OR4E1

Summary

OR4E1 (olfactory receptor family 4 subfamily E member 1, HGNC:8296) is a protein-coding gene on chromosome 14q11.2, encoding Olfactory receptor 4E1 (P0C645). Odorant 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 26687 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001317107

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8296
Approved symbol	OR4E1
Name	olfactory receptor family 4 subfamily E member 1
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000276240
Ensembl biotype	protein_coding
Entrez	26687

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000641792

RefSeq mRNA: 1 — MANE Select: NM_001317107 NM_001317107

CCDS: CCDS86370

Canonical transcript exons

ENST00000641792 — 2 exons

Exon	Start	End
ENSE00003812224	21673090	21673818
ENSE00003812949	21667886	21670952

Expression profiles

Bgee: expression breadth tissue_specific, 10 present calls, max score 60.09.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	60.09	gold quality
leukocyte	CL:0000738	58.39	gold quality
granulocyte	CL:0000094	55.84	gold quality
blood	UBERON:0000178	53.00	gold quality
stromal cell of endometrium	CL:0002255	48.55	gold quality
sural nerve	UBERON:0015488	47.41	gold quality
lymph node	UBERON:0000029	46.30	silver quality
vermiform appendix	UBERON:0001154	46.28	silver quality
ventricular zone	UBERON:0003053	43.57	gold quality
spleen	UBERON:0002106	43.16	gold quality
bone marrow	UBERON:0002371	42.89	gold quality
colonic epithelium	UBERON:0000397	41.29	gold quality
primary visual cortex	UBERON:0002436	41.27	gold quality
gall bladder	UBERON:0002110	40.85	gold quality
ganglionic eminence	UBERON:0004023	40.58	gold quality
endometrium	UBERON:0001295	40.44	gold quality
skeletal muscle tissue	UBERON:0001134	39.09	gold quality
bone marrow cell	CL:0002092	38.01	gold quality
cortex of kidney	UBERON:0001225	37.73	gold quality
placenta	UBERON:0001987	37.72	gold quality
muscle tissue	UBERON:0002385	37.59	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
rectum	UBERON:0001052	36.40	gold quality
mucosa of transverse colon	UBERON:0004991	36.27	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	35.88	gold quality
calcaneal tendon	UBERON:0003701	35.79	gold quality
mucosa of stomach	UBERON:0001199	35.21	gold quality
right coronary artery	UBERON:0001625	35.09	gold quality
superior frontal gyrus	UBERON:0002661	35.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.95

Regulation

Is transcription factor: no

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Or4e1	ENSMUSG00000057564
mus_musculus	Or4e5	ENSMUSG00000059887
rattus_norvegicus	Or4e1	ENSRNOG00000039435
rattus_norvegicus	Or4e5	ENSRNOG00000077613

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), OR2AT4 (ENSG00000171561), OR1A1 (ENSG00000172146), OR1A2 (ENSG00000172150), OR4C11 (ENSG00000172188), OR4X2 (ENSG00000172208), OR4D9 (ENSG00000172742), OR10K1 (ENSG00000173285), OR1L1 (ENSG00000173679), OR7D4 (ENSG00000174667), OR4S2 (ENSG00000174982), OR4B1 (ENSG00000175619), OR4D11 (ENSG00000176200)

Protein

Protein identifiers

Olfactory receptor 4E1 — P0C645 (reviewed: P0C645)

Alternative names: Olfactory receptor OR14-43

All UniProt accessions (1): P0C645

UniProt curated annotations — full annotation on UniProt →

Function. Odorant receptor.

Subcellular location. Cell membrane.

Polymorphism. There at least 2 alleles for OR4E1. A non-functional allele results from a polymorphism at position 197 (dbSNP rs199890040), which leads to a frameshift, premature truncation of the coding region and hence pseudogenization. The presence of various combinations of functional (olfactory receptors) and non-functional (olfactory receptor segregating pseudogenes) alleles may underlie differences in olfactory sensitivity between individuals (hyperosmia, hyposmia or even anosmia).

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

RefSeq proteins (1): NP_001304036* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000725	Olfact_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050427	Olfactory_Receptors	Family

Pfam: PF13853

UniProt features (21 total): topological domain 8, transmembrane region 7, sequence variant 3, chain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C645-F1	86.99	0.53

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): 101–183

Glycosylation sites (1): 8

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 18 (showing top): GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION, HANSON_HRAS_SIGNALING_VIA_NFKB, MCDOWELL_ACUTE_LUNG_INJURY_UP, GOMF_OLFACTORY_RECEPTOR_ACTIVITY, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_ODORANT_BINDING, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_SENSORY_PERCEPTION_OF_SMELL, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_DETECTION_OF_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION, REACTOME_OLFACTORY_SIGNALING_PATHWAY, REACTOME_SENSORY_PERCEPTION, GOBP_DETECTION_OF_CHEMICAL_STIMULUS

GO Biological Process (4): detection of chemical stimulus involved in sensory perception of smell (GO:0050911), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), sensory perception of smell (GO:0007608)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), olfactory receptor activity (GO:0004984), odorant binding (GO:0005549)

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

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Olfactory Signaling Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transmembrane signaling receptor activity	2
sensory perception of smell	1
detection of chemical stimulus involved in sensory perception	1
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
sensory perception of chemical stimulus	1
G protein-coupled receptor signaling pathway	1
detection of chemical stimulus involved in sensory perception of smell	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

102 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OR4E1	JAKMIP2	Q96AA8	507
OR4E1	IMPG1	Q17R60	471
OR4E1	FAM194C	Q8ND61	401
OR4E1	TMEM39B	Q9GZU3	311
OR4E1	URB2	Q14146	290
OR4E1	CELF2	O95319	274
OR4E1	MYO3B	Q8WXR4	265
OR4E1	MPPED1	O15442	263
OR4E1	LRFN4	Q6PJG9	232
OR4E1	ELMOD2	Q8IZ81	226
OR4E1	GIPC2	Q8TF65	226
OR4E1	CFAP44	Q96MT7	222
OR4E1	TMEM132D	Q14C87	222
OR4E1	XKR4	Q5GH76	220
OR4E1	RASEF	Q8IZ41	220

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A096LPK9, A0A0X1KG70, A6NHA9, A6NMZ5, P0C604, P0C623, P0C645, P0DN82, P58180, P58182, Q15615, Q60881, Q6IF82, Q8IXE1, Q8N0Y3, Q8NGA8, Q8NGB4, Q8NGB6, Q8NGC2, Q8NGC3, Q8NGD0, Q8NGD1, Q8NGD2, Q8NGD5, Q8NGE8, Q8NGF4, Q8NGF8, Q8NGF9, Q8NGI4, Q8NGI6, Q8NGJ0, Q8NGJ1, Q8NGL6, Q8NGM1, Q8NGN0, Q8NGN8, Q8NGX5, Q8NH05, Q8NH42, Q8NH49

Diamond homologs: A0A096LPK9, A0A0X1KG70, A6NHA9, A6NMZ5, O60412, O76099, O95013, P0C604, P0C623, P0C645, P0DN82, P23270, P23275, P58173, P58180, P58182, Q15615, Q60878, Q60881, Q60888, Q6IEV9, Q6IEY1, Q6IF82, Q7TQQ0, Q8IXE1, Q8N0Y3, Q8N628, Q8NGA8, Q8NGB2, Q8NGB4, Q8NGB6, Q8NGB8, Q8NGB9, Q8NGC2, Q8NGC3, Q8NGC4, Q8NGC6, Q8NGD0, Q8NGD1, Q8NGD2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2064 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:21670710:A:G	C76R	0.952
14:21670570:C:A	M122I	0.950
14:21670570:C:G	M122I	0.950
14:21670570:C:T	M122I	0.950
14:21670393:G:C	F181L	0.945
14:21670393:G:T	F181L	0.945
14:21670395:A:G	F181L	0.945
14:21670174:G:C	F254L	0.940
14:21670174:G:T	F254L	0.940
14:21670176:A:G	F254L	0.940
14:21670559:C:G	R126P	0.938
14:21670388:C:G	C183S	0.931
14:21670389:A:T	C183S	0.931
14:21670390:G:C	F182L	0.931
14:21670390:G:T	F182L	0.931
14:21670392:A:G	F182L	0.931
14:21670479:A:G	W153R	0.929
14:21670479:A:T	W153R	0.929
14:21670624:C:A	Q104H	0.924
14:21670624:C:G	Q104H	0.924
14:21670315:A:C	S207R	0.923
14:21670315:A:T	S207R	0.923
14:21670317:T:G	S207R	0.923
14:21670075:G:C	N287K	0.911
14:21670075:G:T	N287K	0.911
14:21670562:T:G	D125A	0.902
14:21670389:A:G	C183R	0.900
14:21670618:G:C	F106L	0.900
14:21670618:G:T	F106L	0.900
14:21670620:A:G	F106L	0.900

dbSNP variants (sampled 300 via entrez): RS1000457839 (14:21667767 C>T), RS1000850434 (14:21670478 C>A,T), RS1001091285 (14:21673857 A>G), RS1001924199 (14:21667781 T>A), RS1001956944 (14:21667465 T>C), RS1003031047 (14:21669487 T>C), RS1003080504 (14:21669791 A>G,T), RS1003592480 (14:21674375 G>A), RS1003596971 (14:21669045 G>C), RS1003627868 (14:21668806 A>G), RS1004527556 (14:21669964 C>A,T), RS1004854489 (14:21675752 T>C), RS1004991804 (14:21670108 A>C), RS1005792876 (14:21671203 G>A), RS1006031767 (14:21672824 T>C)

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

1 associations (top):

Study	Trait	p-value
GCST012041_4	Sleep activity levels	2.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

1 total (human), top 1 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Caffeine	increases phosphorylation	1

Clinical trials (associated diseases)

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