OR2AT4

Summary

OR2AT4 (olfactory receptor family 2 subfamily AT member 4, HGNC:19620) is a protein-coding gene on chromosome 11q13.4, encoding Olfactory receptor 2AT4 (A6NND4). Olfactory receptor.

Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome.

Source: NCBI Gene 341152 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_001405852

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19620
Approved symbol	OR2AT4
Name	olfactory receptor family 2 subfamily AT member 4
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000171561
Ensembl biotype	protein_coding
Entrez	341152

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000305159, ENST00000641504, ENST00000641541, ENST00000641593, ENST00000641931

RefSeq mRNA: 2 — MANE Select: NM_001405852 NM_001005285, NM_001405852

CCDS: CCDS31639

Canonical transcript exons

ENST00000641504 — 2 exons

Exon	Start	End
ENSE00003811572	75081753	75090364
ENSE00003813679	75096828	75096876

Expression profiles

Bgee: expression breadth tissue_specific, 2 present calls, max score 57.23.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0164 / max 5.6703, expressed in 13 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121335	0.0164	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	57.23	silver quality
ventricular zone	UBERON:0003053	46.50	gold quality
bone marrow	UBERON:0002371	45.03	gold quality
monocyte	CL:0000576	44.50	gold quality
bone marrow cell	CL:0002092	44.40	gold quality
leukocyte	CL:0000738	43.53	gold quality
skeletal muscle tissue	UBERON:0001134	43.43	gold quality
muscle tissue	UBERON:0002385	43.20	gold quality
cortical plate	UBERON:0005343	43.20	gold quality
stromal cell of endometrium	CL:0002255	41.97	silver quality
calcaneal tendon	UBERON:0003701	41.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	41.87	gold quality
superior frontal gyrus	UBERON:0002661	41.21	gold quality
placenta	UBERON:0001987	40.87	gold quality
colonic epithelium	UBERON:0000397	40.81	gold quality
blood	UBERON:0000178	40.62	gold quality
liver	UBERON:0002107	39.39	gold quality
lymph node	UBERON:0000029	39.15	gold quality
primary visual cortex	UBERON:0002436	38.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	38.74	gold quality
adrenal tissue	UBERON:0018303	38.34	gold quality
prefrontal cortex	UBERON:0000451	38.17	gold quality
smooth muscle tissue	UBERON:0001135	37.66	gold quality
lower esophagus mucosa	UBERON:0035834	37.63	gold quality
vermiform appendix	UBERON:0001154	37.49	gold quality
ganglionic eminence	UBERON:0004023	37.12	gold quality
muscle of leg	UBERON:0001383	37.06	gold quality
gastrocnemius	UBERON:0001388	36.64	gold quality
granulocyte	CL:0000094	36.52	gold quality
tonsil	UBERON:0002372	36.39	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.06
E-GEOD-98556	no	56.37
E-GEOD-99795	no	19.42

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• OR2AT4 is involved in human keratinocyte re-epithelialization during wound-healing processes (PMID:24999593)
• Study shows that human hair follicles (HF) can engage in chemosensation and that the specific activation of OR2AT4 is required to sustain HF growth. (PMID:30228264)
• Identification of Key Biomarkers and Immune Infiltration in Sporadic Vestibular Schwannoma Basing Transcriptome-Wide Profiling. (PMID:35092815)
• Preliminary evidence that Merkel cells exert chemosensory functions in human epidermis. (PMID:37587642)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Or2at4	ENSMUSG00000073998
rattus_norvegicus	Olr35	ENSRNOG00000030788

Paralogs (130): OR1I1 (ENSG00000094661), OR12D3 (ENSG00000112462), OR7A10 (ENSG00000127515), OR7C2 (ENSG00000127529), OR7C1 (ENSG00000127530), OR1E2 (ENSG00000127780), OR1J1 (ENSG00000136834), OR1L4 (ENSG00000136939), OR4D1 (ENSG00000141194), OR4K1 (ENSG00000155249), OR3A3 (ENSG00000159961), OR7G1 (ENSG00000161807), OR1Q1 (ENSG00000165202), OR1K1 (ENSG00000165204), OR4K2 (ENSG00000165762), OR4D6 (ENSG00000166884), OR1F1 (ENSG00000168124), OR4K14 (ENSG00000169484), OR4K15 (ENSG00000169488), OR7G3 (ENSG00000170920), OR7G2 (ENSG00000170923), OR1M1 (ENSG00000170929), OR4D5 (ENSG00000171014), OR1L6 (ENSG00000171459), OR1L3 (ENSG00000171481), OR1L8 (ENSG00000171496), OR1N2 (ENSG00000171501), OR1N1 (ENSG00000171505), OR1A1 (ENSG00000172146), OR1A2 (ENSG00000172150), OR4C11 (ENSG00000172188), OR4X2 (ENSG00000172208), OR4D9 (ENSG00000172742), OR10K1 (ENSG00000173285), OR1L1 (ENSG00000173679), OR7D4 (ENSG00000174667), OR4S2 (ENSG00000174982), OR4B1 (ENSG00000175619), OR4D11 (ENSG00000176200), OR4K17 (ENSG00000176230)

Protein

Protein identifiers

Olfactory receptor 2AT4 — A6NND4 (reviewed: A6NND4)

Alternative names: Olfactory receptor OR11-265

All UniProt accessions (2): A6NND4, A0A126GWB1

UniProt curated annotations — full annotation on UniProt →

Function. Olfactory receptor. Activated by the synthetic sandalwood odorant sandalore. Endogenous ligand is unknown. The activity of this receptor is probably mediated by G proteins which induce elevation of intracellular Ca(2+), a cAMP-dependent pathway and phosphorylation of MAPK1/ERK2, MAPK3/ERK1 and p38 MAPKs. Activation of OR2AT4 induces proliferation, migration, and re-epithelialization during wound-healing processes of keratinocytes. Stimulation of OR2AT4 by sandalore promotes hair growth by decreasing apoptosis and increasing production of the anagen-prolonging growth factor IGF1 as well as other pathways involving various kinases.

Subcellular location. Cell membrane.

Tissue specificity. Detected in the keratinocytes of the epidermis (at protein level). Detected in hair follicles in proximal outer root sheath and hair matrix keratinocytes (at protein level).

Induction. Down-regulated during spontaneous, apoptosis-driven hair follicles regression (catagen).

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

RefSeq proteins (2): NP_001005285, NP_001392781* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000725	Olfact_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050939	Olfactory_GPCR1	Family

Pfam: PF13853

UniProt features (18 total): topological domain 8, transmembrane region 7, chain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NND4-F1	90.05	0.71

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 (1): 102–184

Glycosylation sites (1): 7

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-381753	Olfactory Signaling Pathway
R-HSA-9752946	Expression and translocation of olfactory receptors

MSigDB gene sets: 24 (showing top): GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, chr11q13, KEGG_OLFACTORY_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, GOBP_POSITIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_ERK1_AND_ERK2_CASCADE, GOMF_OLFACTORY_RECEPTOR_ACTIVITY, 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 (5): signal transduction (GO:0007165), positive regulation of ERK1 and ERK2 cascade (GO:0070374), G protein-coupled receptor signaling pathway (GO:0007186), sensory perception of smell (GO:0007608), detection of chemical stimulus involved in sensory perception of smell (GO:0050911)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), olfactory receptor activity (GO:0004984)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Sensory Perception	1
Olfactory Signaling Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transmembrane signaling receptor activity	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
G protein-coupled receptor activity	1
signal transduction	1
sensory perception of chemical stimulus	1
sensory perception of smell	1
detection of chemical stimulus involved in sensory perception	1
G protein-coupled receptor signaling pathway	1
detection of chemical stimulus involved in sensory perception of smell	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

180 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OR2AT4	C9orf43	Q8TAL5	451
OR2AT4	ZNF772	Q68DY9	445
OR2AT4	AMZ1	Q400G9	416
OR2AT4	CCDC57	Q2TAC2	403
OR2AT4	ORMDL2	Q53FV1	401
OR2AT4	FASTKD3	Q14CZ7	400
OR2AT4	NKAIN4	Q8IVV8	393
OR2AT4	RDM1	Q8NG50	387
OR2AT4	STK31	Q9BXU1	385
OR2AT4	DNAJC12	Q9UKB3	377
OR2AT4	CMYA5	Q8N3K9	374
OR2AT4	FREM2	Q5SZK8	369
OR2AT4	MESP2	Q0VG99	369
OR2AT4	KRT75	O95678	368
OR2AT4	RTP2	Q5QGT7	364

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A3KFT3, A6NM03, A6NND4, O14581, O60412, O76099, P34982, P35898, Q0VAX9, Q15612, Q15622, Q60887, Q60891, Q8N349, Q8NG80, Q8NG83, Q8NG84, Q8NG85, Q8NG92, Q8NG95, Q8NG99, Q8NGC7, Q8NGC9, Q8NGE0, Q8NGE9, Q8NGQ5, Q8NGR1, Q8NGR6, Q8NGR9, Q8NGU1, Q8NGX1, Q8NGY2, Q8NGY6, Q8NGY9, Q8NH03, Q8NH16, Q8NHA4, Q8NHA8, Q95157, Q9GZK7

Diamond homologs: A0A3B3IT45, A4D2G3, A6NF89, A6NGY5, A6NL08, A6NL26, A6NMU1, A6NND4, O88628, P0C629, P0C646, P0C7N1, P0C7T3, P23266, P23273, P23274, P30954, Q13606, Q60888, Q62007, Q6IF63, Q6IFG1, Q6W049, Q8NGA6, Q8NGF0, Q8NGF1, Q8NGF3, Q8NGG8, Q8NGH5, Q8NGH6, Q8NGH7, Q8NGH8, Q8NGH9, Q8NGI0, Q8NGI1, Q8NGI2, Q8NGI3, Q8NGI7, Q8NGJ2, Q8NGJ3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

323 predictions. Top by Δscore:

Variant	Effect	Δscore
11:75089396:CAT:C	donor_gain	0.6900
11:75089217:A:AC	donor_gain	0.6800
11:75089218:C:CC	donor_gain	0.6800
11:75089045:A:C	acceptor_gain	0.6700
11:75088823:CAGCG:C	acceptor_gain	0.6600
11:75089033:CAGGA:C	acceptor_gain	0.6600
11:75089693:A:AC	donor_gain	0.6600
11:75088826:CG:C	acceptor_gain	0.6500
11:75088827:G:C	acceptor_gain	0.6500
11:75088827:G:GC	acceptor_gain	0.6400
11:75088955:CACG:C	donor_gain	0.6400
11:75088956:ACGA:A	donor_gain	0.6400
11:75088957:CGA:C	donor_gain	0.6400
11:75088957:CGAC:C	donor_gain	0.6400
11:75088958:G:GC	donor_gain	0.6200
11:75088959:A:AA	donor_gain	0.6000
11:75089060:C:CT	acceptor_gain	0.6000
11:75089333:G:C	donor_gain	0.6000
11:75088809:ACATC:A	donor_gain	0.5900
11:75088813:C:A	donor_gain	0.5900
11:75088737:G:C	donor_gain	0.5800
11:75089397:A:C	donor_gain	0.5800
11:75088773:GGGTC:G	acceptor_gain	0.5700
11:75088956:A:AC	donor_gain	0.5600
11:75088957:C:CC	donor_gain	0.5600
11:75089000:T:TA	donor_gain	0.5500
11:75089461:TGGGG:T	donor_gain	0.5500
11:75089725:G:C	donor_gain	0.5500
11:75088829:G:C	acceptor_gain	0.5400
11:75089350:C:CT	donor_gain	0.5400

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000691923 (11:75095015 G>A), RS1001222369 (11:75094654 A>G), RS1001444272 (11:75098564 TC>T), RS1001673348 (11:75089396 C>T), RS1001827432 (11:75095813 G>A,T), RS1002125545 (11:75089023 G>A), RS1002292929 (11:75091801 T>G), RS1002345162 (11:75091545 T>C), RS1002833908 (11:75097274 T>C), RS1003074568 (11:75091006 G>A,C), RS1003472609 (11:75096717 A>G), RS1003668444 (11:75092616 T>C), RS1003826364 (11:75096950 G>T), RS1004320674 (11:75088441 T>C), RS1004733158 (11:75097183 C>T)

Disease associations

OMIM: gene `` | 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: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
Cadmium	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Malathion	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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