OR5K4

Summary

OR5K4 (olfactory receptor family 5 subfamily K member 4, HGNC:31291) is a protein-coding gene on chromosome 3q11.2, encoding Olfactory receptor 5K4 (A6NMS3). 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 403278 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 68 total — 1 pathogenic
• MANE Select transcript: NM_001005517

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31291
Approved symbol	OR5K4
Name	olfactory receptor family 5 subfamily K member 4
Location	3q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196098
Ensembl biotype	protein_coding
Entrez	403278

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000354924

RefSeq mRNA: 1 — MANE Select: NM_001005517 NM_001005517

CCDS: CCDS33802

Canonical transcript exons

ENST00000354924 — 1 exons

Exon	Start	End
ENSE00001423802	98353854	98354819

Expression profiles

Bgee: expression breadth tissue_specific, 4 present calls, max score 54.69.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	54.69	gold quality
granulocyte	CL:0000094	38.05	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	36.21	silver quality
bone marrow cell	CL:0002092	36.16	gold quality
sural nerve	UBERON:0015488	36.11	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
urinary bladder	UBERON:0001255	30.28	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
liver	UBERON:0002107	28.33	gold quality
duodenum	UBERON:0002114	28.14	gold quality
leukocyte	CL:0000738	27.64	gold quality
lymph node	UBERON:0000029	27.57	gold quality
calcaneal tendon	UBERON:0003701	27.45	gold quality
tonsil	UBERON:0002372	27.05	gold quality
monocyte	CL:0000576	26.97	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.19	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	24.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.15

Regulation

Is transcription factor: no

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Or5k15	ENSMUSG00000044029
mus_musculus	Or5k16	ENSMUSG00000090629
mus_musculus	Or5k17	ENSMUSG00000090951
rattus_norvegicus	Or5k17	ENSRNOG00000072023
rattus_norvegicus	Or5k15	ENSRNOG00000077350
rattus_norvegicus	Or5k16	ENSRNOG00000084658

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 5K4 — A6NMS3 (reviewed: A6NMS3)

All UniProt accessions (1): A6NMS3

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_001005517* (*=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-A6NMS3-F1	86.95	0.56

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: 19 (showing top): GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION, GOMF_OLFACTORY_RECEPTOR_ACTIVITY, ZHENG_IL22_SIGNALING_DN, 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, RAO_BOUND_BY_SALL4_ISOFORM_B, REACTOME_OLFACTORY_SIGNALING_PATHWAY, REACTOME_SENSORY_PERCEPTION, GOBP_DETECTION_OF_CHEMICAL_STIMULUS

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

78 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OR5K4	SPIRE2	Q8WWL2	447
OR5K4	SELENOM	Q8WWX9	431
OR5K4	STATH	P02808	419
OR5K4	NPY5R	Q15761	396
OR5K4	LIMK2	P53671	353
OR5K4	ZNF276	Q8N554	349
OR5K4	NPY1R	P25929	329
OR5K4	BCAN	Q96GW7	308
OR5K4	FBN2	P35556	305
OR5K4	TCF25	Q9BQ70	251
OR5K4	FANCA	O15360	248
OR5K4	OSBP2	Q969R2	247
OR5K4	MSRB3	Q8IXL7	200
OR5K4	NR6A1	Q15406	160
OR5K4	TRPC1	P48995	108

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	59
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2579175	GRCh38/hg38 3q11.1-21.2(chr3:93979547-124774010)x1	Pathogenic

SpliceAI

210 predictions. Top by Δscore:

Variant	Effect	Δscore
3:98354093:GAT:G	donor_gain	0.8600
3:98354093:G:GT	donor_gain	0.7900
3:98353991:G:GA	donor_gain	0.7500
3:98354094:A:G	donor_gain	0.7300
3:98354029:T:G	donor_gain	0.7000
3:98354096:G:GG	donor_gain	0.7000
3:98354174:T:A	acceptor_gain	0.7000
3:98353940:G:GA	donor_gain	0.6600
3:98354097:T:G	donor_gain	0.6600
3:98354080:CT:C	donor_gain	0.6500
3:98353990:T:TA	donor_gain	0.6400
3:98354095:T:G	donor_gain	0.6300
3:98354098:T:A	donor_gain	0.6100
3:98354005:T:TA	donor_gain	0.6000
3:98354006:A:AA	donor_gain	0.6000
3:98354100:G:GT	donor_gain	0.6000
3:98354462:A:AG	acceptor_gain	0.5800
3:98354142:T:G	donor_gain	0.5700
3:98354623:T:G	acceptor_gain	0.5700
3:98353963:TCACC:T	donor_gain	0.5600
3:98354554:GAG:G	donor_gain	0.5500
3:98354034:A:G	donor_gain	0.5400
3:98353976:G:T	donor_gain	0.5300
3:98354118:G:GT	donor_gain	0.5300
3:98354626:ATATT:A	acceptor_gain	0.5300
3:98354532:A:AG	acceptor_gain	0.4900
3:98354552:AAGAG:A	donor_loss	0.4900
3:98354553:AGAG:A	donor_loss	0.4900
3:98354555:AG:A	donor_loss	0.4900
3:98354556:GG:G	donor_loss	0.4900

AlphaMissense

2119 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:98354355:T:C	F168L	0.916
3:98354357:C:A	F168L	0.916
3:98354357:C:G	F168L	0.916
3:98353887:T:C	F12L	0.885
3:98353889:C:A	F12L	0.885
3:98353889:C:G	F12L	0.885
3:98353944:T:C	F31L	0.830
3:98353946:C:A	F31L	0.830
3:98353946:C:G	F31L	0.830
3:98354382:T:C	F177L	0.829
3:98354384:T:A	F177L	0.829
3:98354384:T:G	F177L	0.829
3:98354218:G:C	R122P	0.789
3:98354604:T:C	F251L	0.779
3:98354606:T:A	F251L	0.779
3:98354606:T:G	F251L	0.779
3:98354715:A:C	S288R	0.778
3:98354717:T:A	S288R	0.778
3:98354717:T:G	S288R	0.778
3:98354723:A:C	R290S	0.777
3:98354723:A:T	R290S	0.777
3:98353888:T:C	F12S	0.772
3:98354385:T:C	F178L	0.767
3:98354387:C:A	F178L	0.767
3:98354387:C:G	F178L	0.767
3:98353935:T:C	F28L	0.758
3:98353937:T:A	F28L	0.758
3:98353937:T:G	F28L	0.758
3:98354207:G:A	M118I	0.747
3:98354207:G:C	M118I	0.747

dbSNP variants (sampled 300 via entrez): RS1000354659 (3:98353962 G>A), RS1001629350 (3:98352625 C>T), RS1001914737 (3:98352888 C>A), RS1004036109 (3:98354443 T>G), RS1005694319 (3:98353373 G>A), RS1005920053 (3:98354994 T>A), RS1006031197 (3:98352028 G>A,T), RS1006080474 (3:98352447 A>G), RS1008507248 (3:98353730 G>A), RS1008812755 (3:98353143 A>G), RS1009112945 (3:98353515 A>G), RS1010162230 (3:98352468 A>G,T), RS1010234081 (3:98352600 T>C), RS1014354009 (3:98353274 G>A,T), RS1014779178 (3:98353577 A>C,G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:190300, MIM:615433

GenCC curated gene-disease

Mondo (2): essential tremor (MONDO:0003233), chromosome 3q13.31 deletion syndrome (MONDO:0014185)

Orphanet (2): 3q13 microdeletion syndrome (Orphanet:1621), 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 (2)

Descriptor	Name	Tree numbers
D020329	Essential Tremor	C10.228.662.350
C536808	Chromosome 3, monosomy 3q13 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
Benzo(a)pyrene	increases methylation	1
Aflatoxin B1	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