OR4E2

Summary

OR4E2 (olfactory receptor family 4 subfamily E member 2, HGNC:8297) is a protein-coding gene on chromosome 14q11.2, encoding Olfactory receptor 4E2 (Q8NGC2). Olfactory receptor that is activated by the binding of organosulfur odorants with thioether groups such as (methylthio)methanethiol (MTMT) and bis(methylthiomethyl) disulfide.

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 26686 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_001001912

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8297
Approved symbol	OR4E2
Name	olfactory receptor family 4 subfamily E member 2
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000221977
Ensembl biotype	protein_coding
Entrez	26686

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000641524

RefSeq mRNA: 1 — MANE Select: NM_001001912 NM_001001912

CCDS: CCDS41916

Canonical transcript exons

ENST00000641524 — 4 exons

Exon	Start	End
ENSE00003812048	21665075	21667642
ENSE00003812303	21660653	21660746
ENSE00003812923	21656502	21656589
ENSE00003813324	21653835	21653939

Expression profiles

Bgee: expression breadth tissue_specific, 6 present calls, max score 37.89.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	37.89	gold 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
hindlimb stylopod muscle	UBERON:0004252	36.19	silver quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
mucosa of transverse colon	UBERON:0004991	34.19	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
mucosa of stomach	UBERON:0001199	32.94	gold quality
leukocyte	CL:0000738	32.77	gold quality
monocyte	CL:0000576	32.62	gold quality
muscle tissue	UBERON:0002385	32.17	gold quality
cortex of kidney	UBERON:0001225	31.89	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
blood	UBERON:0000178	31.39	silver quality
ectocervix	UBERON:0012249	30.93	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
urinary bladder	UBERON:0001255	30.89	silver quality
liver	UBERON:0002107	30.73	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
vermiform appendix	UBERON:0001154	29.22	gold quality
prefrontal cortex	UBERON:0000451	29.20	gold quality
lymph node	UBERON:0000029	28.76	gold quality
right uterine tube	UBERON:0001302	28.71	gold quality
gall bladder	UBERON:0002110	28.45	gold quality
gastrocnemius	UBERON:0001388	28.21	gold quality
duodenum	UBERON:0002114	28.14	gold quality
kidney	UBERON:0002113	27.96	gold quality
uterine cervix	UBERON:0000002	27.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.11

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Or4e2	ENSMUSG00000035626
rattus_norvegicus	Or4e2	ENSRNOG00000071420

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 4E2 — Q8NGC2 (reviewed: Q8NGC2)

Alternative names: Olfactory receptor OR14-42

All UniProt accessions (1): A0A126GVR8

UniProt curated annotations — full annotation on UniProt →

Function. Olfactory receptor that is activated by the binding of organosulfur odorants with thioether groups such as (methylthio)methanethiol (MTMT) and bis(methylthiomethyl) disulfide. Also binds odorants cis-cyclooctene and tert-butyl mercaptan. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.

Subcellular location. Cell membrane.

Activity regulation. Copper binding enhances receptor activity in response to odorant binding.

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

RefSeq proteins (1): NP_001001912* (*=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 (23 total): topological domain 8, transmembrane region 7, binding site 3, sequence variant 2, chain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NGC2-F1	88.48	0.61

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 (3): 105; 109; 260

Disulfide bonds (1): 97–179

Glycosylation sites (1): 5

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 31 (showing top): GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, KEGG_OLFACTORY_TRANSDUCTION, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, 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, ZNF92_TARGET_GENES, GSE17721_POLYIC_VS_CPG_24H_BMDC_DN, REACTOME_OLFACTORY_SIGNALING_PATHWAY

GO Biological Process (5): 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), detection of chemical stimulus involved in sensory perception (GO:0050907)

GO Molecular Function (5): G protein-coupled receptor activity (GO:0004930), olfactory receptor activity (GO:0004984), odorant binding (GO:0005549), metal ion binding (GO:0046872), copper ion binding (GO:0005507)

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
sensory perception of chemical stimulus	2
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	1
detection of chemical stimulus	1
detection of stimulus involved in sensory perception	1
G protein-coupled receptor signaling pathway	1
detection of chemical stimulus involved in sensory perception of smell	1
binding	1
cation binding	1
transition metal ion binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

174 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OR4E2	KRTAP12-3	P60328	652
OR4E2	TMEM235	A6NFC5	590
OR4E2	C1QTNF8	P60827	507
OR4E2	SPATA31D3	P0C874	448
OR4E2	CPLANE1	Q9H799	412
OR4E2	SPATA31D4	Q6ZUB0	407
OR4E2	LHFPL6	Q9Y693	400
OR4E2	ASIC4	Q96FT7	370
OR4E2	FMO1	Q01740	351
OR4E2	SSTR4	P31391	322
OR4E2	GSTM4	Q03013	311
OR4E2	GRIN3B	O60391	308
OR4E2	PDE1C	Q14123	305
OR4E2	TRDV1	A0A1B0GX56	284
OR4E2	LIMK2	P53671	270

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

283 predictions. Top by Δscore:

Variant	Effect	Δscore
14:21665500:G:GG	donor_gain	0.7000
14:21665908:ACAGT:A	acceptor_gain	0.6700
14:21665497:A:T	donor_gain	0.6600
14:21665723:T:TA	acceptor_gain	0.6600
14:21665498:GA:G	donor_gain	0.6400
14:21665499:A:AG	donor_gain	0.6200
14:21665770:GCT:G	acceptor_gain	0.6200
14:21665488:A:AG	donor_gain	0.6100
14:21665769:A:AG	acceptor_gain	0.6100
14:21665770:G:GG	acceptor_gain	0.6100
14:21665721:C:A	acceptor_gain	0.6000
14:21665747:T:TA	acceptor_gain	0.6000
14:21665639:A:G	acceptor_gain	0.5900
14:21665959:G:GT	donor_gain	0.5900
14:21665448:T:G	donor_gain	0.5800
14:21665765:A:AG	acceptor_gain	0.5800
14:21665718:G:A	acceptor_gain	0.5700
14:21665758:C:CA	acceptor_gain	0.5700
14:21665910:AGT:A	acceptor_gain	0.5600
14:21665911:GTG:G	acceptor_gain	0.5600
14:21665737:AT:A	acceptor_gain	0.5500
14:21665436:G:GT	donor_gain	0.5300
14:21665636:TCAAG:T	acceptor_gain	0.5300
14:21665637:CAAGC:C	acceptor_gain	0.5300
14:21665717:T:TA	acceptor_gain	0.5300
14:21665484:T:G	donor_gain	0.5200
14:21665821:G:GG	donor_gain	0.5200
14:21665952:GAA:G	donor_gain	0.5200
14:21665710:T:TA	acceptor_gain	0.5100
14:21665766:CTCA:C	acceptor_loss	0.5100

AlphaMissense

2056 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:21665116:T:C	F12L	0.879
14:21665118:T:A	F12L	0.879
14:21665118:T:G	F12L	0.879
14:21665614:T:C	F178L	0.823
14:21665616:C:A	F178L	0.823
14:21665616:C:G	F178L	0.823
14:21665436:G:A	M118I	0.799
14:21665436:G:C	M118I	0.799
14:21665436:G:T	M118I	0.799
14:21665173:T:C	F31L	0.787
14:21665175:C:A	F31L	0.787
14:21665175:C:G	F31L	0.787
14:21665362:T:C	F94L	0.712
14:21665364:T:A	F94L	0.712
14:21665364:T:G	F94L	0.712
14:21665386:T:C	F102L	0.709
14:21665388:C:A	F102L	0.709
14:21665388:C:G	F102L	0.709
14:21665848:T:C	F256L	0.673
14:21665850:C:A	F256L	0.673
14:21665850:C:G	F256L	0.673
14:21665608:A:C	S176R	0.668
14:21665610:C:A	S176R	0.668
14:21665610:C:G	S176R	0.668
14:21665263:T:C	F61L	0.646
14:21665265:C:A	F61L	0.646
14:21665265:C:G	F61L	0.646
14:21665713:T:C	F211L	0.644
14:21665715:C:A	F211L	0.644
14:21665715:C:G	F211L	0.644

dbSNP variants (sampled 300 via entrez): RS1000292511 (14:21659409 G>A), RS1000397979 (14:21653847 G>T), RS1000447210 (14:21655585 A>G), RS1000457839 (14:21667767 C>T), RS1000478454 (14:21655852 T>C), RS1000746335 (14:21654704 T>G), RS1001567085 (14:21660644 T>G), RS1001591815 (14:21666205 T>A,C), RS1001836818 (14:21662295 G>A,T), RS1001924199 (14:21667781 T>A), RS1001956944 (14:21667465 T>C), RS1002304077 (14:21661624 T>C), RS1002310551 (14:21662660 T>C), RS1002412304 (14:21656425 C>A), RS1002422126 (14:21656107 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

0 associations (top):

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
Benzo(a)pyrene	increases methylation	1

Clinical trials (associated diseases)

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