TAS2R46

Summary

TAS2R46 (taste 2 receptor member 46, HGNC:18877) is a protein-coding gene on chromosome 12p13.2, encoding Taste receptor type 2 member 46 (P59540). Receptor that may play a role in the perception of bitterness and is gustducin-linked.

TAS2R46 belongs to the large TAS2R receptor family. TAS2Rs are expressed on the surface of taste receptor cells and mediate the perception of bitterness through a G protein-coupled second messenger pathway (Conte et al., 2002 [PubMed 12584440]). For further information on TAS2Rs, see MIM 604791.

Source: NCBI Gene 259292 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 1 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_176887

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18877
Approved symbol	TAS2R46
Name	taste 2 receptor member 46
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Aliases	T2R54
Ensembl gene	ENSG00000226761
Ensembl biotype	protein_coding
OMIM	612774
Entrez	259292

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000533467

RefSeq mRNA: 1 — MANE Select: NM_176887 NM_176887

CCDS: CCDS53748

Canonical transcript exons

ENST00000533467 — 1 exons

Exon	Start	End
ENSE00002166585	11061365	11062294

Expression profiles

Bgee: expression breadth broad, 42 present calls, max score 74.80.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.80	gold quality
adrenal tissue	UBERON:0018303	67.11	gold quality
corpus callosum	UBERON:0002336	65.37	gold quality
calcaneal tendon	UBERON:0003701	59.51	gold quality
bone marrow cell	CL:0002092	57.83	silver quality
tonsil	UBERON:0002372	51.17	silver quality
colonic epithelium	UBERON:0000397	50.90	silver quality
sural nerve	UBERON:0015488	49.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	49.47	gold quality
skeletal muscle tissue	UBERON:0001134	48.36	gold quality
stromal cell of endometrium	CL:0002255	42.39	silver quality
muscle tissue	UBERON:0002385	42.07	gold quality
ventricular zone	UBERON:0003053	40.81	gold quality
right coronary artery	UBERON:0001625	40.60	silver quality
leukocyte	CL:0000738	40.52	gold quality
urinary bladder	UBERON:0001255	40.47	silver quality
monocyte	CL:0000576	40.28	gold quality
ganglionic eminence	UBERON:0004023	39.97	gold quality
liver	UBERON:0002107	39.37	gold quality
granulocyte	CL:0000094	38.15	gold quality
mucosa of transverse colon	UBERON:0004991	36.95	silver quality
lung	UBERON:0002048	36.63	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
right ovary	UBERON:0002118	36.17	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	35.98	gold quality
blood	UBERON:0000178	35.31	gold quality
adrenal gland	UBERON:0002369	34.40	gold quality
primary visual cortex	UBERON:0002436	34.30	gold quality
kidney	UBERON:0002113	33.56	gold quality
stomach	UBERON:0000945	33.51	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 7)

• MSC express the bitter taste receptor, TAS2R46, a protein more typically localized to the taste bud. Expression was also confirmed in VSMCs. (PMID:23520545)
• Gastrointestinal cancer risk is not associated with any TAS2R46 genotypes since there were no significant differences in genotype frequencies between cancer patients and controls (PMID:28552880)
• TAS2R46G>A rs2708381 is not associated with recurrent pregnancy loss in Korean women. (PMID:30203366)
• Absinthin, an agonist of the bitter taste receptor hTAS2R46, uncovers an ER-to-mitochondria Ca(2+)-shuttling event. (PMID:31248983)
• Structural basis for strychnine activation of human bitter taste receptor TAS2R46. (PMID:36108005)
• Bitter Taste Receptor 46 (hTAS2R46) Protects Monocytes/Macrophages from Oxidative Stress. (PMID:39000432)
• Single-Nucleotide Polymorphisms of TAS2R46 Affect the Receptor Downstream Calcium Regulation in Histamine-Challenged Cells. (PMID:39056786)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tas2r136	ENSMUSG00000053217
mus_musculus	Tas2r120	ENSMUSG00000059382
rattus_norvegicus	Tas2r120	ENSRNOG00000021445
rattus_norvegicus	Tas2r136	ENSRNOG00000029561

Paralogs (23): TAS2R8 (ENSG00000121314), TAS2R10 (ENSG00000121318), TAS2R7 (ENSG00000121377), TAS2R9 (ENSG00000121381), TAS2R3 (ENSG00000127362), TAS2R4 (ENSG00000127364), TAS2R5 (ENSG00000127366), TAS2R16 (ENSG00000128519), TAS2R1 (ENSG00000169777), TAS2R60 (ENSG00000185899), TAS2R42 (ENSG00000186136), TAS2R19 (ENSG00000212124), TAS2R50 (ENSG00000212126), TAS2R14 (ENSG00000212127), TAS2R13 (ENSG00000212128), TAS2R41 (ENSG00000221855), TAS2R40 (ENSG00000221937), TAS2R39 (ENSG00000236398), TAS2R43 (ENSG00000255374), TAS2R20 (ENSG00000255837), TAS2R30 (ENSG00000256188), TAS2R31 (ENSG00000256436), TAS2R38 (ENSG00000257138)

Protein

Protein identifiers

Taste receptor type 2 member 46 — P59540 (reviewed: P59540)

Alternative names: Taste receptor type 2 member 54

All UniProt accessions (1): P59540

UniProt curated annotations — full annotation on UniProt →

Function. Receptor that may play a role in the perception of bitterness and is gustducin-linked. May play a role in sensing the chemical composition of the gastrointestinal content. The activity of this receptor may stimulate alpha gustducin, mediate PLC-beta-2 activation and lead to the gating of TRPM5. In airway epithelial cells, binding of bitter compounds increases the intracellular calcium ion concentration and stimulates ciliary beat frequency.

Subcellular location. Membrane. Cell projection. Cilium membrane.

Tissue specificity. Expressed in subsets of taste receptor cells of the tongue and exclusively in gustducin-positive cells. Expressed on ciliated airway epithelium.

Miscellaneous. Most taste cells may be activated by a limited number of bitter compounds; individual taste cells can discriminate among bitter stimuli.

Similarity. Belongs to the G-protein coupled receptor T2R family.

RefSeq proteins (1): NP_795368* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007960	TAS2R	Family

Pfam: PF05296

UniProt features (35 total): helix 11, topological domain 8, transmembrane region 7, turn 3, glycosylation site 2, chain 1, sequence variant 1, sequence conflict 1, strand 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
9W0R	ELECTRON MICROSCOPY	2.7
9W0U	ELECTRON MICROSCOPY	2.9
7XP4	ELECTRON MICROSCOPY	3.01
7XP6	ELECTRON MICROSCOPY	3.01
7XP5	ELECTRON MICROSCOPY	3.08
9W0W	ELECTRON MICROSCOPY	3.2
9W0S	ELECTRON MICROSCOPY	3.3
9W0T	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P59540-F1	86.06	0.43

Antibody-complex structures (SAbDab): 3 — 7XP4, 7XP5, 7XP6

Functional residue map

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

Glycosylation sites (2): 161, 176

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events
R-HSA-420499	Class C/3 (Metabotropic glutamate/pheromone receptors)
R-HSA-9717207	Sensory perception of sweet, bitter, and umami (glutamate) taste
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding
R-HSA-9709957	Sensory Perception
R-HSA-9717189	Sensory perception of taste

MSigDB gene sets: 32 (showing top): GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, GOBP_DETECTION_OF_CHEMICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION_OF_TASTE, GOBP_SENSORY_PERCEPTION_OF_TASTE, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION, GOCC_CELL_PROJECTION_MEMBRANE, GOCC_PLASMA_MEMBRANE_REGION, GOCC_CILIARY_MEMBRANE, GOCC_CILIUM, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_BITTER_TASTE_RECEPTOR_ACTIVITY, GOMF_TASTE_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_DETECTION_OF_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION

GO Biological Process (4): detection of chemical stimulus involved in sensory perception of bitter taste (GO:0001580), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), sensory perception of taste (GO:0050909)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), bitter taste receptor activity (GO:0033038)

GO Cellular Component (5): plasma membrane (GO:0005886), membrane (GO:0016020), ciliary membrane (GO:0060170), cilium (GO:0005929), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by GPCR	2
GPCR downstream signalling	1
GPCR ligand binding	1
Sensory perception of taste	1
Signal Transduction	1
Sensory Perception	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
detection of chemical stimulus involved in sensory perception of taste	1
sensory perception of bitter taste	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
sensory perception of chemical stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
detection of chemical stimulus involved in sensory perception of bitter taste	1
taste receptor activity	1
membrane	1
cell periphery	1
cilium	1
cell projection membrane	1
bounding membrane of organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

326 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAS2R46	GNAT3	A8MTJ3	907
TAS2R46	PLCB2	Q00722	898
TAS2R46	TAS1R2	Q8TE23	606
TAS2R46	TAS1R1	Q7RTX1	574
TAS2R46	PKD2L1	Q9P0L9	521
TAS2R46	ZNF799	Q96GE5	479
TAS2R46	PKD1L3	Q7Z443	456
TAS2R46	TRPM5	Q9NZQ8	438
TAS2R46	TAS1R3	Q7RTX0	431
TAS2R46	OR6C1	Q96RD1	416
TAS2R46	OR4C16	Q8NGL9	408
TAS2R46	OR5M3	Q8NGP4	390
TAS2R46	HCN4	Q9Y3Q4	387
TAS2R46	FAM170B	A6NMN3	370
TAS2R46	TAS2R4	Q9NYW5	363

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: P0DSN6, P0DTE0, P59537, P59538, P59539, P59540, P59541, P59542, P59543, P59544, Q5Y4Y8, Q5Y4Y9, Q5Y4Z5, Q5Y4Z8, Q5Y500, Q645T2, Q645T3, Q645T4, Q645T6, Q645V2, Q645V3, Q645V4, Q645V6, Q645V7, Q645Z2, Q645Z6, Q645Z7, Q645Z9, Q646A0, Q646A1, Q646B4, Q646B9, Q646C0, Q646C1, Q646C2, Q646C3, Q646E0, Q646E1, Q646E2, Q646E3

Diamond homologs: P0DSN6, P0DTE0, P59528, P59530, P59537, P59538, P59539, P59540, P59541, P59542, P59543, P59544, Q5Y4Y8, Q5Y4Y9, Q5Y4Z5, Q5Y4Z8, Q5Y500, Q645T0, Q645T2, Q645T3, Q645T4, Q645T6, Q645T7, Q645U8, Q645V1, Q645V2, Q645V3, Q645V4, Q645V6, Q645V7, Q645V8, Q645V9, Q645Z2, Q645Z5, Q645Z6, Q645Z7, Q645Z9, Q646A0, Q646A1, Q646A2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

332 predictions. Top by Δscore:

Variant	Effect	Δscore
12:11061900:A:AC	donor_gain	0.7500
12:11061418:C:CC	acceptor_gain	0.7100
12:11061672:T:C	acceptor_gain	0.7000
12:11061413:CAAAA:C	acceptor_gain	0.6600
12:11061684:T:TC	acceptor_gain	0.6400
12:11061671:C:CC	acceptor_gain	0.6300
12:11061550:C:CC	acceptor_gain	0.6100
12:11061672:T:TC	acceptor_gain	0.6100
12:11061700:T:TC	acceptor_gain	0.6100
12:11061921:A:C	donor_gain	0.6100
12:11061925:T:A	donor_gain	0.6100
12:11061929:C:CC	acceptor_gain	0.6100
12:11062109:TAA:T	donor_gain	0.6100
12:11062056:A:AC	donor_gain	0.6000
12:11062057:C:CC	donor_gain	0.6000
12:11061687:C:CT	acceptor_gain	0.5900
12:11061559:T:TC	acceptor_gain	0.5700
12:11061689:C:CT	acceptor_gain	0.5700
12:11061705:A:T	acceptor_gain	0.5700
12:11062058:TTCTA:T	donor_gain	0.5700
12:11062059:TCTAT:T	donor_gain	0.5700
12:11061555:A:C	acceptor_gain	0.5600
12:11061680:A:C	acceptor_gain	0.5600
12:11061849:A:C	acceptor_gain	0.5600
12:11061668:CAT:C	acceptor_gain	0.5500
12:11061682:G:C	acceptor_gain	0.5500
12:11061857:C:CT	acceptor_gain	0.5500
12:11061669:ATC:A	acceptor_loss	0.5400
12:11061670:TCT:T	acceptor_loss	0.5400
12:11062057:CTT:C	donor_gain	0.5400

AlphaMissense

2038 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:11061986:G:C	S103R	0.880
12:11061986:G:T	S103R	0.880
12:11061988:T:G	S103R	0.880
12:11061941:A:C	F118L	0.861
12:11061941:A:T	F118L	0.861
12:11061943:A:G	F118L	0.861
12:11062010:G:C	S95R	0.843
12:11062010:G:T	S95R	0.843
12:11062012:T:G	S95R	0.843
12:11061593:G:C	F234L	0.834
12:11061593:G:T	F234L	0.834
12:11061595:A:G	F234L	0.834
12:11062217:G:C	F26L	0.823
12:11062217:G:T	F26L	0.823
12:11062219:A:G	F26L	0.823
12:11062117:A:G	W60R	0.822
12:11062117:A:T	W60R	0.822
12:11061992:G:C	S101R	0.815
12:11061992:G:T	S101R	0.815
12:11061994:T:G	S101R	0.815
12:11061956:G:C	F113L	0.802
12:11061956:G:T	F113L	0.802
12:11061958:A:G	F113L	0.802
12:11062244:A:C	F17L	0.772
12:11062244:A:T	F17L	0.772
12:11062246:A:G	F17L	0.772
12:11062223:A:C	N24K	0.769
12:11062223:A:T	N24K	0.769
12:11062006:A:G	W97R	0.759
12:11062006:A:T	W97R	0.759

dbSNP variants (sampled 300 via entrez): RS1001601109 (12:11061640 G>A,C,T), RS1001611851 (12:11063919 A>T), RS1001843224 (12:11063059 C>G,T), RS1001935966 (12:11062882 T>A), RS1003278837 (12:11062539 A>G), RS1004956487 (12:11062183 T>C), RS1004959373 (12:11061082 G>A,T), RS1005728733 (12:11064257 G>A), RS1006369114 (12:11060893 G>A), RS1007395972 (12:11063046 T>C), RS1008989995 (12:11062811 A>C), RS1009083273 (12:11062460 T>A,C), RS1009086984 (12:11061891 C>T), RS1009274633 (12:11062816 T>C), RS1010221329 (12:11063005 TA>T,TAA)

Disease associations

OMIM: gene MIM:612774 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002144_3	Bitter taste perception	3.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523253 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 73,457 (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
CHEMBL434	ISOPROTERENOL	4	40,234
CHEMBL52440	DEXTROMETHORPHAN	4	33,223

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Taste 2 receptors

Most potent curated ligand interactions (12 total), top 12:

Ligand	Action	Affinity	Parameter
lactucopicrin	Agonist	6.46	pEC50
strychnine	Agonist	6.37	pEC50
oligoporin D	Agonist	5.82	pEC50
3β-hydroxydihydrocostunolide	Antagonist	5.33	pIC50
grosheimin	Agonist	5.25	pEC50
absinthin	Agonist	5.0	pEC50
bengalensol	Agonist	4.92	pEC50
andrographolide	Agonist	4.89	pEC50
amarogentin	Agonist	4.17	pEC50
picrotoxinin	Agonist	4.15	pEC50
denatonium	Agonist	3.62	pEC50
colchicine	Agonist	2.8	pEC50

ChEMBL bioactivities

16 potent at pChembl≥5 of 35 total, top 16 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.31	EC50	4.9	nM	ISOPROTERENOL
6.16	EC50	690	nM	STRYCHNINE
5.96	EC50	1100	nM	CHEMBL4535452
5.96	EC50	1100	nM	CHEMBL4446651
5.56	EC50	2740	nM	CHEMBL4582048
5.32	IC50	4810	nM	CHEMBL4440983
5.32	IC50	4810	nM	CHEMBL4582048
5.31	IC50	4930	nM	CHEMBL4440983
5.31	IC50	4930	nM	CHEMBL4582048
5.27	EC50	5390	nM	CHEMBL4582048
5.17	IC50	6780	nM	CHEMBL4440983
5.17	IC50	6780	nM	CHEMBL4582048
5.08	EC50	8300	nM	DIHYDRO COSTUNOLIDE
5.08	EC50	8300	nM	CHEMBL4564347
5.07	EC50	8600	nM	COSTUNOLIDE
5.07	EC50	8600	nM	CHEMBL4435198

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-methyl-4-isothiazolin-3-one	decreases expression	1
CGP 52608	affects binding, increases reaction	1
MT19c compound	increases expression	1
Ethanol	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases expression	1
Folic Acid	affects cotreatment, increases expression	1
Silicon Dioxide	decreases expression	1

ChEMBL screening assays

101 unique, capped per target: 81 functional, 20 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4417681	Functional	Activation of full-length human TAS2R46 expressed in HEK293T/Galpha16-gustducin 44 cells assessed as effect on calcium flux by measuring deltaF/F0 ratio at 100 mM by Fluo-4 dye based FLIPR assay	Methods to identify tas2r modulators
CHEMBL4624177	Binding	Agonist activity at human TAS2R46 expressed in human BEAS2B cells assessed as antiinflammatory activity by measuring reduction in PMA-induced iNOS mRNA level at 10 uM incubated for 18 hrs by qRT-PCR analysis	Anti-inflammatory Activity of Absinthin and Derivatives in Human Bronchoepithelial Cells. — J Nat Prod

Clinical trials (associated diseases)

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