OR5K3

Summary

OR5K3 (olfactory receptor family 5 subfamily K member 3, HGNC:31290) is a protein-coding gene on chromosome 3q11.2, encoding Olfactory receptor 5K3 (A6NET4). 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 403277 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 67 total
• MANE Select transcript: NM_001005516

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31290
Approved symbol	OR5K3
Name	olfactory receptor family 5 subfamily K member 3
Location	3q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000206536
Ensembl biotype	protein_coding
Entrez	403277

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000383695

RefSeq mRNA: 1 — MANE Select: NM_001005516 NM_001005516

CCDS: CCDS33803

Canonical transcript exons

ENST00000383695 — 1 exons

Exon	Start	End
ENSE00001498172	98390666	98391631

Expression profiles

Bgee: expression breadth tissue_specific, 4 present calls, max score 93.64.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.64	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
bone marrow cell	CL:0002092	36.16	gold quality
skeletal muscle tissue	UBERON:0001134	35.62	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
calcaneal tendon	UBERON:0003701	34.18	silver quality
muscle tissue	UBERON:0002385	32.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
urinary bladder	UBERON:0001255	31.82	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
monocyte	CL:0000576	30.25	silver quality
leukocyte	CL:0000738	30.01	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
liver	UBERON:0002107	28.42	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
right lung	UBERON:0002167	26.90	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.22	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
primary visual cortex	UBERON:0002436	24.61	gold quality
gastrocnemius	UBERON:0001388	24.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.49

Regulation

Is transcription factor: no

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Or5k8	ENSMUSG00000060663
mus_musculus	Or5k3	ENSMUSG00000062608
mus_musculus	Or5k14	ENSMUSG00000063137
rattus_norvegicus	Or5k3	ENSRNOG00000072759
rattus_norvegicus	Or5k8	ENSRNOG00000073358
rattus_norvegicus	Olr1564	ENSRNOG00000081801
rattus_norvegicus	Olr1563	ENSRNOG00000084932
rattus_norvegicus	Or5k14	ENSRNOG00000086873

Paralogs (96): OR5C1 (ENSG00000148215), OR5F1 (ENSG00000149133), OR8K1 (ENSG00000150261), OR5M9 (ENSG00000150269), OR14K1 (ENSG00000153230), OR8J3 (ENSG00000167822), OR5I1 (ENSG00000167825), OR5AU1 (ENSG00000169327), OR9K2 (ENSG00000170605), OR8B12 (ENSG00000170953), OR10H3 (ENSG00000171936), OR8I2 (ENSG00000172154), OR8U1 (ENSG00000172199), OR10V1 (ENSG00000172289), OR5A1 (ENSG00000172320), OR5A2 (ENSG00000172324), OR5B12 (ENSG00000172362), OR5B2 (ENSG00000172365), OR9I1 (ENSG00000172377), OR9G4 (ENSG00000172457), OR5AR1 (ENSG00000172459), OR5AP2 (ENSG00000172464), OR8J1 (ENSG00000172487), OR5B3 (ENSG00000172769), OR10W1 (ENSG00000172772), OR5M3 (ENSG00000174937), OR5J2 (ENSG00000174957), OR10H4 (ENSG00000176231), OR5AN1 (ENSG00000176495), OR14C36 (ENSG00000177174), OR6B3 (ENSG00000178586), OR10Q1 (ENSG00000180475), OR8G2P (ENSG00000181214), OR5AK2 (ENSG00000181273), OR5AK3P (ENSG00000181282), OR5M8 (ENSG00000181371), OR8D4 (ENSG00000181518), OR8H1 (ENSG00000181693), OR8K5 (ENSG00000181752), OR8H3 (ENSG00000181761)

Protein

Protein identifiers

Olfactory receptor 5K3 — A6NET4 (reviewed: A6NET4)

All UniProt accessions (1): A6NET4

UniProt curated annotations — full annotation on UniProt →

Function. Odorant receptor.

Subcellular location. Cell membrane.

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

RefSeq proteins (1): NP_001005516* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF13853

UniProt features (19 total): topological domain 8, transmembrane region 7, chain 1, glycosylation site 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NET4-F1	82.94	0.42

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): 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: 16 (showing top): GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION, 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, GOMF_MOLECULAR_TRANSDUCER_ACTIVITY, chr3q11

GO Biological Process (4): 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 of smell (GO:0050911)

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
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
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
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

114 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OR5K3	TAS2R3	Q9NYW6	483
OR5K3	TAS2R4	Q9NYW5	460
OR5K3	M1AP	Q8TC57	447
OR5K3	PDZRN4	Q6ZMN7	434
OR5K3	TAS2R1	Q9NYW7	423
OR5K3	KLHL1	Q9NR64	400
OR5K3	SPATA22	Q8NHS9	395
OR5K3	PEAR1	Q5VY43	393
OR5K3	STXBP3	O00186	377
OR5K3	HIBADH	P31937	367
OR5K3	CATSPER1	Q8NEC5	365
OR5K3	SEMA4F	O95754	357
OR5K3	TRIM36	Q9NQ86	348
OR5K3	PRLH	P81277	327
OR5K3	CDH12	P55289	324

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A6NDH6, A6NDL8, A6NET4, A6NHG9, A6NKK0, A6NMS3, P0DN80, P23268, P34982, P35898, Q60887, Q60892, Q7TRF3, Q7TS48, Q8NG80, Q8NG85, Q8NGA0, Q8NGE2, Q8NGF7, Q8NGI8, Q8NGL4, Q8NGS5, Q8NGU1, Q8NGU2, Q8NGV6, Q8NGV7, Q8NGY2, Q8NGY6, Q8NGY9, Q8NH16, Q8NH92, Q8NHB7, Q8NHB8, Q8NHC5, Q8NHC6, Q8NHC7, Q8VEX5, Q8VEX6, Q8VF13, Q8VFB9

Diamond homologs: A6NDH6, A6NET4, A6NHG9, A6NKK0, A6NL26, A6NMS3, O95221, P0C626, P0C628, P0C7N1, P0C7N5, P0DMU2, P0DN80, P34985, P37068, P37070, P37071, P37072, Q13606, Q15617, Q15620, Q60880, Q60882, Q60884, Q60886, Q60893, Q60894, Q6UXT6, Q7TS48, Q8N127, Q8N146, Q8N162, Q8NG75, Q8NG78, Q8NGC0, Q8NGF4, Q8NGF7, Q8NGG0, Q8NGG1, Q8NGG2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

317 predictions. Top by Δscore:

Variant	Effect	Δscore
3:98390905:GAT:G	donor_gain	0.8100
3:98390752:G:GA	donor_gain	0.7600
3:98390938:GAT:G	donor_gain	0.7600
3:98390986:T:A	acceptor_gain	0.7200
3:98390732:C:G	donor_gain	0.6900
3:98390951:GAAT:G	donor_gain	0.6900
3:98391140:G:GT	donor_gain	0.6600
3:98390930:G:GT	donor_gain	0.6400
3:98390955:G:GG	donor_gain	0.6300
3:98390712:GATT:G	donor_gain	0.6200
3:98390734:G:GT	donor_gain	0.6000
3:98390905:G:GT	donor_gain	0.6000
3:98390948:TATGA:T	donor_gain	0.6000
3:98390949:ATGAA:A	donor_gain	0.6000
3:98390950:TGAAT:T	donor_gain	0.6000
3:98390951:GAATG:G	donor_gain	0.6000
3:98390983:T:TA	acceptor_gain	0.6000
3:98390737:GACT:G	donor_gain	0.5900
3:98390841:T:G	donor_gain	0.5900
3:98390907:T:G	donor_gain	0.5900
3:98390947:G:GG	donor_gain	0.5900
3:98391143:G:GG	donor_gain	0.5700
3:98391340:A:AG	acceptor_gain	0.5700
3:98391417:A:AG	donor_gain	0.5700
3:98390846:A:G	donor_gain	0.5600
3:98391418:T:G	donor_gain	0.5600
3:98390803:G:GA	donor_gain	0.5500
3:98390857:C:T	donor_gain	0.5500
3:98390694:C:G	donor_gain	0.5400
3:98391331:A:AG	acceptor_gain	0.5400

AlphaMissense

2129 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:98390699:T:C	F12L	0.793
3:98390701:C:A	F12L	0.793
3:98390701:C:G	F12L	0.793
3:98391167:T:C	F168L	0.767
3:98391169:C:A	F168L	0.767
3:98391169:C:G	F168L	0.767
3:98391194:T:C	F177L	0.630
3:98391196:T:A	F177L	0.630
3:98391196:T:G	F177L	0.630
3:98391197:T:C	F178L	0.608
3:98391199:C:A	F178L	0.608
3:98391199:C:G	F178L	0.608
3:98390747:T:C	F28L	0.597
3:98390749:T:A	F28L	0.597
3:98390749:T:G	F28L	0.597
3:98391002:T:C	F113L	0.587
3:98391004:T:A	F113L	0.587
3:98391004:T:G	F113L	0.587
3:98390966:T:C	F101L	0.583
3:98390968:T:A	F101L	0.583
3:98390968:T:G	F101L	0.583
3:98390714:T:C	F17L	0.565
3:98390716:T:A	F17L	0.565
3:98390716:T:G	F17L	0.565

dbSNP variants (sampled 300 via entrez): RS1000910470 (3:98389337 A>G), RS1002103723 (3:98388789 G>C), RS1002538118 (3:98388970 T>C), RS1003862058 (3:98390676 A>G), RS1005140018 (3:98389773 G>C), RS1005424298 (3:98388692 T>C), RS1005481123 (3:98388990 A>G), RS1005536720 (3:98389305 A>G), RS1007764024 (3:98392011 C>T), RS1008400100 (3:98392052 CTTT>C,CTT), RS1009765586 (3:98389756 G>A), RS1013027622 (3:98390051 T>A,C,G), RS1013236586 (3:98390207 A>ATG), RS1013838299 (3:98390265 A>T), RS1014986353 (3:98391463 G>A,C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:190300

GenCC curated gene-disease

Mondo (1): essential tremor (MONDO:0003233)

Orphanet (1): NON RARE IN EUROPE: Hereditary essential tremor (Orphanet:862)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020329	Essential Tremor	C10.228.662.350

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00439699	PHASE4	COMPLETED	A Pilot Clinical Trial Of Memantine for Essential Tremor
NCT00584376	PHASE4	COMPLETED	Pregabalin (Lyrica) for the Treatment of Essential Tremor
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02111369	PHASE4	COMPLETED	Propranolol and Botulinum Toxin for Essential Vocal Tremor
NCT02495883	PHASE4	COMPLETED	Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response
NCT00018564	PHASE3	COMPLETED	Novel Therapies for Essential Tremor
NCT00236496	PHASE3	COMPLETED	A Comparison of the Efficacy and Safety of Topiramate Versus Placebo in Treating Tremor of Unknown Cause.
NCT01441284	PHASE3	WITHDRAWN	Efficacy of Pramipexole Extended Release in the Treatment of Essential Tremor
NCT04193527	PHASE3	COMPLETED	A Study to Evaluate the Diagnostic Efficacy of DaTSCAN™ Ioflupane (123I) Injection in Single Photon Emission Computed Tomography (SPECT) for the Diagnosis of Parkinsonian Syndrome (PS) in Chinese Patients
NCT04265209	PHASE3	COMPLETED	[18F] LBT-999 PET Compared to [123I]-FP/CIT SPECT to Distinguish Between Parkinson’s Diseases and Essential Tremor
NCT06087276	PHASE3	ENROLLING_BY_INVITATION	Essential 3 - Decentralized, Phase 3 Study Evaluating the Safety and Efficacy of Ulixacaltamide in Essential Tremor (ET)
NCT00080366	PHASE2	COMPLETED	Octanol to Treat Essential Tremor
NCT00102596	PHASE2	COMPLETED	Clinical Trial Characterizing the Bioavailability of 1-Octanol in Adults With Ethanol-responsive Essential Tremor
NCT00223743	PHASE2	COMPLETED	A Safety/Efficacy Trial of Zonisamide for Essential Tremor
NCT00321087	PHASE2	TERMINATED	A Study of T2000 in Essential Tremor
NCT00598078	PHASE2	COMPLETED	Multiple-dose,Double-blind,Placebo-controlled Study of Sodium Oxybate in Patients With Essential Tremor
NCT00655278	PHASE2	TERMINATED	T2000 in Essential Tremor - Open Label Continuation
NCT01332695	PHASE2	COMPLETED	A Pilot Efficacy and Safety Study of ST101 in Essential Tremor
NCT02277106	PHASE2	COMPLETED	Evaluate SAGE-547 in Participants With Essential Tremor
NCT02551848	PHASE2	UNKNOWN	Kinematic-based BoNT-A Injections for Bilateral ET
NCT02668146	PHASE2	UNKNOWN	An Efficacy/Safety Study of Perampanel for Reducing Essential Tremor
NCT02978781	PHASE2	COMPLETED	A Study to Evaluate SAGE-217 in Participants With Essential Tremor
NCT03101241	PHASE2	COMPLETED	A Phase 2 RCT Study of CX-8998 for Essential Tremor
NCT03688685	PHASE2	COMPLETED	A Clinical Study to Evaluate CAD-1883 in Essential Tremor
NCT03780426	PHASE2	COMPLETED	tSMS in Essential Tremor
NCT04305275	PHASE2	COMPLETED	A Study to Evaluate the Efficacy, Safety, and Tolerability of SAGE-324 in Participants With Essential Tremor
NCT04727658	PHASE2	TERMINATED	Linac FRACtionated Radiosurgical THALamotomie in Tremors (FRACTHAL)
NCT04880616	PHASE2	COMPLETED	Safety, Efficacy, and Tolerability of NBI-827104 for the Treatment of Essential Tremor
NCT05021978	PHASE2	COMPLETED	A Clinical Trial of PRAX-944 in Participants With Essential Tremor
NCT05021991	PHASE2	COMPLETED	A Clinical Trial of 2 Doses of PRAX-944 in Participants With Essential Tremor
NCT05122650	PHASE2	COMPLETED	A Study To Assess the Safety and Efficacy of JZP385 in the Treatment of Adults With Moderate to Severe Essential Tremor (ET)
NCT05173012	PHASE2	COMPLETED	Study to Evaluate SAGE-324 in Participants With Essential Tremor
NCT05387642	PHASE2	WITHDRAWN	A Clinical Trial of PRAX-114 in Participants With Essential Tremor
NCT06312800	PHASE2	WITHDRAWN	Acamprosate and Methazolamide for Essential Tremor
NCT06821906	PHASE2	RECRUITING	Stereotactic Radiosurgery in the Treatment of Essential Tremor
NCT07074002	PHASE2	RECRUITING	Proof of Concept Study on BP1.4979 Effect on Essential Tremor
NCT07103265	PHASE2	NOT_YET_RECRUITING	Developing a New LIFU Neuromodulation Method to Suppress Tremor
NCT00001986	PHASE1	COMPLETED	1-Octanol to Treat Essential Tremor
NCT00016679	PHASE1	COMPLETED	1-Octanol to Treat Essential Tremor
NCT01304758	PHASE1	COMPLETED	ExAblate Transcranial MR Guided Focused Ultrasound in the Treatment of Essential Tremor