BDKRB2

Summary

BDKRB2 (bradykinin receptor B2, HGNC:1030) is a protein-coding gene on chromosome 14q32.2, encoding B2 bradykinin receptor (P30411). Receptor for bradykinin.

This gene encodes a receptor for bradykinin. The 9 aa bradykinin peptide elicits many responses including vasodilation, edema, smooth muscle spasm and pain fiber stimulation. Bradykinin is released upon activation by pathophysiologic conditions such as trauma and inflammation, and binds to its kinin receptors, B1 and B2. The B2 receptor associates with G proteins that stimulate a phosphatidylinositol-calcium second messenger system.

Source: NCBI Gene 624 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 59 total
• Druggable target: yes — 18 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001379692

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1030
Approved symbol	BDKRB2
Name	bradykinin receptor B2
Location	14q32.2
Locus type	gene with protein product
Status	Approved
Aliases	BK-2
Ensembl gene	ENSG00000168398
Ensembl biotype	protein_coding
OMIM	113503
Entrez	624

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000539359, ENST00000542454, ENST00000554311, ENST00000877850, ENST00000877851, ENST00000877852, ENST00000968196

RefSeq mRNA: 2 — MANE Select: NM_001379692 NM_000623, NM_001379692

CCDS: CCDS9942

Canonical transcript exons

ENST00000554311 — 3 exons

Exon	Start	End
ENSE00002264876	96204839	96204959
ENSE00002479630	96240403	96244164
ENSE00003638900	96237069	96237181

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 97.09.

FANTOM5 (CAGE): breadth broad, TPM avg 4.9703 / max 212.0385, expressed in 898 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141329	4.9703	898
141330	0.3272	159

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	97.09	gold quality
mucosa of urinary bladder	UBERON:0001259	96.18	gold quality
pancreatic ductal cell	CL:0002079	94.50	gold quality
cervix squamous epithelium	UBERON:0006922	93.77	silver quality
tongue squamous epithelium	UBERON:0006919	92.30	gold quality
cervix epithelium	UBERON:0004801	91.72	silver quality
tendon of biceps brachii	UBERON:0008188	91.56	gold quality
gingiva	UBERON:0001828	89.95	gold quality
cartilage tissue	UBERON:0002418	89.58	gold quality
gingival epithelium	UBERON:0001949	89.57	gold quality
gall bladder	UBERON:0002110	88.66	gold quality
squamous epithelium	UBERON:0006914	88.31	gold quality
ectocervix	UBERON:0012249	87.66	gold quality
uterine cervix	UBERON:0000002	86.81	gold quality
endocervix	UBERON:0000458	86.41	gold quality
epithelium of esophagus	UBERON:0001976	86.36	gold quality
esophagus mucosa	UBERON:0002469	85.95	gold quality
epithelial cell of pancreas	CL:0000083	85.67	silver quality
esophagus squamous epithelium	UBERON:0006920	85.57	gold quality
colonic mucosa	UBERON:0000317	85.23	gold quality
urinary bladder	UBERON:0001255	85.12	gold quality
lower esophagus mucosa	UBERON:0035834	85.04	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.02	gold quality
nasal cavity epithelium	UBERON:0005384	85.01	gold quality
buccal mucosa cell	CL:0002336	84.83	silver quality
mucosa of paranasal sinus	UBERON:0005030	84.63	gold quality
oral cavity	UBERON:0000167	84.53	gold quality
vagina	UBERON:0000996	84.40	gold quality
mammalian vulva	UBERON:0000997	84.10	gold quality
rectum	UBERON:0001052	82.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-7	yes	71.03
E-ENAD-21	yes	57.06
E-ANND-3	yes	8.47
E-MTAB-7249	yes	5.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, DDIT3, GLI2, IRX1, KLF4, MAF, TFAP2A, TP53, TP73, USF1, ZFP42

miRNA regulators (miRDB)

80 targeting BDKRB2, 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-513A-5P	100.00	69.77	2465
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-6871-3P	99.43	68.85	741

Literature-anchored findings (GeneRIF, showing 40)

• B1 and B2 receptor expression was enhanced in tumor cells and tissue adjacent to gastric cancer compared with gastric ulcers. (PMID:11710536)
• Two cysteine residues located in the carboxyterminal domain of the bradykinin B2 receptor are palmitoylated and play a critical role in the response of the receptor to ligand binding. (PMID:11747451)
• Bradykinin can also induce antimitogenic effects using an alternative signal transduction pathway for the B2 receptor. (PMID:11908480)
• presence of B2R was studied in uteri obtained in luteal phase and in idiopathic pregnancy loss as well as in preterm and term pregnancies (PMID:11954665)
• Bradykinin B2 receptor exon 1 polymorphism may represent a susceptibility marker for nephropathy progression in diabetic patients. (PMID:12025967)
• Exon 1 polymorphism of the B2BKR gene does not influence the clinical status of patients with hereditary angioedema. (PMID:12039525)
• Bradykinin B2 receptors are upregulated by inflammatory stimuli in bronchial epithelial cells. (PMID:12063092)
• Blood pressure in patients with primary aldosteronism is influenced by bradykinin B(2) receptor polymorphism. (PMID:12107246)
• the C-terminal domain participates intimately in the efficacy of B1R and B2R G(q/11) coupling by contributing both positive and negative regulatory epitopes. (PMID:12130679)
• B2R is constitutively targeted to caveolae-related lipid rafts in HEK293 cells and appears to shuttle the agonist through these domains, whereas B1R may be there by default. (PMID:12450400)
• elevated level of BK found in tissue injury,is one of the major risk factors for development of Alzheimer’s disease (PMID:12489797)
• Susceptibility to develop cough is associated with a genetic variant of the bradykinin B2 receptor promoter. (PMID:12522467)
• Bradykinin is a powerful spasmogen via B(2) receptor activation in the normal and, especially, in the inflamed human gallbladder. (PMID:12851878)
• B1 and B2 bradykinin receptors form a complex with enhanced signaling capacity (PMID:15033977)
• the C-58T B2R gene polymorphism is not associated with different levels of insulin resistance within a population of obese patients. (PMID:15114524)
• AT2 receptor-mediated vasodilation in the human heart is mediated by B2 receptors. (PMID:15117835)
• Y305A mutation induces a receptor conformation which is prone to ligand-independent phosphorylation and internalization. The mutated receptor binds to, but does not activate, its cognate heterotrimeric G protein G(q/11). (PMID:15161928)
• BK has mitogenic actions in cultured human epithelial breast cells; the activation of PKC-delta through B2 receptor acts in concert with ERK and PI3K pathways to induce cell proliferation. (PMID:15281091)
• slow internalization of B(1)KB(2) was also accompanied by a lack of agonist-induced phosphorylation, that in contrast was observed for B(1)YB(2) and B(1)CB(2), suggesting that putative helix 8 is either directly or indirectly involved (PMID:15634338)
• the two bradykinin receptors may play a role in blood pressure regulation (PMID:15643125)
• kinins may affect the life span of human keratinocytes via BK2 activation (PMID:15654972)
• study shows that bradykinin upregulates IL-1beta- and TNFalpha-stimulated IL-8 production via BK B2 receptor and that PKC signal pathway seems to be involved in the upregulation of the cytokine-induced IL-8 production in gingival fibroblasts (PMID:15664665)
• B2R polymorphism has a potential role in the earlier development of chronic renal failure in susceptible individuals. (PMID:15771553)
• bradykinin receptors in inflammatory bowel disease may reflect intestinal inflammation (PMID:15805101)
• polymorphism (-58 T/C) in the promoter region of BDKRB might be a risk factor and might have a synergetic effect with the ACE for LVH in hypertensives, but it is not associated with hypertension in the Japanese population (PMID:15894833)
• These results identify novel pretranslational effects of the B2-VNTR region to act as a potent negative regulator of heterologous gene expression and support the notion that the bradykinin B2 3’-UTR may impact endogenous receptor regulation. (PMID:16144969)
• B(2) receptor activation results in signaling via at least dual pathways - G(s)- and G(q)-mediated signaling. (PMID:16263113)
• Addition of BK or AngII to the cell line expressing WT AT1aR and BKB2R downregulated the expression of collagen alpha1(I) (COL1A1) mRNA. However, these effectors did not have this effect in cells expressing the mutant receptors. (PMID:16294326)
• Both the nitric oxide synthase 3 (NOS3) and bradykinin receptor B2 (BDKRB2) genes are associated with the ultra-endurance performance that occurred during Ironman Triathlons. (PMID:16461337)
• Importantly, receptor sialylation and N-glycosylation participate with disulfide bonding in the stabilization of the cell surface human B2 receptor dimers. (PMID:16489763)
• Confocal laser scanning microscopy and immunogold staining revealed that the recombinant receptor was predominantly localized intracellularly. (PMID:16740128)
• Data show that mechanical perturbation of the plasma membrane leads to ligand-independent conformational transitions in the bradykinin B2 G protein-coupled receptor. (PMID:17030791)
• Heterodimer formation between angiotensin converting enzyme and B2 receptors can be a mechanism for ACE inhibitors to augment kinin activity at cellular level. (PMID:17077303)
• kinins modulate receptor endocytosis to rapidly decrease B2R and increase B1R on the cell surface. (PMID:17110500)
• human embryonic stem cells can be differentiated effectively into the epithelial lineage and that when differentiated express functional, signaling AT1 and BKB2 receptors (PMID:17299793)
• The novel finding that kinin receptors are constitutively expressed in immature hMo-DC suggests that these receptors may be expressed in the absence of proinflammatory stimuli. (PMID:17327486)
• Kinin B1 and B2 receptors synergistically potentiate IL-1- and TNFalpha-induced PG biosynthesis in osteoblasts by a mechanism involving increased levels of COX-2, resulting in increased RANKL (PMID:17328065)
• Membrane disruption halts B(2)R internalization, invasion, and filopodia formation, which can be recovered with addition of cholesterol; functional recovery is severely impaired in the presence of CD13 antagonists (PMID:17363739)
• receptors are pre-coupled with their corresponding G proteins in the basal state of cells thereby limiting the response to an external signal to a defined stoichiometry that allows for a rapid and directed cellular response (PMID:17420253)
• B2 receptor BE1 +9/+9 genotype has differential effects on blood pressure and vascular resistance in white and black Americans. (PMID:17522594)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	BDKRB2	ENSDARG00000043664
mus_musculus	Bdkrb2	ENSMUSG00000021070
rattus_norvegicus	Bdkrb2	ENSRNOG00000047300
caenorhabditis_elegans		WBGENE00015559

Paralogs (7): BDKRB1 (ENSG00000100739), APLNR (ENSG00000134817), AGTR1 (ENSG00000144891), GPR15 (ENSG00000154165), GPR25 (ENSG00000170128), RXFP4 (ENSG00000173080), AGTR2 (ENSG00000180772)

Protein

Protein identifiers

B2 bradykinin receptor — P30411 (reviewed: P30411)

All UniProt accessions (1): P30411

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for bradykinin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system.

Subunit / interactions. Forms a complex with PECAM1 and GNAQ. Interacts with PECAM1.

Subcellular location. Cell membrane.

Tissue specificity. Ubiquitous. Widespread in normal smooth muscle tissue and neurons.

Similarity. Belongs to the G-protein coupled receptor 1 family. Bradykinin receptor subfamily. BDKRB2 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P30411-1	Long	yes
P30411-2	Short

RefSeq proteins (2): NP_000614, NP_001366621* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000496	Brdyknn_rcpt	Family
IPR001504	Brdyknn_2_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (51 total): helix 14, topological domain 8, transmembrane region 7, modified residue 6, turn 4, glycosylation site 3, strand 3, sequence variant 2, chain 1, lipid moiety-binding region 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7F6I	ELECTRON MICROSCOPY	2.8
7F2O	ELECTRON MICROSCOPY	2.9
7F6H	ELECTRON MICROSCOPY	2.9
9UVT	ELECTRON MICROSCOPY	3.29
9LFD	ELECTRON MICROSCOPY	3.6
9UVU	ELECTRON MICROSCOPY	3.69

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30411-F1	79.79	0.49

Antibody-complex structures (SAbDab): 1 — 7F2O

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 (7): 156, 347, 366, 369, 373, 375, 351

Disulfide bonds (1): 130–211

Glycosylation sites (3): 30, 39, 207

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-418594	G alpha (i) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 213 (showing top): BROWNE_HCMV_INFECTION_6HR_DN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_BY_P53_CLASS_MEDIATOR, GOBP_INFLAMMATORY_RESPONSE, MODULE_64, MODULE_329, MODULE_70, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, MODULE_289, GOBP_MUSCLE_CONTRACTION, GOBP_APOPTOTIC_SIGNALING_PATHWAY

GO Biological Process (18): smooth muscle contraction (GO:0006939), inflammatory response (GO:0006954), cell surface receptor signaling pathway (GO:0007166), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of cytosolic calcium ion concentration (GO:0007204), blood circulation (GO:0008015), response to salt stress (GO:0009651), regulation of vasoconstriction (GO:0019229), vasoconstriction (GO:0042310), vasodilation (GO:0042311), regulation of vascular permeability (GO:0043114), arachidonate secretion (GO:0050482), negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator (GO:1902239), intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator (GO:1990127), system process (GO:0003008), signal transduction (GO:0007165), negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress (GO:1902219)

GO Molecular Function (7): protease binding (GO:0002020), phosphatidylinositol-4,5-bisphosphate phospholipase C activity (GO:0004435), bradykinin receptor activity (GO:0004947), type 1 angiotensin receptor binding (GO:0031702), protein heterodimerization activity (GO:0046982), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (3): endosome (GO:0005768), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
GPCR downstream signalling	2
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
blood vessel diameter maintenance	3
signal transduction	2
regulation of biological quality	2
intrinsic apoptotic signaling pathway in response to osmotic stress	2
muscle contraction	1
defense response	1
enzyme-linked receptor protein signaling pathway	1
G protein-coupled receptor activity	1
circulatory system process	1
response to osmotic stress	1
vasoconstriction	1
regulation of blood circulation	1
vascular process in circulatory system	1
blood circulation	1
icosanoid secretion	1
arachidonate transport	1
negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress	1
regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator	1
negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1
intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator	1
intrinsic apoptotic signaling pathway by p53 class mediator	1
multicellular organismal process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of intrinsic apoptotic signaling pathway in response to osmotic stress	1
negative regulation of intrinsic apoptotic signaling pathway	1
enzyme binding	1
C-type glycerophospholipase activity	1
G protein-coupled peptide receptor activity	1
angiotensin receptor binding	1
protein dimerization activity	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
binding	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1

Protein interactions and networks

STRING

1072 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BDKRB2	KNG1	P01042	999
BDKRB2	AGTR1	P30556	945
BDKRB2	AGT	P01019	900
BDKRB2	ACE	P12821	884
BDKRB2	KLK4	Q9Y5K2	849
BDKRB2	GNAQ	P50148	815
BDKRB2	MTUS1	Q9ULD2	720
BDKRB2	TRPA1	O75762	705
BDKRB2	KLK1	P06870	687
BDKRB2	KLKB1	P03952	668
BDKRB2	TRPV1	Q8NER1	636
BDKRB2	KLK2	P20151	625
BDKRB2	AGTRAP	Q6RW13	612
BDKRB2	CHRM3	P20309	604
BDKRB2	TRPM8	Q7Z2W7	601

IntAct

32 interactions, top by confidence:

A	B	Type	Score
BDKRB2	KNG1	psi-mi:“MI:0915”(physical association)	0.400
BDKRB2	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
BDKRB2	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	BDKRB2	psi-mi:“MI:0915”(physical association)	0.400
CD81	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
CD82	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
CLCA4	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
EFS	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
INF2	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
AATK	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
SYNE1	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
MPI	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
PEX16	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
SLC2A8	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
SLC35A4	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
SPG7	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
SPNS1	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
SYNGR2	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
TMEM11	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
TMEM70	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
TPI1	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
USP4	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
HERC2	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
AP2M1	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
NIF3L1	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
AGTR1	BDKRB2	psi-mi:“MI:0915”(physical association)	0.370
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): NOS1 (Affinity Capture-Western), AGTR1 (Two-hybrid), CD81 (Two-hybrid), CD82 (Two-hybrid), CLCA4 (Two-hybrid), EFS (Two-hybrid), INF2 (Two-hybrid), AATK (Two-hybrid), SYNE1 (Two-hybrid), MPI (Two-hybrid), PEX16 (Two-hybrid), SLC2A8 (Two-hybrid), SLC35A4 (Two-hybrid), SPG7 (Two-hybrid), SPNS1 (Two-hybrid)

ESM2 similar proteins: A0A4W3GG95, A7YY44, B0F9W3, B0UXR0, B2GV46, B3G515, B5X337, E7FEL0, O00398, O46685, O70526, P21556, P25023, P25105, P25116, P26824, P30411, P30558, P32299, P43657, P46002, P46093, P49019, P50132, P56488, Q00991, Q15743, Q1JQB3, Q28642, Q3UFD7, Q4G072, Q4KLH9, Q61038, Q62035, Q80Z39, Q8BFQ3, Q8BFU7, Q8BLG2, Q8BMC0, Q8BUD0

Diamond homologs: A6QNL7, B0F9W3, B3G515, F1MV99, F7EQ49, O08858, O08878, O09047, O15218, O35210, O55197, O70526, O77590, O88680, P21109, P25023, P25024, P25095, P25104, P29089, P29754, P29755, P30411, P30555, P30556, P30937, P30938, P31391, P32299, P32303, P34976, P35343, P35346, P35351, P35370, P35373, P35374, P35377, P35411, P41146

SIGNOR signaling

31 interactions.

A	Effect	B	Mechanism
SRC	up-regulates	BDKRB2	phosphorylation
GRK4	“down-regulates activity”	BDKRB2	phosphorylation
PRKCD	“down-regulates activity”	BDKRB2	phosphorylation
GRK3	“down-regulates activity”	BDKRB2	phosphorylation
GRK6	“down-regulates activity”	BDKRB2	phosphorylation
GRK5	“down-regulates activity”	BDKRB2	phosphorylation
GRK2	“down-regulates activity”	BDKRB2	phosphorylation
BDKRB2	“up-regulates activity”	GNAI1	binding
BDKRB2	“up-regulates activity”	GNAI3	binding
BDKRB2	“up-regulates activity”	GNAO1	binding
BDKRB2	“up-regulates activity”	GNAQ	binding
BDKRB2	“up-regulates activity”	GNA14	binding
BDKRB2	“up-regulates activity”	GNA15	binding
BDKRB2	“up-regulates activity”	GNA12	binding
BDKRB2	“up-regulates activity”	GNA13	binding
Kallidin	“up-regulates activity”	BDKRB2	“chemical activation”
IRX1	“down-regulates quantity by repression”	BDKRB2	“transcriptional regulation”
BDKRB2	up-regulates	Vascular_Permeability
KNG1	“up-regulates activity”	BDKRB2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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.

GO biological processes:

GO term	Partners	Fold	FDR
receptor internalization	5	60.0×	3e-06
intracellular protein transport	5	12.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

864 predictions. Top by Δscore:

Variant	Effect	Δscore
14:96204957:AAG:A	donor_loss	1.0000
14:96204958:AGGT:A	donor_loss	1.0000
14:96204959:GGTG:G	donor_loss	1.0000
14:96204960:G:GA	donor_loss	1.0000
14:96204957:AAGG:A	donor_loss	0.9900
14:96204958:AGG:A	donor_loss	0.9900
14:96204959:GGT:G	donor_loss	0.9900
14:96204960:G:T	donor_loss	0.9900
14:96204961:T:A	donor_loss	0.9900
14:96237067:A:AG	acceptor_gain	0.9900
14:96237068:G:GA	acceptor_gain	0.9900
14:96237068:GC:G	acceptor_gain	0.9900
14:96237178:TCAGG:T	donor_loss	0.9900
14:96237179:CAGGT:C	donor_loss	0.9900
14:96237180:AGGTG:A	donor_loss	0.9900
14:96237181:GGT:G	donor_loss	0.9900
14:96237183:T:G	donor_loss	0.9900
14:96204956:GAAG:G	donor_gain	0.9800
14:96237068:GCCCA:G	acceptor_gain	0.9800
14:96240401:A:AG	acceptor_gain	0.9800
14:96240402:G:GG	acceptor_gain	0.9800
14:96204820:A:G	donor_gain	0.9700
14:96237065:TCA:T	acceptor_loss	0.9700
14:96237067:AGCCC:A	acceptor_loss	0.9700
14:96237068:GCC:G	acceptor_gain	0.9700
14:96237843:G:T	donor_gain	0.9700
14:96240402:GC:G	acceptor_gain	0.9700
14:96237184:GAG:G	donor_loss	0.9600
14:96240402:GCGCC:G	acceptor_gain	0.9600
14:96204930:G:GT	donor_gain	0.9500

AlphaMissense

2586 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:96240782:A:C	S152R	0.996
14:96240784:C:A	S152R	0.996
14:96240784:C:G	S152R	0.996
14:96240716:T:A	C130S	0.995
14:96240717:G:C	C130S	0.995
14:96240755:A:C	S143R	0.995
14:96240757:C:A	S143R	0.995
14:96240757:C:G	S143R	0.995
14:96241163:T:C	F279L	0.995
14:96241165:C:A	F279L	0.995
14:96241165:C:G	F279L	0.995
14:96240697:G:C	W123C	0.994
14:96240697:G:T	W123C	0.994
14:96240792:G:C	R155P	0.994
14:96240872:T:A	W182R	0.994
14:96240872:T:C	W182R	0.994
14:96240860:A:C	S178R	0.992
14:96240862:C:A	S178R	0.992
14:96240862:C:G	S178R	0.992
14:96241301:A:C	S325R	0.992
14:96241303:C:A	S325R	0.992
14:96241303:C:G	S325R	0.992
14:96240695:T:A	W123R	0.991
14:96240695:T:C	W123R	0.991
14:96240758:A:C	S144R	0.991
14:96240760:C:A	S144R	0.991
14:96240760:C:G	S144R	0.991
14:96240959:T:A	C211S	0.991
14:96240960:G:C	C211S	0.991
14:96241035:C:G	P236R	0.991

dbSNP variants (sampled 300 via entrez): RS1000022034 (14:96232997 T>C), RS1000062201 (14:96227589 G>A), RS1000124055 (14:96208683 T>A), RS1000159767 (14:96227894 C>G,T), RS1000174964 (14:96216119 T>C), RS1000312703 (14:96203189 T>C,G), RS1000347082 (14:96203476 G>A), RS1000410527 (14:96227459 G>A), RS1000531523 (14:96227694 T>C,G), RS1000563419 (14:96212367 T>G), RS1000682157 (14:96207526 G>A,T), RS1000775285 (14:96217648 T>G), RS1000786396 (14:96203038 A>T), RS1000878703 (14:96217980 T>A), RS1001034008 (14:96231545 C>G)

Disease associations

OMIM: gene MIM:113503 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary angioedema with normal C1Inh (MONDO:0100567)

Orphanet (1): Hereditary angioedema with normal C1Inh (Orphanet:528647)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001356_20	Gout	1.000000e-07
GCST003170_9	Subcutaneous adipose tissue	5.000000e-08
GCST004069_5	Cerebrospinal fluid AB1-42 levels	5.000000e-06
GCST005003_3	Mumps	5.000000e-12
GCST007159_11	Corneal astigmatism	7.000000e-06
GCST010818_16	Gut microbiota alpha diversity (PD_whole_tree index)	9.000000e-06
GCST90006993_11	Gut microbiota relative abundance (unclassified genus belonging to the order Clostridiales)	5.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0008404	susceptibility to mumps measurement
EFO:1002040	Corneal astigmatism
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3157 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

18 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 544,964 (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
CHEMBL1201303	PYRVINIUM	4	1,797
CHEMBL1201304	INDOCYANINE GREEN ACID FORM	4	7,044
CHEMBL1401	NITAZOXANIDE	4	9,504
CHEMBL1617	RIFAXIMIN	4	13,380
CHEMBL2028850	ICATIBANT	4	108
CHEMBL374478	RIFAMPIN	4	93,834
CHEMBL43	AMSACRINE	4	82,326
CHEMBL535	SUNITINIB	4	79,020
CHEMBL56367	NIMESULIDE	4	25,455
CHEMBL633	AMIODARONE	4	29,704
CHEMBL83	TAMOXIFEN	4	171,635
CHEMBL41286	DIACEREIN	3	5,090
CHEMBL1182210	BENZETHONIUM	2	5,188
CHEMBL2105864	LABRADIMIL	2	467
CHEMBL218427	FASITIBANT	2	14
CHEMBL266195	ALPRENOLOL	2	14,586
CHEMBL406291	BRADYKININ	2	5,784
CHEMBL541758	FASITIBANT CHLORIDE	2	28

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

PharmGKB clinical annotations

6 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1799722	Efficacy	3	enalapril
rs1799722	Toxicity	3	enalapril;imidapril;lisinopril	Cough;Essential hypertension
rs1799722	Metabolism/PK	3	atorvastatin
rs1799722	Toxicity	4	Ace Inhibitors;Plain	Cough
rs8012552	Toxicity	3	Ace Inhibitors;Plain	Cough;Hypertension
rs8016905	Toxicity	3	Ace Inhibitors;Plain	Cough

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1799722	BDKRB2	3	3.00	4	Ace Inhibitors;Plain;atorvastatin;enalapril;enalapril;imidapril;lisinopril
rs8012552	BDKRB2	3	2.00	1	Ace Inhibitors;Plain
rs8016905	BDKRB2	3	3.25	1	Ace Inhibitors;Plain
rs5224	BDKRB2		0.00	0
rs71103505	BDKRB2		0.00	0
rs1046248	BDKRB2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Bradykinin receptors

Most potent curated ligand interactions (29 total), top 25:

Ligand	Action	Affinity	Parameter
[125I]-HPP-icatibant	Antagonist	10.52	pKd
B-9430	Antagonist	9.6	pKi
[3H]BK (human, mouse, rat)	Full agonist	9.4	pKd
[3H]NPC17731	Antagonist	9.4	pKd
deucrictibant	Antagonist	9.33	pKi
compound 3 [PMID: 32636746]	Antagonist	9.3	pKi
bradykinin	Full agonist	9.3	pIC50
kallidin	Full agonist	9.3	pIC50
FR191413	Full agonist	9.2	pIC50
JMV1116	Full agonist	9.2	pKi
Met-Lys-bradykinin	Full agonist	8.7	pIC50
NG291	Agonist	8.7	pIC50
JMV1431	Antagonist	8.4	pKi
icatibant	Antagonist	8.4	pA2
anatibant	Antagonist	8.2	pKi
FR173657	Antagonist	8.1	pIC50
NPC 17731	Antagonist	8.1	pKi
[Tyr8]bradykinin	Full agonist	8.0	pIC50
labradimil	Full agonist	7.5	pIC50
FR190997	Full agonist	7.3	pKi
FR167344	Antagonist	7.2	pIC50
WIN 64338	Antagonist	7.2	pKi
NPC-349	Antagonist	7.0	pIC50
NPC-567	Antagonist	6.9	pIC50
NPC 18565	Antagonist	6.6	pKi

ChEMBL bioactivities

738 potent at pChembl≥5 of 777 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.60	Ki	0.02512	nM	ICATIBANT
10.47	EC50	0.03388	nM	CHEMBL1627325
10.40	Ki	0.03981	nM	CHEMBL1956864
10.31	EC50	0.04898	nM	BRADYKININ
10.30	Ki	0.05012	nM	FASITIBANT
10.30	Ki	0.05012	nM	CHEMBL415366
10.30	Ki	0.05012	nM	CHEMBL387452
10.30	Kd	0.05012	nM	FASITIBANT
10.30	IC50	0.05	nM	FASITIBANT CHLORIDE
10.30	Ki	0.05012	nM	CHEMBL1956855
10.30	Ki	0.05012	nM	CHEMBL1956856
10.30	Ki	0.05012	nM	CHEMBL1956863
10.30	Ki	0.05012	nM	CHEMBL1956876
10.22	Ki	0.06	nM	ICATIBANT
10.20	Ki	0.0631	nM	CHEMBL1956719
10.20	Ki	0.0631	nM	CHEMBL1956858
10.20	Ki	0.0631	nM	CHEMBL1956870
10.19	Ki	0.064	nM	ICATIBANT
10.19	Ki	0.065	nM	BRADYKININ
10.15	Ki	0.07	nM	CHEMBL440257
10.10	Ki	0.08	nM	CHEMBL3142396
10.10	Ki	0.07943	nM	CHEMBL373607
10.10	Ki	0.07943	nM	CHEMBL1956720
10.10	Ki	0.07943	nM	CHEMBL1956722
10.10	Ki	0.07943	nM	CHEMBL1956854
10.10	Ki	0.07943	nM	CHEMBL1956862
10.00	Ki	0.1	nM	CHEMBL221285
10.00	Ki	0.1	nM	CHEMBL1956853
10.00	Ki	0.1	nM	CHEMBL1956857
10.00	Ki	0.1	nM	CHEMBL1956861
9.96	Ki	0.11	nM	BRADYKININ
9.91	Kd	0.123	nM	CHEMBL1956856
9.90	Ki	0.1259	nM	CHEMBL220478
9.90	Ki	0.1259	nM	CHEMBL375354
9.90	Ki	0.1259	nM	CHEMBL1956718
9.90	Ki	0.1259	nM	CHEMBL1956721
9.90	Ki	0.1259	nM	CHEMBL1956723
9.82	Ki	0.15	nM	CHEMBL109123
9.80	Ki	0.1585	nM	CHEMBL218636
9.80	Kd	0.1585	nM	CHEMBL415366
9.80	Ki	0.1585	nM	CHEMBL1956875
9.78	Ki	0.166	nM	CHEMBL3038098
9.77	IC50	0.17	nM	CHEMBL3216880
9.74	Ki	0.18	nM	CHEMBL5274928
9.74	IC50	0.18	nM	CHEMBL543070
9.74	Ki	0.182	nM	ICATIBANT
9.70	Ki	0.1995	nM	CHEMBL218540
9.70	Ki	0.1995	nM	CHEMBL415151
9.70	Ki	0.1995	nM	CHEMBL374224
9.70	Ki	0.1995	nM	CHEMBL374272

PubChem BioAssay actives

690 with measured affinity, of 2153 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
(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[2-[[(2S)-1-[(2S)-1-[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	375520: Antagonist activity at human recombinant bradykinin 2 receptor expressed in CHO cells assessed as inhibition of bradykinin-induced intracellular calcium mobilization	ec50	<0.0001	uM
(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2R)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-oxobutanoyl]amino]-3,3-dimethylbutanoyl]amino]-3-methylbutanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]amino]hexanoyl]amino]-3-hydroxypropanoic acid	375520: Antagonist activity at human recombinant bradykinin 2 receptor expressed in CHO cells assessed as inhibition of bradykinin-induced intracellular calcium mobilization	ec50	<0.0001	uM
6-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]-1-methylpiperazin-1-ium-1-yl]hexyl-trimethylazanium;bis(2,2,2-trifluoroacetate)	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	<0.0001	uM
Icatibant	263934: Binding affinity to human bradykinin B2 receptor transfected in CHO cells	ki	<0.0001	uM
[(2S)-6-amino-1-[4-[1-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]cyclopentanecarbonyl]piperazin-1-yl]-1-oxohexan-2-yl]-trimethylazanium	277734: Displacement of [3H]BK from human bradykinin B2 receptor transfected in CHO cells	ki	0.0001	uM
[(4S)-4-amino-5-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperazin-1-yl]-5-oxopentyl]-trimethylazanium	277734: Displacement of [3H]BK from human bradykinin B2 receptor transfected in CHO cells	ki	0.0001	uM
[(4S)-4-amino-5-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperazin-1-yl]-5-oxopentyl]-trimethylazanium chloride	421293: Displacement of [3H]bradykinin from human recombinant B2 receptor expressed in HEK293 cells	ic50	0.0001	uM
[(4S)-4-amino-5-[4-[1-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]cyclopentanecarbonyl]piperazin-1-yl]-5-oxopentyl]-trimethylazanium	277734: Displacement of [3H]BK from human bradykinin B2 receptor transfected in CHO cells	ki	0.0001	uM
[(3S)-6-amino-1-[4-[1-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]cyclopentanecarbonyl]piperazin-1-yl]-1-oxohexan-3-yl]-trimethylazanium	277734: Displacement of [3H]BK from human bradykinin B2 receptor transfected in CHO cells	ki	0.0001	uM
[(4S)-4-amino-5-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]-1-methylpiperidine-4-carbonyl]piperazin-1-yl]-5-oxopentyl]-trimethylazanium	277734: Displacement of [3H]BK from human bradykinin B2 receptor transfected in CHO cells	ki	0.0001	uM
[(2S)-6-(diaminomethylideneamino)-1-[4-[1-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]cyclopentanecarbonyl]piperazin-1-yl]-1-oxohexan-2-yl]-trimethylazanium	277734: Displacement of [3H]BK from human bradykinin B2 receptor transfected in CHO cells	ki	0.0001	uM
[(4S)-4-amino-5-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]thiane-4-carbonyl]piperazin-1-yl]-5-oxopentyl]-trimethylazanium	277734: Displacement of [3H]BK from human bradykinin B2 receptor transfected in CHO cells	ki	0.0001	uM
8-methyl-3-(2-oxopropyl)-1-(2-phenylethyl)-1,3,8-triazaspiro[4.5]decan-4-one	43285: Affinity to human Bradykinin receptor B2 in CHO cell membranes determined by displacement of [3H]-NPC 17731	ki	0.0001	uM
(2R)-2-[[2-[3-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-1-[(2S)-1-[(2S)-2-[[(2S)-2,6-diaminohexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]acetyl]amino]-3-thiophen-2-ylpropanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxo-2,3-dihydro-1,5-benzothiazepin-5-yl]acetyl]amino]-5-(diaminomethylideneamino)pentanoic acid	43290: Binding affinity towards human cloned Bradykinin receptor B2 expressed in CHO cells by [3H]bradykinin displacement.	ki	0.0001	uM
2-[(5S)-5-amino-6-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperazin-1-yl]-6-oxohexyl]guanidine;2,2,2-trifluoroacetic acid	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
4-[[1-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperidin-4-yl]methylamino]butyl-trimethylazanium;2,2,2-trifluoroacetate	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
2,4-dichloro-N-[4-[4-[(2S)-2,5-diaminopentanoyl]piperazine-1-carbonyl]oxan-4-yl]-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]benzenesulfonamide;2,2,2-trifluoroacetic acid	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
N-[4-[4-(5-aminopentanoyl)piperazine-1-carbonyl]oxan-4-yl]-2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]benzenesulfonamide;2,2,2-trifluoroacetic acid	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
3-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]-1-methylpiperazin-1-ium-1-yl]propyl-trimethylazanium;bis(2,2,2-trifluoroacetate)	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
[5-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperazin-1-yl]-5-oxopentyl]-trimethylazanium;2,2,2-trifluoroacetate	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
4-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]-1-methylpiperazin-1-ium-1-yl]butyl-trimethylazanium;bis(2,2,2-trifluoroacetate)	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
[2-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperazin-1-yl]-2-oxoethyl]-trimethylazanium;2,2,2-trifluoroacetate	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
N-[4-[4-[(2S)-2-amino-6-(dimethylamino)hexanoyl]piperazine-1-carbonyl]oxan-4-yl]-2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]benzenesulfonamide;2,2,2-trifluoroacetic acid	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
[6-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperazin-1-yl]-6-oxohexyl]-trimethylazanium;2,2,2-trifluoroacetate	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
2,4-dichloro-N-[4-[4-[5-(dimethylamino)pentanoyl]piperazine-1-carbonyl]oxan-4-yl]-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]benzenesulfonamide;2,2,2-trifluoroacetic acid	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
2,4-dichloro-N-[4-[4-[(2S)-2,6-diaminohexanoyl]piperazine-1-carbonyl]oxan-4-yl]-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]benzenesulfonamide;2,2,2-trifluoroacetic acid	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
5-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]-1-methylpiperazin-1-ium-1-yl]pentyl-trimethylazanium;bis(2,2,2-trifluoroacetate)	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
6-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperazin-1-yl]hexyl-trimethylazanium;2,2,2-trifluoroacetate	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
2-[(4S)-4-amino-5-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperazin-1-yl]-5-oxopentyl]guanidine;2,2,2-trifluoroacetic acid	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
[4-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperazin-1-yl]-4-oxobutyl]-trimethylazanium;2,2,2-trifluoroacetate	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
N-[4-[4-[(2S)-2-amino-5-(dimethylamino)pentanoyl]piperazine-1-carbonyl]oxan-4-yl]-2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]benzenesulfonamide;2,2,2-trifluoroacetic acid	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0001	uM
(2S)-2-[[(2S)-1-[(3S)-2-[(2S)-2-[[(2S)-2-[[2-[[(2S)-1-[(2S)-1-[(2R)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]acetyl]amino]-3-thiophen-2-ylpropanoyl]amino]-3-hydroxypropanoyl]-3,4-dihydro-1H-isoquinoline-3-carbonyl]-2,3-dihydroindole-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid	43292: Ability to bind to human cloned B2 receptor in competition binding experiments with [3H]- bradykinin	ki	0.0001	uM
[(2S)-1-[4-[1-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]cyclopentanecarbonyl]piperazin-1-yl]-1-oxo-6-(trimethylazaniumyl)hexan-2-yl]-trimethylazanium	277734: Displacement of [3H]BK from human bradykinin B2 receptor transfected in CHO cells	ki	0.0002	uM
N-[1-[4-[(2S)-2,6-bis(dimethylamino)hexanoyl]piperazine-1-carbonyl]cyclopentyl]-2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]benzenesulfonamide	277734: Displacement of [3H]BK from human bradykinin B2 receptor transfected in CHO cells	ki	0.0002	uM
[(2S)-1-[4-[1-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]cyclopentanecarbonyl]piperazin-1-yl]-1-oxo-5-(trimethylazaniumyl)pentan-2-yl]-trimethylazanium	277734: Displacement of [3H]BK from human bradykinin B2 receptor transfected in CHO cells	ki	0.0002	uM
[(4S)-5-[4-[1-acetyl-4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]piperidine-4-carbonyl]piperazin-1-yl]-4-amino-5-oxopentyl]-trimethylazanium	277734: Displacement of [3H]BK from human bradykinin B2 receptor transfected in CHO cells	ki	0.0002	uM
2-[[(2S,3aS,6aS)-1-[(3R)-2-[(2S)-2-[[(2S)-2-[[2-[[(2S,4R)-1-[(2S)-1-[(2S)-2-[[(2R)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]acetyl]amino]-3-thiophen-2-ylpropanoyl]amino]-3-hydroxypropanoyl]-3,4-dihydro-1H-isoquinoline-3-carbonyl]-3,3a,4,5,6,6a-hexahydro-2H-cyclopenta[b]pyrrole-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid	1954035: Binding affinity to B2 bradykinin receptor (unknown origin)	ki	0.0002	uM
4-[[2-[2,4-dichloro-3-[(4-imidazol-1-yl-2-methylquinolin-8-yl)oxymethyl]-N-methylanilino]-2-oxoethyl]carbamoylamino]-N-pyridin-4-ylbenzamide;hydrochloride	43156: In vitro inhibitory activity towards human bradykinin receptor B2 expressed in CHO cells using [3H]BK (1.0 nM) as a radioligand	ic50	0.0002	uM
4-[(E)-3-[[2-[2,4-dichloro-N-methyl-3-[(2-methyl-4-pyrazol-1-ylquinolin-8-yl)oxymethyl]anilino]-2-oxoethyl]amino]-3-oxoprop-1-enyl]-N,N-dimethylbenzamide;hydrochloride	43156: In vitro inhibitory activity towards human bradykinin receptor B2 expressed in CHO cells using [3H]BK (1.0 nM) as a radioligand	ic50	0.0002	uM
2-[[1-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperidin-4-yl]methylamino]ethyl-trimethylazanium;2,2,2-trifluoroacetate	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0002	uM
[7-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperazin-1-yl]-7-oxoheptyl]-trimethylazanium;2,2,2-trifluoroacetate	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0002	uM
3-[[1-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperidin-4-yl]methylamino]propyl-trimethylazanium;2,2,2-trifluoroacetate	648773: Displacement of [3H]-Bradykinin from human bradykinin B2 receptor expressed in CHO cells membrane after 60 mins by scintillation counting	ki	0.0002	uM
(2S)-2-[[2-[[(3R)-2-[(2S)-2-[[(2S)-2-[[2-[[(2S,4R)-1-[(2S)-1-[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]acetyl]amino]-3-thiophen-2-ylpropanoyl]amino]-3-hydroxypropanoyl]-3,4-dihydro-1H-isoquinoline-3-carbonyl]-(cyclohexylmethyl)amino]acetyl]amino]-5-(diaminomethylideneamino)pentanoic acid	43145: Binding affinity towards Bradykinin receptor B2 in human S34 clone cells	ki	0.0002	uM
(2S)-2-[[2-[[(3R)-2-[(2S)-2-[[(2S)-2-[[2-[[(2S,4R)-1-[(2S)-1-[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]acetyl]amino]-3-thiophen-2-ylpropanoyl]amino]-3-hydroxypropanoyl]-3,4-dihydro-1H-isoquinoline-3-carbonyl]-cyclohexylamino]acetyl]amino]-5-(diaminomethylideneamino)pentanoic acid	43299: Binding affinity towards Bradykinin receptor B2 in human S34 clone cells	ki	0.0002	uM
(2S)-2-[[2-[[(3R)-2-[(2S)-2-[[(2S)-2-[[2-[[(2R,4S)-1-[(2R,4S)-1-[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]-4-hydroxypyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]acetyl]amino]-3-thiophen-2-ylpropanoyl]amino]-3-hydroxypropanoyl]-3,4-dihydro-1H-isoquinoline-3-carbonyl]-cyclohexylamino]acetyl]amino]-5-(diaminomethylideneamino)pentanoic acid	43145: Binding affinity towards Bradykinin receptor B2 in human S34 clone cells	ki	0.0002	uM
4-[(E)-3-[[2-[2,4-dichloro-N-methyl-3-[(2-methyl-4-pyrazol-1-ylquinolin-8-yl)oxymethyl]anilino]-2-oxoethyl]amino]-3-oxoprop-1-enyl]-N-methylbenzamide;tetrahydrochloride	43156: In vitro inhibitory activity towards human bradykinin receptor B2 expressed in CHO cells using [3H]BK (1.0 nM) as a radioligand	ic50	0.0002	uM
4-[(E)-3-[[2-[2,4-dichloro-N-methyl-3-[[2-methyl-4-(1,2,4-triazol-1-yl)quinolin-8-yl]oxymethyl]anilino]-2-oxoethyl]amino]-3-oxoprop-1-enyl]-N-methylbenzamide;tetrahydrochloride	43156: In vitro inhibitory activity towards human bradykinin receptor B2 expressed in CHO cells using [3H]BK (1.0 nM) as a radioligand	ic50	0.0002	uM
[(4S)-4-amino-6-[4-[1-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]cyclopentanecarbonyl]piperazin-1-yl]-6-oxohexyl]-trimethylazanium	277734: Displacement of [3H]BK from human bradykinin B2 receptor transfected in CHO cells	ki	0.0002	uM
4-[(E)-3-[[1-[2,4-dichloro-3-[(4-imidazol-1-yl-2-methylquinolin-8-yl)oxymethyl]phenyl]pyrrol-2-yl]methylamino]-3-oxoprop-1-enyl]-N,N-dimethylbenzamide	1564242: Displacement of [3H]bradykinin from human recombinant bradykinin B2 receptor expressed in CHO cells incubated for 2 hrs by liquid scintillation counter	ic50	0.0003	uM
2-[(5S)-5-amino-6-[4-[1-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]cyclopentanecarbonyl]piperazin-1-yl]-6-oxohexyl]guanidine	277735: Antagonist potency at human bradykinin B2 receptor assessed as effect on inositol monophosphate accumulation in CHOdhfr- cells	kd	0.0003	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	4
Benzo(a)pyrene	affects methylation, increases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, affects expression, increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
icatibant	affects binding, decreases activity, decreases reaction, increases activity	2
FR 173657	increases activity, affects binding, decreases activity, decreases reaction	2
MEN 11270	affects binding, decreases activity, decreases reaction, increases activity	2
Resveratrol	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Tretinoin	increases expression	2
aristolochic acid I	decreases expression	1
allyl isothiocyanate	increases activity, increases reaction	1
methyleugenol	increases expression	1
terbufos	increases methylation	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression, decreases expression	1
diallyl trisulfide	decreases expression	1
15-acetyldeoxynivalenol	increases expression	1
CGP 52608	increases reaction, affects binding	1
FR 190997	affects binding, decreases reaction, increases activity	1
LF 16-0687	affects binding, decreases reaction, increases activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression, increases expression	1
Arsenic Trioxide	increases expression	1

ChEMBL screening assays

225 unique, capped per target: 186 binding, 38 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000164	Binding	Binding affinity to CCK1 receptor	Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists. — J Med Chem
CHEMBL1001563	Functional	Antagonist activity at human recombinant bradykinin 2 receptor expressed in CHO cells assessed as inhibition of bradykinin-induced intracellular calcium mobilization	Further studies at neuropeptide s position 5: discovery of novel neuropeptide S receptor antagonists. — J Med Chem
CHEMBL4810227	ADMET	Inhibition of BK2 (unknown origin) at 0.1 to 1 uM	Discovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. — J Med Chem

Cellosaurus cell lines

10 cell lines: 4 cancer cell line, 4 spontaneously immortalized cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7KY	Ubigene A-549 BDKRB2 KO	Cancer cell line	Male
CVCL_D9YJ	Ubigene HeLa BDKRB2 KO	Cancer cell line	Female
CVCL_E3KZ	CHO-K1 BDKRB2 clone #14	Spontaneously immortalized cell line	Female
CVCL_H403	CHO-K1/B2/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KB33	GeneBLAzer Bradykinin-B2-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female
CVCL_KW41	PathHunter CHO-K1 BDKRB2 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ34	PathHunter HEK 293 BDKRB2 beta-arrestin	Transformed cell line	Female
CVCL_KZ79	PathHunter U2OS BDKRB2 Activated GPCR Internalization	Cancer cell line	Female
CVCL_YK03	HEK293 BDKRB2 HiTSeeker	Transformed cell line	Female
CVCL_YK32	U2OS BDKRB2 HiTSeeker	Cancer cell line	Female

Clinical trials (associated diseases)

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