
4BD6	X-RAY DIFFRACTION	2.49
4ZIH	X-RAY DIFFRACTION	2.5
5W5X	X-RAY DIFFRACTION	2.5
3PL7	X-RAY DIFFRACTION	2.61
4BD7	X-RAY DIFFRACTION	2.8
6XY6	X-RAY DIFFRACTION	2.91
4BDU	X-RAY DIFFRACTION	3
4UF2	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q07812-F1	86.71	0.61

Antibody-complex structures (SAbDab): 3 — 2G5B, 5W5X, 5W5Z

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 (3): 1, 128, 190

Mutagenesis-validated functional residues (8):

Position	Phenotype
21	reduces interaction with bcl2l11, homooligomerization and triggering of apoptosis.
74	strongly reduced interaction with mcl1, bcl2, bcl2l1 and bcl2l2. no effect on cytochrome c release and subsequent apopto
128	partial loss of polyubiquitination.
172–192	enhanced fiber formation with humanin.
184	constitutive cytoplasmic location.
184	constitutive mitochondrial location. enhanced fiber formation with humanin.
189	no loss of polyubiquitination.
190	partial loss of polyubiquitination.

Function

Pathways and Gene Ontology

Reactome pathways

22 pathways

ID	Pathway
R-HSA-111457	Release of apoptotic factors from the mitochondria
R-HSA-114294	Activation, translocation and oligomerization of BAX
R-HSA-5620971	Pyroptosis
R-HSA-6803204	TP53 Regulates Transcription of Genes Involved in Cytochrome C Release
R-HSA-6804114	TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest
R-HSA-8878166	Transcriptional regulation by RUNX2
R-HSA-9603505	NTRK3 as a dependence receptor
R-HSA-109581	Apoptosis
R-HSA-109606	Intrinsic Pathway for Apoptosis
R-HSA-111471	Apoptotic factor-mediated response
R-HSA-162582	Signal Transduction
R-HSA-166520	Signaling by NTRKs
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5218859	Regulated Necrosis
R-HSA-5357801	Programmed Cell Death
R-HSA-5633008	TP53 Regulates Transcription of Cell Death Genes
R-HSA-6791312	TP53 Regulates Transcription of Cell Cycle Genes
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9034015	Signaling by NTRK3 (TRKC)

MSigDB gene sets: 661 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_TRANSMEMBRANE_ELECTROCHEMICAL_GRADIENT, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_EPITHELIUM_DEVELOPMENT, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_MAMMARY_GLAND_MORPHOGENESIS, GOBP_CELLULAR_RESPONSE_TO_VIRUS, GOBP_REGULATION_OF_PROTEIN_BINDING, GOBP_GLAND_MORPHOGENESIS, GOBP_B_CELL_HOMEOSTASIS

GO Biological Process (111): ovarian follicle development (GO:0001541), neuron migration (GO:0001764), T cell homeostatic proliferation (GO:0001777), B cell homeostasis (GO:0001782), B cell apoptotic process (GO:0001783), kidney development (GO:0001822), release of cytochrome c from mitochondria (GO:0001836), blood vessel remodeling (GO:0001974), myeloid cell homeostasis (GO:0002262), B cell negative selection (GO:0002352), B cell homeostatic proliferation (GO:0002358), positive regulation of B cell apoptotic process (GO:0002904), glycosphingolipid metabolic process (GO:0006687), regulation of nitrogen utilization (GO:0006808), apoptotic process (GO:0006915), germ cell development (GO:0007281), mitochondrial fusion (GO:0008053), extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), apoptotic mitochondrial changes (GO:0008637), fertilization (GO:0009566), response to toxic substance (GO:0009636), response to salt stress (GO:0009651), 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 mitochondrial membrane potential (GO:0010917), hypothalamus development (GO:0021854), cerebral cortex development (GO:0021987), positive regulation of protein-containing complex assembly (GO:0031334), negative regulation of protein binding (GO:0032091), endoplasmic reticulum calcium ion homeostasis (GO:0032469), negative regulation of endoplasmic reticulum calcium ion concentration (GO:0032471), release of matrix enzymes from mitochondria (GO:0032976), regulation of mammary gland epithelial cell proliferation (GO:0033599), cellular response to unfolded protein (GO:0034620), cellular response to UV (GO:0034644), ectopic germ cell programmed cell death (GO:0035234), odontogenesis of dentin-containing tooth (GO:0042475), regulation of apoptotic process (GO:0042981)

GO Molecular Function (9): lipid binding (GO:0008289), channel activity (GO:0015267), Hsp70 protein binding (GO:0030544), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), BH3 domain binding (GO:0051434), protein binding (GO:0005515), protein-folding chaperone binding (GO:0051087)

GO Cellular Component (17): nucleus (GO:0005634), nuclear envelope (GO:0005635), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), mitochondrial permeability transition pore complex (GO:0005757), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020), pore complex (GO:0046930), extracellular exosome (GO:0070062), Bcl-2 family protein complex (GO:0097136), BAX complex (GO:0097144), BAK complex (GO:0097145), mitochondrial membrane (GO:0031966), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Intrinsic Pathway for Apoptosis	2
Generic Transcription Pathway	2
Programmed Cell Death	2
Transcriptional Regulation by TP53	2
Apoptotic factor-mediated response	1
Regulated Necrosis	1
TP53 Regulates Transcription of Cell Death Genes	1
TP53 Regulates Transcription of Cell Cycle Genes	1
Signaling by NTRK3 (TRKC)	1
Apoptosis	1
Signaling by Receptor Tyrosine Kinases	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membrane-bounded organelle	3
cytoplasm	3
apoptotic signaling pathway	2
mitochondrion organization	2
binding	2
protein binding	2
protein dimerization activity	2
endomembrane system	2
mitochondrial envelope	2
organelle membrane	2
Bcl-2 family protein complex	2
female gonad development	1
anatomical structure development	1
cell migration	1
generation of neurons	1
T cell proliferation	1
T cell homeostasis	1
lymphocyte homeostasis	1
lymphocyte apoptotic process	1
animal organ development	1
renal system development	1
apoptotic mitochondrial changes	1
tissue remodeling	1
immune system process	1
homeostasis of number of cells	1
B cell selection	1
B cell proliferation	1
homeostatic process	1
B cell apoptotic process	1
regulation of B cell apoptotic process	1
positive regulation of lymphocyte apoptotic process	1
glycolipid metabolic process	1
sphingolipid metabolic process	1
nitrogen utilization	1
regulation of response to nutrient levels	1
programmed cell death	1
execution phase of apoptosis	1
developmental process involved in reproduction	1
gamete generation	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

268 interactions, top by confidence:

A	B	Type	Score
BAX	BAX	psi-mi:“MI:0407”(direct interaction)	0.970
BCL2L1	BAX	psi-mi:“MI:0407”(direct interaction)	0.970
BAX	BCL2L1	psi-mi:“MI:0915”(physical association)	0.970
BCL2L1	BAX	psi-mi:“MI:0915”(physical association)	0.970
BAX	BAX	psi-mi:“MI:0915”(physical association)	0.970
BCL2L1	BAX	psi-mi:“MI:0403”(colocalization)	0.970
BAX	BCL2L1	psi-mi:“MI:0403”(colocalization)	0.970
BAX	BCL2L1	psi-mi:“MI:0407”(direct interaction)	0.970

BioGRID (275): BAX (Reconstituted Complex), ZBTB24 (Reconstituted Complex), BAX (Affinity Capture-Western), BCL2 (Reconstituted Complex), BCL2L1 (Reconstituted Complex), CASP9 (Co-fractionation), CASP8 (Co-fractionation), CASP7 (Co-fractionation), CASP3 (Co-fractionation), CYCS (Co-fractionation), BAX (Affinity Capture-Western), BAX (FRET), BAX (Affinity Capture-Western), BCL2 (Reconstituted Complex), BAX (Co-fractionation)

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, Q8HYS5, P97287, Q9Z1P3, Q90ZN1

SIGNOR signaling

53 interactions.

A	Effect	B	Mechanism
TP53	up-regulates	BAX	binding
MAPK10	up-regulates	BAX
MAPK8	up-regulates	BAX
MAPK9	up-regulates	BAX
GSK3B	up-regulates	BAX	phosphorylation
BID	up-regulates	BAX	binding
SH3GLB1	up-regulates	BAX	binding
PYCARD	up-regulates	BAX	relocalization
MCL1	down-regulates	BAX	binding
BCL2L11	“up-regulates activity”	BAX	binding
BCL2L2	down-regulates	BAX	binding
PRKCZ	“down-regulates activity”	BAX	phosphorylation
BAX	up-regulates	CYCS
AIFM1	up-regulates	BAX
BAX	up-regulates	DIABLO
ENDOG	up-regulates	BAX
TP53	“up-regulates activity”	BAX	binding
BBC3	up-regulates	BAX	relocalization
BBC3	up-regulates	BAX	binding
AKT	“down-regulates activity”	BAX	phosphorylation
AKT1	“down-regulates activity”	BAX	phosphorylation
GFI1	“down-regulates quantity by repression”	BAX	“transcriptional regulation”
ETS1	“down-regulates quantity by repression”	BAX	“transcriptional regulation”
ING1	“up-regulates quantity by expression”	BAX	“transcriptional regulation”
WWTR1	“up-regulates quantity by expression”	BAX	“transcriptional regulation”
NR4A3	“up-regulates quantity by expression”	BAX	“transcriptional regulation”
AATF	“down-regulates quantity”	BAX	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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	6	42.9×	2e-06
Apoptosis	6	24.6×	2e-05
Programmed Cell Death	6	21.4×	4e-05
KEAP1-NFE2L2 pathway	5	14.7×	1e-03
Interleukin-4 and Interleukin-13 signaling	5	12.6×	2e-03
Signaling by Interleukins	5	7.8×	1e-02
Cytokine Signaling in Immune system	7	7.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
release of cytochrome c from mitochondria	8	110.1×	2e-12
positive regulation of release of cytochrome c from mitochondria	5	75.1×	9e-07
extrinsic apoptotic signaling pathway in absence of ligand	8	73.4×	5e-11
regulation of mitochondrial membrane potential	5	53.3×	5e-06
intrinsic apoptotic signaling pathway in response to DNA damage	7	44.5×	4e-08
positive regulation of protein-containing complex assembly	5	33.0×	5e-05
neuron apoptotic process	5	18.2×	5e-04
positive regulation of apoptotic process	12	13.3×	2e-08

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	31
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
9512	NM_138761.4(BAX):c.121del (p.Glu41fs)	Pathogenic
9513	NM_138761.4(BAX):c.199G>A (p.Gly67Arg)	Pathogenic
9514	NM_138761.4(BAX):c.115_121del (p.Gly39fs)	Pathogenic
4278421	NM_138761.4(BAX):c.474+50_474+63del	Likely pathogenic

SpliceAI

837 predictions. Top by Δscore:

Variant	Effect	Δscore
19:48955118:G:GT	donor_gain	1.0000
19:48955597:GGG:G	donor_gain	1.0000
19:48955598:GGG:G	donor_gain	1.0000
19:48955831:GAGGT:G	donor_gain	1.0000
19:48955881:G:GT	donor_gain	1.0000
19:48955888:G:GT	donor_gain	1.0000
19:48960807:CA:C	acceptor_loss	1.0000
19:48960808:A:AG	acceptor_gain	1.0000
19:48960808:AGGCC:A	acceptor_loss	1.0000
19:48960809:G:GG	acceptor_gain	1.0000
19:48960809:GGC:G	acceptor_gain	1.0000
19:48960809:GGCC:G	acceptor_gain	1.0000
19:48960809:GGCCC:G	acceptor_gain	1.0000
19:48960907:G:T	donor_gain	1.0000
19:48954932:G:GT	donor_gain	0.9900
19:48954943:G:GT	donor_gain	0.9900
19:48954943:G:T	donor_gain	0.9900
19:48955199:G:GT	donor_gain	0.9900
19:48955598:GG:G	donor_gain	0.9900
19:48955599:GG:G	donor_gain	0.9900
19:48955685:A:AG	acceptor_gain	0.9900
19:48955686:G:GA	acceptor_gain	0.9900
19:48955686:GT:G	acceptor_gain	0.9900
19:48955686:GTTTC:G	acceptor_gain	0.9900
19:48955812:A:T	donor_gain	0.9900
19:48955814:A:AG	donor_gain	0.9900
19:48955815:G:GG	donor_gain	0.9900
19:48955855:G:GT	donor_gain	0.9900
19:48956293:T:TA	donor_gain	0.9900
19:48956329:TCAAG:T	donor_loss	0.9900

AlphaMissense

1250 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:48955788:T:C	L63P	1.000
19:48956283:T:A	W107R	1.000
19:48956283:T:C	W107R	1.000
19:48956285:G:C	W107C	1.000
19:48956285:G:T	W107C	1.000
19:48960855:T:A	W139R	1.000
19:48960855:T:C	W139R	1.000
19:48960891:T:A	W151R	1.000
19:48960891:T:C	W151R	1.000
19:48960893:G:C	W151C	1.000
19:48960893:G:T	W151C	1.000
19:48960912:T:A	W158R	1.000
19:48960912:T:C	W158R	1.000
19:48960914:G:C	W158C	1.000
19:48960914:G:T	W158C	1.000
19:48961592:G:A	G179R	1.000
19:48961592:G:C	G179R	1.000
19:48955580:G:T	G23W	0.999
19:48955581:G:A	G23E	0.999
19:48955590:T:C	L26S	0.999
19:48955593:T:C	L27P	0.999
19:48955688:T:C	F30L	0.999
19:48955689:T:C	F30S	0.999
19:48955690:C:A	F30L	0.999
19:48955690:C:G	F30L	0.999
19:48955788:T:A	L63H	0.999
19:48955800:G:A	G67E	0.999
19:48955809:T:C	L70P	0.999
19:48956239:T:C	F92S	0.999
19:48956262:T:C	F100L	0.999

dbSNP variants (sampled 300 via entrez): RS1000548611 (19:48961828 C>T), RS1000626610 (19:48955274 G>A), RS1000696499 (19:48956722 C>G), RS1001000787 (19:48956422 C>T), RS1001083041 (19:48955480 T>C), RS1001083757 (19:48956801 G>A), RS1001314589 (19:48961102 T>G), RS1001421827 (19:48955456 C>CT), RS1002464330 (19:48961466 C>A,T), RS1002801456 (19:48955214 G>C), RS1002853492 (19:48959519 A>T), RS1002961804 (19:48954349 GA>G,GAA,GAAAAA,GAAAAAAAAA), RS1003096964 (19:48954631 C>G), RS1003134531 (19:48954078 T>C), RS1003320475 (19:48958670 A>G)

Disease associations

OMIM: gene MIM:600040 | disease phenotypes: MIM:613477

GenCC curated gene-disease

Disease	Classification	Inheritance
leukemia, acute lymphocytic, susceptibility to, 1	Limited	Unknown

Mondo (4): developmental and epileptic encephalopathy, 5 (MONDO:0013277), colon carcinoma (MONDO:0002032), T-cell acute lymphoblastic leukemia (MONDO:0004963), leukemia, acute lymphocytic, susceptibility to, 1 (MONDO:0013108)

Orphanet (1): West syndrome (Orphanet:3451)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0002891	Uterine leiomyosarcoma
HP:0003003	Colon cancer
HP:0005584	Renal cell carcinoma
HP:0006716	Hereditary nonpolyposis colorectal carcinoma
HP:0006721	Acute lymphoblastic leukemia
HP:0006740	Transitional cell carcinoma of the bladder
HP:0006753	Neoplasm of the stomach
HP:0010982	Polygenic inheritance

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST003831_37	Asthma	8.000000e-06
GCST004606_44	Eosinophil count	1.000000e-10
GCST004623_38	Neutrophil percentage of granulocytes	3.000000e-09
GCST004624_51	Sum eosinophil basophil counts	1.000000e-11
GCST90002381_353	Eosinophil count	3.000000e-17
GCST90002382_473	Eosinophil percentage of white cells	3.000000e-12
GCST90002388_378	Lymphocyte count	8.000000e-12
GCST90002400_292	Plateletcrit	7.000000e-09
GCST90002407_634	White blood cell count	6.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004587	lymphocyte count
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL3883286 (PROTEIN-PROTEIN INTERACTION), CHEMBL3885513 (PROTEIN-PROTEIN INTERACTION), CHEMBL3885514 (PROTEIN-PROTEIN INTERACTION), CHEMBL3885515 (PROTEIN-PROTEIN INTERACTION), CHEMBL5318 (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

39 potent at pChembl≥5 of 53 total, top 39 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.64	IC50	23	nM	ABT 737
7.37	IC50	43	nM	CHEMBL4579601
7.37	Ki	43	nM	CHEMBL4868313
6.61	IC50	247	nM	CHEMBL4790235
6.60	IC50	250	nM	CHEMBL4790235
6.60	IC50	250	nM	CHEMBL5282360
6.59	Kd	255	nM	CHEMBL4578793
6.56	EC50	278.1	nM	CHEMBL4790235
6.41	EC50	392.9	nM	CHEMBL4794290
6.27	EC50	531.7	nM	CHEMBL4784916
6.27	EC50	537.8	nM	CHEMBL4779693
6.16	EC50	700	nM	CHEMBL3417402
6.15	EC50	703.9	nM	CHEMBL4777011
6.14	EC50	719.3	nM	CHEMBL4778142
6.14	EC50	724.7	nM	CHEMBL4761391
6.10	Ki	800	nM	CHEMBL3417402
6.09	EC50	808.6	nM	CHEMBL4780328
6.07	EC50	855.7	nM	CHEMBL4756429
6.06	EC50	873.9	nM	CHEMBL4754714
6.03	EC50	924.9	nM	CHEMBL4758680
6.01	EC50	967.1	nM	CHEMBL4797324
6.00	Ki	1000	nM	CHEMBL3417409
6.00	EC50	992.2	nM	CHEMBL4776616
5.96	Ki	1100	nM	CHEMBL3417395
5.94	EC50	1144	nM	CHEMBL4753330
5.92	Ki	1200	nM	CHEMBL3417407
5.89	Ki	1300	nM	CHEMBL3417406
5.89	Ki	1300	nM	CHEMBL3417408
5.77	Ki	1700	nM	CHEMBL3417404
5.65	EC50	2218	nM	CHEMBL4790418
5.60	Ki	2500	nM	CHEMBL3417410
5.52	IC50	3000	nM	CHEMBL4438921
5.48	IC50	3300	nM	CHEMBL4783072
5.48	IC50	3300	nM	CHEMBL5266955
5.48	IC50	3310	nM	CHEMBL3417395
5.40	IC50	4000	nM	CHEMBL5278460
5.22	IC50	6000	nM	CHEMBL5271207
5.09	EC50	8200	nM	CHEMBL3417395
5.04	Ki	9100	nM	CHEMBL3417403

PubChem BioAssay actives

39 with measured affinity, of 92 total; 34 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	515597: Inhibition of GST-tagged Bcl-xl/FITC-conjugated Bax interaction by fluorescence polarisation assay	ic50	0.0230	uM
2-[(2-nitrofluoren-9-ylidene)methyl]phenol	1568133: Displacement of fluorescent Bak BH3 peptide domain from human recombinant Bax by competition fluorescence polarization assay	ic50	0.0430	uM
2-[(E)-(2-nitrofluoren-9-ylidene)methyl]phenol	1762559: Displacement of Bak BH3 domain peptide from human Bax by competitive fluorescence polarization assay	ki	0.0430	uM
5-phenyl-2-(4-phenyl-1,3-thiazol-2-yl)-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-3-one	1973784: Displacement of FITC-labeled BIM SAHBA2 from human full length BAX trigger site expressed in Escherichia coli measured for 20 mins by competitive fluorescence polarization assay	ic50	0.2470	uM
5-phenyl-2-(4-phenyl-4,5-dihydro-1,3-thiazol-2-yl)-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-3-one	1938209: Binding affinity to recombinant human full length GST-tagged BAX expressed in Escherichia coli BL21 (DE3) measured after 20 mins by fluorescence polarization assay	ic50	0.2500	uM
1-hydroxy-3-[(4-methylpiperazin-1-yl)-pyridin-2-ylmethyl]-2-phenylindole	1938207: Binding affinity to recombinant human BAX assessed as dissociation constant by ITC analysis	kd	0.2550	uM
N-hydroxy-4-[[[4-[2-[3-oxo-5-phenyl-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-2-yl]-1,3-thiazol-4-yl]benzoyl]amino]methyl]benzamide	1677517: Binding affinity to recombinant human full length His-tagged BAX expressed in Escherichia coli BL21 (DE3) cells preincubated for 30 min followed by FITC-BIM addition and measured after 20 mins by fluorescence polarization assay	ec50	0.3929	uM
N-hydroxy-8-[4-[2-[3-oxo-5-phenyl-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-2-yl]-1,3-thiazol-4-yl]phenoxy]octanamide	1677517: Binding affinity to recombinant human full length His-tagged BAX expressed in Escherichia coli BL21 (DE3) cells preincubated for 30 min followed by FITC-BIM addition and measured after 20 mins by fluorescence polarization assay	ec50	0.5317	uM
N-hydroxy-4-[[4-[2-[3-oxo-5-phenyl-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-2-yl]-1,3-thiazol-4-yl]phenoxy]methyl]benzamide	1677517: Binding affinity to recombinant human full length His-tagged BAX expressed in Escherichia coli BL21 (DE3) cells preincubated for 30 min followed by FITC-BIM addition and measured after 20 mins by fluorescence polarization assay	ec50	0.5378	uM
2-[3-[4-(dimethylamino)phenyl]-5-hydroxyphenyl]-4-[(2-ethoxyphenyl)diazenyl]-5-methyl-1H-pyrazol-3-one	1200232: Activation of Bax in human HuH7 cells assessed as inhibition of mitochondrial accumulation of fluorescent probe Mitotracker Red after 12 to 72 hrs by spectrophotometric analysis	ec50	0.7000	uM
4-[2-[3-oxo-5-phenyl-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-2-yl]-1,3-thiazol-4-yl]benzoic acid	1677517: Binding affinity to recombinant human full length His-tagged BAX expressed in Escherichia coli BL21 (DE3) cells preincubated for 30 min followed by FITC-BIM addition and measured after 20 mins by fluorescence polarization assay	ec50	0.7039	uM
N-[5-(hydroxyamino)-5-oxopentyl]-4-[2-[3-oxo-5-phenyl-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-2-yl]-1,3-thiazol-4-yl]benzamide	1677517: Binding affinity to recombinant human full length His-tagged BAX expressed in Escherichia coli BL21 (DE3) cells preincubated for 30 min followed by FITC-BIM addition and measured after 20 mins by fluorescence polarization assay	ec50	0.7193	uM
N-hydroxy-4-[4-[2-[3-oxo-5-phenyl-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-2-yl]-1,3-thiazol-4-yl]phenoxy]butanamide	1677517: Binding affinity to recombinant human full length His-tagged BAX expressed in Escherichia coli BL21 (DE3) cells preincubated for 30 min followed by FITC-BIM addition and measured after 20 mins by fluorescence polarization assay	ec50	0.7247	uM
N-[6-(hydroxyamino)-6-oxohexyl]-4-[2-[3-oxo-5-phenyl-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-2-yl]-1,3-thiazol-4-yl]benzamide	1677517: Binding affinity to recombinant human full length His-tagged BAX expressed in Escherichia coli BL21 (DE3) cells preincubated for 30 min followed by FITC-BIM addition and measured after 20 mins by fluorescence polarization assay	ec50	0.8086	uM
N-hydroxy-7-[4-[2-[3-oxo-5-phenyl-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-2-yl]-1,3-thiazol-4-yl]phenoxy]heptanamide	1677517: Binding affinity to recombinant human full length His-tagged BAX expressed in Escherichia coli BL21 (DE3) cells preincubated for 30 min followed by FITC-BIM addition and measured after 20 mins by fluorescence polarization assay	ec50	0.8557	uM
N-oxo-4-[2-[3-oxo-5-phenyl-4-[2-(1,3-thiazol-2-yl)hydrazinyl]-1H-pyrazol-2-yl]-1,3-thiazol-4-yl]benzamide	1677517: Binding affinity to recombinant human full length His-tagged BAX expressed in Escherichia coli BL21 (DE3) cells preincubated for 30 min followed by FITC-BIM addition and measured after 20 mins by fluorescence polarization assay	ec50	0.8739	uM
N-hydroxy-6-[4-[2-[3-oxo-5-phenyl-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-2-yl]-1,3-thiazol-4-yl]phenoxy]hexanamide	1677517: Binding affinity to recombinant human full length His-tagged BAX expressed in Escherichia coli BL21 (DE3) cells preincubated for 30 min followed by FITC-BIM addition and measured after 20 mins by fluorescence polarization assay	ec50	0.9249	uM
N-hydroxy-5-[4-[2-[3-oxo-5-phenyl-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-2-yl]-1,3-thiazol-4-yl]phenoxy]pentanamide	1677517: Binding affinity to recombinant human full length His-tagged BAX expressed in Escherichia coli BL21 (DE3) cells preincubated for 30 min followed by FITC-BIM addition and measured after 20 mins by fluorescence polarization assay	ec50	0.9671	uM
(E)-N-hydroxy-3-[4-[[4-[2-[3-oxo-5-phenyl-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-2-yl]-1,3-thiazol-4-yl]phenoxy]methyl]phenyl]prop-2-enamide	1677517: Binding affinity to recombinant human full length His-tagged BAX expressed in Escherichia coli BL21 (DE3) cells preincubated for 30 min followed by FITC-BIM addition and measured after 20 mins by fluorescence polarization assay	ec50	0.9922	uM
2-[3-[4-(dimethylamino)phenyl]-5-hydroxyphenyl]-5-methyl-4-(naphthalen-2-yldiazenyl)-1H-pyrazol-3-one	1200214: Displacement of FITC-BIM from recombinant N-terminal GST-tagged human BAX expressed in Escherichia coli after 30 mins by fluorescence polarization assay	ki	1.0000	uM
4-[(2-ethoxyphenyl)diazenyl]-5-methyl-2-(4-phenyl-1,3-thiazol-2-yl)-1H-pyrazol-3-one	1200214: Displacement of FITC-BIM from recombinant N-terminal GST-tagged human BAX expressed in Escherichia coli after 30 mins by fluorescence polarization assay	ki	1.1000	uM
N-[7-(hydroxyamino)-7-oxoheptyl]-4-[2-[3-oxo-5-phenyl-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-2-yl]-1,3-thiazol-4-yl]benzamide	1677517: Binding affinity to recombinant human full length His-tagged BAX expressed in Escherichia coli BL21 (DE3) cells preincubated for 30 min followed by FITC-BIM addition and measured after 20 mins by fluorescence polarization assay	ec50	1.1439	uM
4-[(2-ethoxyphenyl)diazenyl]-2-[3-hydroxy-5-(4-propan-2-ylphenyl)phenyl]-5-methyl-1H-pyrazol-3-one	1200214: Displacement of FITC-BIM from recombinant N-terminal GST-tagged human BAX expressed in Escherichia coli after 30 mins by fluorescence polarization assay	ki	1.2000	uM
2-[3-(3-aminophenyl)-5-hydroxyphenyl]-4-[(2-ethoxyphenyl)diazenyl]-5-methyl-1H-pyrazol-3-one	1200214: Displacement of FITC-BIM from recombinant N-terminal GST-tagged human BAX expressed in Escherichia coli after 30 mins by fluorescence polarization assay	ki	1.3000	uM
2-[3-[4-(dimethylamino)phenyl]phenyl]-4-[(2-ethoxyphenyl)diazenyl]-5-methyl-1H-pyrazol-3-one	1200214: Displacement of FITC-BIM from recombinant N-terminal GST-tagged human BAX expressed in Escherichia coli after 30 mins by fluorescence polarization assay	ki	1.3000	uM
4-[(2-ethoxyphenyl)diazenyl]-2-(3-hydroxy-5-pyridin-4-ylphenyl)-5-methyl-1H-pyrazol-3-one	1200214: Displacement of FITC-BIM from recombinant N-terminal GST-tagged human BAX expressed in Escherichia coli after 30 mins by fluorescence polarization assay	ki	1.7000	uM
N-[[4-[(E)-3-(hydroxyamino)-3-oxoprop-1-enyl]phenyl]methyl]-4-[2-[3-oxo-5-phenyl-4-(1,3-thiazol-2-yldiazenyl)-1H-pyrazol-2-yl]-1,3-thiazol-4-yl]benzamide	1677517: Binding affinity to recombinant human full length His-tagged BAX expressed in Escherichia coli BL21 (DE3) cells preincubated for 30 min followed by FITC-BIM addition and measured after 20 mins by fluorescence polarization assay	ec50	2.2181	uM
(4E)-4-benzylidene-5-methyl-2-(4-phenyl-1,3-thiazol-2-yl)pyrazol-3-one	1200214: Displacement of FITC-BIM from recombinant N-terminal GST-tagged human BAX expressed in Escherichia coli after 30 mins by fluorescence polarization assay	ki	2.5000	uM
N-[(E)-1,3-benzodioxol-5-ylmethylideneamino]-1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxamide	1653208: Activation of Bax in human SMMC7721 cells	ic50	3.0000	uM
4-[(2-ethoxyphenyl)diazenyl]-5-methyl-2-(5-phenyl-1,3-thiazol-2-yl)-1H-pyrazol-3-one	1677521: Activation of BAX (unknown origin)	ic50	3.3000	uM
4-[(2-ethoxyphenyl)diazenyl]-5-methyl-2-(4-phenyl-4,5-dihydro-1,3-thiazol-2-yl)-1H-pyrazol-3-one	1938209: Binding affinity to recombinant human full length GST-tagged BAX expressed in Escherichia coli BL21 (DE3) measured after 20 mins by fluorescence polarization assay	ic50	3.3000	uM
N-[(2S)-1-[[(2R,3S)-3-amino-6-(2-methoxyethoxymethoxy)-2,3-dihydro-1-benzofuran-2-yl]methyl-[(4-bromophenyl)methyl]amino]-1-oxo-3-phenylpropan-2-yl]benzamide	1938211: Inhibition of recombinant human BAX expressed in Escherichia coli BL21 (DE3) assessed as inhibition of liposome permeabilization and measured for 2 hrs by fluorescence analysis	ic50	4.0000	uM
N-[(2S)-1-[[(2R,3S)-2-(aminomethyl)-6-(2-methoxyethoxymethoxy)-2,3-dihydro-1-benzofuran-3-yl]-[(4-bromophenyl)methyl]amino]-1-oxo-3-phenylpropan-2-yl]benzamide	1938211: Inhibition of recombinant human BAX expressed in Escherichia coli BL21 (DE3) assessed as inhibition of liposome permeabilization and measured for 2 hrs by fluorescence analysis	ic50	6.0000	uM
4-[(2-ethoxyphenyl)diazenyl]-2-(3-hydroxy-5-phenylphenyl)-5-methyl-1H-pyrazol-3-one	1200214: Displacement of FITC-BIM from recombinant N-terminal GST-tagged human BAX expressed in Escherichia coli after 30 mins by fluorescence polarization assay	ki	9.1000	uM

CTD chemical–gene interactions

1275 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	affects localization, affects cotreatment, increases localization, increases expression, increases activity (+9 more)	79
Cisplatin	increases expression, affects cotreatment, increases activity, increases reaction, decreases response to substance (+12 more)	64
Doxorubicin	affects expression, increases response to substance, decreases expression, affects cotreatment, affects response to substance (+9 more)	47
Resveratrol	increases localization, affects folding, affects expression, affects localization, decreases reaction (+13 more)	46
Quercetin	affects binding, affects cotreatment, increases activity, increases reaction, increases response to substance (+9 more)	43
Acetylcysteine	increases localization, increases cleavage, increases abundance, affects folding, affects expression (+8 more)	41
Hydrogen Peroxide	affects reaction, decreases abundance, increases abundance, affects expression, decreases expression (+5 more)	38
Fluorouracil	increases reaction, increases response to substance, affects expression, affects cotreatment, decreases expression (+5 more)	27
1-Methyl-4-phenylpyridinium	decreases reaction, affects reaction, increases cleavage, affects response to substance, increases reaction (+2 more)	26
sodium arsenite	affects reaction, increases cleavage, decreases expression, affects localization, affects cotreatment (+6 more)	25
Plant Extracts	affects cotreatment, decreases expression, decreases reaction, increases localization, increases expression (+3 more)	19
Benzo(a)pyrene	affects cotreatment, increases expression, affects methylation, increases methylation, increases abundance (+4 more)	18
Curcumin	affects reaction, increases expression, affects localization, increases reaction, decreases reaction (+2 more)	18
bisphenol A	affects cotreatment, decreases expression, increases expression, decreases reaction, affects expression	17
Tretinoin	decreases reaction, increases expression, increases cleavage, affects cotreatment	16
Paclitaxel	decreases reaction, affects binding, increases phosphorylation, increases expression, increases reaction (+2 more)	16
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects expression, increases expression, affects cotreatment, increases activity, decreases expression (+4 more)	15
Cadmium Chloride	affects cotreatment, decreases expression, decreases reaction, increases abundance, increases expression (+2 more)	14
SB 203580	increases reaction, affects reaction, decreases reaction, affects cotreatment, increases localization (+6 more)	13
pyrazolanthrone	increases expression, affects localization, increases cleavage, affects cotreatment, decreases reaction (+5 more)	13
Paraquat	affects response to substance, increases reaction, decreases expression, increases expression, affects cotreatment (+4 more)	13
Glucose	increases reaction, decreases reaction, increases expression, affects cotreatment, affects reaction	12
Melatonin	increases expression, affects binding, decreases expression, increases activity, affects cotreatment (+3 more)	12
Rotenone	decreases reaction, increases expression, affects reaction, increases reaction, affects expression	12
Cadmium	decreases reaction, increases abundance, increases expression, affects cotreatment, decreases expression (+2 more)	11
Estradiol	decreases reaction, increases reaction, affects expression, increases expression, affects cotreatment (+1 more)	11
ochratoxin A	decreases reaction, increases expression, decreases expression, affects cotreatment, increases response to substance (+3 more)	10
Etoposide	affects folding, affects localization, decreases expression, decreases folding, increases expression (+5 more)	10
Lipopolysaccharides	decreases reaction, increases expression, affects reaction, affects binding, increases reaction	10
Particulate Matter	affects localization, decreases reaction, increases expression, decreases expression, increases abundance (+1 more)	10

ChEMBL screening assays

49 unique, capped per target: 47 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1250999	Binding	Inhibition of GST-tagged Bcl-xl/FITC-conjugated Bax interaction by fluorescence polarisation assay	Synthesis and biological activities of new di- and trimeric quinoline derivatives. — Bioorg Med Chem
CHEMBL1007222	Functional	Activation of Bax in human HL60 cells assessed as nuclear translocation 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

443 cell lines: 437 cancer cell line, 4 induced pluripotent stem cell, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0065	Jurkat	Cancer cell line	Male
CVCL_0244	DG-75	Cancer cell line	Male
CVCL_0354	J.CaM1.6	Cancer cell line	Male
CVCL_0367	Jurkat E6.1	Cancer cell line	Male
CVCL_0584	Jurkat Wurzburg	Cancer cell line	Male
CVCL_0D86	JPX-9	Cancer cell line	Male
CVCL_1061	Jurkat clone A3	Cancer cell line	Male
CVCL_1316	J.RT3-T3.5	Cancer cell line	Male
CVCL_1E01	JLTRG	Cancer cell line	Male
CVCL_1E02	JLTRG-R5	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01169220	PHASE4	COMPLETED	Bowel Preparation for Inpatient Colonoscopy
NCT01170754	PHASE4	COMPLETED	Miralax (PEG 3350) vs. Golytely as Bowel Preparation for Screening Colonoscopy
NCT02052557	PHASE4	COMPLETED	The Effect of Exparel on Post Operative Pain and Narcotic Use After Colon Surgery
NCT02078726	PHASE4	COMPLETED	Glucagon Use in Colonoscopies
NCT02231203	PHASE4	COMPLETED	Effect of Omega-3 Fatty Acids on the Perioperative Immune Response and Erythrocyte Function
NCT02314871	PHASE4	COMPLETED	Effects of Different Types of Perioperative Analgesia on Minimal Residual Disease Development After Colon Cancer Surgery
NCT02746432	PHASE4	UNKNOWN	Insulin Therapy Reduce Post-Operative Inflammatory Response After Curative Colorectal Cancer Resection: Randomization Controlled Trial
NCT02887365	PHASE4	UNKNOWN	A Phase II Study of Tegafur-Uracil as Maintenance Chemotherapy in Patients With Stage II of Colon Cancer
NCT02937506	PHASE4	COMPLETED	Patient Satisfaction With Propofol for Out Patient Colonoscopy
NCT02958566	PHASE4	UNKNOWN	Multimodal Narcotic Limited Perioperative Pain Control With Colorectal Surgery
NCT04269369	PHASE4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT04311099	PHASE4	COMPLETED	Optimal Peripheral Nerve Block After Minimally Invasive Colon Surgery
NCT04709770	PHASE4	UNKNOWN	Low-volume vs High-volume Polyethylene Glycol Based Bowel Preparation for Colonoscopy in People Receiving Hemodialysis
NCT05250648	PHASE4	RECRUITING	Clinical Trial on HIPEC With Mitomycin C in Colon Cancer Peritoneal Metastases (GECOP-MMC)
NCT02393859	PHASE3	COMPLETED	Phase 3 Trial of Blinatumomab vs Standard Chemotherapy in Pediatric Subjects With HIgh-Risk (HR) First Relapse B-precursor Acute Lymphoblastic Leukemia (ALL)
NCT04307576	PHASE3	RECRUITING	A Treatment Study Protocol for Participants 0-45 Years With Acute Lymphoblastic Leukaemia
NCT00002968	PHASE3	COMPLETED	Edrecolomab in Treating Patients With Stage II Colon Cancer
NCT00003835	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Stage III Colon Cancer
NCT00003873	PHASE3	COMPLETED	Fluorouracil With or Without Eniluracil in Treating Patients With Advanced Colorectal Cancer
NCT00004931	PHASE3	COMPLETED	Fluorouracil Plus Leucovorin With or Without Oxaliplatin in Treating Patients With Stage II or Stage III Colon Cancer
NCT00005036	PHASE3	COMPLETED	Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer
NCT00005094	PHASE3	COMPLETED	Celecoxib to Prevent Colorectal Cancer in Patients Who Have Undergone Surgery to Remove Polyps
NCT00025337	PHASE3	COMPLETED	Combination Chemotherapy With or Without Bevacizumab Compared With Bevacizumab Alone in Treating Patients With Advanced or Metastatic Colorectal Cancer That Has Been Previously Treated
NCT00070122	PHASE3	TERMINATED	Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer
NCT00079274	PHASE3	COMPLETED	Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer
NCT00096278	PHASE3	COMPLETED	Fluorouracil, Leucovorin, and Oxaliplatin With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II or Stage III Colon Cancer
NCT00188305	PHASE3	COMPLETED	A Randomized Trial of Cancer Risk and Health Education in Relatives of Colorectal Cancer Patients
NCT00195585	PHASE3	COMPLETED	Study Evaluating Isovorin in Colon Cancer
NCT00217737	PHASE3	ACTIVE_NOT_RECRUITING	Oxaliplatin, Leucovorin, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer
NCT00230646	PHASE3	COMPLETED	Promoting Physical Activity After Colorectal Cancer
NCT00309530	PHASE3	COMPLETED	Randomized Study on Adjuvant Chemotherapy and Adjuvant Chemo-Immunotherapy in Colon Carcinoma Dukes C
NCT00309543	PHASE3	COMPLETED	Randomized Trial on Adjuvant Chemotherapy in Colon Carcinoma Dukes B
NCT00337389	PHASE3	UNKNOWN	Phase III Randomized Study of 5-FU, CoFactor, and Avastin vs. 5-FU, LV and Avastin for First-Line Colorectal Cancer.
NCT00467922	PHASE3	COMPLETED	An Assessment of Goal-Directed Intraoperative Fluid Management in Hand Assisted Laparoscopic Colectomy
NCT00499369	PHASE3	TERMINATED	Irinotecan and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer That Progressed During First-Line Therapy
NCT00509444	PHASE3	COMPLETED	Cancer Prevention and Treatment Among African American Older Adults: Treatment Trial
NCT00646607	PHASE3	COMPLETED	FOLFOX-4 3months Versus 6 Months and Bevacizumab as Adjuvant Therapy for Patients With Stage II/III Colon Cancer
NCT00687830	PHASE3	COMPLETED	Efficacy of Morning-only Bowel Preparation for Afternoon Colonoscopy.
NCT00756548	PHASE3	COMPLETED	BLI850-302: BLI850 vs an Approved Active Control Bowel Preparation in Adult Subjects Undergoing Colonoscopy
NCT00756977	PHASE3	COMPLETED	BLI850 vs an Active Control Bowel Preparation in Adult Subjects Undergoing Colonoscopy