OR4F21

Summary

OR4F21 (olfactory receptor family 4 subfamily F member 21, HGNC:19583) is a protein-coding gene on chromosome 8p23.3, encoding Olfactory receptor 4F21 (O95013). 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 441308 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 58 total — 1 pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001005504

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19583
Approved symbol	OR4F21
Name	olfactory receptor family 4 subfamily F member 21
Location	8p23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000176269
Ensembl biotype	protein_coding
Entrez	441308

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000320901

RefSeq mRNA: 1 — MANE Select: NM_001005504 NM_001005504

CCDS: CCDS34792

Canonical transcript exons

ENST00000320901 — 1 exons

Exon	Start	End
ENSE00002115557	166086	167024

Expression profiles

Bgee: expression breadth broad, 65 present calls, max score 82.82.

Top tissues by expression

98 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	82.82	gold quality
lower esophagus mucosa	UBERON:0035834	50.05	gold quality
right coronary artery	UBERON:0001625	44.25	gold quality
bone marrow cell	CL:0002092	41.64	gold quality
adrenal tissue	UBERON:0018303	40.60	silver 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
ganglionic eminence	UBERON:0004023	35.49	gold quality
islet of Langerhans	UBERON:0000006	34.57	silver quality
bone marrow	UBERON:0002371	34.54	gold quality
right uterine tube	UBERON:0001302	34.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
duodenum	UBERON:0002114	33.35	silver quality
uterine cervix	UBERON:0000002	33.02	silver quality
placenta	UBERON:0001987	32.84	silver quality
pancreas	UBERON:0001264	32.79	gold quality
liver	UBERON:0002107	32.59	gold quality
endometrium	UBERON:0001295	32.37	silver quality
muscle tissue	UBERON:0002385	32.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
endocervix	UBERON:0000458	31.56	silver quality
blood	UBERON:0000178	31.29	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	31.26	gold quality
body of pancreas	UBERON:0001150	31.19	gold quality
right ovary	UBERON:0002118	31.17	silver quality
sural nerve	UBERON:0015488	30.93	gold quality
metanephros cortex	UBERON:0010533	30.70	silver quality
prefrontal cortex	UBERON:0000451	30.47	gold quality
body of stomach	UBERON:0001161	30.35	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.20

Regulation

Is transcription factor: no

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Or4f7	ENSMUSG00000093804
rattus_norvegicus		ENSRNOG00000072324
rattus_norvegicus	Or4f7	ENSRNOG00000073873
rattus_norvegicus	Or4f7c	ENSRNOG00000076105

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 4F21 — O95013 (reviewed: O95013)

All UniProt accessions (1): O95013

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_001005504* (*=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 (20 total): topological domain 8, transmembrane region 7, sequence conflict 2, chain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95013-F1	90.19	0.67

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: 15 (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_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, chr8p23, GOBP_NERVOUS_SYSTEM_PROCESS

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

116 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OR4F21	ZNF487	B1APH4	581
OR4F21	GARIN5A	Q6IPT2	573
OR4F21	RNF208	Q9H0X6	479
OR4F21	ZNF596	Q8TC21	472
OR4F21	ZNF791	Q3KP31	444
OR4F21	KBTBD11	O94819	432
OR4F21	ERICH1	Q86X53	420
OR4F21	KLHDC7B	Q96G42	417
OR4F21	TDRP	Q86YL5	380
OR4F21	MICALL2	Q8IY33	348
OR4F21	MFHAS1	Q9Y4C4	325
OR4F21	SCRN1	Q12765	325
OR4F21	FBXO25	Q8TCJ0	324
OR4F21	DYNLRB1	Q9NP97	323
OR4F21	TMEM41B	Q5BJD5	321

IntAct

2 interactions, top by confidence:

A	B	Type	Score
OR4F21	RAB34	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (2): RAB34 (Proximity Label-MS), OR4F21 (Negative Genetic)

ESM2 similar proteins: A6NDH6, A6NDL8, A6NET4, A6NHG9, A6NKK0, A6NMS3, O95013, P0C628, P0DN80, P23268, P34982, P35898, Q15612, Q7TRF3, Q7TS48, Q8NG80, Q8NG85, Q8NGA0, Q8NGE2, Q8NGF7, Q8NGI8, Q8NGL4, Q8NGS5, Q8NGU1, Q8NGU2, Q8NGV6, Q8NGV7, Q8NGY2, Q8NGY6, Q8NGY9, Q8NH16, Q8NH92, Q8NHB7, Q8NHB8, Q8NHC6, Q8NHC7, Q8VEX5, Q8VEX6, Q8VF13, Q8VFB9

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	51
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1330178	GRCh37/hg19 8p23.3-23.1(chr8:10501-7214947)x1	Pathogenic

SpliceAI

313 predictions. Top by Δscore:

Variant	Effect	Δscore
8:166659:T:C	donor_gain	0.9700
8:166699:C:CT	donor_gain	0.9200
8:166915:G:A	donor_gain	0.8500
8:166700:C:CT	donor_gain	0.8400
8:166644:A:AC	donor_gain	0.8300
8:166645:C:CC	donor_gain	0.8300
8:167000:C:CT	donor_gain	0.7800
8:167000:CCA:C	donor_gain	0.7100
8:166648:AGGG:A	donor_gain	0.7000
8:166698:A:AC	donor_gain	0.6300
8:166402:A:AC	donor_gain	0.5800
8:166403:C:CC	donor_gain	0.5800
8:166403:CA:C	donor_gain	0.5800
8:167001:C:CT	donor_gain	0.5800
8:166526:C:CC	acceptor_gain	0.5600
8:166902:T:TA	donor_gain	0.5300
8:166169:CAA:C	acceptor_gain	0.5200
8:166416:A:AC	donor_gain	0.5200
8:166417:C:CC	donor_gain	0.5200
8:166646:A:C	donor_gain	0.5100
8:166648:A:AC	donor_gain	0.5100
8:166658:AT:A	donor_gain	0.5100
8:166961:C:CA	donor_gain	0.5100
8:167002:A:AC	donor_gain	0.5100
8:167003:C:CC	donor_gain	0.5100
8:166167:GACAA:G	acceptor_gain	0.4900
8:167016:T:A	donor_gain	0.4900
8:166914:TGCC:T	donor_gain	0.4800
8:166993:TCAGA:T	donor_gain	0.4800
8:166172:C:CC	acceptor_gain	0.4700

AlphaMissense

2041 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:166521:G:C	F168L	0.878
8:166521:G:T	F168L	0.878
8:166523:A:G	F168L	0.878
8:166494:G:C	F177L	0.869
8:166494:G:T	F177L	0.869
8:166496:A:G	F177L	0.869
8:166989:A:C	F12L	0.851
8:166989:A:T	F12L	0.851
8:166991:A:G	F12L	0.851
8:166911:G:C	S38R	0.815
8:166911:G:T	S38R	0.815
8:166913:T:G	S38R	0.815
8:166272:A:C	F251L	0.797
8:166272:A:T	F251L	0.797
8:166274:A:G	F251L	0.797
8:166497:G:C	S176R	0.755
8:166497:G:T	S176R	0.755
8:166499:T:G	S176R	0.755
8:166275:G:C	F250L	0.738
8:166275:G:T	F250L	0.738
8:166277:A:G	F250L	0.738
8:166539:A:C	F162L	0.701
8:166539:A:T	F162L	0.701
8:166541:A:G	F162L	0.701
8:166743:A:C	F94L	0.684
8:166743:A:T	F94L	0.684
8:166745:A:G	F94L	0.684
8:166293:G:C	S244R	0.680
8:166293:G:T	S244R	0.680
8:166295:T:G	S244R	0.680

dbSNP variants (sampled 300 via entrez): RS1008794619 (8:167616 A>G), RS1010748579 (8:166619 T>C), RS1014497226 (8:166466 G>C), RS1018875181 (8:167626 C>G), RS1027771873 (8:167713 G>C), RS1028808029 (8:167475 G>A,T), RS1029277820 (8:166641 C>A,T), RS1033118821 (8:166570 C>G), RS1036126458 (8:166166 A>G), RS1045688233 (8:166467 T>C,G), RS1045978677 (8:167168 A>G), RS1054915661 (8:167437 A>T), RS1055962934 (8:167031 A>T), RS1056415485 (8:166417 C>G), RS112889880 (8:167229 A>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): obesity disorder (MONDO:0011122)

Orphanet (3): Non-syndromic bicoronal craniosynostosis (Orphanet:35099), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001513	Obesity

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

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

Chemical	Actions (top 5)	PubMed papers
Sunitinib	increases expression	1
Cadmium	decreases expression	1
Hydrogen Peroxide	decreases expression	1
Malathion	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00076362	PHASE4	COMPLETED	Pediatric Hypothalamic Obesity
NCT00079547	PHASE4	COMPLETED	The Safety and Effectiveness of Low and High Carbohydrate Diets
NCT00115063	PHASE4	TERMINATED	LOSS- Louisiana Obese Subjects Study
NCT00134303	PHASE4	COMPLETED	Trial Comparing Metformin Versus Placebo in Non Alcoholic Steatohepatitis (NASH) Patients Receiving Bariatric Surgery for Obesity
NCT00143936	PHASE4	COMPLETED	The Safety and Efficacy of Low and High Carbohydrate Diets
NCT00143962	PHASE4	COMPLETED	Comparison of Two Approaches to Weight Loss Follow-Up Study
NCT00152360	PHASE4	COMPLETED	The Effect of Xenical on Weight and Risk Factors
NCT00176306	PHASE4	COMPLETED	Levofloxacin Pharmacokinetics (PK) in the Severely Obese
NCT00203450	PHASE4	COMPLETED	Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial
NCT00205504	PHASE4	COMPLETED	Oral Contraceptives in the Metabolic Syndrome
NCT00229229	PHASE4	TERMINATED	Comparison of 4 Diets in the Management of Overweight Patients With Vascular Disease
NCT00234988	PHASE4	COMPLETED	A Phase IV, Multi-Center, Open-Label Trial of Sibutramine in Combination With a Hypocaloric Diet in Obese and Overweight Thai Subjects.
NCT00264589	PHASE4	COMPLETED	Exercise Training and Cardiovascular Function in Obesity and in Type 2 Diabetes
NCT00288873	PHASE4	COMPLETED	Characterization of Hyperparathyroidism and Vitamin D Deficiency in Obesity
NCT00298857	PHASE4	TERMINATED	A Pharmacokinetic Study to Compare the Dosing of Valproic Acid in Subjects With Different Body Weights
NCT00315146	PHASE4	COMPLETED	Optimizing Body Composition for Function in Older Adults
NCT00319202	PHASE4	TERMINATED	Clinical Trial to Assess the Effects of Candesartan on the Carbohydrate Metabolism of Obese Subjects
NCT00327912	PHASE4	UNKNOWN	Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Biliopancreatic Diversion (BPD)- Duodenal Switch for Superobesity
NCT00352287	PHASE4	COMPLETED	Study to Determine the Effects of Human Growth Hormone and Pioglitazone in Overweight, Prediabetic Adults
NCT00353054	PHASE4	COMPLETED	Effect of Calcium/Vitamin D Supplementation on Body Weight and Fat Loss.
NCT00390637	PHASE4	COMPLETED	Diet, Obesity and Genes (DiOGenes)
NCT00415688	PHASE4	COMPLETED	Lifestyle Modification for Obesity-Related Type 2 Diabetes
NCT00433641	PHASE4	COMPLETED	Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes
NCT00440375	PHASE4	COMPLETED	Effects of Rosiglitazone on Bone in Postmenopausal Diabetic Women
NCT00453557	PHASE4	COMPLETED	Mechanism of Growth Hormone Effects on Adipose Tissue
NCT00456885	PHASE4	COMPLETED	The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women
NCT00463112	PHASE4	COMPLETED	Effect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS
NCT00512187	PHASE4	COMPLETED	Moderate Weight Loss Makes Obese Patients With Severe Chronic Plaque Psoriasis Responsive to Sub-Optimal Dose of Cyclosporine: an Investigator Blinded, Controlled, Randomized Clinical Trial
NCT00516919	PHASE4	COMPLETED	Study of Behavioral Weight Loss Therapy for Obesity and Binge Eating in Monolingual Hispanic Persons
NCT00522470	PHASE4	COMPLETED	Effects of Rosiglitazone on Serum Ghrelin and Peptide YY Levels
NCT00537810	PHASE4	COMPLETED	Treatment of Binge Eating in Obese Patients in Primary Care
NCT00538486	PHASE4	COMPLETED	A Randomized, Double-Blind, Active Control Trial Comparing Effects of Telmisartan, Candesartan and Amlodipine, Alone or Plus Metformin, on Non-Diabetic, Obese Hypertensive Patients
NCT00584389	PHASE4	TERMINATED	The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition
NCT00585182	PHASE4	COMPLETED	Study to Evaluate Weight-based Enoxaparin Dosing in Obese Medical Patients at Risk for DVT
NCT00632840	PHASE4	COMPLETED	Pharmacological Regulation of Fat Transport in Metabolic Syndrome
NCT00636142	PHASE4	COMPLETED	Effects of Infliximab on Insulin Sensitivity and Beta Cell Function in Insulin Resistant Human Obesity
NCT00675987	PHASE4	COMPLETED	A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients
NCT00694811	PHASE4	COMPLETED	Effects of Re-Feeding Duration on Weight Maintenance After Weight Loss With Very-Low-Energy Diets (VLEDs)
NCT00699413	PHASE4	TERMINATED	Supplements for Controlling Resistance to Insulin
NCT00729963	PHASE4	COMPLETED	Sibutramine Versus Continuous Positive Airway Pressure (CPAP)in Obstructive Sleep Apnea (OSA) Patients