TAS2R40

Summary

TAS2R40 (taste 2 receptor member 40, HGNC:18885) is a protein-coding gene on chromosome 7q34, encoding Taste receptor type 2 member 40 (P59535). Gustducin-coupled receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract.

This gene encodes a member of the bitter taste receptor family which belong to the G protein-coupled receptor superfamily and are predominantly expressed in taste receptor cells of the tongue and palate epithelia. This intronless taste receptor gene encodes a seven-transmembrane receptor protein, functioning as a bitter taste receptor. This gene is clustered together with eight other taste receptor genes on chromosome 7. A decrease in the expression of this gene is associated with hypogeusia.

Source: NCBI Gene 259286 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 43 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_176882

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18885
Approved symbol	TAS2R40
Name	taste 2 receptor member 40
Location	7q34
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000221937
Ensembl biotype	protein_coding
OMIM	613964
Entrez	259286

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000408947

RefSeq mRNA: 1 — MANE Select: NM_176882 NM_176882

CCDS: CCDS43662

Canonical transcript exons

ENST00000408947 — 1 exons

Exon	Start	End
ENSE00001569176	143222037	143223079

Expression profiles

Bgee: expression breadth broad, 35 present calls, max score 61.35.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	61.35	gold quality
blood	UBERON:0000178	58.70	gold quality
leukocyte	CL:0000738	52.76	gold quality
monocyte	CL:0000576	52.75	gold quality
sural nerve	UBERON:0015488	49.26	silver quality
spleen	UBERON:0002106	49.18	gold quality
vermiform appendix	UBERON:0001154	46.08	gold quality
caecum	UBERON:0001153	44.64	gold quality
right lung	UBERON:0002167	44.62	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
medial globus pallidus	UBERON:0002477	41.27	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
bone marrow cell	CL:0002092	40.86	gold quality
globus pallidus	UBERON:0001875	40.82	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
granulocyte	CL:0000094	40.35	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tas2r200.2	ENSDARG00000074066
danio_rerio	tas2r200.1	ENSDARG00000079880
mus_musculus	Tas2r144	ENSMUSG00000051917
rattus_norvegicus	Tas2r144	ENSRNOG00000028130

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), TAS2R46 (ENSG00000226761), TAS2R39 (ENSG00000236398), TAS2R43 (ENSG00000255374), TAS2R20 (ENSG00000255837), TAS2R30 (ENSG00000256188), TAS2R31 (ENSG00000256436), TAS2R38 (ENSG00000257138)

Protein

Protein identifiers

Taste receptor type 2 member 40 — P59535 (reviewed: P59535)

Alternative names: G-protein coupled receptor 60, Taste receptor type 2 member 58

All UniProt accessions (1): P59535

UniProt curated annotations — full annotation on UniProt →

Function. Gustducin-coupled receptor 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.

Subcellular location. Membrane.

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

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_795363* (*=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 variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P59535-F1	81.19	0.36

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): 170, 179

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: 41 (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, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_BITTER_TASTE_RECEPTOR_ACTIVITY, GOMF_TASTE_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, MIKKELSEN_MCV6_LCP_WITH_H3K27ME3, OCT_Q6, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_DETECTION_OF_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION, GOBP_SENSORY_PERCEPTION_OF_BITTER_TASTE

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 (2): plasma membrane (GO:0005886), membrane (GO:0016020)

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	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
cellular anatomical structure	1

Protein interactions and networks

STRING

236 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAS2R40	SCNN1B	P51168	337
TAS2R40	TAS1R2	Q8TE23	333
TAS2R40	PLCB2	Q00722	255
TAS2R40	ZNF615	Q8N8J6	251
TAS2R40	TAS2R50	P59544	250
TAS2R40	TAS2R30	P59541	242
TAS2R40	ERI2	A8K979	239
TAS2R40	TAS2R31	P59538	234
TAS2R40	TAS2R43	P59537	234
TAS2R40	TAS2R14	Q9NYV8	232
TAS2R40	TAS2R20	P59543	227
TAS2R40	TAS2R3	Q9NYW6	224
TAS2R40	PKD1L3	Q7Z443	224
TAS2R40	GNAT3	A8MTJ3	222
TAS2R40	TAS2R38	P59533	219

IntAct

0 interactions, top by confidence:

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, P59535, P59536, P59551, Q2AB83, Q50KZ9, Q645S5, Q645T0, Q645T3, Q645T4, Q645T7, Q645T9, Q645U2, Q645U4, Q645U5, Q645U6, Q645U8, Q645U9, Q645V0, Q645V1, Q645V8, Q645V9, Q645Y3, Q645Y7, Q645Y8, Q645Y9, Q645Z0, Q645Z2, Q645Z4, Q645Z5, Q645Z7, Q646A2, Q646A3, Q646A9, Q646B0, Q646B1, Q646B2, Q646B5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

256 predictions. Top by Δscore:

Variant	Effect	Δscore
7:143222887:T:G	acceptor_gain	0.8500
7:143222901:A:AG	acceptor_gain	0.8500
7:143222902:G:GG	acceptor_gain	0.8500
7:143222677:T:TA	acceptor_gain	0.8100
7:143222884:A:G	acceptor_gain	0.8000
7:143222209:GGGC:G	donor_gain	0.7900
7:143222877:AC:A	acceptor_gain	0.7900
7:143222923:A:G	acceptor_gain	0.7600
7:143222210:GGC:G	donor_gain	0.7400
7:143222673:AACAT:A	acceptor_gain	0.7300
7:143222878:C:CA	acceptor_gain	0.7200
7:143222211:GC:G	donor_gain	0.7100
7:143222902:GTTC:G	acceptor_gain	0.7100
7:143222883:A:AG	acceptor_gain	0.7000
7:143222902:GTTCC:G	acceptor_gain	0.7000
7:143222878:C:G	acceptor_gain	0.6900
7:143222885:C:G	acceptor_gain	0.6900
7:143222886:A:AG	acceptor_gain	0.6900
7:143222182:G:GT	donor_gain	0.6800
7:143222678:G:A	acceptor_gain	0.6800
7:143222902:GT:G	acceptor_gain	0.6800
7:143222701:T:G	acceptor_gain	0.6700
7:143222900:CAGTT:C	acceptor_loss	0.6700
7:143222901:A:AC	acceptor_loss	0.6700
7:143222902:G:GC	acceptor_loss	0.6700
7:143222761:G:T	donor_gain	0.6600
7:143222858:A:AG	acceptor_gain	0.6600
7:143222896:C:G	acceptor_gain	0.6600
7:143222147:G:GA	donor_gain	0.6500
7:143222212:C:G	donor_gain	0.6500

AlphaMissense

2146 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:143222703:T:C	F209L	0.865
7:143222705:C:A	F209L	0.865
7:143222705:C:G	F209L	0.865
7:143222547:A:C	S157R	0.859
7:143222549:C:A	S157R	0.859
7:143222549:C:G	S157R	0.859
7:143222268:A:C	S64R	0.855
7:143222270:C:A	S64R	0.855
7:143222270:C:G	S64R	0.855
7:143222190:T:C	F38L	0.837
7:143222192:C:A	F38L	0.837
7:143222192:C:G	F38L	0.837
7:143222184:A:C	S36R	0.825
7:143222186:T:A	S36R	0.825
7:143222186:T:G	S36R	0.825
7:143222430:T:C	F118L	0.815
7:143222432:C:A	F118L	0.815
7:143222432:C:G	F118L	0.815
7:143222385:T:C	F103L	0.782
7:143222387:T:A	F103L	0.782
7:143222387:T:G	F103L	0.782
7:143222832:T:C	F252L	0.776
7:143222834:T:A	F252L	0.776
7:143222834:T:G	F252L	0.776
7:143222406:T:A	W110R	0.753
7:143222406:T:C	W110R	0.753
7:143222826:A:C	S250R	0.719
7:143222828:C:A	S250R	0.719
7:143222828:C:G	S250R	0.719
7:143222367:T:C	F97L	0.708

dbSNP variants (sampled 300 via entrez): RS1000682814 (7:143221394 G>A), RS1000821727 (7:143221142 G>A), RS1001510229 (7:143223452 A>G,T), RS1002116890 (7:143220219 G>A), RS1003801078 (7:143221368 G>A), RS1004196094 (7:143221571 A>G), RS1005417690 (7:143220268 A>C), RS1005491313 (7:143220497 T>G), RS1006160007 (7:143220361 T>A,C), RS1006641243 (7:143220893 A>T), RS1006745027 (7:143220858 A>G), RS1007042096 (7:143221231 A>G), RS1008617834 (7:143222485 G>A), RS1011617924 (7:143223161 C>A,T), RS1012447527 (7:143221660 G>T)

Disease associations

OMIM: gene MIM:613964 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523250 (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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
cohumulone	Agonist	7.4	pEC50
GIV3727	Antagonist	5.2	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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
arsenite	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1
Asbestos, Crocidolite	affects expression	1
Zinc Sulfate	increases expression	1
Particulate Matter	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4419015	Functional	Agonist activity at recombinant human N-terminal rat ST3 receptor-fused TAS2R40 expressed in HEK293T cells co-expressing Galpha16gust44 assessed as increase in intracellular calcium level at 100 uM by FLIPR assay	Methods of identifying antagonists of the hTAS2R46 bitter taste receptor

Clinical trials (associated diseases)

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