BAD

Summary

BAD (BCL2 associated agonist of cell death, HGNC:936) is a protein-coding gene on chromosome 11q13.1, encoding Bcl2-associated agonist of cell death (Q92934). Promotes cell death.

The protein encoded by this gene is a member of the BCL-2 family. BCL-2 family members are known to be regulators of programmed cell death. This protein positively regulates cell apoptosis by forming heterodimers with BCL-xL (B-cell lymphoma-extra large) and BCL-2, and reversing their death repressor activity. Proapoptotic activity of this protein is regulated through its phosphorylation. Protein kinases AKT and MAP kinase, as well as protein phosphatase calcineurin were found to be involved in the regulation of this protein. Alternative splicing of this gene results in two transcript variants which encode the same isoform.

Source: NCBI Gene 572 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 34 total — 1 pathogenic
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_032989

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:936
Approved symbol	BAD
Name	BCL2 associated agonist of cell death
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	BCL2L8, BBC2
Ensembl gene	ENSG00000002330
Ensembl biotype	protein_coding
OMIM	603167
Entrez	572

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 17 protein_coding, 1 retained_intron

ENST00000309032, ENST00000394531, ENST00000394532, ENST00000492141, ENST00000493798, ENST00000544271, ENST00000544785, ENST00000853722, ENST00000853723, ENST00000853724, ENST00000853725, ENST00000853726, ENST00000853727, ENST00000853728, ENST00000853729, ENST00000853730, ENST00000954633, ENST00000954634

RefSeq mRNA: 2 — MANE Select: NM_032989 NM_004322, NM_032989

CCDS: CCDS8065

Canonical transcript exons

ENST00000309032 — 4 exons

Exon	Start	End
ENSE00001518739	64284631	64284665
ENSE00001699918	64269830	64270337
ENSE00003483111	64271613	64271803
ENSE00003585519	64284182	64284376

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 97.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.1233 / max 96.6072, expressed in 1804 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120379	15.5323	1804
120378	0.3208	163
120382	0.1515	45
120380	0.0951	29
120381	0.0235	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	97.21	gold quality
right frontal lobe	UBERON:0002810	97.12	gold quality
right atrium auricular region	UBERON:0006631	96.87	gold quality
lower esophagus mucosa	UBERON:0035834	96.75	gold quality
apex of heart	UBERON:0002098	96.58	gold quality
body of stomach	UBERON:0001161	96.34	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.29	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.28	gold quality
lower esophagus	UBERON:0013473	96.15	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.15	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.09	gold quality
right coronary artery	UBERON:0001625	96.01	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.81	gold quality
left coronary artery	UBERON:0001626	95.72	gold quality
left adrenal gland cortex	UBERON:0035825	95.70	gold quality
left lobe of thyroid gland	UBERON:0001120	95.45	gold quality
right uterine tube	UBERON:0001302	95.42	gold quality
left adrenal gland	UBERON:0001234	95.39	gold quality
ascending aorta	UBERON:0001496	95.31	gold quality
right adrenal gland	UBERON:0001233	95.30	gold quality
right adrenal gland cortex	UBERON:0035827	95.28	gold quality
right lobe of thyroid gland	UBERON:0001119	95.27	gold quality
thoracic aorta	UBERON:0001515	95.26	gold quality
transverse colon	UBERON:0001157	95.25	gold quality
metanephros cortex	UBERON:0010533	95.04	gold quality
left uterine tube	UBERON:0001303	95.02	gold quality
popliteal artery	UBERON:0002250	94.97	gold quality
tibial artery	UBERON:0007610	94.97	gold quality
aorta	UBERON:0000947	94.93	gold quality
prefrontal cortex	UBERON:0000451	94.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.23
E-GEOD-36552	no	64.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, HMOX1, MITF, MLLT11, NFKB, NR3C1, PAX1, PPARG, RELA, STAT3, TP53, VSX2

miRNA regulators (miRDB)

7 targeting BAD, 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-302C-5P	99.97	72.56	3642
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-1292-5P	96.74	62.14	238
HSA-MIR-6084	89.09	62.33	58

Literature-anchored findings (GeneRIF, showing 40)

• expression in normal, hyperplastic and carcinomatous human prostate (PMID:11781193)
• Protein kinase A RIalpha antisense inhibition of PC3M prostate cancer cell growth: Bcl-2 hyperphosphorylation, Bax up-regulation, and Bad-hypophosphorylation (PMID:11839683)
• results suggest that direct interaction of Bad with pro-survival members of the Bcl-2 family contributes to the progress of Sindbis virus-induced apoptosis (PMID:11878929)
• Na-butyrate and trichostatin A increased the expression of the Bad protein. The results suggest that HDAC inhibitors such as SB and TSA induce apoptosis through an increase in Bad protein in human glioma cells in vitro. (PMID:11908866)
• BAD cleavage and apoptosis in tumor cells in response to raloxifene (PMID:12084714)
• effects of paclitaxel on BAD phosphorylation in ovarian cancer cells (PMID:12087097)
• role of PI3-kinase-dependent phosphorylation and altered transcription in cytokine-mediated neutrophil survival (PMID:12239175)
• study suggests that the cleavage of 14-3-3 protein during apoptosis promotes cell death by releasing the associated Bad protein from the 14-3-3 protein and facilitates Bad translocation to the mitochondria and its interaction with Bcl-x(L) (PMID:12657644)
• BAD-mediated sensitivity of prosstatic cancer cells to TRAIL depends on the phosphorylation status of BAD WT and tBAD. (PMID:12754297)
• BAD is a substrate for pim-2 oncogene proto-oncogene (PMID:12954615)
• Mutation of BAD within the BH3 domain modulates its apoptotic function. (PMID:12965220)
• Bad is increased in quercetin-treated nasopharyngeal carcinoma cells (PMID:14767529)
• Bad gene is occasionally mutated in colon cancer (PMID:15033904)
• constitutively active Rac1 is shown to stimulate the phosphorylation of Bad, thereby suppressing drug-induced caspase activation and apoptosis in human lymphoma cells; Rac1 activation leads to Bad phosphorylation specifically at serine-75 (PMID:15226424)
• mechanisms that regulate the conversion of BAD from an anti-death to a pro-death factor include alternative splicing that produces N-terminally truncated BAD(S)and conversion by caspases into a pro-death fragment that resembles the short splice variant (PMID:15231831)
• degraded during Chlamydia trachomatis infection (PMID:15731037)
• A recombinant fusion protein linking human granulocyte-macrophage colony-stimulating factor to the N-terminus of the proapoptotic protein BAD delivers BAD into tumor cells, where it restores the apoptotic pathway. (PMID:15751984)
• AR and IGF1 cooperate to prevent apoptosis by activating a specific PKC-p90(rsk)-dependent pathway, which leads to Bad and Bax inactivation. (PMID:15767261)
• Pak1-dependent Raf-1 phosphorylation regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association (PMID:15849194)
• BAD induces apoptosis upon detecting the coincidence of G2/M phase and growth factor deprivation (PMID:15901741)
• Bax, Bad, and Bim are upregulated, while Bcl-2 is downregulated in human neuroblastoma cells treated with propargylamine (PMID:16148027)
• Bcl-xL mRNA overexpression may suggest poor prognosis in NSCLC. (PMID:16297499)
• There was no somatic mutation of BH3 domains of Bad, Bmf and Bcl-G genes in transitional cell carcinoma samples. The data presented here indicate that BH3 domain mutation of these genes is rare in TCCs and may not contribute to the pathogenesis of TCCs. (PMID:16484005)
• the interaction of BAD with membranes is tied to binding of 14-3-3 protein and activation and membrane translocation of Bcl-XL (PMID:16603546)
• Sequestration of BAD away from mitochondria provides C. trachomatis with mechanism to protect host cell from apoptosis via interaction of a C. trachomatis-encoded inclusion protein with host-cell phosphoserine-binding protein. (BAD protein) (PMID:16710454)
• antiapoptotic signaling pathways activated by vasoactive intestinal polypeptide, epidermal growth factor, and phosphatidylinositol 3-kinase in prostate cancer cells converge on BAD (PMID:16728406)
• Phosphorylation of BAD or inhibition of its translocation to the mitochondria are critical survival pathways in LNCaP tumor cells. (PMID:16767165)
• Cytogenetic investigation of a nodal diffuse large B cell lymphoma carrying an IGH-BCL2-fusion revealed a homogeneously staining region at chromosome 1p21-22. (PMID:16785131)
• doxorubicin-stimulated phosphorylation of Bad in cells expressing dominant negative p38 MAPK was impeded by the inhibition of PI3-kinase (PMID:16843435)
• EGF protects prostate cancer cells from apoptosis by inducing BAD phosphorylation via redundant signaling pathways (PMID:16847055)
• Bad translocation to mitochondria plays a critical role in Tetrahydrocannabinol-induced apoptosis in Jurkat cells. (PMID:16908594)
• AKT-induced BAD phosphorylation and its subsequent cytoplasmic sequestration by 14-3-3zeta is a major mechanism responsible for the postponement of UVB-induced apoptosis in human keratinocytes. (PMID:16932738)
• The high expression of bad in Hodgkin and Reed-Sternberg cells in most classical Hodgkin’s lymphomas (HLs)indicates that this protein may play predominant role in the regulation of apoptosis in classical HLs. (PMID:16949642)
• Mycobacterium leprae inhibits apoptosis in THP-1 cells by downregulation of Bad and Bak and upregulation of Mcl-1 gene expression. (PMID:16978419)
• Raf-1 and B-Raf promote protein kinase C theta interaction with BAD. (PMID:17011751)
• dissociation of Bad from Bcl-xL and an increase in the intracellular level of Bcl-xL are responsible for development of acquired TRAIL resistance (PMID:17110373)
• Akt/Bad pathway generates a progressive resistance to apoptosis, at a time HTLV-I genes expression is silenced. (PMID:17287851)
• Expression of p-BAD was increased in the colorectal cancer cells and may possibly alter the cell death regulation during colorectal tumorigenesis. (PMID:17393317)
• p53 can form a complex with dephosphorylated Bad thereby converting it to a pro-apoptotic player. (PMID:17404594)
• GATA1 and GFI1B interplay to regulate bcl-X protein transcription. (PMID:17420275)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bad	ENSMUSG00000024959
rattus_norvegicus	Bad	ENSRNOG00000021147
drosophila_melanogaster	CG15530	FBGN0039752

Protein

Protein identifiers

Bcl2-associated agonist of cell death — Q92934 (reviewed: Q92934)

Alternative names: Bcl-2-binding component 6, Bcl-2-like protein 8, Bcl-xL/Bcl-2-associated death promoter, Bcl2 antagonist of cell death

All UniProt accessions (5): Q92934, A8MXU7, F5GYS3, F5H1R6, F5H3B1

UniProt curated annotations — full annotation on UniProt →

Function. Promotes cell death. Successfully competes for the binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of heterodimerization of these proteins with BAX. Can reverse the death repressor activity of Bcl-X(L), but not that of Bcl-2. Appears to act as a link between growth factor receptor signaling and the apoptotic pathways.

Subunit / interactions. Forms heterodimers with the anti-apoptotic proteins, Bcl-X(L), Bcl-2 and Bcl-W. Also binds protein S100A10. The Ser-75/Ser-99 phosphorylated form binds 14-3-3 proteins. Interacts with AKT1 and PIM3. Interacts (via BH3 domain) with NOL3 (via CARD domain); preventing the association of BAD with BCL2. Interacts with HIF3A (via C-terminus domain); the interaction reduces the binding between BAD and BAX. Interacts with GIMAP3/IAN4 and GIMAP5/IAN5.

Subcellular location. Mitochondrion outer membrane. Cytoplasm.

Tissue specificity. Expressed in a wide variety of tissues.

Post-translational modifications. Phosphorylated on one or more of Ser-75, Ser-99, Ser-118 and Ser-134 in response to survival stimuli, which blocks its pro-apoptotic activity. Phosphorylation on Ser-99 or Ser-75 promotes heterodimerization with 14-3-3 proteins. This interaction then facilitates the phosphorylation at Ser-118, a site within the BH3 motif, leading to the release of Bcl-X(L) and the promotion of cell survival. Ser-99 is the major site of AKT/PKB phosphorylation, Ser-118 the major site of protein kinase A (CAPK) phosphorylation. Phosphorylation at Ser-99 by PKB/AKT1 is almost completely blocked by the apoptotic C-terminus cleavage product of PKN2 generated by caspases-3 activity during apoptosis. Methylation at Arg-94 and Arg-96 by PRMT1 inhibits Akt-mediated phosphorylation at Ser-99.

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.

RefSeq proteins (2): NP_004313, NP_116784* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018868	BAD	Family

Pfam: PF10514

UniProt features (23 total): modified residue 12, region of interest 2, mutagenesis site 2, compositionally biased region 2, chain 1, sequence variant 1, helix 1, strand 1, short sequence motif 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9QNL	X-RAY DIFFRACTION	1.3
9O14	X-RAY DIFFRACTION	1.73
9O16	X-RAY DIFFRACTION	1.73
9O15	X-RAY DIFFRACTION	1.99
7Q16	X-RAY DIFFRACTION	2.36
1G5J	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92934-F1	61.91	0.01

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 (12): 94, 96, 97, 99, 99, 118, 134, 161, 1, 25, 75, 91

Mutagenesis-validated functional residues (2):

Position	Phenotype
94	decreased methylation; when associated with k-96.
96	decreased methylation; when associated with k-94.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-111447	Activation of BAD and translocation to mitochondria
R-HSA-111453	BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
R-HSA-193648	NRAGE signals death through JNK
R-HSA-198323	AKT phosphorylates targets in the cytosol
R-HSA-5674400	Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-109581	Apoptosis
R-HSA-109606	Intrinsic Pathway for Apoptosis
R-HSA-114452	Activation of BH3-only proteins
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-193704	p75 NTR receptor-mediated signalling
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE
R-HSA-2219528	PI3K/AKT Signaling in Cancer
R-HSA-5357801	Programmed Cell Death
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-73887	Death Receptor Signaling
R-HSA-9006925	Intracellular signaling by second messengers

MSigDB gene sets: 420 (showing top): GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, CHIBA_RESPONSE_TO_TSA_UP, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_B_CELL_ACTIVATION, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_INSULIN_SECRETION, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS

GO Biological Process (35): release of cytochrome c from mitochondria (GO:0001836), glucose catabolic process (GO:0006007), apoptotic process (GO:0006915), extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), positive regulation of autophagy (GO:0010508), positive regulation of mitochondrial membrane potential (GO:0010918), cytokine-mediated signaling pathway (GO:0019221), positive regulation of insulin secretion (GO:0032024), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), glucose homeostasis (GO:0042593), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), type B pancreatic cell proliferation (GO:0044342), positive regulation of B cell differentiation (GO:0045579), positive regulation of T cell differentiation (GO:0045582), positive regulation of proteolysis (GO:0045862), ADP metabolic process (GO:0046031), ATP metabolic process (GO:0046034), regulation of mitochondrial membrane permeability (GO:0046902), pore complex assembly (GO:0046931), positive regulation of epithelial cell proliferation (GO:0050679), cellular response to mechanical stimulus (GO:0071260), cellular response to nicotine (GO:0071316), cellular response to lipid (GO:0071396), cellular response to hypoxia (GO:0071456), positive regulation of release of cytochrome c from mitochondria (GO:0090200), extrinsic apoptotic signaling pathway (GO:0097191), extrinsic apoptotic signaling pathway in absence of ligand (GO:0097192), intrinsic apoptotic signaling pathway (GO:0097193), positive regulation of intrinsic apoptotic signaling pathway in response to osmotic stress (GO:1902220), positive regulation of type B pancreatic cell development (GO:2000078), regulation of apoptotic process (GO:0042981), epithelial cell proliferation (GO:0050673), apoptotic signaling pathway (GO:0097190)

GO Molecular Function (6): phospholipid binding (GO:0005543), lipid binding (GO:0008289), protein kinase binding (GO:0019901), protein phosphatase binding (GO:0019903), cysteine-type endopeptidase activator activity (GO:0140608), protein binding (GO:0005515)

GO Cellular Component (9): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), BAD-BCL-2 complex (GO:0097138), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm end piece (GO:0097229), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Intrinsic Pathway for Apoptosis	2
Signal Transduction	2
Activation of BH3-only proteins	1
Cell death signalling via NRAGE, NRIF and NADE	1
PIP3 activates AKT signaling	1
PI3K/AKT Signaling in Cancer	1
Programmed Cell Death	1
Apoptosis	1
Intracellular signaling by second messengers	1
Death Receptor Signaling	1
p75 NTR receptor-mediated signalling	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
sperm flagellum	3
apoptotic signaling pathway	2
apoptotic process	2
regulation of apoptotic process	2
positive regulation of lymphocyte differentiation	2
purine ribonucleotide metabolic process	2
binding	2
cytoplasm	2
apoptotic mitochondrial changes	1
glucose metabolic process	1
hexose catabolic process	1
programmed cell death	1
execution phase of apoptosis	1
extrinsic apoptotic signaling pathway	1
DNA damage response	1
intrinsic apoptotic signaling pathway	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
positive regulation of membrane potential	1
regulation of mitochondrial membrane potential	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
positive regulation of insulin secretion	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
carbohydrate homeostasis	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
epithelial cell proliferation	1
B cell differentiation	1
regulation of B cell differentiation	1
positive regulation of B cell activation	1
T cell differentiation	1
regulation of T cell differentiation	1

Protein interactions and networks

STRING

818 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BAD	BCL2L1	Q07817	964
BAD	BCL2	P10415	926
BAD	TP53BP2	Q13625	774
BAD	BID	P55957	678
BAD	BAX	P55269	676
BAD	MCL1	Q07820	646
BAD	RTL10	Q7L3V2	617
BAD	BAK1	Q16611	612
BAD	BCL2L11	O43521	574
BAD	AKT1	P31749	572
BAD	CASP3	P42574	570
BAD	CASP9	P55211	568
BAD	WASF1	Q92558	543
BAD	BBC3	Q96PG8	540
BAD	GCK	P35557	535

IntAct

165 interactions, top by confidence:

A	B	Type	Score
BCL2L1	BAD	psi-mi:“MI:0915”(physical association)	0.980
BAD	BCL2L1	psi-mi:“MI:0915”(physical association)	0.980
BAD	BCL2L1	psi-mi:“MI:2364”(proximity)	0.980
BCL2L1	BAD	psi-mi:“MI:2364”(proximity)	0.980

BioGRID (256): BAD (Protein-peptide), BAD (Biochemical Activity), BAD (Biochemical Activity), BAD (Far Western), BAD (Reconstituted Complex), BAD (Reconstituted Complex), BAD (Affinity Capture-Western), BCL2L1 (Affinity Capture-Western), BCL2 (Reconstituted Complex), BCL2L1 (Two-hybrid), BCL2L1 (Affinity Capture-Western), YWHAZ (Affinity Capture-Western), BAD (Affinity Capture-Western), SFN (Affinity Capture-Western), BAD (Affinity Capture-Western)

ESM2 similar proteins: A0A0D1DRJ3, A0A3G1DJJ7, A1A5P0, C5DF10, E9PSU6, F5HDE4, O13412, O13415, O35147, O74428, O74461, O74504, P08318, P09272, P09310, P09512, P10471, P11625, P17523, P17524, P34469, P40572, P40688, P41884, P43598, Q01582, Q02362, Q06428, Q17QW1, Q18LF8, Q32LJ5, Q4JQW6, Q53QW1, Q61337, Q6DR24, Q6SW99, Q751K7, Q75BH9, Q75BX3, Q75DQ4

Diamond homologs: O35147, Q61337, Q92934

SIGNOR signaling

115 interactions.

A	Effect	B	Mechanism
MAPK8	down-regulates	BAD	phosphorylation
CASP3	“up-regulates activity”	BAD	cleavage
BAD	“down-regulates activity”	BCL2	relocalization
BAD	“down-regulates activity”	BCL2L1	binding
BAD	down-regulates	BCL2L2	binding
BAD	“up-regulates activity”	TP53	binding
RAF1	down-regulates	BAD	phosphorylation
RPS6KA1	“down-regulates activity”	BAD	phosphorylation
PRKCE	down-regulates	BAD	phosphorylation
PRKD1	down-regulates	BAD	phosphorylation
PRKCI	down-regulates	BAD	phosphorylation
PAK1	down-regulates	BAD	phosphorylation
AVP	down-regulates	BAD
PRKACA	down-regulates	BAD	phosphorylation
RPS6KA2	down-regulates	BAD	phosphorylation
RPS6KA3	down-regulates	BAD	phosphorylation
MAPK3	down-regulates	BAD	phosphorylation
IKBKB	down-regulates	BAD	phosphorylation
“Survival Factors”	down-regulates	BAD
IKK-complex	down-regulates	BAD	phosphorylation
AKT	“down-regulates activity”	BAD	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 61 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	9	155.7×	8e-17
Activation of BH3-only proteins	11	124.1×	6e-19
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	106.9×	1e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	106.9×	1e-11
Intrinsic Pathway for Apoptosis	12	79.9×	2e-18
FOXO-mediated transcription	8	61.1×	3e-11
Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models	5	59.0×	5e-07
RHO GTPases activate PKNs	7	50.5×	3e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	34.6×	1e-04
intrinsic apoptotic signaling pathway in response to DNA damage	5	30.6×	2e-04
negative regulation of autophagy	5	24.5×	3e-04
intracellular protein localization	8	15.8×	3e-05
regulation of apoptotic process	6	9.4×	3e-03
protein phosphorylation	6	7.7×	6e-03
positive regulation of apoptotic process	6	6.4×	1e-02
negative regulation of apoptotic process	9	5.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	26
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3244550	NC_000011.9:g.(?63731700)(64572142_?)del	Pathogenic

SpliceAI

1798 predictions. Top by Δscore:

Variant	Effect	Δscore
11:64270335:CTT:C	acceptor_gain	1.0000
11:64270338:C:CC	acceptor_gain	1.0000
11:64271608:CTCA:C	donor_loss	1.0000
11:64271610:CA:C	donor_loss	1.0000
11:64271612:C:CA	donor_loss	1.0000
11:64271799:AGCGC:A	acceptor_gain	1.0000
11:64271800:GCGC:G	acceptor_gain	1.0000
11:64271801:CGC:C	acceptor_gain	1.0000
11:64271801:CGCC:C	acceptor_gain	1.0000
11:64271802:GC:G	acceptor_gain	1.0000
11:64271803:CC:C	acceptor_gain	1.0000
11:64271803:CCTG:C	acceptor_loss	1.0000
11:64271804:C:CC	acceptor_gain	1.0000
11:64271816:A:T	acceptor_gain	1.0000
11:64284178:TTA:T	donor_loss	1.0000
11:64284179:TA:T	donor_loss	1.0000
11:64284180:A:AC	donor_gain	1.0000
11:64284180:AC:A	donor_gain	1.0000
11:64284180:ACCT:A	donor_gain	1.0000
11:64284180:ACCTC:A	donor_gain	1.0000
11:64284181:C:CA	donor_gain	1.0000
11:64284181:CC:C	donor_gain	1.0000
11:64284181:CCT:C	donor_gain	1.0000
11:64284181:CCTC:C	donor_gain	1.0000
11:64284181:CCTCC:C	donor_gain	1.0000
11:64286878:CCAG:C	donor_loss	1.0000
11:64286879:CAGG:C	donor_loss	1.0000
11:64286882:G:C	donor_loss	1.0000
11:64287015:G:GG	donor_gain	1.0000
11:64288059:T:TA	acceptor_gain	1.0000

AlphaMissense

1107 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:64271650:A:G	L114P	0.997
11:64271628:A:C	F121L	0.996
11:64271628:A:T	F121L	0.996
11:64271630:A:G	F121L	0.996
11:64271637:A:C	S118R	0.995
11:64271637:A:T	S118R	0.995
11:64271638:C:A	S118I	0.995
11:64271639:T:G	S118R	0.995
11:64271650:A:T	L114H	0.995
11:64271659:C:T	G111D	0.994
11:64271641:A:G	M117T	0.991
11:64271629:A:C	F121C	0.990
11:64271629:A:G	F121S	0.990
11:64271640:C:A	M117I	0.989
11:64271640:C:G	M117I	0.989
11:64271640:C:T	M117I	0.989
11:64271659:C:A	G111V	0.989
11:64284363:G:C	F2L	0.989
11:64284363:G:T	F2L	0.989
11:64284365:A:G	F2L	0.989
11:64271647:C:G	R115P	0.988
11:64271660:C:G	G111R	0.985
11:64284358:A:G	I4T	0.984
11:64271663:A:C	Y110D	0.983
11:64271660:C:A	G111C	0.980
11:64271662:T:G	Y110S	0.978
11:64271671:G:T	A107E	0.978
11:64284348:A:C	F7L	0.977
11:64284348:A:T	F7L	0.977
11:64284350:A:G	F7L	0.977

dbSNP variants (sampled 300 via entrez): RS1000009542 (11:64272887 G>C), RS1000679595 (11:64276575 C>T), RS1000873868 (11:64270016 C>A,T), RS1000999174 (11:64286294 T>A,C,G), RS1001012410 (11:64273643 G>A), RS1001687847 (11:64285813 A>G), RS1002127223 (11:64285932 C>A,G,T), RS1002257584 (11:64280816 C>T), RS1002405235 (11:64275144 A>G), RS1002535512 (11:64282499 C>T), RS1002742237 (11:64276771 C>T), RS1002976022 (11:64269938 A>C,G), RS1002999837 (11:64282081 G>A), RS1003113635 (11:64278809 C>T), RS1003218777 (11:64285259 TA>T)

Disease associations

OMIM: gene MIM:603167 | disease phenotypes: MIM:131100

GenCC curated gene-disease

Mondo (1): multiple endocrine neoplasia type 1 (MONDO:0007540)

Orphanet (1): Multiple endocrine neoplasia type 1 (Orphanet:652)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001622_1	Sarcoidosis	3.000000e-18
GCST004132_98	Crohn’s disease	5.000000e-06
GCST004785_38	Vitiligo	5.000000e-08
GCST006979_799	Heel bone mineral density	9.000000e-11
GCST008047_1	Platelet count	5.000000e-08
GCST90020025_1875	Waist-to-hip ratio adjusted for BMI	2.000000e-10
GCST90020027_1492	Waist-hip index	4.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004309	platelet count
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018761	Multiple Endocrine Neoplasia Type 1	C04.588.322.400.500; C04.651.600.500; C04.700.630.500; C16.320.700.630.500; C19.344.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3817 (SINGLE PROTEIN), CHEMBL5169266 (PROTEIN-PROTEIN INTERACTION), CHEMBL5169267 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 66,995 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3137309	VENETOCLAX	4	9,389
CHEMBL408194	OBATOCLAX	3	2,914
CHEMBL443684	NAVITOCLAX	3	4,791
CHEMBL51483	GOSSYPOL	3	13,973
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL417799	SANGUINARIUM	2	8,822
CHEMBL5754780	ASARETOCLAX	2	14
CHEMBL376408	ABT 737	1	4,288

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs671976	BAD, GPR137		0.00	0

Binding affinities (BindingDB)

5 measured of 5 human assays (5 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-chloro-3-[3-(4-chloro-3,5-dimethylphenoxy)propyl]-1-benzothiophene-2-carboxylic acid	IC50	2400 nM	US-10093646: 1-pyridazin-/triazin-3-yl-piper(-azine)/idine/pyrolidine derivatives and compositions thereof for inhibiting the activity of SHP2
6-chloro-3-(3-naphthalen-1-yloxypropyl)-1-benzothiophene-2-carboxylic acid	IC50	3300 nM	US-10093646: 1-pyridazin-/triazin-3-yl-piper(-azine)/idine/pyrolidine derivatives and compositions thereof for inhibiting the activity of SHP2
3-(3-naphthalen-1-yloxypropyl)-1-benzothiophene-2-carboxylic acid	IC50	10000 nM	US-10093646: 1-pyridazin-/triazin-3-yl-piper(-azine)/idine/pyrolidine derivatives and compositions thereof for inhibiting the activity of SHP2
3-(3-naphthalen-1-yloxypropyl)-1-benzofuran-2-carboxylic acid	IC50	21000 nM	US-10093646: 1-pyridazin-/triazin-3-yl-piper(-azine)/idine/pyrolidine derivatives and compositions thereof for inhibiting the activity of SHP2
3-[3-(4-chloro-3,5-dimethylphenoxy)propyl]-1-benzothiophene-2-carboxylic acid	IC50	41000 nM	US-10093646: 1-pyridazin-/triazin-3-yl-piper(-azine)/idine/pyrolidine derivatives and compositions thereof for inhibiting the activity of SHP2

ChEMBL bioactivities

105 potent at pChembl≥5 of 237 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.22	Ki	0.6	nM	ABT 737
8.85	Ki	1.4	nM	CHEMBL448740
7.85	Ki	14	nM	CHEMBL508864
7.52	EC50	30	nM	CHEMBL1915438
7.52	EC50	30	nM	CHEMBL1915449
7.44	IC50	36	nM	CHEMBL402005
7.40	EC50	40	nM	CHEMBL1915641
7.30	EC50	50	nM	CHEMBL1915448
7.26	Kd	55	nM	CHEMBL5765179
7.26	Kd	55	nM	CHEMBL5800976
7.26	Kd	55	nM	CHEMBL5900615
7.26	Kd	55	nM	CHEMBL5745497
7.26	Kd	55	nM	CHEMBL5805527
7.26	Kd	55	nM	VENETOCLAX
7.26	Kd	55	nM	NAVITOCLAX
7.26	IC50	55	nM	ASARETOCLAX
7.26	IC50	55	nM	VENETOCLAX
7.05	EC50	90	nM	CHEMBL1915445
7.00	Ki	100	nM	CHEMBL4872320
7.00	EC50	100	nM	CHEMBL1915645
7.00	EC50	100	nM	CHEMBL1915651
6.85	EC50	140	nM	CHEMBL1915442
6.70	IC50	200	nM	CHEMBL5394521
6.70	EC50	200	nM	CHEMBL1915650
6.68	EC50	210	nM	CHEMBL1915646
6.60	IC50	250	nM	CHEMBL481581
6.60	Ki	250	nM	CHEMBL4872671
6.60	Ki	250	nM	CHEMBL4864929
6.52	Ki	300	nM	CHEMBL4855114
6.44	Ki	360	nM	CHEMBL4870608
6.40	IC50	400	nM	CHEMBL502066
6.34	Ki	460	nM	GOSSYPOL
6.31	Ki	490	nM	CHEMBL4860820
6.31	Ki	490	nM	EPIGALOCATECHIN GALLATE
6.28	Ki	530	nM	CHEMBL4852823
6.28	EC50	530	nM	CHEMBL1915636
6.25	Ki	560	nM	CHEMBL4864735
6.20	Ki	638	nM	CHEMBL376055
6.18	Ki	660	nM	CHEMBL4870458
6.12	EC50	760	nM	CHEMBL1914471
6.10	Ki	800	nM	CHEMBL4846508
6.09	IC50	808	nM	CHEMBL508392
6.09	Ki	820	nM	CHEMBL4856143
6.09	Ki	820	nM	CHEMBL4870837
6.06	Ki	870	nM	CHEMBL4876348
6.05	EC50	890	nM	CHEMBL1915647
6.01	Ki	970	nM	CHEMBL404899
6.01	EC50	980	nM	CHEMBL1915648
6.00	Ki	1000	nM	OBATOCLAX
6.00	IC50	990	nM	CHEMBL2314176

PubChem BioAssay actives

105 with measured affinity, of 167 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
4-[4-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide	405509: Binding affinity to BH3 binding groove of BclXL	ki	0.0005	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide	318565: Binding affinity to Bcl-XL assessed as inhibition of Bcl-XL-BAD derived peptide interaction	ki	0.0006	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[3-cyano-4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]phenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0010	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0010	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0010	uM
4-[4-[[2-(4-chlorophenyl)cyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0010	uM
4-[4-[[2-(4-chlorophenyl)cyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0010	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethyl)phenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0010	uM
4-[4-[[2-(4-chlorophenyl)cyclohepten-1-yl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0010	uM
4-[4-[[4-(4-chlorophenyl)-3,6-dihydro-2H-pyran-5-yl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0010	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-(2,2,2-trifluoroacetyl)phenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0010	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-methylphenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0010	uM
4-[4-[[(1Z)-2-(4-chlorophenyl)cycloocten-1-yl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0010	uM
4-[4-[[2-(4-chlorophenyl)cyclopenten-1-yl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0010	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethoxy)phenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0010	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-methylsulfonylphenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0010	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[3-nitro-4-(2-phenylsulfanylethylamino)phenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0010	uM
4-[4-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0014	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]phenyl]sulfonylbenzamide	389260: Displacement of fluorescein labeled BAD peptide from Bcl-XL by fluorescence polarization assay	ki	0.0140	uM
N-(2-chlorophenyl)-7-(1H-1,2,4-triazol-5-yl)benzo[c][2,6]naphthyridin-5-amine	630778: Inhibition of BAD phosphorylation at Ser112 in human MV-4-11 cells assessed as phospho-BAD level after 4 hrs by ELISA	ec50	0.0300	uM
N-[2-chloro-4-(4-methylpiperazin-1-yl)phenyl]-7-(1H-1,2,4-triazol-5-yl)benzo[c][2,6]naphthyridin-5-amine	630778: Inhibition of BAD phosphorylation at Ser112 in human MV-4-11 cells assessed as phospho-BAD level after 4 hrs by ELISA	ec50	0.0300	uM
4-(4-fluorophenyl)-N-[3-nitro-4-(2-thiopyran-1-ylethylamino)phenyl]sulfonylbenzamide	318572: Binding affinity to Bcl-XL	ic50	0.0360	uM
N-[2-fluoro-4-(2-pyrrolidin-1-ylethoxy)phenyl]-7-(1H-1,2,4-triazol-5-yl)benzo[c][2,6]naphthyridin-5-amine	630778: Inhibition of BAD phosphorylation at Ser112 in human MV-4-11 cells assessed as phospho-BAD level after 4 hrs by ELISA	ec50	0.0400	uM
N-[2-chloro-4-(2-morpholin-4-ylethoxy)phenyl]-7-(1H-1,2,4-triazol-5-yl)benzo[c][2,6]naphthyridin-5-amine	630778: Inhibition of BAD phosphorylation at Ser112 in human MV-4-11 cells assessed as phospho-BAD level after 4 hrs by ELISA	ec50	0.0500	uM
3-chloro-4-[[7-(1H-1,2,4-triazol-5-yl)benzo[c][2,6]naphthyridin-5-yl]amino]phenol	630778: Inhibition of BAD phosphorylation at Ser112 in human MV-4-11 cells assessed as phospho-BAD level after 4 hrs by ELISA	ec50	0.0900	uM
2-[3-(3-chlorophenyl)-1-(naphthalen-1-ylmethyl)indol-4-yl]benzoic acid	1754974: Binding affinity to Bcl-2 (unknown origin) by fluorescence polarization competition assay	ki	0.1000	uM
5-(2-chloro-3-methoxyanilino)-N-methylbenzo[c][2,6]naphthyridine-7-carboxamide	630778: Inhibition of BAD phosphorylation at Ser112 in human MV-4-11 cells assessed as phospho-BAD level after 4 hrs by ELISA	ec50	0.1000	uM
5-(2,6-difluoroanilino)benzo[c][2,6]naphthyridine-7-carboxamide	630778: Inhibition of BAD phosphorylation at Ser112 in human MV-4-11 cells assessed as phospho-BAD level after 4 hrs by ELISA	ec50	0.1000	uM
N-(2-fluorophenyl)-7-(1H-1,2,4-triazol-5-yl)benzo[c][2,6]naphthyridin-5-amine	630778: Inhibition of BAD phosphorylation at Ser112 in human MV-4-11 cells assessed as phospho-BAD level after 4 hrs by ELISA	ec50	0.1400	uM
(4S)-4-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-amino-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]propanoyl]amino]propanoyl]amino]-5-amino-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	1992018: Inhibition of BAD/His-SUMO tagged BCL-XL (1 to 209 residues; missing 27 to 82 residues) (unknown origin) overexpressed in Escherichia coli BL21 protein-protein interaction by fluorescence anisotropy competition assay	ic50	0.2000	uM
5-(2-fluoroanilino)-N-methylbenzo[c][2,6]naphthyridine-7-carboxamide	630778: Inhibition of BAD phosphorylation at Ser112 in human MV-4-11 cells assessed as phospho-BAD level after 4 hrs by ELISA	ec50	0.2000	uM
5-(2-chloroanilino)-N-ethylbenzo[c][2,6]naphthyridine-7-carboxamide	630778: Inhibition of BAD phosphorylation at Ser112 in human MV-4-11 cells assessed as phospho-BAD level after 4 hrs by ELISA	ec50	0.2100	uM
2-[3-(2-methylphenyl)-1-(2-naphthalen-1-yloxyethyl)indol-4-yl]benzoic acid	1754974: Binding affinity to Bcl-2 (unknown origin) by fluorescence polarization competition assay	ki	0.2500	uM
2-[1-(2-naphthalen-1-yloxyethyl)-3-[3-(trifluoromethyl)phenyl]indol-4-yl]benzoic acid	1754974: Binding affinity to Bcl-2 (unknown origin) by fluorescence polarization competition assay	ki	0.2500	uM
1-[2-[(3S)-3-(aminomethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]phenyl]-N,N-dibutyl-4-chloro-5-methylpyrazole-3-carboxamide	410735: Inhibition of GST fused Bcl-xL binding to biotinylated 16 mer Bak-BH3 peptide by HTRF-LANCE assay	ic50	0.2500	uM
2-[3-(2-ethylphenyl)-1-(2-naphthalen-1-yloxyethyl)indol-4-yl]benzoic acid	1754974: Binding affinity to Bcl-2 (unknown origin) by fluorescence polarization competition assay	ki	0.3000	uM
2-[3-(3-methylphenyl)-1-(2-naphthalen-1-yloxyethyl)indol-4-yl]benzoic acid	1754974: Binding affinity to Bcl-2 (unknown origin) by fluorescence polarization competition assay	ki	0.3600	uM
N,N-dibutyl-1-[2-(3,4-dihydro-1H-isoquinoline-2-carbonyl)-4-[(2-phenylsulfanylacetyl)amino]phenyl]-5-methylpyrazole-3-carboxamide	410737: Inhibition of GST fused Bcl-xL binding to biotinylated 26 mer Bak-BH3 peptide by HTRF-LANCE assay	ic50	0.4000	uM
7-(8-formyl-1,6,7-trihydroxy-3-methyl-5-propan-2-ylnaphthalen-2-yl)-2,3,8-trihydroxy-6-methyl-4-propan-2-ylnaphthalene-1-carbaldehyde	1754974: Binding affinity to Bcl-2 (unknown origin) by fluorescence polarization competition assay	ki	0.4600	uM
4-chloro-2-[1-(3-naphthalen-1-yloxypropyl)indol-4-yl]benzoic acid	1754974: Binding affinity to Bcl-2 (unknown origin) by fluorescence polarization competition assay	ki	0.4900	uM
[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl] 3,4,5-trihydroxybenzoate	1858755: Binding affinity to Bcl-2/Bad (unknown origin) assessed as inhibition constant by fluorescence polarisation assay	ki	0.4900	uM
2-[3-(3-methoxyphenyl)-1-(naphthalen-1-ylmethyl)indol-4-yl]benzoic acid	1754974: Binding affinity to Bcl-2 (unknown origin) by fluorescence polarization competition assay	ki	0.5300	uM
N-(2,6-difluorophenyl)-7-(1H-1,2,4-triazol-5-yl)benzo[c][2,6]naphthyridin-5-amine	630778: Inhibition of BAD phosphorylation at Ser112 in human MV-4-11 cells assessed as phospho-BAD level after 4 hrs by ELISA	ec50	0.5300	uM
2-[3-(3-methylphenyl)-1-(3-naphthalen-1-yloxypropyl)indol-4-yl]benzoic acid	1754974: Binding affinity to Bcl-2 (unknown origin) by fluorescence polarization competition assay	ki	0.5600	uM
N-(2-phenylethyl)-2-[2,3,4-trihydroxy-5-[methyl(3-phenylpropyl)sulfamoyl]benzoyl]-3,4-dihydro-1H-isoquinoline-7-sulfonamide	281471: Displacement of FAM-Bak BH3 peptide from human Bcl-xL by FP-based binding assay	ki	0.6380	uM
2-[3-(2-methylphenyl)-1-(naphthalen-1-ylmethyl)indol-4-yl]benzoic acid	1754974: Binding affinity to Bcl-2 (unknown origin) by fluorescence polarization competition assay	ki	0.6600	uM
5-(2,6-difluoroanilino)-N-methylbenzo[c][2,6]naphthyridine-7-carboxamide	630778: Inhibition of BAD phosphorylation at Ser112 in human MV-4-11 cells assessed as phospho-BAD level after 4 hrs by ELISA	ec50	0.7600	uM
2-[3-(4-methylphenyl)-1-(naphthalen-1-ylmethyl)indol-4-yl]benzoic acid	1754974: Binding affinity to Bcl-2 (unknown origin) by fluorescence polarization competition assay	ki	0.8000	uM
1-[2-[(3S)-3-(aminomethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-4-[(2-phenoxyacetyl)amino]phenyl]-N,N-dibutyl-4-chloro-5-methylpyrazole-3-carboxamide	410737: Inhibition of GST fused Bcl-xL binding to biotinylated 26 mer Bak-BH3 peptide by HTRF-LANCE assay	ic50	0.8080	uM
2-[3-(2-methoxyphenyl)-1-(2-naphthalen-1-yloxyethyl)indol-4-yl]benzoic acid	1754974: Binding affinity to Bcl-2 (unknown origin) by fluorescence polarization competition assay	ki	0.8200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	increases reaction, decreases expression, increases activity, affects cotreatment, increases expression (+3 more)	12
Quercetin	affects cotreatment, increases expression, decreases phosphorylation, increases reaction, affects binding	10
Doxorubicin	affects expression, decreases phosphorylation, increases reaction, decreases expression, increases expression	8
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases activity, increases reaction, decreases reaction, increases phosphorylation, decreases phosphorylation	6
Resveratrol	affects cotreatment, decreases expression, decreases reaction, increases expression	6
U 0126	affects cotreatment, increases expression, decreases expression, decreases reaction, increases phosphorylation (+2 more)	4
Cadmium Chloride	decreases expression, increases expression, increases reaction, affects phosphorylation	4
sodium arsenite	decreases reaction, increases expression, increases abundance	3
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	increases response to substance, decreases phosphorylation, decreases reaction, increases phosphorylation	3
(+)-JQ1 compound	affects cotreatment, increases expression, decreases expression	3
Cannabidiol	decreases expression, increases expression, affects cotreatment	3
Cisplatin	increases response to substance, increases phosphorylation, decreases reaction, decreases response to substance, increases expression (+2 more)	3
Indomethacin	increases expression, decreases expression, increases localization, affects cotreatment	3
Plant Extracts	affects cotreatment, decreases expression, decreases reaction, increases expression	3
Tretinoin	affects cotreatment, increases expression, decreases phosphorylation	3
vernodalol	increases expression	2
juglone	affects cotreatment, increases expression	2
bisphenol A	decreases expression	2
salvin	decreases phosphorylation, increases reaction, increases expression	2
sulindac sulfide	decreases expression, increases localization, affects binding, increases reaction	2
4-hydroxy-2-nonenal	decreases expression, increases expression	2
vasicinone	decreases reaction, increases expression	2
cyanoginosin LR	increases phosphorylation	2
arctigenin	decreases phosphorylation, increases expression, increases reaction	2
naphtho(1,2-b)furan-4,5-dione	decreases reaction, increases expression	2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases phosphorylation, increases expression	2
SN50 peptide	decreases expression, decreases reaction, decreases phosphorylation	2
4-(1H-imidazol-1-yl)retinoic acid	increases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	2
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases phosphorylation, increases reaction, increases expression, affects cotreatment	2

ChEMBL screening assays

36 unique, capped per target: 35 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1019893	Binding	Inhibition of GST fused Bcl-xL binding to biotinylated 16 mer Bak-BH3 peptide by HTRF-LANCE assay	Tetrahydroisoquinoline amide substituted phenyl pyrazoles as selective Bcl-2 inhibitors. — Bioorg Med Chem Lett
CHEMBL939221	Functional	Reduction of BAD phosphorylation in human MV4-11 cells at 1 uM by Western blot	A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. — Proc Natl Acad Sci U S A

Cellosaurus cell lines

9 cell lines: 9 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8BR	Abcam HCT 116 BAD KO	Cancer cell line	Male
CVCL_B9DV	Abcam A-549 BAD KO	Cancer cell line	Male
CVCL_D2DY	Abcam MCF-7 BAD KO	Cancer cell line	Female
CVCL_E0ZS	Ubigene NCI-H1975 BAD KO	Cancer cell line	Female
CVCL_F1LT	HyCyte A-549 KO-hBAD	Cancer cell line	Male
CVCL_F1N3	HyCyte BT-549 KO-hBAD	Cancer cell line	Female
CVCL_F1RN	HyCyte MDA-MB-231 KO-hBAD	Cancer cell line	Female
CVCL_SE60	HAP1 BAD (-) 1	Cancer cell line	Male
CVCL_XL94	HAP1 BAD (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001277	PHASE2	COMPLETED	Studies of Elevated Parathyroid Activity
NCT00454363	PHASE2	COMPLETED	Pazopanib Hydrochloride in Treating Patients With Advanced Neuroendocrine Cancer
NCT02101918	PHASE2	COMPLETED	Ziv-Aflibercept in Treating and Computed Tomography Perfusion Imaging in Predicting Response in Patients With Pancreatic Neuroendocrine Tumors That Are Metastatic or Cannot Be Removed by Surgery
NCT03950609	PHASE2	ACTIVE_NOT_RECRUITING	Lenvatinib and Everolimus in Treating Patients With Advanced, Unresectable Carcinoid Tumors
NCT02831179	PHASE1	WITHDRAWN	Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor
NCT03001349	EARLY_PHASE1	TERMINATED	68Ga-DOTA-TOC PET/CT in Imaging Participants With Neuroendocrine Tumors
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01794676	Not specified	COMPLETED	Genetic Evaluation of Families With Endocrine Cancers
NCT03043508	Not specified	UNKNOWN	Overall and Disease Specific Survival in Patients With Confirmed MEN1 With or Without PNET (Pancreatic Neuroendocrine Tumors)
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03966612	Not specified	RECRUITING	Study and Monitoring of Multiple Endocrine Neoplasia Type 1
NCT05037461	Not specified	RECRUITING	Precision Radiotherapy Using MR-linac for Pancreatic Neuroendocrine Tumours in MEN1 Patients
NCT05061784	Not specified	COMPLETED	Routine Transcervical Thymectomy in MEN-1 Patients
NCT05554744	Not specified	UNKNOWN	EUS-FNI for MEN1-related Pancreatic Neuroendocrine Tumors
NCT06523582	Not specified	RECRUITING	Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients
NCT06790251	Not specified	NOT_YET_RECRUITING	Institution of an Italian Multicenter Database of Patients With Multiple Endocrine Neoplasia Type 1 (MENNET1 Database)
NCT07272187	Not specified	RECRUITING	Endoscopic Ultrasound-guided Radiofrequency Ablation for Upper Gastrointestinal Tract Lesions