TAAR6

Summary

TAAR6 (trace amine associated receptor 6, HGNC:20978) is a protein-coding gene on chromosome 6q23.2, encoding Trace amine-associated receptor 6 (Q96RI8). Olfactory receptor specific for trace amines, such as beta-phenylethylamine (beta-PEA).

This gene encodes a seven-transmembrane G-protein-coupled receptor that likely functions as a receptor for endogenous trace amines. Mutations in this gene may be associated with schizophrenia.

Source: NCBI Gene 319100 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 55 total
• Druggable target: yes
• MANE Select transcript: NM_175067

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20978
Approved symbol	TAAR6
Name	trace amine associated receptor 6
Location	6q23.2
Locus type	gene with protein product
Status	Approved
Aliases	TA4
Ensembl gene	ENSG00000146383
Ensembl biotype	protein_coding
OMIM	608923
Entrez	319100

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000275198

RefSeq mRNA: 1 — MANE Select: NM_175067 NM_175067

CCDS: CCDS5155

Canonical transcript exons

ENST00000275198 — 1 exons

Exon	Start	End
ENSE00000975618	132570322	132571359

Expression profiles

Bgee: expression breadth tissue_specific, 8 present calls, max score 39.50.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	39.50	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
cortex of kidney	UBERON:0001225	32.94	silver quality
adult mammalian kidney	UBERON:0000082	32.88	silver quality
metanephros cortex	UBERON:0010533	32.56	silver quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
corpus callosum	UBERON:0002336	29.40	gold quality
tonsil	UBERON:0002372	29.19	gold quality
lymph node	UBERON:0000029	28.96	gold quality
blood	UBERON:0000178	28.86	silver quality
liver	UBERON:0002107	28.58	gold quality
duodenum	UBERON:0002114	28.14	gold quality
primary visual cortex	UBERON:0002436	27.73	gold quality
temporal lobe	UBERON:0001871	27.07	gold quality
amygdala	UBERON:0001876	26.99	gold quality
leukocyte	CL:0000738	26.83	gold quality
monocyte	CL:0000576	26.76	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.48

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 17)

• TRAR4 is preferentially expressed in those brain regions that have been implicated in the pathophysiology of schizophrenia. (PMID:15329799)
• Analysis of haplotype blocks revealed no significant association of the TRAR4 region with schizophrenia. (PMID:16189505)
• 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)
• This study strongly support association of the TAAR6 gene with susceptibility to both schizophrenia and bipolar disorder in Korean patients. (PMID:17097106)
• The trace amine associate receptor 6 (TAAR6) gene is associated with schizophrenia in the Irish study of high-density schizophrenia families.( (PMID:17505468)
• although data do not provide evidence for an altered receptor activity of this TA4 polymorphism, an involvement in bipolar affective disorder cannot be excluded based on our in vitro data (PMID:17895926)
• No association of trace amine receptor genes with bipolar disorder. (PMID:17957234)
• We reported an association between TAAR6 (trace amine associated receptor 6 gene) variations and schizophrenia (SZ). We now report an association of a set of TAAR6 variations and clinical presentation and outcome in a sample of 240 SZ Korean patients. (PMID:18583103)
• Trace amine associated receptor 6 is not important for the development of schizophrenia in our family samples. (PMID:18628684)
• Here we demonstrate that TAAR6 is not associated with schizophrenia in the ICCSS sample. (PMID:18973992)
• an epistastic effect between a set of TAAR6 and HSP-70 gene variations has a role in major mood disorders (PMID:19582769)
• Analysis of epistasis between a set of variations located in the TAAR6 and HSP-70 genes found weak associations with the risk of psychosis and response to antipsychotic treatment (PMID:19643584)
• This study provides preliminary evidence that HSP-70 may play a role in the disrupted mechanisms that lead to BPD. (PMID:19766166)
• The results of this study suggested a possible role of TAAR6 in antidepressant response and suicide behavior in patients with depressive disorder (PMID:20493543)
• Among the 15 SNPs and seven haplotypes of TAAR6, rs7772821 (T>G) on the 3’-UTR showed the strongest correlation with inhaled corticosteroid-induced %DeltaFEV1 in asthmatics. (PMID:25919112)
• Search for Structural Basis of Interactions of Biogenic Amines with Human TAAR1 and TAAR6 Receptors. (PMID:35008636)
• Public Transcriptomic Data Meta-Analysis Demonstrates TAAR6 Expression in the Mental Disorder-Related Brain Areas in Human and Mouse Brain. (PMID:36139098)

Cross-species orthologs

0 orthologs

Paralogs (25): DRD4 (ENSG00000069696), HRH3 (ENSG00000101180), HRH2 (ENSG00000113749), CHRM3 (ENSG00000133019), HRH4 (ENSG00000134489), TAAR5 (ENSG00000135569), GPR84 (ENSG00000139572), GPR161 (ENSG00000143147), TAAR2 (ENSG00000146378), 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 6 — Q96RI8 (reviewed: Q96RI8)

Alternative names: Trace amine receptor 4

All UniProt accessions (1): Q96RI8

UniProt curated annotations — full annotation on UniProt →

Function. Olfactory receptor specific for trace amines, such as beta-phenylethylamine (beta-PEA). Trace amine compounds are enriched in animal body fluids and act on trace amine-associated receptors (TAARs) to elicit both intraspecific and interspecific innate behaviors. Beta-PEA-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 at low abundance in various brain tissues, as well as in fetal liver, but not in the cerebellum or placenta. In the brain, comparable levels of expression in basal ganglia, frontal cortex, substantia nigra, amygdala and hippocampus, highest expression in hippocampus and lowest expression in basal ganglia.

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-22-Cys-186) connecting the N-terminus to the extracellular Loop 2 (ECL2), which is required for agonist-induced receptor activation.

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

RefSeq proteins (1): NP_778237* (*=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 (28 total): topological domain 8, sequence variant 8, transmembrane region 7, glycosylation site 2, disulfide bond 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RI8-F1	90.84	0.73

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): 22–186, 105–190

Glycosylation sites (2): 4, 19

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: 23 (showing top): GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_SENSORY_PERCEPTION, 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, GOMF_TRACE_AMINE_RECEPTOR_ACTIVITY, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_G_ALPHA_S_SIGNALLING_EVENTS

GO Biological Process (4): 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), signal transduction (GO:0007165)

GO Molecular Function (2): trace-amine receptor activity (GO:0001594), G protein-coupled receptor activity (GO:0004930)

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
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
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled amine receptor activity	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

466 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAAR6	MOXD1	Q6UVY6	757
TAAR6	DAOA	P59103	685
TAAR6	STX7	O15400	684
TAAR6	ZDHHC8	Q9ULC8	645
TAAR6	PPP3CC	P48454	627
TAAR6	DTNBP1	Q96EV8	616
TAAR6	RGS4	P49798	554
TAAR6	ZNF804A	Q7Z570	545
TAAR6	PRODH	O43272	542
TAAR6	DISC1	Q9NRI5	534
TAAR6	NOS1AP	O75052	531
TAAR6	PRODH	O43272	520
TAAR6	SERF1A	O75920	517
TAAR6	COMT	P21964	491
TAAR6	CNGA2	Q16280	485

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: O02667, O13076, O77621, P0C0L6, P0DMS8, P25099, P28190, P28647, P29275, P29276, P35342, P35382, P47745, P47936, P49892, P79945, Q0VC81, Q1LZD0, Q28309, Q32ZE2, Q56H79, Q5QD05, Q5QD06, Q5QD07, Q5QD08, Q5QD10, Q5QD11, Q5QD12, Q5QD13, Q5QD21, Q5RF57, Q5W8W0, Q60612, Q60614, Q61618, Q6W3F4, Q6W5P4, Q7TQP3, Q8BZP8, Q923X5

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

290 predictions. Top by Δscore:

Variant	Effect	Δscore
6:132570597:G:GT	donor_gain	0.9900
6:132570623:G:GT	donor_gain	0.9800
6:132570481:A:AG	donor_gain	0.9700
6:132570602:TGGA:T	donor_gain	0.9700
6:132570603:GGAG:G	donor_gain	0.9700
6:132570624:G:T	donor_gain	0.9700
6:132570428:ACAT:A	donor_gain	0.9500
6:132570598:A:T	donor_gain	0.9500
6:132570624:G:GT	donor_gain	0.9500
6:132570626:G:GT	donor_gain	0.9500
6:132570594:C:A	donor_gain	0.9300
6:132570627:GAGTT:G	donor_gain	0.9300
6:132570562:G:GG	donor_gain	0.9100
6:132570686:ACTT:A	acceptor_gain	0.9000
6:132570587:GCATG:G	donor_gain	0.8800
6:132570376:AATGG:A	donor_gain	0.8700
6:132570705:CGACA:C	acceptor_loss	0.8700
6:132570706:GACAG:G	acceptor_loss	0.8700
6:132570707:ACAG:A	acceptor_loss	0.8700
6:132570708:CAGGT:C	acceptor_loss	0.8700
6:132570709:AGG:A	acceptor_loss	0.8700
6:132570377:A:G	donor_gain	0.8600
6:132570597:G:T	donor_gain	0.8600
6:132570426:G:GG	donor_gain	0.8500
6:132570430:A:G	donor_gain	0.8500
6:132570687:C:G	acceptor_gain	0.8500
6:132570557:TCTTG:T	donor_loss	0.8300
6:132570559:TTG:T	donor_loss	0.8300
6:132570560:TG:T	donor_loss	0.8300
6:132570561:GG:G	donor_loss	0.8300

AlphaMissense

2261 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:132570499:T:C	F60L	0.987
6:132570501:C:A	F60L	0.987
6:132570501:C:G	F60L	0.987
6:132571120:T:C	F267L	0.983
6:132571122:T:A	F267L	0.983
6:132571122:T:G	F267L	0.983
6:132571273:T:C	F318L	0.983
6:132571275:T:A	F318L	0.983
6:132571275:T:G	F318L	0.983
6:132570790:T:A	W157R	0.978
6:132570790:T:C	W157R	0.978
6:132570722:T:A	V134D	0.975
6:132570555:T:A	D78E	0.972
6:132570555:T:G	D78E	0.972
6:132570615:G:C	W98C	0.972
6:132570615:G:T	W98C	0.972
6:132570980:T:A	I220K	0.971
6:132570718:G:C	A133P	0.970
6:132570711:G:C	R130S	0.969
6:132570711:G:T	R130S	0.969
6:132570471:C:A	N50K	0.967
6:132570471:C:G	N50K	0.967
6:132571090:G:C	A257P	0.967
6:132570710:G:T	R130M	0.966
6:132570613:T:A	W98R	0.964
6:132570613:T:C	W98R	0.964
6:132571213:T:A	W298R	0.964
6:132571213:T:C	W298R	0.964
6:132570553:G:C	D78H	0.959
6:132571274:T:C	F318S	0.959

dbSNP variants (sampled 300 via entrez): RS1000356134 (6:132571540 T>C), RS1000808578 (6:132570746 C>T), RS1001407950 (6:132569738 A>T), RS1002360919 (6:132568655 C>A,T), RS1003278758 (6:132570056 G>A), RS1003935408 (6:132568980 C>T), RS1007129518 (6:132570267 A>G), RS1008368145 (6:132569539 T>G), RS10085309 (6:132569014 G>C,T), RS1009053464 (6:132569376 A>C), RS1013509015 (6:132569757 C>T), RS1013644601 (6:132570006 T>G), RS1014147147 (6:132568616 A>G), RS1015356289 (6:132569540 G>A,T), RS1015780756 (6:132568981 T>C)

Disease associations

OMIM: gene MIM:608923 | 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
GCST006222_4	Cerebellum growth	2.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523910 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4305746	Efficacy	3	aripiprazole	Schizophrenia
rs7772821	Efficacy	3	corticosteroids	Asthma

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4305746	TAAR6	3	1.75	1	aripiprazole
rs7772821	TAAR6	3	2.00	1	corticosteroids

GtoPdb / IUPHAR curated pharmacology

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

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Polychlorinated Biphenyls	affects expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883607	Binding	PRESTO-Tango GPCRome screening (TAAR6)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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