TAAR9

Summary

TAAR9 (trace amine associated receptor 9, HGNC:20977) is a protein-coding gene on chromosome 6q23.2, encoding Trace amine-associated receptor 9 (Q96RI9). Olfactory receptor specific for trace amines, such as N,N-dimethylcyclohexylamine (DMCHA) and beta-phenylethylamine (beta-PEA).

TAAR9 is a member of a large family of rhodopsin G protein-coupled receptors (GPCRs, or GPRs). GPCRs contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins.

Source: NCBI Gene 134860 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 63 total
• Druggable target: yes
• MANE Select transcript: NM_175057

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20977
Approved symbol	TAAR9
Name	trace amine associated receptor 9
Location	6q23.2
Locus type	gene with protein product
Status	Approved
Aliases	TA3, TAR3
Ensembl gene	ENSG00000237110
Ensembl biotype	protein_coding
OMIM	608282
Entrez	134860

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000434551

RefSeq mRNA: 1 — MANE Select: NM_175057 NM_175057

CCDS: CCDS75520

Canonical transcript exons

ENST00000434551 — 1 exons

Exon	Start	End
ENSE00003978234	132538277	132539336

Expression profiles

Bgee: expression breadth tissue_specific, 1 present calls, max score 44.07.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of hip	UBERON:0001554	44.07	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
granulocyte	CL:0000094	42.64	silver 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
oviduct epithelium	UBERON:0004804	41.17	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
cortical plate	UBERON:0005343	40.77	silver 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
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
cartilage tissue	UBERON:0002418	40.06	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
deltoid	UBERON:0001476	39.83	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality
parotid gland	UBERON:0001831	39.81	gold quality
oocyte	CL:0000023	39.80	gold quality
urethra	UBERON:0000057	39.80	gold quality
heart right ventricle	UBERON:0002080	39.79	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 1)

• 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)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Taar9	ENSMUSG00000037424
rattus_norvegicus	Taar9	ENSRNOG00000026096

Paralogs (25): DRD4 (ENSG00000069696), HRH3 (ENSG00000101180), HRH2 (ENSG00000113749), CHRM3 (ENSG00000133019), HRH4 (ENSG00000134489), TAAR5 (ENSG00000135569), 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)

Protein

Protein identifiers

Trace amine-associated receptor 9 — Q96RI9 (reviewed: Q96RI9)

Alternative names: Trace amine receptor 3

All UniProt accessions (1): Q96RI9

UniProt curated annotations — full annotation on UniProt →

Function. Olfactory receptor specific for trace amines, such as N,N-dimethylcyclohexylamine (DMCHA) and beta-phenylethylamine (beta-PEA). In contrast to mouse and rat orthologs, not activated by triethylamine, cadaverine (CAD) or spermidine. 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. Trace amine-binding causes a conformation change that triggers signaling via G(s)-class of G alpha proteins (GNAL or GNAS). In mature olfactory sensory neurons, TAAR9 is coupled with GNAL/G(olf)G alpha protein and mediates activation of adenylate cyclase activity to activate cAMP signaling and eventually transmit odorant signals to achieve membrane depolarization. In immature olfactory sensory neurons, TAAR9 is coupled with GNAS/G(s) G alpha proteins.

Subcellular location. Cell membrane.

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_778227* (*=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 (24 total): topological domain 8, transmembrane region 7, binding site 2, glycosylation site 2, disulfide bond 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RI9-F1	90.39	0.70

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 (2): 112; 113

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: 28 (showing top): GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, TGCTGAY_UNKNOWN, MARTIN_VIRAL_GPCR_SIGNALING_UP, 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

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 (3): trace-amine receptor activity (GO:0001594), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

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
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

576 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAAR9	RBM8A	Q9Y5S9	447
TAAR9	AVPR2	P30518	424
TAAR9	MUC21	Q5SSG8	417
TAAR9	TAAR1	Q96RJ0	393
TAAR9	OR52H1	Q8NGJ2	390
TAAR9	RHO	P08100	352
TAAR9	ADCY3	O60266	344
TAAR9	OR52B6	Q8NGF0	328
TAAR9	MXRA8	Q9BRK3	314
TAAR9	CNGA2	Q16280	308
TAAR9	CAGE1	Q8TC20	300
TAAR9	OR2T1	O43869	299
TAAR9	VNN1	O95497	286
TAAR9	OR52E8	Q6IFG1	285
TAAR9	SLC18B1	Q6NT16	281

IntAct

13 interactions, top by confidence:

A	B	Type	Score
TUSC5	TAAR9	psi-mi:“MI:0915”(physical association)	0.560
SLC41A1	TAAR9	psi-mi:“MI:0915”(physical association)	0.560
RAMP1	TAAR9	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	TAAR9	psi-mi:“MI:0915”(physical association)	0.400
TAAR9	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	TAAR9	psi-mi:“MI:0915”(physical association)	0.400
TUSC5	TAAR9	psi-mi:“MI:0915”(physical association)	0.000
SLC41A1	TAAR9	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2): TAAR9 (Two-hybrid), TAAR9 (Two-hybrid)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

225 predictions. Top by Δscore:

Variant	Effect	Δscore
6:132539236:AAT:A	acceptor_gain	0.8000
6:132539238:T:TA	acceptor_gain	0.7500
6:132538560:G:GG	donor_gain	0.7400
6:132538555:GCACA:G	donor_gain	0.7300
6:132538559:A:AG	donor_gain	0.7300
6:132538531:TGG:T	donor_gain	0.7100
6:132538532:GGG:G	donor_gain	0.7100
6:132538564:G:GT	donor_gain	0.6700
6:132538598:T:G	donor_gain	0.6600
6:132538337:GAAC:G	donor_gain	0.6400
6:132539124:G:GG	donor_gain	0.6400
6:132538797:ACG:A	acceptor_gain	0.6300
6:132538533:G:GT	donor_gain	0.6200
6:132538565:G:T	donor_gain	0.6200
6:132538798:C:G	acceptor_gain	0.6200
6:132539123:A:AG	donor_gain	0.6200
6:132539236:A:AG	acceptor_gain	0.6100
6:132538447:TC:T	donor_gain	0.6000
6:132538574:GAGCT:G	donor_gain	0.6000
6:132538576:GCT:G	donor_gain	0.6000
6:132538586:C:CG	donor_gain	0.6000
6:132538338:A:T	donor_gain	0.5900
6:132538797:AC:A	acceptor_gain	0.5800
6:132539029:A:T	donor_gain	0.5700
6:132539128:T:G	donor_gain	0.5500
6:132539127:A:AG	donor_gain	0.5400
6:132538344:AAC:A	donor_gain	0.5300
6:132538449:A:AG	donor_gain	0.5300
6:132538587:T:G	donor_gain	0.5300
6:132538340:C:G	donor_gain	0.5100

AlphaMissense

2275 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:132538467:T:C	F60L	0.987
6:132538469:C:A	F60L	0.987
6:132538469:C:G	F60L	0.987
6:132539088:T:C	F267L	0.987
6:132539090:T:A	F267L	0.987
6:132539090:T:G	F267L	0.987
6:132539241:T:C	F318L	0.980
6:132539243:T:A	F318L	0.980
6:132539243:T:G	F318L	0.980
6:132538583:G:C	W98C	0.970
6:132538583:G:T	W98C	0.970
6:132538779:A:C	S164R	0.967
6:132538781:C:A	S164R	0.967
6:132538781:C:G	S164R	0.967
6:132538523:C:A	D78E	0.965
6:132538523:C:G	D78E	0.965
6:132538439:C:A	N50K	0.962
6:132538439:C:G	N50K	0.962
6:132538687:C:A	A133D	0.957
6:132538690:T:A	V134D	0.957
6:132538758:T:A	W157R	0.956
6:132538758:T:C	W157R	0.956
6:132538679:A:C	R130S	0.954
6:132538679:A:T	R130S	0.954
6:132538581:T:A	W98R	0.953
6:132538581:T:C	W98R	0.953
6:132539181:T:A	W298R	0.953
6:132539181:T:C	W298R	0.953
6:132538857:T:A	C190S	0.951
6:132538858:G:C	C190S	0.951

dbSNP variants (sampled 300 via entrez): RS1000175830 (6:132539569 G>T), RS1000909537 (6:132538134 G>T), RS1001508997 (6:132537775 G>A), RS1001834822 (6:132537076 T>C), RS1002111942 (6:132536431 G>T), RS1003087853 (6:132538030 A>T), RS1007048144 (6:132538949 A>T), RS1007585178 (6:132537367 T>A), RS1009530080 (6:132537732 C>A), RS1010054738 (6:132538114 A>C), RS1010413621 (6:132539523 A>G), RS1010949583 (6:132536378 G>A), RS1011118692 (6:132536918 C>A,T), RS1011149895 (6:132536664 T>C), RS1011420038 (6:132538356 A>G,T)

Disease associations

OMIM: gene MIM:608282 | 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): CHEMBL4523911 (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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
CGP 52608	affects binding, increases reaction	1
Valproic Acid	decreases methylation	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
CHEMBL4883609	Binding	PRESTO-Tango GPCRome screening (TAAR9)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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