TAS2R4

Summary

TAS2R4 (taste 2 receptor member 4, HGNC:14911) is a protein-coding gene on chromosome 7q34, encoding Taste receptor type 2 member 4 (Q9NYW5). Gustducin-coupled receptor for denatonium and N(6)-propyl-2-thiouracil implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract.

This gene encodes a member of a family of candidate taste receptors that are members of the G protein-coupled receptor superfamily and that are specifically expressed by taste receptor cells of the tongue and palate epithelia. These apparently intronless genes encode a 7-transmembrane receptor protein, functioning as a bitter taste receptor. This gene is clustered with another 3 candidate taste receptor genes in chromosome 7 and is genetically linked to loci that influence bitter perception.

Source: NCBI Gene 50832 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 48 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_016944

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14911
Approved symbol	TAS2R4
Name	taste 2 receptor member 4
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	T2R4
Ensembl gene	ENSG00000127364
Ensembl biotype	protein_coding
OMIM	604869
Entrez	50832

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000247881

RefSeq mRNA: 1 — MANE Select: NM_016944 NM_016944

CCDS: CCDS5868

Canonical transcript exons

ENST00000247881 — 1 exons

Exon	Start	End
ENSE00000872186	141776674	141781691

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 84.11.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.18	silver quality
sural nerve	UBERON:0015488	73.71	gold quality
buccal mucosa cell	CL:0002336	70.22	silver quality
cerebellar hemisphere	UBERON:0002245	68.36	gold quality
cerebellar cortex	UBERON:0002129	68.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	68.16	gold quality
cerebellum	UBERON:0002037	65.91	gold quality
tibialis anterior	UBERON:0001385	65.03	silver quality
colonic epithelium	UBERON:0000397	64.43	silver quality
right uterine tube	UBERON:0001302	63.65	gold quality
cortical plate	UBERON:0005343	62.87	gold quality
mucosa of urinary bladder	UBERON:0001259	62.14	gold quality
nucleus accumbens	UBERON:0001882	60.44	gold quality
Brodmann (1909) area 9	UBERON:0013540	59.53	gold quality
calcaneal tendon	UBERON:0003701	59.34	gold quality
prefrontal cortex	UBERON:0000451	59.28	gold quality
right ovary	UBERON:0002118	58.94	gold quality
ventricular zone	UBERON:0003053	58.67	silver quality
right frontal lobe	UBERON:0002810	58.46	gold quality
anterior cingulate cortex	UBERON:0009835	58.20	gold quality
cingulate cortex	UBERON:0003027	58.17	gold quality
caudate nucleus	UBERON:0001873	58.05	gold quality
left ovary	UBERON:0002119	57.95	gold quality
putamen	UBERON:0001874	57.53	gold quality
ganglionic eminence	UBERON:0004023	57.25	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	56.73	gold quality
body of uterus	UBERON:0009853	56.68	gold quality
body of pancreas	UBERON:0001150	56.50	gold quality
tibial nerve	UBERON:0001323	56.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.71

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 12)

• This study demonistrated that human TAS2R4 play the role of food preference behavior. (PMID:22794107)
• these results show that rhodopsin N-terminal 33 amino acids enhance expression of T2R4 by 2.5-fold and do not cause perturbations in the receptor structure. (PMID:23159609)
• Data indicate that the itter blockers and agonists share the same orthosteric site in bitter taste receptor T2R4. (PMID:25059668)
• The antagonist ability of ABA was tested using another T2R4 agonist, yohimbine. Our results suggest that ABA does not inhibit yohimbine-induced T2R4 activity. (PMID:25844797)
• Data indicate that KLK/R motif in C-terminus performs functional role in bitter taste receptor T2R4 signaling. (PMID:25858111)
• demonstrate that Lys117, an important CRAC residue, is crucial in the reported cholesterol sensitivity of T2R4. Interestingly, cholesterol sensitivity of T2R4 was observed at quinine concentrations in the lower mM range. (PMID:27288892)
• This study is the first to show an inhibitory downstream action of a T2R4 agonist on Rac1 function. (PMID:27873143)
• In summary, genetic variations in T2R3/4 bitterness receptors may modify the papillary thyroid carcinoma (PTC) risk, and the genetically modified thyroid hormone level by those variations may be linked with the PTC-T2Rs association (PMID:30301923)
• Chemosensory bitter taste receptors T2R4 and T2R14 activation attenuates proliferation and migration of breast cancer cells. (PMID:31894529)
• Bitter receptor member TAS2R4 may have neurobiological function beyond acting as a bitter receptor. (PMID:32159211)
• Genetic Variation in the Bitter Receptors Responsible for Epicatechin Detection Are Associated with BMI in an Elderly Cohort. (PMID:33572225)
• Differential Activation of TAS2R4 May Recover Ability to Taste Propylthiouracil for Some TAS2R38 AVI Homozygotes. (PMID:38732607)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tas2r200.2	ENSDARG00000074066
danio_rerio	tas2r200.1	ENSDARG00000079880
mus_musculus	Tas2r108	ENSMUSG00000037140
rattus_norvegicus	Tas2r108	ENSRNOG00000012195

Paralogs (23): TAS2R8 (ENSG00000121314), TAS2R10 (ENSG00000121318), TAS2R7 (ENSG00000121377), TAS2R9 (ENSG00000121381), TAS2R3 (ENSG00000127362), 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), TAS2R43 (ENSG00000255374), TAS2R20 (ENSG00000255837), TAS2R30 (ENSG00000256188), TAS2R31 (ENSG00000256436), TAS2R38 (ENSG00000257138)

Protein

Protein identifiers

Taste receptor type 2 member 4 — Q9NYW5 (reviewed: Q9NYW5)

All UniProt accessions (1): Q9NYW5

UniProt curated annotations — full annotation on UniProt →

Function. Gustducin-coupled receptor for denatonium and N(6)-propyl-2-thiouracil implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5. In airway epithelial cells, binding of denatonium 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 palate epithelium and exclusively in gustducin-positive cells. Expressed on airway ciliated epithelium.

Miscellaneous. Several bitter taste receptors are expressed in a single taste receptor cell.

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

RefSeq proteins (1): NP_058640* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007960	TAS2R	Family
IPR030055	TAS2R4	Family

Pfam: PF05296

UniProt features (26 total): topological domain 8, transmembrane region 7, sequence variant 7, glycosylation site 3, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9M8K	ELECTRON MICROSCOPY	3
9M8L	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYW5-F1	84.64	0.47

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 (3): 164, 165, 169

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: 54 (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, OCT1_B, 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, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP

GO Biological Process (5): detection of chemical stimulus involved in sensory perception of bitter taste (GO:0001580), respiratory gaseous exchange by respiratory system (GO:0007585), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), 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 (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
detection of chemical stimulus involved in sensory perception of taste	2
transmembrane signaling receptor activity	2
cellular anatomical structure	2
sensory perception of bitter taste	1
multicellular organismal process	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
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

402 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAS2R4	GNAT3	A8MTJ3	918
TAS2R4	PLCB2	Q00722	888
TAS2R4	TAS1R2	Q8TE23	820
TAS2R4	TAS1R3	Q7RTX0	816
TAS2R4	TRPM5	Q9NZQ8	641
TAS2R4	TULP3	O75386	547
TAS2R4	TAS1R1	Q7RTX1	540
TAS2R4	SLC5A1	P13866	511
TAS2R4	OPRD1	P41143	483
TAS2R4	TAS2R3	Q9NYW6	479
TAS2R4	OR10A4	Q9H209	478
TAS2R4	OR5K3	A6NET4	460
TAS2R4	SSTR3	P32745	453
TAS2R4	OR51A7	Q8NH64	451
TAS2R4	OR52E8	Q6IFG1	447

IntAct

0 interactions, top by confidence:

BioGRID (1): TAS2R4 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: P04201, P12526, P23749, P30554, P35410, P59534, P59535, Q3KNA1, Q3UG50, Q3UG61, Q4VHE7, Q645S5, Q645U4, Q645Y7, Q645Y8, Q645Y9, Q646A9, Q646B0, Q646C8, Q646D3, Q646F0, Q646F1, Q67ER9, Q67ES7, Q67ET0, Q67ET2, Q7TN38, Q7TN41, Q7TN44, Q7TN51, Q7TQA5, Q7TQA6, Q7TQB8, Q8CIP3, Q8R4G1, Q8TDS7, Q8VCJ6, Q91WW2, Q91WW3, Q91ZB8

Diamond homologs: P59530, P59532, P59534, P59536, P59537, P59539, P59540, P59541, P59551, Q2AB83, Q50KZ9, Q5Y4Y8, Q5Y4Z0, Q5Y4Z8, Q5Y500, Q645S2, Q645S5, Q645T0, Q645T4, Q645T7, Q645U1, Q645U2, Q645U4, Q645U6, Q645U7, Q645U8, Q645V1, Q645V3, Q645V8, Q645V9, Q645Y3, Q645Y4, Q645Y5, Q645Y7, Q645Y8, Q645Z0, Q645Z5, Q645Z7, Q646A2, Q646A3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

194 predictions. Top by Δscore:

Variant	Effect	Δscore
7:141780609:GCACA:G	acceptor_gain	0.9600
7:141780608:A:AG	acceptor_gain	0.9200
7:141780609:G:GG	acceptor_gain	0.9200
7:141778479:A:AG	donor_gain	0.8400
7:141778483:G:GG	donor_gain	0.7800
7:141778479:A:G	donor_gain	0.7400
7:141778482:A:AG	donor_gain	0.7400
7:141778712:A:T	donor_gain	0.6900
7:141779085:A:AG	acceptor_gain	0.6900
7:141779163:T:G	donor_gain	0.6500
7:141780604:A:C	acceptor_gain	0.6300
7:141780595:TACA:T	acceptor_gain	0.5600
7:141780597:C:G	acceptor_gain	0.5500
7:141780610:C:G	acceptor_gain	0.5400
7:141780598:A:T	acceptor_gain	0.5200
7:141778481:GA:G	donor_gain	0.5100
7:141779090:A:AG	acceptor_gain	0.5100
7:141778718:C:A	donor_gain	0.5000
7:141779089:C:G	acceptor_gain	0.5000
7:141780594:A:T	acceptor_gain	0.4800
7:141779171:C:CG	donor_gain	0.4700
7:141780605:CACAG:C	acceptor_gain	0.4700
7:141780609:GCAC:G	acceptor_gain	0.4700
7:141779164:G:GG	donor_gain	0.4500
7:141780498:A:T	acceptor_gain	0.4500
7:141780596:A:T	acceptor_gain	0.4500
7:141779155:G:GT	donor_gain	0.4400
7:141778486:AAGAT:A	donor_gain	0.4300
7:141778500:A:AG	donor_gain	0.4300
7:141780503:A:T	acceptor_gain	0.4300

AlphaMissense

1949 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:141778771:A:C	S95R	0.953
7:141778773:T:A	S95R	0.953
7:141778773:T:G	S95R	0.953
7:141778546:G:A	G20R	0.950
7:141778546:G:C	G20R	0.950
7:141779064:T:A	N192K	0.950
7:141779064:T:G	N192K	0.950
7:141778560:T:A	N24K	0.949
7:141778560:T:G	N24K	0.949
7:141778636:A:C	S50R	0.945
7:141778638:C:A	S50R	0.945
7:141778638:C:G	S50R	0.945
7:141778854:G:C	K122N	0.945
7:141778854:G:T	K122N	0.945
7:141779191:T:C	F235L	0.934
7:141779193:C:A	F235L	0.934
7:141779193:C:G	F235L	0.934
7:141778840:T:C	F118L	0.930
7:141778842:T:A	F118L	0.930
7:141778842:T:G	F118L	0.930
7:141779096:T:C	L203S	0.928
7:141778894:T:C	C136R	0.926
7:141778768:A:C	S94R	0.925
7:141778770:C:A	S94R	0.925
7:141778770:C:G	S94R	0.925
7:141778666:G:A	G60R	0.924
7:141778666:G:C	G60R	0.924
7:141778797:T:A	N103K	0.923
7:141778797:T:G	N103K	0.923
7:141778777:T:A	W97R	0.922

dbSNP variants (sampled 300 via entrez): RS1000367134 (7:141777657 A>G), RS1000400104 (7:141782090 T>C), RS1000419230 (7:141778000 A>G), RS1000781380 (7:141777781 A>G), RS1001548850 (7:141778131 C>G,T), RS1001996581 (7:141778388 G>A), RS1002079323 (7:141778345 T>TCATGAATGGCA), RS1002612498 (7:141779773 G>A), RS1003562300 (7:141780601 T>C,G), RS1003742180 (7:141779691 A>G), RS1004022577 (7:141780823 A>G,T), RS1005118715 (7:141774919 C>T), RS1005321190 (7:141781456 A>C), RS1005422620 (7:141775923 C>G), RS1005453641 (7:141776060 T>C)

Disease associations

OMIM: gene MIM:604869 | 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
GCST001961_2	Anorexia nervosa	2.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3309107 (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 (5 total), top 5:

Ligand	Action	Affinity	Parameter
L-Trp-Trp-Trp	Agonist	4.52	pEC50
abscisic acid	Antagonist	4.46	pIC50
azithromycin	Agonist	4.13	pEC50
stevioside	Agonist	3.47	pEC50
colchicine	Agonist	2.99	pEC50

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

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases mutagenesis	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	increases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
Hydrogen Peroxide	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Thiram	increases expression	1
Asbestos, Crocidolite	affects expression	1
Okadaic Acid	decreases expression	1
Lactic Acid	increases expression	1
Permethrin	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 7 functional, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3361956	Binding	Agonist activity at human TAS2R4 expressed in U2OS cells by Ga16gust44 Clone 2B FLIPR/summary (Abse5) assay	Identification of diarylsulfonamides as agonists of the free fatty acid receptor 4 (FFA4/GPR120). — Bioorg Med Chem Lett
CHEMBL4346424	Functional	Antagonist activity at recombinant human TAS2R4 transiently expressed in HEK293T co-expressing Galpha16gust44 assessed as inhibition of chloroquine-induced intracellular calcium level by measuring remaining activity at 25 uM by fluo-4AM dye	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.