OR4K1

Summary

OR4K1 (olfactory receptor family 4 subfamily K member 1, HGNC:14726) is a protein-coding gene on chromosome 14q11.2, encoding Olfactory receptor 4K1 (Q8NGD4). Odorant receptor. It is a selective cancer dependency (DepMap: 24.0% of cell lines).

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 79544 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 124 total
• Cancer dependency (DepMap): dependent in 24.0% of screened cell lines
• MANE Select transcript: NM_001004063

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14726
Approved symbol	OR4K1
Name	olfactory receptor family 4 subfamily K member 1
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000155249
Ensembl biotype	protein_coding
Entrez	79544

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000285600, ENST00000641172, ENST00000641429

RefSeq mRNA: 1 — MANE Select: NM_001004063 NM_001004063

CCDS: CCDS32025

Canonical transcript exons

ENST00000641172 — 2 exons

Exon	Start	End
ENSE00003813185	19930917	19931145
ENSE00003814029	19935648	19936757

Expression profiles

Bgee: expression breadth tissue_specific, 1 present calls, max score 37.22.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	37.22	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
sural nerve	UBERON:0015488	35.78	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
muscle tissue	UBERON:0002385	32.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
gall bladder	UBERON:0002110	31.55	silver quality
leukocyte	CL:0000738	30.48	gold quality
monocyte	CL:0000576	30.13	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
liver	UBERON:0002107	29.41	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
urinary bladder	UBERON:0001255	29.00	gold quality
duodenum	UBERON:0002114	28.14	gold quality
right coronary artery	UBERON:0001625	27.63	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	27.60	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
blood	UBERON:0000178	26.69	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
placenta	UBERON:0001987	25.81	gold quality
ectocervix	UBERON:0012249	25.26	gold quality
right lobe of liver	UBERON:0001114	25.24	gold quality
muscle of leg	UBERON:0001383	25.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.45

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 24.0% of screened cell lines.

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Or4k1	ENSMUSG00000050030
rattus_norvegicus	Or4k1	ENSRNOG00000075484
rattus_norvegicus		ENSRNOG00000082236

Paralogs (130): OR1I1 (ENSG00000094661), OR12D3 (ENSG00000112462), OR7A10 (ENSG00000127515), OR7C2 (ENSG00000127529), OR7C1 (ENSG00000127530), OR1E2 (ENSG00000127780), OR1J1 (ENSG00000136834), OR1L4 (ENSG00000136939), OR4D1 (ENSG00000141194), 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), OR4K17 (ENSG00000176230)

Protein

Protein identifiers

Olfactory receptor 4K1 — Q8NGD4 (reviewed: Q8NGD4)

Alternative names: Olfactory receptor OR14-19

All UniProt accessions (1): Q8NGD4

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_001004063* (*=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-Q8NGD4-F1	83.88	0.45

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): 97–189

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: 17 (showing top): GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, KEGG_OLFACTORY_TRANSDUCTION, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION, 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, GOBP_DETECTION_OF_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION, REACTOME_OLFACTORY_SIGNALING_PATHWAY, REACTOME_SENSORY_PERCEPTION, PULVER_FOREY_PERTURB_ACCUMULATION_S, GOBP_DETECTION_OF_CHEMICAL_STIMULUS, GOMF_MOLECULAR_TRANSDUCER_ACTIVITY

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 (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-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
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

236 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OR4K1	PCDHB6	Q9Y5E3	416
OR4K1	PCDHB15	Q9Y5E8	414
OR4K1	PCDHB10	Q9UN67	411
OR4K1	PCDHB1	Q9Y5F3	410
OR4K1	PCDHB3	Q9Y5E6	404
OR4K1	PCDHB5	Q9Y5E4	397
OR4K1	POTEM	A6NI47	397
OR4K1	UGT2B10	P36537	395
OR4K1	HNRNPCL3	B7ZW38	391
OR4K1	HNRNPCL2	B2RXH8	391
OR4K1	PRAMEF2	O60811	380
OR4K1	SCGB1C1	Q8TD33	367
OR4K1	SCGB1C2	P0DMR2	367
OR4K1	UGT2A3	Q6UWM9	364
OR4K1	SLC25A26	Q70HW3	338

IntAct

0 interactions, top by confidence:

BioGRID (2): OR4K1 (Synthetic Lethality), OR4K1 (Positive Genetic)

ESM2 similar proteins: A0A096LPK9, A0A0X1KG70, A6NCV1, O95221, P0C7N1, P0C7N5, Q60881, Q60888, Q6IEU7, Q8NGA8, Q8NGB6, Q8NGC6, Q8NGD0, Q8NGD1, Q8NGD2, Q8NGD4, Q8NGD5, Q8NGE8, Q8NGF8, Q8NGI4, Q8NGI6, Q8NGJ1, Q8NGM9, Q8NGP8, Q8NGP9, Q8NGS9, Q8NGT0, Q8NH01, Q8NH10, Q8NH18, Q8NH21, Q8NH41, Q8NH42, Q8NH43, Q8NH49, Q8NH69, Q8NH85, Q8VEW5, Q8VF65, Q8VFD3

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	109
Likely benign	6
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

319 predictions. Top by Δscore:

Variant	Effect	Δscore
14:19935691:GTGTC:G	donor_gain	0.8600
14:19935692:TGTCT:T	donor_gain	0.8600
14:19935693:GTCTG:G	donor_gain	0.8600
14:19936511:T:A	acceptor_gain	0.7800
14:19935699:G:GG	donor_gain	0.7700
14:19936492:A:AG	acceptor_gain	0.7300
14:19936492:ACT:A	acceptor_gain	0.7200
14:19936358:G:GG	donor_gain	0.7000
14:19936404:G:GA	donor_gain	0.6700
14:19936494:T:A	acceptor_gain	0.6700
14:19936523:T:G	acceptor_gain	0.6600
14:19936490:ACACT:A	acceptor_gain	0.6500
14:19936501:A:AG	acceptor_gain	0.6500
14:19936441:ATAT:A	acceptor_gain	0.6300
14:19936357:A:AG	donor_gain	0.6200
14:19936443:AT:A	acceptor_gain	0.6200
14:19936491:C:G	acceptor_gain	0.6200
14:19936444:T:TA	acceptor_gain	0.6100
14:19936520:T:G	acceptor_gain	0.6100
14:19936442:T:G	acceptor_gain	0.6000
14:19936401:A:AG	donor_gain	0.5900
14:19936402:G:GG	donor_gain	0.5900
14:19936490:A:AG	acceptor_gain	0.5900
14:19936454:GCA:G	acceptor_gain	0.5800
14:19936508:T:A	acceptor_gain	0.5800
14:19936441:ATATG:A	acceptor_gain	0.5500
14:19936453:A:AG	acceptor_gain	0.5500
14:19936454:G:GG	acceptor_gain	0.5500
14:19936493:C:G	acceptor_gain	0.5500
14:19935731:G:T	donor_gain	0.5400

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000110483 (14:19933762 T>C), RS1000206036 (14:19924156 T>C), RS1000445322 (14:19927912 G>A), RS1000853480 (14:19930156 T>C), RS1001042059 (14:19935108 C>A,T), RS1001130536 (14:19925563 A>G), RS1001524404 (14:19926957 C>G,T), RS1001858754 (14:19931270 A>G), RS1001889718 (14:19930981 G>A), RS1002058795 (14:19927484 A>C), RS1002126535 (14:19935924 T>A,C), RS1002748662 (14:19935285 C>T), RS1002807649 (14:19927518 T>C), RS1002836403 (14:19927324 T>C), RS1002866960 (14:19932610 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002934_11	Zinc levels	4.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation	1
arsenite	decreases methylation	1
Air Pollutants	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cadmium	decreases expression	1
Tretinoin	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists