BID

Summary

BID (BH3 interacting domain death agonist, HGNC:1050) is a protein-coding gene on chromosome 22q11.21, encoding BH3-interacting domain death agonist (P55957). Induces caspases and apoptosis.

This gene encodes a death agonist that heterodimerizes with either agonist BAX or antagonist BCL2, and thus regulate apoptosis. The encoded protein is a member of the BCL-2 family of cell death regulators. It is a mediator of mitochondrial damage induced by caspase-8 (CASP8); CASP8 cleaves this encoded protein, and the COOH-terminal part translocates to mitochondria where it triggers cytochrome c release. Multiple alternatively spliced transcript variants have been found.

Source: NCBI Gene 637 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 61 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001196

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1050
Approved symbol	BID
Name	BH3 interacting domain death agonist
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000015475
Ensembl biotype	protein_coding
OMIM	601997
Entrez	637

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 24 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000317361, ENST00000342111, ENST00000399765, ENST00000399767, ENST00000473439, ENST00000494097, ENST00000550946, ENST00000551952, ENST00000552886, ENST00000614949, ENST00000622694, ENST00000890844, ENST00000890845, ENST00000890846, ENST00000890847, ENST00000890848, ENST00000890849, ENST00000890850, ENST00000890851, ENST00000890852, ENST00000890853, ENST00000890854, ENST00000890855, ENST00000890856, ENST00000931697, ENST00000931698, ENST00000951445, ENST00000951446

RefSeq mRNA: 7 — MANE Select: NM_001196 NM_001196, NM_001244567, NM_001244569, NM_001244570, NM_001244572, NM_197966, NM_197967

CCDS: CCDS13747, CCDS13748, CCDS13749

Canonical transcript exons

ENST00000622694 — 6 exons

Exon	Start	End
ENSE00001540140	17774381	17774469
ENSE00001946765	17734138	17735591
ENSE00003526724	17750105	17750174
ENSE00003542752	17738017	17738229
ENSE00003565087	17743803	17744013
ENSE00003689682	17739349	17739488

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 96.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.3738 / max 2151.9431, expressed in 1788 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193095	44.1736	1786
193096	4.5852	1631
193094	0.3449	130
193093	0.2379	83
193092	0.0322	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	96.45	gold quality
leukocyte	CL:0000738	96.14	gold quality
mononuclear cell	CL:0000842	96.11	gold quality
blood	UBERON:0000178	96.02	gold quality
granulocyte	CL:0000094	95.97	gold quality
pancreatic ductal cell	CL:0002079	93.04	gold quality
bone marrow	UBERON:0002371	92.29	gold quality
right frontal lobe	UBERON:0002810	91.43	gold quality
cortical plate	UBERON:0005343	91.17	gold quality
bone marrow cell	CL:0002092	90.87	gold quality
prefrontal cortex	UBERON:0000451	90.00	gold quality
periodontal ligament	UBERON:0008266	89.98	gold quality
mucosa of transverse colon	UBERON:0004991	89.96	gold quality
cerebellar hemisphere	UBERON:0002245	89.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.58	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.58	gold quality
cerebellar cortex	UBERON:0002129	89.56	gold quality
right lobe of liver	UBERON:0001114	89.53	gold quality
spleen	UBERON:0002106	89.31	gold quality
cingulate cortex	UBERON:0003027	89.15	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.03	gold quality
ganglionic eminence	UBERON:0004023	88.92	gold quality
caudate nucleus	UBERON:0001873	88.87	gold quality
anterior cingulate cortex	UBERON:0009835	88.86	gold quality
amygdala	UBERON:0001876	88.45	gold quality
nucleus accumbens	UBERON:0001882	88.24	gold quality
vermiform appendix	UBERON:0001154	88.11	gold quality
putamen	UBERON:0001874	87.94	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.68	gold quality
cerebellum	UBERON:0002037	87.62	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	69.58
E-MTAB-8142	yes	63.77
E-CURD-122	yes	33.82
E-HCAD-13	yes	20.58
E-MTAB-9467	yes	19.41
E-HCAD-1	yes	18.09
E-CURD-88	yes	12.67
E-CURD-112	yes	11.04
E-CURD-46	yes	9.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, ETS1, FOXO1, HIF1A, TP53, TP73, ZBTB16

miRNA regulators (miRDB)

65 targeting BID, 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-6867-5P	100.00	82.21	3464
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-4649-3P	99.56	66.90	1783

Literature-anchored findings (GeneRIF, showing 40)

• tBid-induced permeabilization of the outer membrane permits release of cytochrome c and Smac/DIABLO from all domains of intermembrane space. tBid-induced loss of DeltaPsi(m) occurs after cytochrome c release and reflects impairment of oxidative metabolism (PMID:11741882)
• Cytochrome c release upon Fas receptor activation on translocation of full-length bid (PMID:11790791)
• tBID Homooligomerizes in the mitochondrial membrane to induce apoptosis (PMID:11805084)
• calpain-mediated Bid cleavage and calpain-independent Bak modulation: two separate pathways in cisplatin-induced apoptosis (PMID:11940658)
• These data strongly suggest that in TNF-induced apoptosis, Hsp72 specifically interferes with the Bid-dependent apoptotic pathway via inhibition of JNK. (PMID:11971973)
• Cleavage of Bid is required for tyrosine and phenylalanine deficiency-induced apoptosis of human A375 melanoma cells (PMID:12061801)
• Bax oligomerization in mitochondrial membranes requires tBid (caspase-8-cleaved Bid) and a mitochondrial protein (PMID:12193163)
• Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane (PMID:12419244)
• one or more distinct cellular mechanisms regulate Bid cleavage by caspases 8 and 3 in situ. (PMID:12598529)
• identified for the first time a predominant role for the caspase-8/Bid pathway in signaling associated with hyperoxic lung injury and cell death in vivo and in vitro (PMID:12754217)
• The helix H6 of tBid controls mitochondrial binding. A 33 amino acid long domain, which encompassed H6 and H7, behaved as the minimum domain in tBid that was sufficient for mitochondrial binding. (PMID:12766488)
• BID cleavage requires caspase 8 in the course of p53-dependent apoptosis triggered by fast neutrons in lymphoid cells (PMID:12804595)
• Bid-mediated apoptosis requires Bax and Bak (PMID:12808108)
• Bid cleavage by granzyme B is prevented during blockage of CD8T cell lysis by herpes simplex virus-1 Us3 protein kinase (PMID:12934063)
• BID has a role in mediating apoptosis induced by lysosomal disruption (PMID:14581476)
• three novel endogenously expressed isoforms of Bid are distinct in their expression, their cellular localization, and their effects upon cellular apoptosis (PMID:14583606)
• H pylori may enhance Bid, Bax and Bcl-2 mRNA levels and cause deregulation of these apoptosis-associated genes expressions, which may play a role during development of gastric adenocarcinoma induced by H pylori. (PMID:14716828)
• BID is a target of PLZF repression and a candidate gene to mediate the PLZF-induced resistance to apoptosis (PMID:14769944)
• Data show that oxygen deprivation cancer cells provoked decreased mRNA and protein levels of proapoptotic Bid and Bad, and that hypoxia-inducible factor 1 (HIF-1) was dispensable for the down-regulation of Bad but required for that of Bid. (PMID:15024076)
• Bid, cleaved by an undefined aspartate-specific protease, can be a key mediator of the apoptotic response to DNA-damaging anticancer regimens (PMID:15117953)
• Data report the characterization and conformation of tBid protein in lipid membrane environments. (PMID:15123718)
• BID cleavage requires caspase 2 (PMID:15173176)
• The amphipathic helix alpha 7 of Bid inserts in membranes as part of the alpha 6-alpha 7 hairpins in a model chimeric system, showing direct potentiality for this Bid fragment to acquire a membrane inserted state. (PMID:15323553)
• a more detailed model for the reorganization of the structure of BID on membranes (PMID:15501827)
• a specific interaction between Bax Halpha1 and their BH3 domains allows Bid and PUMA to function as “death agonists” of Bax (PMID:15574335)
• Bid mediates apoptotic synergy between TRAIL and DNA damage (PMID:15615731)
• removal of N-terminal domains of Bid by caspase-8 and Mcl-1 by caspase-3 enables the maximal mitochondrial perturbation that potentiates TRAIL-induced apoptosis (PMID:15637055)
• phosphatidylethanolamine could not induce dissociation of caspase-8 cleavage product, tBid, from the amino terminal fragment, nBid (PMID:15809076)
• Cathepsin B substrate, BID, serves as molecular switch between apotosis and autophagy in camptothecin treated breast cancer cells. (PMID:16077201)
• 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)
• Data demonstrate a novel regulation of tBid by Mcl-1 through protein-protein interaction in apoptotic signaling from death receptors to mitochondria. (PMID:16380381)
• Peptide = to BH3 region of proapoptotic protein BID, bound in cleft of antiapoptotic protein BCL-w. Binding induced major conformational rearrangements in both peptide & protein components & led to displacement & unfolding of BCL-w C-terminal alpha-helix. (PMID:16475813)
• MAPK pathway inhibits TRAIL-induced apoptosis in MCF-7 cells by prohibiting anchoring of tBid to the mitochondrial membrane. (PMID:16485030)
• Acyl coenzyme A-binding protein has a role in augmenting bid-induced mitochondrial damage and cell death by activating mu-calpain (PMID:16908521)
• Bid was cleaved upon ASC activation, and suppression of endogenous Bid expression using small-interfering RNAs in type-II cells reduced the ASC-mediated apoptosis (PMID:16964285)
• tBID engages BAX to trigger its pro-apoptotic activity (PMID:16987815)
• membrane targeting of stapled BID BH3 optimizes its ability to activate BAX, supporting a model in which BID directly engages BAX to trigger mitochondrial apoptosis (PMID:17052454)
• Activator BH3-only occupation of BCL2 may prime cancer cells for death, offering a potential explanation for the marked chemosensitivity of certain cancers. (PMID:17200714)
• These findings indicate that phosphorylation of PLS3 by PKC-delta induces PLS3 activation to facilitate mitochondrial targeting of tBid and apoptosis. (PMID:17226776)
• results indicate that BH3-only proteins induce apoptosis at least primarily by engaging the multiple pro-survival relatives guarding Bax and Bak (PMID:17289999)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bid	ENSMUSG00000004446
rattus_norvegicus	Bid	ENSRNOG00000012439

Protein

Protein identifiers

BH3-interacting domain death agonist — P55957 (reviewed: P55957)

Alternative names: p22 BID

All UniProt accessions (3): P55957, A8ASI8, B2ZP79

UniProt curated annotations — full annotation on UniProt →

Function. Induces caspases and apoptosis. Counters the protective effect of BCL2. Induces caspase activation and apoptosis. Translocates to mitochondria following cleavage and disrupts the outer mitochondrial membrane leading to the release of cytochrome c. Induces ICE-like proteases and apoptosis. Induces ICE-like proteases and apoptosis. Does not induce apoptosis. Induces ICE-like proteases and apoptosis.

Subunit / interactions. Forms heterodimers either with the pro-apoptotic protein BAX or the anti-apoptotic protein BCL2. Interacts with PLEKHN1. Interacts with humanin; forms fibers with humanin which results in BID conformational changes and sequestering of BID into the fibers, preventing BID activation. Interacts with ITCH. Interacts with humanin; the interaction prevents BID-induced apoptosis. Interacts with MTCH2.

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

Tissue specificity. Expressed in spleen, pancreas and placenta (at protein level). Expressed in lung, pancreas and spleen (at protein level). Expressed in lung and pancreas (at protein level).

Post-translational modifications. TNF induces caspase-mediated cleavage into a major p15 and minor p13 and p11 products. Cleaved by CASP6 or CASP8 into a major p15 and minor p13 products, leading to release of cytochrome c. Also cleaved by GZMK to generate p15. Ubiquitinated by ITCH; ubiquitination results in proteasome-dependent degradation.

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.

Isoforms (4)

UniProt ID	Names	Canonical?
P55957-1	1, BID(L)	yes
P55957-2	2, BID(EL)
P55957-3	3, BID(S)
P55957-4	4, BID(ES)

RefSeq proteins (7): NP_001187, NP_001231496, NP_001231498, NP_001231499, NP_001231501, NP_932070, NP_932071 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010479	BID	Family
IPR020728	Bcl2_BH3_motif_CS	Conserved_site
IPR036834	Bcl-2-like_sf	Homologous_superfamily

Pfam: PF06393

UniProt features (31 total): helix 10, chain 4, splice variant 4, modified residue 3, sequence variant 3, site 3, strand 2, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
7QTW	X-RAY DIFFRACTION	1.41
5C3F	X-RAY DIFFRACTION	1.43
7M5A	X-RAY DIFFRACTION	1.5
5AJJ	X-RAY DIFFRACTION	1.75
4ZEQ	X-RAY DIFFRACTION	1.8
7M5B	X-RAY DIFFRACTION	1.85
4QVE	X-RAY DIFFRACTION	2.05
4ZII	X-RAY DIFFRACTION	2.19
4ZIG	X-RAY DIFFRACTION	2.2
4BD2	X-RAY DIFFRACTION	2.21
8SM5	X-RAY DIFFRACTION	2.61
7P33	X-RAY DIFFRACTION	2.79
1ZY3	SOLUTION NMR
2BID	SOLUTION NMR
2KBW	SOLUTION NMR
2M5B	SOLUTION NMR
2M5I	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55957-F1	63.12	0.00

Functional residue map

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

Catalytic / active sites (3): 60–61 (cleavage; by casp6); 75–76 (cleavage;by casp6); 99–100 (cleavage)

Post-translational modifications (3): 78, 1, 54

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-111447	Activation of BAD and translocation to mitochondria
R-HSA-111452	Activation and oligomerization of BAK protein
R-HSA-111453	BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
R-HSA-114294	Activation, translocation and oligomerization of BAX
R-HSA-6803204	TP53 Regulates Transcription of Genes Involved in Cytochrome C Release
R-HSA-75108	Activation, myristolyation of BID and translocation to mitochondria
R-HSA-109581	Apoptosis
R-HSA-109606	Intrinsic Pathway for Apoptosis
R-HSA-114452	Activation of BH3-only proteins
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5357801	Programmed Cell Death
R-HSA-5633008	TP53 Regulates Transcription of Cell Death Genes
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 438 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_PROTEIN_TARGETING, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, RAMJAUN_APOPTOSIS_BY_TGFB1_VIA_MAPK1_DN, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RELEASE_OF_CYTOCHROME_C_FROM_MITOCHONDRIA

GO Biological Process (32): release of cytochrome c from mitochondria (GO:0001836), obsolete protein targeting to mitochondrion (GO:0006626), extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625), apoptotic mitochondrial changes (GO:0008637), positive regulation of mitochondrial membrane potential (GO:0010918), positive regulation of protein-containing complex assembly (GO:0031334), regulation of T cell proliferation (GO:0042129), signal transduction in response to DNA damage (GO:0042770), mitochondrial ATP synthesis coupled electron transport (GO:0042775), positive regulation of apoptotic process (GO:0043065), regulation of epithelial cell proliferation (GO:0050678), neuron apoptotic process (GO:0051402), protein-containing complex assembly (GO:0065003), establishment of protein localization to membrane (GO:0090150), positive regulation of release of cytochrome c from mitochondria (GO:0090200), hepatocyte apoptotic process (GO:0097284), mitochondrial outer membrane permeabilization (GO:0097345), supramolecular fiber organization (GO:0097435), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage (GO:1902230), regulation of G1/S transition of mitotic cell cycle (GO:2000045), positive regulation of fibroblast apoptotic process (GO:2000271), positive regulation of extrinsic apoptotic signaling pathway (GO:2001238), positive regulation of intrinsic apoptotic signaling pathway (GO:2001244), apoptotic process (GO:0006915), cellular response to stress (GO:0033554), intracellular signal transduction (GO:0035556), regulation of apoptotic process (GO:0042981), extrinsic apoptotic signaling pathway (GO:0097191), regulation of mitochondrial membrane permeability involved in apoptotic process (GO:1902108), regulation of intracellular signal transduction (GO:1902531), regulation of apoptotic signaling pathway (GO:2001233), positive regulation of apoptotic signaling pathway (GO:2001235)

GO Molecular Function (4): death receptor binding (GO:0005123), ubiquitin protein ligase binding (GO:0031625), cysteine-type endopeptidase regulator activity involved in apoptotic process (GO:0043028), protein binding (GO:0005515)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), membrane (GO:0016020), cytoplasm (GO:0005737), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Intrinsic Pathway for Apoptosis	5
Activation of BH3-only proteins	1
TP53 Regulates Transcription of Cell Death Genes	1
Programmed Cell Death	1
Apoptosis	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	3
cellular anatomical structure	3
apoptotic signaling pathway	2
mitochondrion	2
cytoplasm	2
apoptotic mitochondrial changes	1
extrinsic apoptotic signaling pathway	1
mitochondrion organization	1
positive regulation of membrane potential	1
regulation of mitochondrial membrane potential	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
T cell proliferation	1
regulation of lymphocyte proliferation	1
regulation of T cell activation	1
DNA damage response	1
intracellular signal transduction	1
ATP synthesis coupled electron transport	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
regulation of cell population proliferation	1
epithelial cell proliferation	1
cellular component assembly	1
protein-containing complex organization	1
establishment of protein localization	1
localization within membrane	1
release of cytochrome c from mitochondria	1
positive regulation of organelle organization	1
regulation of release of cytochrome c from mitochondria	1
epithelial cell apoptotic process	1
positive regulation of mitochondrial membrane permeability involved in apoptotic process	1
cellular component organization	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
regulation of intrinsic apoptotic signaling pathway in response to DNA damage	1
negative regulation of intrinsic apoptotic signaling pathway	1
G1/S transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G1/S phase transition	1

Protein interactions and networks

STRING

750 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BID	BCL2	P10415	921
BID	BAX	P55269	914
BID	CASP8	Q14790	817
BID	BCL2L11	O43521	737
BID	DIABLO	Q9NR28	725
BID	MCL1	Q07820	724
BID	MTCH2	Q9Y6C9	710
BID	CYCS	P00001	685
BID	NOD2	Q9HC29	680
BID	BAD	Q92934	678
BID	BAK1	Q16611	656
BID	ATP6V1E1	P36543	649
BID	CFLAR	O15519	646
BID	CASP9	P55211	644
BID	BBC3	Q96PG8	627

IntAct

90 interactions, top by confidence:

A	B	Type	Score
BCL2L1	TP53	psi-mi:“MI:0915”(physical association)	0.880
BID	BCL2	psi-mi:“MI:0407”(direct interaction)	0.870
BCL2	BID	psi-mi:“MI:0915”(physical association)	0.870
BID	BCL2	psi-mi:“MI:0915”(physical association)	0.870
BID	BCL2	psi-mi:“MI:0914”(association)	0.870
BCL2L1	BCL2L11	psi-mi:“MI:0914”(association)	0.870
BCL2L1	BID	psi-mi:“MI:0407”(direct interaction)	0.860
BID	BCL2L1	psi-mi:“MI:0407”(direct interaction)	0.860
BAX	BID	psi-mi:“MI:0915”(physical association)	0.820
BAX	BID	psi-mi:“MI:0407”(direct interaction)	0.820
BID	BAX	psi-mi:“MI:0915”(physical association)	0.820
BAX	BID	psi-mi:“MI:2364”(proximity)	0.820
BID	BAX	psi-mi:“MI:0407”(direct interaction)	0.820
BCL2L2	BID	psi-mi:“MI:0407”(direct interaction)	0.810
BID	BCL2L2	psi-mi:“MI:0407”(direct interaction)	0.810
BID	BAK1	psi-mi:“MI:0407”(direct interaction)	0.760
BAK1	BID	psi-mi:“MI:0407”(direct interaction)	0.760
BID	BAK1	psi-mi:“MI:0915”(physical association)	0.760
BCL2L1	BID	psi-mi:“MI:0407”(direct interaction)	0.750
BID	BCL2L1	psi-mi:“MI:2364”(proximity)	0.750

BioGRID (194): BID (Protein-peptide), BCL2 (Reconstituted Complex), BID (Affinity Capture-Western), BID (Affinity Capture-Western), BID (Co-fractionation), REL (Two-hybrid), AHCYL1 (Two-hybrid), BID (Affinity Capture-RNA), BID (Affinity Capture-RNA), BAK1 (Protein-peptide), BID (Protein-peptide), BID (Protein-peptide), BID (Protein-peptide), BID (Protein-peptide), BID (Protein-peptide)

ESM2 similar proteins: A0JMW6, A1L1L2, A1L2I9, A1L3G9, A4FV45, A7Z033, E7FE40, F1QB30, O02703, O08734, O77737, P53563, P55957, P70345, P70444, Q07812, Q07813, Q07816, Q07817, Q0II48, Q16611, Q1M161, Q1RMX3, Q45T69, Q568Z0, Q5BLE2, Q5EAU9, Q63690, Q64373, Q6DC66, Q6GR21, Q6NRB7, Q7T381, Q8BK03, Q8BM55, Q8BXV2, Q8JGM8, Q8K1H7, Q8N4U5, Q8WY22

Diamond homologs: P55957, P70444, Q4JHS0, Q8JGM8, Q9JLT6

SIGNOR signaling

32 interactions.

A	Effect	B	Mechanism
BID	up-regulates	BAK1	binding
BID	up-regulates	BAX	binding
MTCH2	up-regulates	BID	relocalization
MTCH2	up-regulates	BID	binding
“ER stress”	up-regulates	BID
BID	“down-regulates activity”	BCL2L1	binding
CSNK1A1	“up-regulates activity”	BID	phosphorylation
CSNK1E	“up-regulates activity”	BID	phosphorylation
CSNK2A1	“up-regulates activity”	BID	phosphorylation
CSNK2A2	“up-regulates activity”	BID	phosphorylation
CSNK2B	“up-regulates activity”	BID	phosphorylation
“Caspase 8 complex”	“up-regulates activity”	BID	cleavage
“Caspase-2 PIDDosome”	“up-regulates activity”	BID	cleavage
“HIF-1 complex”	“down-regulates quantity by repression”	BID	“transcriptional regulation”
ITCH	“down-regulates quantity by destabilization”	BID	ubiquitination
hsa-miR-491-5p	“up-regulates quantity by expression”	BID	“post transcriptional regulation”
MAPK8	“up-regulates activity”	BID	phosphorylation
MAPK9	“up-regulates activity”	BID	phosphorylation
ATM	“down-regulates activity”	BID	phosphorylation
BID	“up-regulates activity”	CYCS
CASP8	“up-regulates activity”	BID	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 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	7	55.4×	2e-08
Apoptosis	7	31.8×	5e-07
Programmed Cell Death	7	27.7×	1e-06
Interleukin-4 and Interleukin-13 signaling	5	13.9×	1e-03
Cytokine Signaling in Immune system	7	7.7×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
release of cytochrome c from mitochondria	8	117.0×	6e-13
motor neuron apoptotic process	5	117.0×	7e-08
negative regulation of anoikis	5	92.4×	2e-07
extrinsic apoptotic signaling pathway in absence of ligand	9	87.8×	4e-13
B cell homeostasis	5	58.5×	2e-06
regulation of mitochondrial membrane potential	5	56.6×	2e-06
intrinsic apoptotic signaling pathway in response to DNA damage	8	54.0×	3e-10
positive regulation of intrinsic apoptotic signaling pathway	5	50.1×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1226 predictions. Top by Δscore:

Variant	Effect	Δscore
22:17735590:CCCT:C	acceptor_loss	1.0000
22:17738015:A:AC	donor_gain	1.0000
22:17738016:C:CC	donor_gain	1.0000
22:17738016:CATTT:C	donor_gain	1.0000
22:17738227:GTCC:G	acceptor_loss	1.0000
22:17738228:TCC:T	acceptor_loss	1.0000
22:17738229:CCT:C	acceptor_loss	1.0000
22:17738230:C:CA	acceptor_loss	1.0000
22:17738231:T:G	acceptor_loss	1.0000
22:17739346:CA:C	donor_loss	1.0000
22:17739347:A:AC	donor_gain	1.0000
22:17739347:ACCT:A	donor_gain	1.0000
22:17739348:C:CC	donor_gain	1.0000
22:17739348:CCT:C	donor_gain	1.0000
22:17739348:CCTC:C	donor_gain	1.0000
22:17739485:GAAT:G	acceptor_gain	1.0000
22:17739488:TC:T	acceptor_loss	1.0000
22:17739489:C:CC	acceptor_gain	1.0000
22:17739496:C:CT	acceptor_gain	1.0000
22:17739497:A:T	acceptor_gain	1.0000
22:17739500:C:CT	acceptor_gain	1.0000
22:17739501:A:T	acceptor_gain	1.0000
22:17739506:C:CT	acceptor_gain	1.0000
22:17739507:G:T	acceptor_gain	1.0000
22:17734809:A:C	acceptor_gain	0.9900
22:17735588:TCCC:T	acceptor_gain	0.9900
22:17735589:CCC:C	acceptor_gain	0.9900
22:17735589:CCCC:C	acceptor_gain	0.9900
22:17735590:CC:C	acceptor_gain	0.9900
22:17735590:CCC:C	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000025988 (22:17765441 T>A,C), RS1000051641 (22:17755792 T>C), RS1000105028 (22:17771021 T>C), RS1000108780 (22:17749653 TA>T), RS1000210491 (22:17738882 T>C), RS1000218164 (22:17744357 G>A), RS1000226247 (22:17747567 C>G), RS1000357876 (22:17754616 C>T), RS1000449662 (22:17744131 C>A), RS1000450741 (22:17752712 C>G), RS1000454177 (22:17769402 G>A), RS1000580281 (22:17763676 G>A), RS1000613175 (22:17753054 C>T), RS1000955679 (22:17738656 C>G,T), RS1000972825 (22:17769539 A>AGC)

Disease associations

OMIM: gene MIM:601997 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002875_64	Diisocyanate-induced asthma	1.000000e-06
GCST010988_512	Adult body size	2.000000e-08
GCST90002400_498	Plateletcrit	3.000000e-11
GCST90002402_638	Platelet count	1.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0007985	platelet crit
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL1250414 (SINGLE PROTEIN), CHEMBL3430886 (PROTEIN-PROTEIN INTERACTION), CHEMBL3883285 (PROTEIN-PROTEIN INTERACTION), CHEMBL5169265 (PROTEIN-PROTEIN INTERACTION), CHEMBL5169268 (PROTEIN-PROTEIN INTERACTION), CHEMBL5169271 (PROTEIN-PROTEIN INTERACTION), CHEMBL5169272 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 50,454 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3137309	VENETOCLAX	4	9,389
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL51483	GOSSYPOL	3	13,973
CHEMBL376408	ABT 737	1	4,288

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

ChEMBL bioactivities

154 potent at pChembl≥5 of 168 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.41	IC50	3.9	nM	CHEMBL6147022
8.38	IC50	4.2	nM	CHEMBL6102509
8.35	IC50	4.5	nM	CHEMBL6146278
8.30	IC50	5	nM	CHEMBL6142882
8.27	IC50	5.4	nM	CHEMBL6091960
8.07	IC50	8.5	nM	CHEMBL6143694
8.07	IC50	8.5	nM	CHEMBL6102150
8.04	Kd	9.119	nM	CHEMBL5653589
8.04	ED50	9.119	nM	CHEMBL5653589
8.00	IC50	10	nM	CHEMBL6102006
7.96	IC50	11	nM	CHEMBL6083140
7.85	IC50	14	nM	CHEMBL6145269
7.77	IC50	17	nM	CHEMBL6120357
7.75	IC50	18	nM	CHEMBL6146521
7.72	IC50	19	nM	CHEMBL6108907
7.62	IC50	24	nM	CHEMBL6147348
7.60	IC50	25	nM	CHEMBL1272170
7.54	IC50	29	nM	CHEMBL6141601
7.51	IC50	31	nM	CHEMBL6145093
7.51	IC50	31	nM	CHEMBL6078737
7.48	IC50	33	nM	CHEMBL6133524
7.48	IC50	33	nM	CHEMBL6102527
7.40	IC50	40	nM	CHEMBL6102754
7.37	IC50	43	nM	CHEMBL6145783
7.32	IC50	48	nM	CHEMBL6103426
7.31	IC50	48.5	nM	ABT 737
7.30	IC50	50	nM	CHEMBL6120370
7.24	Ki	58	nM	CHEMBL4848284
7.13	IC50	74	nM	CHEMBL6102979
7.12	IC50	75	nM	CHEMBL6141873
7.11	IC50	77	nM	CHEMBL6133700
7.08	IC50	83	nM	CHEMBL5613621
7.06	IC50	87	nM	CHEMBL6132659
7.05	IC50	90	nM	CHEMBL6087337
6.98	Ki	105	nM	CHEMBL5523629
6.97	Ki	106	nM	CHEMBL5198484
6.96	Ki	110	nM	CHEMBL5549784
6.91	Ki	124	nM	CHEMBL5558580
6.90	Ki	127	nM	CHEMBL5558391
6.85	Ki	140	nM	CHEMBL5532559
6.84	Ki	145	nM	CHEMBL5518045
6.80	Ki	158	nM	CHEMBL5559447
6.75	Ki	178	nM	CHEMBL5558174
6.70	Ki	200	nM	GINKGOLIC ACID 13:0
6.70	Ki	200	nM	CHEMBL4589399
6.66	Ki	218	nM	CHEMBL5557494
6.62	IC50	240	nM	CHEMBL6096613
6.60	Ki	251	nM	CHEMBL5542437
6.59	Ki	256	nM	CHEMBL5517949
6.54	Ki	290	nM	CHEMBL5204188

PubChem BioAssay actives

119 with measured affinity, of 184 total; 50 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
(2R)-2-[5-[3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy-3-[2-[[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy]phenyl]propanoic acid	2066216: Inhibition of MCL-1 (unknown origin)/FAM-BID (unknown origin) interaction measured by fluorescence polarization assay	ki	0.0001	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147947: Binding affinity to human BID incubated for 45 mins by Kinobead based pull down assay	kd	0.0091	uM
3-methyl-5-propan-2-yl-2-(1,4,6,7-tetrahydroxy-3-methyl-5-propan-2-ylnaphthalen-2-yl)naphthalene-1,4,6,7-tetrone	1858754: Inhibition of Mcl-1/Bid (unknown origin) by fluorescence polarization assay	ic50	0.0250	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide	515599: Inhibition of GST-tagged Bcl-xl/FITC-conjugated Bid interaction by fluorescence polarisation assay	ic50	0.0485	uM
3-oxo-7-thiomorpholin-4-ylphenalene-1,2-dicarbonitrile	1858752: Binding affinity to Mcl-1/Bid (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.0580	uM
4-[4-[[1-(4-chloro-2-ethylphenyl)-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.1050	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	1858752: Binding affinity to Mcl-1/Bid (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.1060	uM
4-[4-[[1-(4-chloro-2-ethylphenyl)-6-[ethyl(prop-2-enoyl)amino]-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.1100	uM
4-[4-[[1-(4-chloro-2-ethylphenyl)-6-[prop-2-enoyl(propyl)amino]-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.1240	uM
4-[4-[[1-(4-chlorophenyl)-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.1270	uM
4-[4-[[1-(4-chloro-2-ethylphenyl)-6-[propan-2-yl(prop-2-enoyl)amino]-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.1400	uM
4-[4-[[1-(4-chlorophenyl)-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]-2-(1-methylpyrrolo[2,3-b]pyridin-5-yl)oxybenzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.1450	uM
4-[4-[[1-(4-chloro-2-ethylphenyl)-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.1580	uM
4-[4-[[1-(4-chlorophenyl)-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]-2-phenylbenzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.1780	uM
2-hydroxy-6-[(Z)-tridec-8-enyl]benzoic acid	1635029: Inhibition of His-tagged Mcl-1/5-carboxyfluorescein-Bid (unknown origin) after 1 hr by fluorescence polarization assay	ki	0.2000	uM
2-hydroxy-6-tridecylbenzoic acid	1635029: Inhibition of His-tagged Mcl-1/5-carboxyfluorescein-Bid (unknown origin) after 1 hr by fluorescence polarization assay	ki	0.2000	uM
4-[4-[[1-(4-chloro-2-ethylphenyl)-6-[methyl(prop-2-enoyl)amino]-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.2180	uM
4-[4-[[1-(4-chloro-2-methylphenyl)-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.2510	uM
4-[4-[[1-(2,4-dichlorophenyl)-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.2560	uM
ethyl (2Z,5R)-5-(3-acetylphenyl)-2-[(1-benzylindol-3-yl)methylidene]-3-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate	1858752: Binding affinity to Mcl-1/Bid (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.2900	uM
methyl (2Z,5S)-5-(4-acetylphenyl)-2-[(1-benzylindol-3-yl)methylidene]-3-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate	1858752: Binding affinity to Mcl-1/Bid (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.3200	uM
4-[4-[[1-(4-chlorophenyl)-6-[[methyl(prop-2-enoyl)amino]methyl]-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.3260	uM
1-[3,5-bis(trifluoromethyl)phenyl]-3-[2-[[3-[2-(3,4-dihydroxyphenoxy)phenyl]thiophen-2-yl]sulfonylamino]ethyl]urea	1858827: Binding affinity to Mcl-1/Bid (unknown origin) by fluorescence polarization assay	ki	0.3300	uM
4-[4-[[1-(4-chlorophenyl)-6-[[ethyl(prop-2-enoyl)amino]methyl]-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.3350	uM
(2Z,5R)-2-[(1-benzylindol-3-yl)methylidene]-3-oxo-N,5-diphenyl-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxamide	1858752: Binding affinity to Mcl-1/Bid (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.3600	uM
[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	1858784: Inhibition of Bcl-B/Bid (unknown origin)	ic50	0.3600	uM
4-[4-[[1-(4-chloro-2-fluorophenyl)-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.3610	uM
4-[4-[[1-(4-chlorophenyl)-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]-2-pyridin-4-ylbenzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.3700	uM
4-[4-[[1-(4-chlorophenyl)-6-[methyl(prop-2-enoyl)amino]-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.3730	uM
3-chloro-1-(3,4-dichlorophenyl)-4-(4-methylpiperazin-1-yl)pyrrole-2,5-dione	2066207: Inhibition of BFL-1 (unknown origin)/FITC-conjugated Bid BH3 peptide (unknown origin) interaction by fluorescence polarization assay	ic50	0.4000	uM
4-[4-[[1-(2-chlorophenyl)-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.4090	uM
methyl (2Z,5R)-5-(4-acetylphenyl)-2-[(1-benzylindol-3-yl)methylidene]-3-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate	1858752: Binding affinity to Mcl-1/Bid (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.4200	uM
(NE)-4-methyl-N-[4-oxo-3-(1H-1,2,4-triazol-5-ylsulfanyl)naphthalen-1-ylidene]benzenesulfonamide	1858838: Inhibition of Mcl-1/FITC-labelled Bid (unknown origin) protein protein interaction incubated for 20 to 60 mins by fluorescence polarisation binding assay	ic50	0.4500	uM
1-[4-[2-benzyl-6-(3-fluorophenyl)indazol-3-yl]piperazin-1-yl]prop-2-en-1-one	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.4650	uM
1-[4-[(3-chlorophenyl)methoxy]phenyl]sulfonylindole-2-carboxylic acid	1858808: Binding affinity to Mcl-1/FAM-labelled Bid (unknown origin) incubated for 1 min by fluorescence polarization assay	ki	0.4800	uM
2-[4-[(3-bromophenyl)sulfonylamino]-1-hydroxynaphthalen-2-yl]sulfanylacetic acid	1858752: Binding affinity to Mcl-1/Bid (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.4900	uM
4-[4-[[1-(4-chlorophenyl)-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.5250	uM
6,10-dichloro-5-(2-nitrophenyl)sulfanyl-1-azapentacyclo[10.6.1.03,7.08,19.013,17]nonadeca-8,10,12(19),14-tetraene-2-carboxylic acid	1858827: Binding affinity to Mcl-1/Bid (unknown origin) by fluorescence polarization assay	ki	0.5300	uM
ethyl (2Z,5S)-5-(3-acetylphenyl)-2-[(1-benzylindol-3-yl)methylidene]-3-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate	1858807: Binding affinity to Bcl-2 /Bid (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.5900	uM
2-[[4-[(4-tert-butylphenyl)methyl]piperazin-1-yl]sulfonylamino]-5-(2-phenylethylsulfanyl)benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.6450	uM
2-hydroxy-6-undecylbenzoic acid	1635029: Inhibition of His-tagged Mcl-1/5-carboxyfluorescein-Bid (unknown origin) after 1 hr by fluorescence polarization assay	ki	0.7000	uM
4-[4-[[1-(3-methoxyphenyl)-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.7230	uM
4-[4-[[1-(4-chlorophenyl)-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]-2-[3-(dimethylamino)propyl-methylamino]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.7740	uM
4-[4-[[1-phenyl-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.7810	uM
(2Z,5S)-2-[(1-benzylindol-3-yl)methylidene]-3-oxo-N,5-diphenyl-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxamide	1858807: Binding affinity to Bcl-2 /Bid (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	0.8100	uM
4-[4-[[1-(4-chlorophenyl)-6-[(prop-2-enoylamino)methyl]-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.9130	uM
4-[4-[[1-(4-chloro-2-ethylphenyl)-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.9490	uM
4-[4-[[1-(4-chloro-2-methoxyphenyl)-6-(prop-2-enoylamino)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.9590	uM
4-[4-[[6-[(2-chloroacetyl)amino]-1-(4-chlorophenyl)-3,4-dihydronaphthalen-2-yl]methyl]piperazin-1-yl]benzoic acid	2066213: Inhibition of BFL-1 (unknown origin)/ fluorescein-tagged Bid BH3 peptide (79 to 99) (unknown origin) interaction measured after 24 hrs incubation by fluorescence polarization assay	ki	0.9970	uM
(2Z)-5-(4-fluorophenyl)-2-[[1-[(2-fluorophenyl)methyl]indol-3-yl]methylidene]-3-oxo-N-phenyl-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxamide	1858805: Binding affinity to human N-terminal 8xHis tagged Mcl-1/5-FAM-tagged Bid (unknown origin) assessed as inhibition constant by fluorescence polarization assay	ki	1.0500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	affects cleavage, affects cotreatment, increases expression, decreases expression, increases cleavage (+3 more)	20
Cisplatin	decreases expression, decreases reaction, increases expression, affects expression, increases cleavage (+2 more)	11
Resveratrol	decreases expression, increases activity, increases localization, affects cotreatment, increases expression (+1 more)	10
Vorinostat	decreases reaction, increases cleavage, increases reaction, increases expression, affects cotreatment (+1 more)	10
Plant Extracts	decreases reaction, increases activity, increases cleavage, affects cotreatment, increases expression (+1 more)	8
Quercetin	affects cotreatment, increases cleavage, decreases expression, increases reaction, increases expression	8
Valproic Acid	increases cleavage, decreases expression, increases expression, affects expression, affects cotreatment	8
Bortezomib	affects cotreatment, decreases expression, increases cleavage, increases reaction, increases activity (+1 more)	7
Acetylcysteine	decreases expression, decreases abundance, decreases reaction, increases cleavage, affects cotreatment	7
Doxorubicin	increases localization, increases reaction, decreases reaction, increases activity, increases cleavage (+4 more)	7
alvocidib	increases cleavage, decreases expression, decreases reaction, increases activity, affects cotreatment	5
Genistein	affects binding, decreases expression, affects cotreatment, increases cleavage, increases activity (+1 more)	5
sodium arsenite	decreases expression, increases response to substance, affects cotreatment, increases abundance, increases expression	4
Fluorouracil	increases reaction, decreases reaction, increases response to substance, decreases response to substance, affects cotreatment (+3 more)	4
Paraquat	affects cotreatment, increases expression, decreases expression, increases cleavage	4
Particulate Matter	decreases reaction, increases expression, decreases expression	4
trichostatin A	increases expression, affects expression, affects localization, increases reaction	3
benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone	decreases reaction, increases cleavage, increases activity	3
Celecoxib	increases cleavage, increases reaction, affects cotreatment	3
Arsenic	increases abundance, affects expression, increases expression, affects cotreatment	3
Benzo(a)pyrene	increases expression, decreases reaction, decreases expression	3
Cadmium	decreases reaction, increases cleavage, affects cotreatment, decreases expression, increases abundance (+1 more)	3
Copper	increases cleavage, decreases expression, affects binding, increases expression, affects cotreatment	3
Estradiol	affects cotreatment, decreases expression, decreases reaction, increases expression	3
Tretinoin	decreases expression, affects cotreatment, increases cleavage	3
Reactive Oxygen Species	decreases abundance, increases cleavage, increases abundance, increases expression, decreases reaction (+5 more)	3
Cadmium Chloride	decreases expression, affects cotreatment, increases abundance, increases expression	3
bisphenol A	decreases expression, decreases methylation, increases expression	2
lonidamine	affects cotreatment, increases activity, increases cleavage	2
sulforaphane	affects cotreatment, increases cleavage, increases expression	2

ChEMBL screening assays

44 unique, capped per target: 44 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4477674	Binding	Binding affinity to Bid (unknown origin) assessed as micelles formation at 0.25 to 5 equivalent by 1H NMR spectra analysis	Anacardic Acids from Knema hookeriana as Modulators of Bcl-xL/Bak and Mcl-1/Bid Interactions. — J Nat Prod

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1GH	Abcam SW480 BID KO	Cancer cell line	Male
CVCL_KT40	HeLa SilenciX BID	Cancer cell line	Female

Clinical trials (associated diseases)

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