TAS2R43

Summary

TAS2R43 (taste 2 receptor member 43, HGNC:18875) is a protein-coding gene on chromosome 12p13.2, encoding Taste receptor type 2 member 43 (P59537). Gustducin-coupled receptor immplicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract.

TAS2R43 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 259289 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 5 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_176884

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18875
Approved symbol	TAS2R43
Name	taste 2 receptor member 43
Location	12p13.2
Locus type	gene with protein product
Status	Approved
Aliases	T2R52
Ensembl gene	ENSG00000255374
Ensembl biotype	protein_coding
OMIM	612668
Entrez	259289

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000531678

RefSeq mRNA: 1 — MANE Select: NM_176884 NM_176884

CCDS: CCDS53749

Canonical transcript exons

ENST00000531678 — 1 exons

Exon	Start	End
ENSE00002156831	11091287	11092313

Expression profiles

Bgee: expression breadth broad, 95 present calls, max score 85.78.

Top tissues by expression

112 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	85.78	gold quality
adrenal tissue	UBERON:0018303	62.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	51.85	gold quality
tonsil	UBERON:0002372	49.84	silver quality
calcaneal tendon	UBERON:0003701	49.66	gold quality
sural nerve	UBERON:0015488	49.64	silver quality
bone marrow cell	CL:0002092	48.78	gold quality
apex of heart	UBERON:0002098	45.75	gold quality
cortical plate	UBERON:0005343	45.09	silver quality
bone marrow	UBERON:0002371	43.81	gold quality
urinary bladder	UBERON:0001255	42.98	gold quality
ganglionic eminence	UBERON:0004023	42.41	gold quality
cortex of kidney	UBERON:0001225	42.39	gold quality
ectocervix	UBERON:0012249	41.69	gold quality
liver	UBERON:0002107	41.12	gold quality
ovary	UBERON:0000992	40.77	gold quality
descending thoracic aorta	UBERON:0002345	40.77	gold quality
ventricular zone	UBERON:0003053	40.66	gold quality
mucosa of stomach	UBERON:0001199	40.54	silver quality
left ovary	UBERON:0002119	40.28	gold quality
endometrium	UBERON:0001295	40.18	silver quality
right ovary	UBERON:0002118	40.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	39.70	gold quality
cerebellar cortex	UBERON:0002129	39.47	silver quality
cerebellum	UBERON:0002037	39.35	silver quality
cerebellar hemisphere	UBERON:0002245	39.28	silver quality
rectum	UBERON:0001052	38.48	gold quality
myometrium	UBERON:0001296	38.10	gold quality
monocyte	CL:0000576	38.08	gold quality
uterine cervix	UBERON:0000002	37.54	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.49

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 10)

• hTAS2R43 and hTAS2R44 function as cognate bitter taste receptors and do not contribute to the sweet taste of saccharin and acesulfame K. (PMID:15537898)
• hT2R43 gene allele makes people more sensitive to the bitterness of an artificial sweetener, saccharin; in addition, a closely related gene’s (hT2R44’s) allele also makes people more sensitive to the bitterness of saccharin. (PMID:17702579)
• Our results show that the expression rate of some of the T2R taste receptor genes was increased significantly in patients with phantogeusia. (PMID:22397221)
• Studies indicate that bitter-tasting compounds can have specific physiological effects in Bitter-tasting compounds can have specific physiological effects in type 2 taste receptors (T2Rs)-expressing cells. (PMID:22964302)
• The mutational polymorphism TAS2R43 significantly affects susceptibility to BEN points to a potentially broad role for toxin responses in personal health risks. (PMID:23050764)
• The effect of the TAS2R43 gene on coffee liking is mediated by caffeine and in particular by the H212R variant. (PMID:24647340)
• Study demonstrates that the response profiles of the cat bitter receptors Tas2r38 and Tas2r43 are distinct from those of their orthologous human receptors (PMID:26037485)
• those with at least one sensitive TAS2R38 allele (AP or PP genotype) were more likely to report rejecting liquid medications than were those without a taster allele (AA genotype (PMID:26391354)
• Bitter Sensing TAS2R50 Mediates the trans-Resveratrol-Induced Anti-inflammatory Effect on Interleukin 6 Release in HGF-1 Cells in Culture. (PMID:33461297)
• Human intestinal bitter taste receptors regulate innate immune responses and metabolic regulators in obesity. (PMID:34784295)

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), TAS2R46 (ENSG00000226761), TAS2R39 (ENSG00000236398), TAS2R20 (ENSG00000255837), TAS2R30 (ENSG00000256188), TAS2R31 (ENSG00000256436), TAS2R38 (ENSG00000257138)

Protein

Protein identifiers

Taste receptor type 2 member 43 — P59537 (reviewed: P59537)

Alternative names: Taste receptor type 2 member 52

All UniProt accessions (1): P59537

UniProt curated annotations — full annotation on UniProt →

Function. Gustducin-coupled receptor immplicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5. Activated by the sulfonyl amide sweeteners saccharin and acesulfame K. In airway epithelial cells, binding of bitter compounds increases the intracellular calcium ion concentration and stimulates ciliary beat frequency. May act as chemosensory receptors in airway epithelial cells to detect and eliminate potential noxious agents from the airways.

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 in airway epithelia.

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_795365* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007960	TAS2R	Family

Pfam: PF05296

UniProt features (20 total): topological domain 8, transmembrane region 7, glycosylation site 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9OXA	ELECTRON MICROSCOPY	2.9
9OXB	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P59537-F1	86.82	0.48

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: 28 (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_MOTILE_CILIUM, 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

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

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), taste receptor activity (GO:0008527), bitter taste receptor activity (GO:0033038)

GO Cellular Component (6): plasma membrane (GO:0005886), membrane (GO:0016020), motile cilium (GO:0031514), 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
detection of chemical stimulus involved in sensory perception of taste	2
transmembrane signaling receptor activity	2
cellular anatomical structure	2
cilium	2
sensory perception of bitter taste	1
G protein-coupled receptor activity	1
signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
sensory perception of chemical stimulus	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
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

372 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAS2R43	GNAT3	A8MTJ3	882
TAS2R43	PLCB2	Q00722	867
TAS2R43	TAS1R3	Q7RTX0	522
TAS2R43	TAS1R2	Q8TE23	512
TAS2R43	TAS1R1	Q7RTX1	475
TAS2R43	OR52K2	Q8NGK3	448
TAS2R43	OR2T33	Q8NG76	446
TAS2R43	OR52B6	Q8NGF0	445
TAS2R43	A0A087WY73	A0A087WY73	436
TAS2R43	PKD2L1	Q9P0L9	403
TAS2R43	OR8U1	Q8NH10	398
TAS2R43	SCNN1D	P51172	366
TAS2R43	VN1R4	Q7Z5H5	365
TAS2R43	ANKRD36C	Q5JPF3	365
TAS2R43	NUTM2F	A1L443	359

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

370 predictions. Top by Δscore:

Variant	Effect	Δscore
12:11091492:CAT:C	acceptor_gain	0.7300
12:11091353:C:CC	acceptor_gain	0.7200
12:11091622:C:CT	acceptor_gain	0.7100
12:11091605:TCTTC:T	acceptor_gain	0.7000
12:11091615:A:C	acceptor_gain	0.6900
12:11091619:T:TC	acceptor_gain	0.6700
12:11091624:C:CT	acceptor_gain	0.6700
12:11091635:T:TC	acceptor_gain	0.6700
12:11091856:A:C	donor_gain	0.6600
12:11091860:T:A	donor_gain	0.6600
12:11091625:A:T	acceptor_gain	0.6500
12:11091494:T:TC	acceptor_gain	0.6400
12:11091834:CA:C	donor_gain	0.6400
12:11091835:A:AC	donor_gain	0.6400
12:11091471:T:TA	donor_gain	0.6200
12:11091606:CTT:C	acceptor_gain	0.6200
12:11091617:G:C	acceptor_gain	0.6200
12:11092285:T:TA	donor_gain	0.6100
12:11091640:A:T	acceptor_gain	0.6000
12:11091831:CAACA:C	donor_gain	0.6000
12:11091520:A:AC	donor_gain	0.5900
12:11091643:A:C	acceptor_gain	0.5900
12:11091609:C:CC	acceptor_gain	0.5800
12:11091631:C:CT	acceptor_gain	0.5800
12:11091784:A:C	acceptor_gain	0.5800
12:11091864:C:CC	acceptor_gain	0.5800
12:11091642:C:CT	acceptor_gain	0.5700
12:11091610:T:C	acceptor_gain	0.5600
12:11091632:A:T	acceptor_gain	0.5500
12:11091859:CTCCT:C	acceptor_gain	0.5500

AlphaMissense

2051 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:11091876:A:C	F118L	0.850
12:11091876:A:T	F118L	0.850
12:11091878:A:G	F118L	0.850
12:11091921:G:C	S103R	0.849
12:11091921:G:T	S103R	0.849
12:11091923:T:G	S103R	0.849
12:11092152:G:C	F26L	0.807
12:11092152:G:T	F26L	0.807
12:11092154:A:G	F26L	0.807
12:11092179:A:C	F17L	0.794
12:11092179:A:T	F17L	0.794
12:11092181:A:G	F17L	0.794
12:11091528:G:C	F234L	0.782
12:11091528:G:T	F234L	0.782
12:11091530:A:G	F234L	0.782
12:11091945:G:C	S95R	0.778
12:11091945:G:T	S95R	0.778
12:11091947:T:G	S95R	0.778
12:11091891:G:C	F113L	0.759
12:11091891:G:T	F113L	0.759
12:11091893:A:G	F113L	0.759
12:11092052:A:G	W60R	0.727
12:11092052:A:T	W60R	0.727
12:11092197:A:C	S11R	0.708
12:11092197:A:T	S11R	0.708
12:11092199:T:G	S11R	0.708
12:11091941:A:G	W97R	0.706
12:11091941:A:T	W97R	0.706
12:11092158:A:C	N24K	0.702
12:11092158:A:T	N24K	0.702

dbSNP variants (sampled 300 via entrez): RS1007662416 (12:11094028 T>C), RS1012269965 (12:11091208 ACAGTATAGAAAAAC>A), RS1013805753 (12:11093243 G>A), RS1027600496 (12:11093913 A>C), RS1027736262 (12:11091287 C>T), RS1036946262 (12:11093287 C>A), RS1055252053 (12:11093056 G>A,C), RS111592023 (12:11090830 G>A,C), RS111630914 (12:11092511 T>G), RS111846092 (12:11091361 A>G,T), RS111852557 (12:11090837 A>T), RS111982292 (12:11091833 A>C,G), RS112843826 (12:11092546 A>C), RS112869592 (12:11092322 G>A,C,T), RS112874084 (12:11092516 T>A,C)

Disease associations

OMIM: gene MIM:612668 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002144_2	Bitter taste perception	2.000000e-19
GCST005688_8	Idiopathic intracranial hypertension	6.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523251 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 40,234 (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

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 (13 total), top 13:

Ligand	Action	Affinity	Parameter
aristolochic acid	Agonist	7.1	pEC50
lactucopicrin	Agonist	6.34	pEC50
aloin	Agonist	5.92	pEC50
Cyclolinopeptide 1-Mso,3-Met-CL6	Agonist	5.53	pEC50
bengalensol	Agonist	5.41	pEC50
grosheimin	Agonist	5.16	pEC50
GIV3727	Antagonist	4.95	pIC50
3-methylhexanal	Antagonist	4.13	pIC50
amarogentin	Agonist	4.12	pEC50
citronellal	Antagonist	4.08	pIC50
saccharin	Agonist	2.77	pEC50
acesulfame	Agonist	2.51	pEC50
cyclamate	Antagonist	2.32	pIC50

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.31	EC50	4.9	nM	ISOPROTERENOL

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Folic Acid	affects cotreatment, increases expression, decreases expression	2
alloin	decreases reaction, increases activity	1
pentanal	decreases expression	1
MT19c compound	increases expression	1
Ethanol	affects cotreatment, increases expression	1
Probenecid	decreases reaction, increases activity, decreases activity	1
Silicon Dioxide	decreases expression	1
Valproic Acid	decreases methylation	1
Sodium Selenite	decreases expression	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4346436	Functional	Antagonist activity at recombinant human TAS2R43 transiently expressed in HEK293T co-expressing Galpha16gust44 assessed as inhibition of aristolochic acid-induced intracellular calcium level by measuring remaining activity at 25 uM by fluo-	Discovery and Development of S6821 and S7958 as Potent TAS2R8 Antagonists. — J Med Chem

Clinical trials (associated diseases)

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