TRPM5

Summary

TRPM5 (transient receptor potential cation channel subfamily M member 5, HGNC:14323) is a protein-coding gene on chromosome 11p15.5, encoding Transient receptor potential cation channel subfamily M member 5 (Q9NZQ8). Monovalent cation-selective ion channel activated by intracellular Ca(2+) in a voltage- and temperature-dependent manner.

This gene encodes a member of the transient receptor potential (TRP) protein family, which is a diverse group of proteins with structural features typical of ion channels. This protein plays an important role in taste transduction, and has characteristics of a calcium-activated, non-selective cation channel that carries Na+, K+, and Cs+ ions equally well, but not Ca(2+) ions. It is activated by lower concentrations of intracellular Ca(2+), and inhibited by higher concentrations. It is also a highly temperature-sensitive, heat activated channel showing a steep increase of inward currents at temperatures between 15 and 35 degrees Celsius. This gene is located within the Beckwith-Wiedemann syndrome critical region-1 on chromosome 11p15.5, and has been shown to be imprinted, with exclusive expression from the paternal allele.

Source: NCBI Gene 29850 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 281 total
• Druggable target: yes
• MANE Select transcript: NM_014555

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14323
Approved symbol	TRPM5
Name	transient receptor potential cation channel subfamily M member 5
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	LTRPC5, MTR1
Ensembl gene	ENSG00000070985
Ensembl biotype	protein_coding
OMIM	604600
Entrez	29850

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000528453, ENST00000533060, ENST00000533881, ENST00000696290

RefSeq mRNA: 1 — MANE Select: NM_014555 NM_014555

CCDS: CCDS31340

Canonical transcript exons

ENST00000696290 — 29 exons

Exon	Start	End
ENSE00000331689	2414907	2415047
ENSE00000331693	2412754	2413012
ENSE00000331695	2411635	2411767
ENSE00000690969	2422141	2422321
ENSE00000690971	2421032	2421198
ENSE00000690973	2420222	2420405
ENSE00000691018	2418527	2418591
ENSE00000691080	2418167	2418358
ENSE00000691112	2417727	2417829
ENSE00000691144	2415906	2416024
ENSE00000691187	2415121	2415471
ENSE00000691249	2414715	2414838
ENSE00000691251	2413476	2413588
ENSE00000691252	2413134	2413226
ENSE00000691303	2412135	2412253
ENSE00000691306	2411352	2411526
ENSE00000691307	2407759	2407912
ENSE00000691308	2407119	2407300
ENSE00000691310	2406661	2406793
ENSE00000691392	2405527	2405593
ENSE00000891003	2414061	2414206
ENSE00001486539	2406019	2406091
ENSE00001918479	2404515	2405043
ENSE00003966883	2444431	2444514
ENSE00003966884	2434978	2435098
ENSE00003966885	2422920	2423050
ENSE00003966886	2423343	2423505
ENSE00003966887	2432188	2433345
ENSE00003966888	2427525	2427753

Expression profiles

Bgee: expression breadth broad, 54 present calls, max score 78.48.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	78.48	gold quality
small intestine Peyer’s patch	UBERON:0003454	66.43	gold quality
gingival epithelium	UBERON:0001949	66.34	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	65.92	gold quality
biceps brachii	UBERON:0001507	65.61	gold quality
secondary oocyte	CL:0000655	65.33	gold quality
small intestine	UBERON:0002108	65.04	gold quality
heart right ventricle	UBERON:0002080	64.97	gold quality
seminal vesicle	UBERON:0000998	63.86	silver quality
body of pancreas	UBERON:0001150	63.74	gold quality
transverse colon	UBERON:0001157	62.64	gold quality
gingiva	UBERON:0001828	62.55	gold quality
duodenum	UBERON:0002114	62.15	gold quality
middle temporal gyrus	UBERON:0002771	61.34	gold quality
pericardium	UBERON:0002407	61.31	gold quality
metanephros	UBERON:0000081	61.29	gold quality
Brodmann (1909) area 23	UBERON:0013554	61.29	gold quality
nasal cavity epithelium	UBERON:0005384	61.19	gold quality
metanephros cortex	UBERON:0010533	61.16	gold quality
left lobe of thyroid gland	UBERON:0001120	60.51	gold quality
Brodmann (1909) area 46	UBERON:0006483	60.19	gold quality
thyroid gland	UBERON:0002046	59.85	gold quality
cauda epididymis	UBERON:0004360	59.79	gold quality
right lobe of thyroid gland	UBERON:0001119	59.63	gold quality
caput epididymis	UBERON:0004358	59.06	gold quality
deltoid	UBERON:0001476	58.90	gold quality
myocardium	UBERON:0002349	58.87	gold quality
entorhinal cortex	UBERON:0002728	58.51	gold quality
left adrenal gland cortex	UBERON:0035825	58.32	gold quality
esophagus squamous epithelium	UBERON:0006920	58.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-88	yes	895.26
E-MTAB-9067	yes	12.22
E-ANND-3	yes	6.78
E-MTAB-8410	yes	4.44

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI3

miRNA regulators (miRDB)

15 targeting TRPM5, 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-3613-3P	100.00	76.36	7965
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-550A-3-5P	97.56	65.35	823
HSA-MIR-550A-5P	97.56	65.35	823
HSA-MIR-1271-3P	97.56	64.85	865
HSA-MIR-214-5P	97.34	66.50	617
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-550B-2-5P	96.56	64.61	646
HSA-MIR-3918	96.13	64.65	1300

Literature-anchored findings (GeneRIF, showing 20)

• TRPM5 gene is imprinted, with preferential expression from the paternal allele. (PMID:10607831)
• TRPM5 is a transient Ca2+-activated cation channel responding to rapid changes in [Ca2+]i (PMID:14634208)
• regulation of TRPM5 by Ca2+ mediates sensory activation in the taste system (PMID:14657398)
• data show that extracellular acidification acts through specific residues on transient receptor potential cation channel, subfamily M(TRPM5) to block conduction through two distinct but related mechanisms (PMID:15731110)
• understanding the structural basis for TRPM5 function will ultimately allow the design of pharmaceuticals to enhance or interfere with taste sensations–{REVIEW} (PMID:17217064)
• results suggest TRPM5 may play a role in upregulating endogenous expression of TRPA1, that TRPA1 activation may be an additional trigger for co-expressed calcium-dependent ion channels such as TRPM5, and that TRPM5 may amplify responses to TRPA1 ligands (PMID:21133676)
• common TRPM5 variants are likely to be associated with prediabetic phenotypes; and this may in turn contribute to the development of type 2 diabetes mellitus (PMID:21489577)
• TRPM5-mediated Na(+) entry to promote Ca(2+) uptake via an NCX to trigger MUC5AC secretion (PMID:23741618)
• AZIN1 rs2679757 and TRPM5 rs886277 are associated with the risk of HBV-related liver cirrhosis in Chinese. (PMID:23844940)
• extracellular Zn(2+) inhibits TRPM5 channels, and the residues in the outer pore loop of TRPM5 are critically involved in the inhibition. (PMID:23884414)
• The TRPM5 gene rs34551253 (Ala456Thr) polymorphism may be associated with increased risk of developing primary open angle glaucoma in the Turkish population. (PMID:24019741)
• TrpM5 expression was similar throughout the olfactory glomeruli. (PMID:24288162)
• In a Turkish population, genetic polymorphism in TRPM5 genes modify individual susceptibility to metabolic syndrome. (PMID:25967713)
• Our results suggest roles of TRPM3 and TRPM5 gene variants in the susceptibility to or clinical expression of Systemic sclerosis (PMID:26546534)
• The PKC-dependent effect of GLP-1 on membrane potential and electrical activity was mediated by activation of Na(+)-permeable TRPM4 and TRPM5 channels by mobilization of intracellular Ca(2+) from thapsigargin-sensitive Ca(2+) stores (PMID:26571400)
• genetic association studies in populations in Northern Europe, Maghreb, and Sri Lanka: Data suggest that SNPs in TAS2R50 (rs1376251), TRPM5 (rs800345), and TAS2R16 (rs860170) are associated with cultural food preferences; TAS2R16 (rs860170) strongly differentiates populations and is associated to salicin bitterness perception. (TAS2R = taste receptor type 2) (PMID:28366770)
• TRPM5 Negatively Regulates Calcium-Dependent Responses in Lipopolysaccharide-Stimulated B Lymphocytes. (PMID:32521253)
• Hair Follicle Chemosensation: TRPM5 Signaling Is Required for Anagen Maintenance. (PMID:33773986)
• Novel association between a transient receptor potential cation channel subfamily M member 5 expression quantitative trait locus rs35197079 and decreased susceptibility of gestational diabetes mellitus in a Chinese population. (PMID:33979016)
• Association of TRPM5 Asn235Ser Polymorphism and Trace Elements/Minerals in Chronic Gastritis Patients: a Case-Control Study. (PMID:34767145)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	trpm5	ENSDARG00000059792
mus_musculus	Trpm5	ENSMUSG00000009246
rattus_norvegicus	Trpm5	ENSRNOG00000020484
drosophila_melanogaster	Trpm	FBGN0265194
caenorhabditis_elegans		WBGENE00000425
caenorhabditis_elegans	gon-2	WBGENE00001651
caenorhabditis_elegans		WBGENE00004149
caenorhabditis_elegans		WBGENE00020972
caenorhabditis_elegans		WBGENE00021404
caenorhabditis_elegans		WBGENE00021408

Paralogs (7): TRPM3 (ENSG00000083067), TRPM7 (ENSG00000092439), TRPM6 (ENSG00000119121), TRPM4 (ENSG00000130529), TRPM1 (ENSG00000134160), TRPM2 (ENSG00000142185), TRPM8 (ENSG00000144481)

Protein

Protein identifiers

Transient receptor potential cation channel subfamily M member 5 — Q9NZQ8 (reviewed: Q9NZQ8)

Alternative names: Long transient receptor potential channel 5, MLSN1- and TRP-related gene 1 protein

All UniProt accessions (4): Q9NZQ8, A0A0C4DGF4, E9PQF7, E9PRW0

UniProt curated annotations — full annotation on UniProt →

Function. Monovalent cation-selective ion channel activated by intracellular Ca(2+) in a voltage- and temperature-dependent manner. Mediates the transport of Na(+), K(+) and Cs(+) ions equally well. Activated directly by increase in intracellular Ca(2+), but is impermeable to it. The activation mechanism of TRPM5 involves a multistep process. TRPM5 activation involves ligand binding (i.e., tastant molecule, glucose stimulation) to Gq/G-protein coupled receptors (GPCR) and leads to the breakdown of phosphatidylinositol bisphosphate (PIP2) into diacylglycerol (DAG) and inositol trisphosphate (IP3), IP3 binds to its receptors in the endoplasmic reticulum and cause calcium release. Simultaneously with the intracellular Ca(2+) release, DAG activates the protein kinase C (PKC), which phosphorylates the TRPM5 channel. This phosphorylation combined with the bound Ca(2+), leads to a robust inward current allowing the entry of sodium ions (Na+) into the cell. This ion influx depolarizes the cell membrane, generating action potentials that propagate TRPM5 signals. Is a key player in sensing sweet, umami and bitter stimuli. Involved in insulin secretion by pancreatic beta cells.

Subunit / interactions. Homotetramer.

Subcellular location. Cell membrane.

Tissue specificity. Strongly expressed in fetal brain, liver and kidney, and in adult prostate, testis, ovary, colon and peripheral blood leukocytes. Also expressed in a large proportion of Wilms’ tumors and rhabdomyosarcomas. In monochromosomal cell lines shows exclusive paternal expression.

Post-translational modifications. Ser-129 phosphorylation by PKC, is essential for activating TRPM5 via the G(q) pathway.

Activity regulation. Ca(2+)-activated cation channel. Regulated by PI(4,5)P2 levels. PI(4,5)P 2 reverses the Ca(2+) -induced desensitization of channels. TRPM5 is temperature-sensitive and activated by heat. Heat activation is due to a shift of the voltage-dependent activation curve to negative potentials. The channel is blocked by extracellular acidification.

Domain organisation. Contains two Ca(2+)-binding sites that are allosterically coupled. The binding site in the intracellular domain modulates the voltage dependence and the accessibility of Ca(2+) in the transmembrane domain.

Similarity. Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM5 sub-subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NZQ8-1	1	yes
Q9NZQ8-2	2
Q9NZQ8-3	3

RefSeq proteins (1): NP_055370* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005821	Ion_trans_dom	Domain
IPR041491	TRPM_SLOG	Domain
IPR050927	TRPM	Family
IPR057366	TRPM-like	Domain

Pfam: PF00520, PF18139, PF25508

Catalyzed reactions (Rhea), 2 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (41 total): binding site 10, topological domain 8, transmembrane region 6, sequence variant 5, splice variant 3, region of interest 2, chain 1, intramembrane region 1, coiled-coil region 1, short sequence motif 1, compositionally biased region 1, modified residue 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZQ8-F1	77.66	0.20

Functional residue map

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

Ligand- & substrate-binding residues (10): 222; 338; 347; 350; 351; 782; 785; 808; 811; 1003

Post-translational modifications (1): 129

Mutagenesis-validated functional residues (1):

Position	Phenotype
351	alters the voltage sensitivity. renders trpm5 voltage-sensitive at high ca(2+) concentration.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3295583	TRP channels
R-HSA-9717207	Sensory perception of sweet, bitter, and umami (glutamate) taste

MSigDB gene sets: 116 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_POSITIVE_REGULATION_OF_INSULIN_SECRETION, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN

GO Biological Process (9): metal ion transport (GO:0030001), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), calcium ion transmembrane transport (GO:0070588), monoatomic cation transmembrane transport (GO:0098655), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085), potassium ion transmembrane transport (GO:0071805)

GO Molecular Function (9): monoatomic ion channel activity (GO:0005216), calcium-activated cation channel activity (GO:0005227), potassium channel activity (GO:0005267), sodium channel activity (GO:0005272), calcium ion binding (GO:0005509), identical protein binding (GO:0042802), protein binding (GO:0005515), metal ion binding (GO:0046872), metal ion transmembrane transporter activity (GO:0046873)

GO Cellular Component (5): plasma membrane (GO:0005886), membrane (GO:0016020), dendrite (GO:0030425), monoatomic ion channel complex (GO:0034702), neuronal cell body (GO:0043025)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Stimuli-sensing channels	1
Sensory perception of taste	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic cation transmembrane transport	3
monoatomic cation transport	2
transport	2
monoatomic cation channel activity	2
positive regulation of insulin secretion	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
calcium ion transport	1
monoatomic ion transmembrane transport	1
monoatomic ion transport	1
transmembrane transport	1
sodium ion transport	1
cellular process	1
potassium ion transport	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic ion-gated channel activity	1
ligand-gated monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
sodium ion transmembrane transporter activity	1
metal ion binding	1
protein binding	1
binding	1
cation binding	1
monoatomic cation transmembrane transporter activity	1
metal ion transport	1
membrane	1
cell periphery	1
cellular anatomical structure	1
neuron projection	1
dendritic tree	1
transmembrane transporter complex	1
somatodendritic compartment	1
cell body	1

Protein interactions and networks

STRING

1096 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRPM5	PLCB2	Q00722	979
TRPM5	PKD2L1	Q9P0L9	947
TRPM5	GNAT3	A8MTJ3	946
TRPM5	PKD1L3	Q7Z443	939
TRPM5	TAS1R3	Q7RTX0	860
TRPM5	TAS1R2	Q8TE23	827
TRPM5	TRPC1	P48995	813
TRPM5	CALHM1	Q8IU99	796
TRPM5	TAS1R1	Q7RTX1	788
TRPM5	TRPV2	Q9Y5S1	787
TRPM5	TSSC4	Q9Y5U2	781
TRPM5	POU2F3	Q9UKI9	770
TRPM5	DCLK1	O15075	728
TRPM5	TRPA1	O75762	725
TRPM5	TRPV1	Q8NER1	698

IntAct

5 interactions, top by confidence:

A	B	Type	Score
TRPM5	HPCAL4	psi-mi:“MI:0915”(physical association)	0.560
TRPM5	UGGT1	psi-mi:“MI:0915”(physical association)	0.400
TRPM5	HPCAL4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): HPCAL4 (Two-hybrid), TRPM5 (Proximity Label-MS), TRPM5 (Cross-Linking-MS (XL-MS)), TRPM5 (Cross-Linking-MS (XL-MS)), TRPM5 (Protein-RNA)

ESM2 similar proteins: A0A3Q2HW92, A6NDV4, A6NFX1, A6QLK4, B1AWJ5, F1NCD6, F1NJ67, F1PZV2, O35308, O35595, O70461, O95907, Q08DX7, Q0IHM1, Q0P5C0, Q0P5M9, Q13286, Q14728, Q29611, Q2YDU8, Q3T9M1, Q3U481, Q501I9, Q5R8G5, Q5R9A1, Q5U419, Q60HH0, Q61124, Q66H95, Q6NUT3, Q6UXD7, Q6ZMD2, Q7RTT9, Q8BFQ6, Q8CE47, Q8NA29, Q8R0G7, Q8R139, Q8TB61, Q8VCW4

Diamond homologs: A0A0R4IMY7, A7T1N0, A8DYE2, E9PTA2, J9SQF3, O94759, Q2TV84, Q2WEA5, Q5XIG0, Q7TN37, Q7Z2W7, Q7Z4N2, Q8BVU5, Q8R455, Q8R4D5, Q8TD43, Q91YD4, Q9BW91, Q9ESQ5, Q9HCF6, Q9JJH7, Q9NZQ8, S5UH55, Q09297, Q8CIR4, Q93971, Q923J1, Q925B3, Q96QT4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	235
Likely benign	24
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

5319 predictions. Top by Δscore:

Variant	Effect	Δscore
11:2405525:A:AC	donor_gain	1.0000
11:2405525:ACT:A	donor_gain	1.0000
11:2405526:C:CC	donor_gain	1.0000
11:2405526:CT:C	donor_gain	1.0000
11:2405526:CTC:C	donor_gain	1.0000
11:2406701:T:TA	donor_gain	1.0000
11:2406790:CTCT:C	acceptor_gain	1.0000
11:2406792:CT:C	acceptor_gain	1.0000
11:2406794:C:CC	acceptor_gain	1.0000
11:2406804:C:CT	acceptor_gain	1.0000
11:2407141:AG:A	donor_gain	1.0000
11:2407141:AGCCT:A	donor_gain	1.0000
11:2407145:T:TA	donor_gain	1.0000
11:2411319:C:CA	donor_gain	1.0000
11:2411363:T:TA	donor_gain	1.0000
11:2411494:C:CT	acceptor_gain	1.0000
11:2411495:A:T	acceptor_gain	1.0000
11:2411530:C:CT	acceptor_gain	1.0000
11:2411530:C:T	acceptor_gain	1.0000
11:2411537:C:CT	acceptor_gain	1.0000
11:2411538:A:T	acceptor_gain	1.0000
11:2413125:G:A	donor_gain	1.0000
11:2413133:CCGG:C	donor_gain	1.0000
11:2413223:CTCA:C	acceptor_gain	1.0000
11:2413227:C:CC	acceptor_gain	1.0000
11:2414058:CA:C	donor_loss	1.0000
11:2414059:A:AC	donor_gain	1.0000
11:2414059:AC:A	donor_gain	1.0000
11:2414060:C:CT	donor_gain	1.0000
11:2414060:CC:C	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000041692 (11:2439208 T>G), RS1000052248 (11:2445861 T>C), RS1000067819 (11:2413681 C>A,G,T), RS1000110709 (11:2445584 C>T), RS1000182251 (11:2413477 T>C), RS1000202516 (11:2416992 C>T), RS1000328464 (11:2409987 A>C), RS1000334351 (11:2421169 C>G,T), RS1000514464 (11:2412527 G>T), RS1000530920 (11:2431651 C>T), RS1000544684 (11:2445803 C>G,T), RS1000644720 (11:2416696 C>T), RS1000767306 (11:2420284 C>T), RS1000825226 (11:2442858 C>A), RS1000917971 (11:2436375 C>T)

Disease associations

OMIM: gene MIM:604600 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST009391_1165	Metabolite levels	5.000000e-06
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010460	anthranilic acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1628468 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: vgic — Transient Receptor Potential channels (TRP)

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
compound 39 [PMID: 36402081]	Agonist	7.5	pEC50
Ca2+	Agonist	6.2	pEC50
APV207095A	Potentiation	5.03	pEC50
flufenamic acid	Channel blocker	4.62	pIC50
APV207094A	Potentiation	4.43	pEC50
spermine	Channel blocker	4.43	pIC50
APV207010A	Potentiation	4.42	pEC50
APV206690A	Potentiation	4.04	pEC50
H+	Channel blocker	3.2	pIC50

ChEMBL bioactivities

200 potent at pChembl≥5 of 210 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.89	IC50	1.3	nM	CHEMBL3932326
8.85	IC50	1.4	nM	CHEMBL3926856
8.74	IC50	1.8	nM	CHEMBL3921169
8.52	IC50	3	nM	CHEMBL3984818
8.30	IC50	5	nM	CHEMBL3890861
8.22	IC50	6	nM	CHEMBL3920665
8.10	EC50	7.943	nM	CHEMBL4863993
8.05	IC50	9	nM	CHEMBL3958181
7.95	EC50	11.22	nM	CHEMBL4877000
7.92	IC50	12	nM	CHEMBL3917255
7.77	IC50	17	nM	CHEMBL3952275
7.75	EC50	17.78	nM	CHEMBL4856061
7.62	IC50	24	nM	CHEMBL3910957
7.61	EC50	24.55	nM	CHEMBL4869759
7.54	EC50	28.84	nM	CHEMBL4855103
7.52	IC50	30	nM	CHEMBL3965696
7.43	IC50	37	nM	CHEMBL3918456
7.42	IC50	38	nM	CHEMBL3949870
7.42	EC50	38.02	nM	CHEMBL4857667
7.41	EC50	38.9	nM	CHEMBL4860824
7.40	IC50	40	nM	CHEMBL3954591
7.36	EC50	43.65	nM	CHEMBL4854482
7.35	IC50	45	nM	CHEMBL3964050
7.34	IC50	46	nM	CHEMBL3968083
7.30	EC50	50.12	nM	CHEMBL5177026
7.29	IC50	51	nM	CHEMBL3968112
7.29	IC50	51	nM	CHEMBL3981183
7.28	IC50	53	nM	CHEMBL3914721
7.26	IC50	55	nM	CHEMBL3980338
7.22	IC50	60	nM	CHEMBL3918736
7.20	EC50	63.1	nM	CHEMBL5193084
7.18	IC50	66	nM	CHEMBL3974283
7.10	IC50	80	nM	CHEMBL3971765
7.10	EC50	79.43	nM	CHEMBL5192928
7.07	EC50	85.11	nM	CHEMBL4845759
7.05	IC50	90	nM	CHEMBL3944989
7.05	EC50	89.13	nM	CHEMBL4849726
7.01	EC50	97.72	nM	CHEMBL4873593
7.00	EC50	100	nM	CHEMBL5194924
6.99	EC50	102.3	nM	CHEMBL4862183
6.92	IC50	120	nM	CHEMBL3893648
6.90	EC50	125.9	nM	CHEMBL5192928
6.80	IC50	160	nM	CHEMBL3942291
6.80	EC50	158.5	nM	CHEMBL4869736
6.80	EC50	158.5	nM	CHEMBL4863223
6.77	IC50	170	nM	CHEMBL3928377
6.75	IC50	180	nM	CHEMBL3965662
6.75	IC50	180	nM	CHEMBL3899989
6.70	IC50	200	nM	CHEMBL3951939
6.70	EC50	199.5	nM	CHEMBL5189636

PubChem BioAssay actives

76 with measured affinity, of 128 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
5-chloro-N-[(5-chloro-1,3-thiazol-2-yl)methyl]-1,2-benzothiazol-6-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.0079	uM
5-chloro-N-[(5-chloro-1-methylimidazol-2-yl)methyl]-1,2-benzothiazol-6-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.0112	uM
N-[(5-chloro-1,3-thiazol-2-yl)methyl]-5-methyl-1,2-benzothiazol-6-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.0178	uM
6-chloro-N-[(5-chloro-1,3-thiazol-2-yl)methyl]-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.0245	uM
N-[(5-chloro-1,3-thiazol-2-yl)methyl]-5-fluoro-1,2-benzothiazol-6-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.0288	uM
N-[(5-chloro-1-methylimidazol-2-yl)methyl]-5-methyl-1,2-benzothiazol-6-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.0380	uM
N-[(5-chloro-1,3-thiazol-2-yl)methyl]-6-methyl-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.0389	uM
N-[(5-chloro-1,3-thiazol-2-yl)methyl]-1,2-benzothiazol-6-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.0437	uM
[(1S,3S)-6,7-dichloro-1-phenyl-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	0.0501	uM
[(1S,3S)-6-chloro-1-(3-chloro-5-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	0.0631	uM
(1R,3R)-1-(3-chloro-5-fluorophenyl)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-6-carbonitrile	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	0.0794	uM
N-[(5-chloro-1-methylimidazol-2-yl)methyl]-N-methyl-1,2-benzothiazol-6-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.0851	uM
N-[(5-chloro-1,3-thiazol-2-yl)methyl]-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.0891	uM
N-[(5-chloro-1,3-thiazol-2-yl)methyl]-6-fluoro-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.0977	uM
[(1S,3S)-7-chloro-1-(3-chloro-5-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	0.1000	uM
N-[(5-chloro-1-methylimidazol-2-yl)methyl]-5-fluoro-1,2-benzothiazol-6-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.1023	uM
N-[(5-chloro-1-methylimidazol-2-yl)methyl]-N-(cyclopropylmethyl)-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.1585	uM
N-[(5-chloro-1-methylimidazol-2-yl)methyl]-N-methyl-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.1585	uM
[(1S,3S)-7-chloro-1-(3,5-difluorophenyl)-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	0.1995	uM
[(1S,3S)-7-chloro-1-(3,5-dichlorophenyl)-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	0.1995	uM
3-[(1S,3S)-6-chloro-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-fluorobenzonitrile	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	0.2512	uM
N-[(5-chloro-1-methylimidazol-2-yl)methyl]-1,2-benzothiazol-6-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.2951	uM
5-chloro-N-[(5-chloro-1-methylimidazol-2-yl)methyl]-N-methyl-1,2-benzothiazol-6-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.3090	uM
[(1S,3S)-7-chloro-1-(3-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	0.3162	uM
[(1S,3S)-6-chloro-7-fluoro-1-phenyl-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	0.3162	uM
N-[(5-chloro-1-methylimidazol-2-yl)methyl]-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.3311	uM
N-[(5-chloro-1,3-thiazol-2-yl)methyl]-N-methyl-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.4467	uM
N-[(5-bromo-1-methylimidazol-2-yl)methyl]-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.4571	uM
N-[(5-chloro-1,3-thiazol-2-yl)methyl]-[1,2]thiazolo[5,4-c]pyridin-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.4677	uM
N-[(5-chloro-1-methylimidazol-2-yl)methyl]-N-ethyl-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.4677	uM
N-[[5-(trifluoromethyl)-1,3-thiazol-2-yl]methyl]-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.4898	uM
[(1S,3S)-7-chloro-1-(3-chlorophenyl)-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	0.5012	uM
[(1S,3S)-6-chloro-1-phenyl-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	0.5012	uM
N-[(5-methyl-1,3-thiazol-2-yl)methyl]-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.5754	uM
N-[(E)-(3,4-dimethoxyphenyl)methylideneamino]-2-naphthalen-1-ylacetamide	1896964: Antagonist activity at TRPM5 (unknown origin)	ic50	0.6000	uM
N-[(E)-(3,4-dimethoxyphenyl)methylideneamino]-2-phenylcyclopropane-1-carboxamide	1896964: Antagonist activity at TRPM5 (unknown origin)	ic50	0.6000	uM
(1E)-1-(3-methyl-1,3-benzothiazol-2-ylidene)-3-prop-2-enylthiourea	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	0.6310	uM
[(1S,3S)-7-chloro-1-phenyl-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	0.7943	uM
5-[(5-chloro-1,3-thiazol-2-yl)methoxy]-1,2-benzothiazole	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.8318	uM
N-[(5-chloro-1,3-thiazol-2-yl)methyl]-4-fluoro-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	0.9333	uM
[(1S,3S)-7-chloro-1-(4-chloro-3-methylphenyl)-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	1.0000	uM
N-[(5-chloro-1,3-thiazol-2-yl)methyl]-[1,2]thiazolo[4,5-b]pyridin-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	1.1749	uM
[(1S,3S)-5-chloro-1-phenyl-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	1.2589	uM
N-[(5-chloro-1,3-thiazol-2-yl)methyl]-7-fluoro-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	1.3804	uM
N-[(5-chloro-1,3-thiazol-2-yl)methyl]-1,2-benzothiazol-7-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	1.4454	uM
4-chloro-N-[(5-chloro-1,3-thiazol-2-yl)methyl]-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	1.5849	uM
[(1R,3S)-6-chloro-1-(2-chlorophenyl)-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	1.5849	uM
6-chloro-N-[(5-chloro-1,3-thiazol-2-yl)methyl]-N-methyl-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	1.6218	uM
N-[(5-chloro-1,3-thiazol-2-yl)methyl]-4-methyl-1,2-benzothiazol-5-amine	1765016: Agonist activity at human TRPM5 expressed in CHO-K1 cells maintained at 80 mV final holding potential by syncroPatch assay	ec50	1.7378	uM
[(1S,3S)-6-chloro-1-(3-chloro-5-fluorophenyl)-1,2,3,4-tetrahydro-2,7-naphthyridin-3-yl]methanol	1896973: Agonist activity at human TRPM5 expressed in CHO-K1 cells assessed as increase in relative fluorescence unit measured for 2 mins by FLIPR based membrane potential assay	ec50	1.9953	uM

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	1
9-phenanthrol	decreases activity	1
5-butyl-7-chloro-6-hydroxybenzo(c)quinolizinium	decreases activity	1
(+)-JQ1 compound	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Diazinon	increases methylation	1
Estradiol	increases expression	1
Thiram	increases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Sodium Selenite	decreases expression	1

ChEMBL screening assays

16 unique, capped per target: 16 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3361962	Binding	Blocking of human TRPM5 expressed in HEK293 cells by FLIPR membrane potential/summary (Abse5) assay	Identification of diarylsulfonamides as agonists of the free fatty acid receptor 4 (FFA4/GPR120). — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C7Z1	HAP1 TRPM5 (-) 1	Cancer cell line	Male
CVCL_C7Z2	HAP1 TRPM5 (-) 2	Cancer cell line	Male
CVCL_E2MS	HAP1 TRPM5 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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