OR4C12

Summary

OR4C12 (olfactory receptor family 4 subfamily C member 12, HGNC:15168) is a protein-coding gene on chromosome 11p11.12, encoding Olfactory receptor 4C12 (Q96R67). Acts as a receptor for R-(-)-carvone in pancreatic cells, initiating signaling pathways involving GNAS, elevated intracellular Ca(2+), and increased cAMP levels.

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 283093 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_001005270

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15168
Approved symbol	OR4C12
Name	olfactory receptor family 4 subfamily C member 12
Location	11p11.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000221954
Ensembl biotype	protein_coding
Entrez	283093

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000335238

RefSeq mRNA: 1 — MANE Select: NM_001005270 NM_001005270

CCDS: CCDS31496

Canonical transcript exons

ENST00000335238 — 1 exons

Exon	Start	End
ENSE00002156972	49981473	49982535

Expression profiles

Bgee: expression breadth not_expressed, 0 present calls, max score 37.20.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	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	36.09	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
liver	UBERON:0002107	28.32	gold quality
duodenum	UBERON:0002114	28.14	gold quality
urinary bladder	UBERON:0001255	27.93	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
leukocyte	CL:0000738	26.98	gold quality
monocyte	CL:0000576	26.92	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.25	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
muscle of leg	UBERON:0001383	24.87	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
pancreas	UBERON:0001264	24.02	gold quality
frontal cortex	UBERON:0001870	23.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Or4c12b	ENSMUSG00000045148
mus_musculus	Or4c12	ENSMUSG00000068806
rattus_norvegicus	Or4c12	ENSRNOG00000006706

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 4C12 — Q96R67 (reviewed: Q96R67)

Alternative names: Olfactory receptor OR11-259

All UniProt accessions (1): Q96R67

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a receptor for R-(-)-carvone in pancreatic cells, initiating signaling pathways involving GNAS, elevated intracellular Ca(2+), and increased cAMP levels. Upon activation, promotes glucose-stimulated insulin secretion.

Subcellular location. Cell membrane.

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

RefSeq proteins (1): NP_001005270* (*=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 (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-Q96R67-F1	90.15	0.63

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): 95–187

Glycosylation sites (1): 6

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-381753	Olfactory Signaling Pathway
R-HSA-9752946	Expression and translocation of olfactory receptors

MSigDB gene sets: 21 (showing top): GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, KEGG_OLFACTORY_TRANSDUCTION, GOBP_CARBOHYDRATE_HOMEOSTASIS, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS, 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, RAO_BOUND_BY_SALL4_ISOFORM_A, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY

GO Biological Process (6): glucose homeostasis (GO:0042593), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), 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-2 pathways:

Category	Pathways
Sensory Perception	1
Olfactory Signaling Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transmembrane signaling receptor activity	2
carbohydrate homeostasis	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
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	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

242 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OR4C12	GGTLC2	Q14390	432
OR4C12	RERE	Q9P2R6	414
OR4C12	SPSB3	Q6PJ21	396
OR4C12	ZFP14	Q9HCL3	367
OR4C12	DGKB	Q9Y6T7	336
OR4C12	PCDHGA3	Q9Y5H0	326
OR4C12	BAIAP3	O94812	311
OR4C12	FGGY	Q96C11	307
OR4C12	MTMR7	Q9Y216	298
OR4C12	POTED	Q86YR6	290
OR4C12	PPP1R13B	Q96KQ4	271
OR4C12	GEMIN6	Q8WXD5	270
OR4C12	DHX30	Q7L2E3	269
OR4C12	EEF1D	P29692	261
OR4C12	ACYP2	P14621	256

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TSC22D1	OR4C12	psi-mi:“MI:0915”(physical association)	0.000

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

216 predictions. Top by Δscore:

Variant	Effect	Δscore
11:49982420:C:CT	donor_gain	0.8800
11:49982421:T:TT	donor_gain	0.8800
11:49982427:CGTGA:C	donor_gain	0.8200
11:49982344:AGAG:A	donor_gain	0.7500
11:49982479:G:C	donor_gain	0.7500
11:49982483:CATT:C	donor_gain	0.7500
11:49982426:A:AC	donor_gain	0.7400
11:49982427:C:CC	donor_gain	0.7400
11:49982435:T:A	donor_gain	0.7400
11:49982423:CAAA:C	donor_gain	0.6600
11:49982456:TAAG:T	donor_gain	0.6600
11:49982457:AAGA:A	donor_gain	0.6600
11:49982484:A:C	donor_gain	0.6600
11:49982429:TG:T	donor_gain	0.6500
11:49982482:A:AC	donor_gain	0.6500
11:49982483:C:CC	donor_gain	0.6500
11:49982459:G:GT	donor_gain	0.6300
11:49982486:T:A	donor_gain	0.6100
11:49982428:G:C	donor_gain	0.6000
11:49981677:CA:C	acceptor_gain	0.5900
11:49981674:CACCA:C	acceptor_gain	0.5700
11:49982464:A:AC	donor_gain	0.5700
11:49981804:TTAC:T	donor_gain	0.5500
11:49982385:G:A	donor_gain	0.5500
11:49981862:C:CT	donor_gain	0.5300
11:49982220:C:CA	donor_gain	0.5200
11:49982477:CAG:C	donor_gain	0.5100
11:49981769:C:CT	donor_gain	0.5000
11:49981770:T:TT	donor_gain	0.5000
11:49982425:A:T	donor_gain	0.5000

AlphaMissense

2031 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:49982472:G:C	F10L	0.801
11:49982472:G:T	F10L	0.801
11:49982474:A:G	F10L	0.801
11:49982004:G:C	F166L	0.766
11:49982004:G:T	F166L	0.766
11:49982006:A:G	F166L	0.766
11:49981977:G:C	F175L	0.724
11:49981977:G:T	F175L	0.724
11:49981979:A:G	F175L	0.724
11:49982415:A:C	F29L	0.709
11:49982415:A:T	F29L	0.709
11:49982417:A:G	F29L	0.709
11:49982226:A:C	F92L	0.661
11:49982226:A:T	F92L	0.661
11:49982228:A:G	F92L	0.661
11:49982325:G:C	F59L	0.588
11:49982325:G:T	F59L	0.588
11:49982327:A:G	F59L	0.588
11:49981740:A:C	F254L	0.571
11:49981740:A:T	F254L	0.571
11:49981742:A:G	F254L	0.571

dbSNP variants (sampled 300 via entrez): RS11040695 (11:49981489 C>G,T), RS112073212 (11:49981462 C>T), RS112828389 (11:49984447 T>C,G), RS112929537 (11:49982483 C>T), RS113343706 (11:49981262 C>A), RS114706080 (11:49981972 C>T), RS1159647776 (11:49982965 T>C), RS1159766398 (11:49983996 G>A), RS1160393658 (11:49981406 G>A), RS1161143694 (11:49983781 TAA>T,TA,TAAA), RS1161151595 (11:49982876 A>G), RS1161832411 (11:49983463 G>A), RS1161938661 (11:49984404 A>G), RS1162922909 (11:49982167 A>C), RS1163018545 (11:49983331 T>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:189800

GenCC curated gene-disease

Mondo (2): preeclampsia (MONDO:0005081), prostate cancer (MONDO:0008315)

Orphanet (2): Preeclampsia (Orphanet:275555), Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST010241_194	Apolipoprotein A1 levels	3.000000e-26
GCST010241_386	Apolipoprotein A1 levels	6.000000e-10
GCST010242_323	HDL cholesterol levels	1.000000e-13
GCST010242_528	HDL cholesterol levels	8.000000e-50
GCST010244_207	Triglyceride levels	1.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D011225	Pre-Eclampsia	C12.050.703.395.249
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 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
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	PHASE4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	PHASE4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	PHASE4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	PHASE4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	PHASE4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	PHASE4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	PHASE4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	PHASE4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	PHASE4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	PHASE4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	PHASE4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	PHASE4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
NCT02891174	PHASE4	COMPLETED	The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
NCT02911701	PHASE4	COMPLETED	Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
NCT03171480	PHASE4	COMPLETED	Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
NCT03233880	PHASE4	UNKNOWN	Impact of Antichlamydial Treatment on the Rate of Preeclampsia
NCT03237000	PHASE4	UNKNOWN	Effect of Administering Intravenous Magnesium Sulfate on Fetal Cardiotocography and Neonatal Outcome in Preeclamptic Patients
NCT03506724	PHASE4	COMPLETED	Response to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT03735433	PHASE4	TERMINATED	The Effect of Two Aspirin Dosing Strategies for Obese Women at High Risk for Preeclampsia
NCT03824119	PHASE4	UNKNOWN	Postpartum NSAIDS and Maternal Hypertension
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT04077853	PHASE4	COMPLETED	Progesterone in Expectantly Managed Early-onset Preeclampsia
NCT04158830	PHASE4	WITHDRAWN	Aspirin (ASA) Therapy and Preeclampsia Prevention
NCT04424693	PHASE4	UNKNOWN	Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36
NCT04631627	PHASE4	UNKNOWN	Early Prediction and Randomised Prevention of Preeclampsia With Low Dose Aspirin in Chinese Cohort
NCT04656665	PHASE4	UNKNOWN	The Effectiveness of Aspirin on Preventing Pre-eclampsia
NCT04797949	PHASE4	WITHDRAWN	Adherence to Universal Aspirin Compared to Screening Indicated Aspirin for Prevention of Preeclampsia
NCT04908982	PHASE4	UNKNOWN	Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension
NCT05221164	PHASE4	UNKNOWN	162 mg of Aspirin for Prevention of Preeclampsia
NCT05294952	PHASE4	UNKNOWN	co Ihibtory Receptor in Preeclampsia
NCT05514847	PHASE4	ACTIVE_NOT_RECRUITING	Low Dose Aspirin for Preterm Preeclampsia Preventionmg/day Dose in High-risk Patients
NCT05586373	PHASE4	COMPLETED	Ibuprofen vs Dipyrone After C-section in Preeclampsia
NCT06069102	PHASE4	COMPLETED	Optimal Blood Pressure Treatment Thresholds Postpartum
NCT06107335	PHASE4	NOT_YET_RECRUITING	Effect of Albumin Versus Routine Care on Hemodynamic Response and Stability in Patients With Preeclampsia Guided by a Non-invasive Hemodynamic Monitoring System During Cesarean Delivery With Spinal Anesthesia
NCT06281665	PHASE4	RECRUITING	Treatment With Aspirin After Preeclampsia: TAP Trial