TAAR5

Summary

TAAR5 (trace amine associated receptor 5, HGNC:30236) is a protein-coding gene on chromosome 6q23.2, encoding Trace amine-associated receptor 5 (O14804). Olfactory receptor specific for trimethylamine, a trace amine.

Enables trimethylamine receptor activity. Involved in adenylate cyclase-activating G protein-coupled receptor signaling pathway. Is active in plasma membrane.

Source: NCBI Gene 9038 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 59 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_003967

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30236
Approved symbol	TAAR5
Name	trace amine associated receptor 5
Location	6q23.2
Locus type	gene with protein product
Status	Approved
Aliases	PNR
Ensembl gene	ENSG00000135569
Ensembl biotype	protein_coding
OMIM	607405
Entrez	9038

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000258034

RefSeq mRNA: 2 — MANE Select: NM_003967 NM_001389527, NM_003967

CCDS: CCDS5156

Canonical transcript exons

ENST00000258034 — 1 exons

Exon	Start	End
ENSE00000919228	132588592	132589741

Expression profiles

Bgee: expression breadth tissue_specific, 1 present calls, max score 97.76.

Top tissues by expression

237 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	97.76	gold quality
buccal mucosa cell	CL:0002336	75.91	gold quality
myocardium	UBERON:0002349	67.79	gold quality
tendon of biceps brachii	UBERON:0008188	58.78	gold quality
nasal cavity epithelium	UBERON:0005384	55.24	gold quality
cartilage tissue	UBERON:0002418	53.66	gold quality
sperm	CL:0000019	50.66	gold quality
oocyte	CL:0000023	48.12	gold quality
quadriceps femoris	UBERON:0001377	46.94	gold quality
gingiva	UBERON:0001828	46.89	gold quality
vastus lateralis	UBERON:0001379	46.79	gold quality
gingival epithelium	UBERON:0001949	45.88	gold quality
cardia of stomach	UBERON:0001162	44.42	gold quality
upper leg skin	UBERON:0004262	44.28	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
pharyngeal mucosa	UBERON:0000355	43.03	gold quality
amniotic fluid	UBERON:0000173	42.90	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
trachea	UBERON:0003126	42.13	gold quality
ventral tegmental area	UBERON:0002691	41.39	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
biceps brachii	UBERON:0001507	41.20	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
parotid gland	UBERON:0001831	40.76	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
granulocyte	CL:0000094	40.48	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
mucosa of sigmoid colon	UBERON:0004993	40.41	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.80

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• Previous studies reported TAAR expression in brain. This paper found TAAR expression only in olfactory epithelial cells and that each TAAR detects a unique set of amine ligands. TAARs seem to function as a family of chemosensory receptors for amines. (PMID:16878137)
• Human trace amine-associated receptor TAAR5 can be activated by trimethylamine. (PMID:23393561)
• The murine and human TAAR5 (hTAAR5) display significant basal activity in the Gq/11 pathway. (PMID:25706283)
• Sequence Variants in TAAR5 and Other Loci Affect Human Odor Perception and Naming. (PMID:33035477)
• Pattern of TAAR5 Expression in the Human Brain Based on Transcriptome Datasets Analysis. (PMID:34445502)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	taar13d	ENSDARG00000110650
danio_rerio	taar13b	ENSDARG00000112016
danio_rerio	taar13c	ENSDARG00000112794
danio_rerio	taar13a	ENSDARG00000113793
danio_rerio	taar13e	ENSDARG00000115277
mus_musculus	Taar5	ENSMUSG00000069706
rattus_norvegicus	Taar5	ENSRNOG00000039869

Paralogs (25): DRD4 (ENSG00000069696), HRH3 (ENSG00000101180), HRH2 (ENSG00000113749), CHRM3 (ENSG00000133019), HRH4 (ENSG00000134489), GPR84 (ENSG00000139572), GPR161 (ENSG00000143147), TAAR2 (ENSG00000146378), TAAR6 (ENSG00000146383), TAAR8 (ENSG00000146385), TAAR1 (ENSG00000146399), DRD3 (ENSG00000151577), HTR4 (ENSG00000164270), CHRM1 (ENSG00000168539), DRD5 (ENSG00000169676), HTR1A (ENSG00000178394), HTR1D (ENSG00000179546), CHRM4 (ENSG00000180720), CHRM2 (ENSG00000181072), DRD1 (ENSG00000184845), CHRM5 (ENSG00000184984), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), GPR52 (ENSG00000203737), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

Trace amine-associated receptor 5 — O14804 (reviewed: O14804)

Alternative names: Putative neurotransmitter receptor

All UniProt accessions (1): O14804

UniProt curated annotations — full annotation on UniProt →

Function. Olfactory receptor specific for trimethylamine, a trace amine. Also activated at lower level by dimethylethylamine. Trimethylamine is a bacterial metabolite found in some animal odors, and to humans it is a repulsive odor associated with bad breath and spoiled food. Trimethylamine-binding causes a conformation change that triggers signaling via G(s)-class of G alpha proteins (GNAL or GNAS).

Subcellular location. Cell membrane.

Tissue specificity. Expressed almost exclusively in skeletal muscle and selected areas of the brain, such amygdala, hippocampus, caudate nucleus, thalamus and hypothalamus. Weak expression is also find in substantia nigra.

Domain organisation. In addition to the well known disulfide bond common to G-protein coupled receptor 1 family, trace amine-associated receptors (TAARs) contain an unique disulfide bond (Cys-24-Cys-188) connecting the N-terminus to the extracellular Loop 2 (ECL2), which is required for agonist-induced receptor activation.

Miscellaneous. Polymorphic variants of this gene are not associated with specific anosmia for trimethylamine.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (2): NP_001376456, NP_003958* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR009132	TAAR_fam	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050569	TAAR	Family

Pfam: PF00001

UniProt features (27 total): topological domain 8, transmembrane region 7, sequence conflict 5, disulfide bond 2, sequence variant 2, chain 1, region of interest 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14804-F1	84.94	0.51

Functional residue map

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

Disulfide bonds (2): 24–188, 99–192

Glycosylation sites (1): 21

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-375280	Amine ligand-binding receptors
R-HSA-418555	G alpha (s) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 38 (showing top): GOBP_COGNITION, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, LHX3_01, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_SENSORY_PERCEPTION, TAATTA_CHX10_01, GOBP_ADENYLATE_CYCLASE_ACTIVATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOMF_G_PROTEIN_COUPLED_AMINE_RECEPTOR_ACTIVITY, REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS, chr6q23, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_SENSORY_PERCEPTION_OF_SMELL, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (6): signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), sensory perception of smell (GO:0007608), cognition (GO:0050890), sensory perception of chemical stimulus (GO:0007606)

GO Molecular Function (3): trace-amine receptor activity (GO:0001594), G protein-coupled receptor activity (GO:0004930), trimethylamine receptor activity (GO:1990081)

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

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
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
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
sensory perception of chemical stimulus	1
nervous system process	1
sensory perception	1
G protein-coupled amine receptor activity	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
trace-amine receptor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

652 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAAR5	MOXD1	Q6UVY6	905
TAAR5	STX7	O15400	833
TAAR5	FMO3	P31513	530
TAAR5	OR1C1	Q15619	514
TAAR5	VNN1	O95497	493
TAAR5	OR1A1	Q9P1Q5	488
TAAR5	OR52K2	Q8NGK3	482
TAAR5	OR52A1	Q9UKL2	462
TAAR5	OR2J3	O76001	456
TAAR5	CNGA2	Q16280	454
TAAR5	OR5A2	Q8NGI9	445
TAAR5	OR5A1	Q8NGJ0	445
TAAR5	OR2J1	Q9GZK6	438
TAAR5	OR7D4	Q8NG98	436
TAAR5	OR52H1	Q8NGJ2	432

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: O02667, O14804, P29275, P29276, Q1LZD0, Q32ZE2, Q5QD04, Q5QD05, Q5QD06, Q5QD07, Q5QD08, Q5QD09, Q5QD10, Q5QD11, Q5QD12, Q5QD13, Q5QD14, Q5QD15, Q5QD16, Q5QD17, Q5QD21, Q5QD23, Q5QD24, Q5QD25, Q5QD28, Q5QD29, Q5QNP2, Q5W8W0, Q60614, Q6W3F4, Q8HZ64, Q923X5, Q923X6, Q923X8, Q923X9, Q923Y0, Q923Y1, Q923Y2, Q923Y3, Q923Y4

Diamond homologs: A0A678XMK4, O02662, O02666, O14804, O19091, O42574, O70528, O77680, O77700, P07700, P11617, P17124, P18089, P21728, P23944, P25021, P25100, P25102, P25115, P28221, P28565, P35405, P35406, P42289, P42290, P42291, P43141, P46626, P47747, P47800, P49145, P50406, P53452, P53454, P60021, P61752, P79400, P97288, P97292, P97714

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	48
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2685213	GRCh37/hg19 6q22.31-23.3(chr6:120218852-137160850)x1	Pathogenic

SpliceAI

218 predictions. Top by Δscore:

Variant	Effect	Δscore
6:132588754:CCA:C	acceptor_gain	0.7900
6:132588755:CAC:C	acceptor_gain	0.7900
6:132588757:C:CC	acceptor_gain	0.7800
6:132588755:CA:C	acceptor_gain	0.6900
6:132588760:G:C	acceptor_gain	0.6600
6:132588757:C:T	acceptor_loss	0.6500
6:132588760:G:GC	acceptor_gain	0.6500
6:132589658:TCAGC:T	donor_gain	0.6400
6:132589555:G:A	donor_gain	0.6100
6:132589244:A:AC	donor_gain	0.5900
6:132589245:C:CC	donor_gain	0.5900
6:132588759:G:C	acceptor_loss	0.5700
6:132589043:A:C	acceptor_gain	0.5700
6:132589533:T:A	donor_gain	0.5600
6:132589042:C:CT	acceptor_gain	0.5400
6:132589052:C:CT	acceptor_gain	0.5300
6:132589625:TTCA:T	donor_loss	0.5200
6:132589626:TCA:T	donor_loss	0.5200
6:132589627:CACCT:C	donor_loss	0.5200
6:132589628:A:AG	donor_loss	0.5200
6:132589657:TTCAG:T	donor_gain	0.5200
6:132588753:ACCA:A	acceptor_gain	0.5100
6:132588754:CCAC:C	acceptor_gain	0.5100
6:132589033:CAAG:C	acceptor_gain	0.5100
6:132589037:C:CC	acceptor_gain	0.5100
6:132588752:AACCA:A	acceptor_gain	0.5000
6:132588812:C:CT	acceptor_gain	0.5000
6:132589053:A:T	acceptor_gain	0.5000
6:132589630:C:G	donor_loss	0.5000
6:132589043:A:AC	acceptor_gain	0.4900

AlphaMissense

2201 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:132589292:C:G	R132P	0.975
6:132589212:A:G	W159R	0.968
6:132589212:A:T	W159R	0.968
6:132589501:G:C	F62L	0.964
6:132589501:G:T	F62L	0.964
6:132589503:A:G	F62L	0.964
6:132588751:A:C	F312L	0.959
6:132588751:A:T	F312L	0.959
6:132588753:A:G	F312L	0.959
6:132589367:C:G	C107S	0.958
6:132589368:A:T	C107S	0.958
6:132589311:A:G	C126R	0.956
6:132588883:G:C	F268L	0.952
6:132588883:G:T	F268L	0.952
6:132588885:A:G	F268L	0.952
6:132589447:G:C	D80E	0.950
6:132589447:G:T	D80E	0.950
6:132589293:G:T	R132S	0.947
6:132589387:C:A	W100C	0.947
6:132589387:C:G	W100C	0.947
6:132588897:A:G	C264R	0.945
6:132589448:T:G	D80A	0.944
6:132589215:C:G	G158R	0.942
6:132589215:C:T	G158R	0.942
6:132589448:T:A	D80V	0.942
6:132589449:C:G	D80H	0.940
6:132589531:A:C	N52K	0.940
6:132589531:A:T	N52K	0.940
6:132589053:A:G	C212R	0.939
6:132588813:A:G	W292R	0.938

dbSNP variants (sampled 300 via entrez): RS1000171485 (6:132593326 C>G,T), RS1000219906 (6:132597187 T>C), RS1000258358 (6:132613280 G>A), RS1000273676 (6:132596902 C>G,T), RS1000311572 (6:132608385 C>T), RS1000363555 (6:132608043 A>T), RS1000426141 (6:132613678 T>G), RS1000621473 (6:132602517 C>T), RS1000858588 (6:132612108 G>A), RS1000859144 (6:132613452 A>G,T), RS1001090681 (6:132604880 G>A,C), RS1001124474 (6:132598079 T>C), RS1001176707 (6:132597752 G>A), RS1001222584 (6:132595915 C>T), RS1001226409 (6:132601179 A>G)

Disease associations

OMIM: gene MIM:607405 | 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
GCST011623_4	Odorant perception	6.000000e-15

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3714046 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — TAAR2, TAAR3, TAAR4p, TAAR5, TAAR6, TAAR8, TAAR9

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
trimethylamine	Full agonist	6.52	pEC50
dimethylethylamine	Full agonist	6.15	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
5.36	EC50	4400	nM	CHEMBL1182312

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	2
trimethylamine	increases activity	1
N,N-dimethylethylamine	increases activity	1
CGP 52608	affects binding, increases reaction	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Catechin	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3788460	Binding	Inverse agonist activity at human TAAR5 expressed in HEK293 cells by Alphascreen assay	A homology modelling-driven study leading to the discovery of the first mouse trace amine-associated receptor 5 (TAAR5) antagonists — Medchemcomm

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KZ16	PathHunter CHO-K1 TAAR5 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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