OR4C46

Summary

OR4C46 (olfactory receptor family 4 subfamily C member 46, HGNC:31271) is a protein-coding gene on chromosome 11q11, encoding Olfactory receptor 4C46 (A6NHA9). Odorant receptor. It is a selective cancer dependency (DepMap: 43.8% 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 119749 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 92 total
• Cancer dependency (DepMap): dependent in 43.8% of screened cell lines
• MANE Select transcript: NM_001004703

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31271
Approved symbol	OR4C46
Name	olfactory receptor family 4 subfamily C member 46
Location	11q11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185926
Ensembl biotype	protein_coding
OMIM	614273
Entrez	119749

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000328188

RefSeq mRNA: 1 — MANE Select: NM_001004703 NM_001004703

CCDS: CCDS73288

Canonical transcript exons

ENST00000328188 — 1 exons

Exon	Start	End
ENSE00001731289	54603069	54603998

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
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
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
monocyte	CL:0000576	28.98	gold quality
leukocyte	CL:0000738	28.86	gold quality
liver	UBERON:0002107	28.63	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
urinary bladder	UBERON:0001255	27.09	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.00	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	25.15	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
pancreas	UBERON:0001264	24.41	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
gastrocnemius	UBERON:0001388	24.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.64

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 43.8% of screened cell lines.

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Or4c10b	ENSMUSG00000049057
mus_musculus	Or4c10	ENSMUSG00000049149
mus_musculus	Or4c106	ENSMUSG00000061798
mus_musculus	Or4c105	ENSMUSG00000064084
rattus_norvegicus	Or4c10b	ENSRNOG00000071986
rattus_norvegicus	Olr655	ENSRNOG00000072336
rattus_norvegicus	Or4c10	ENSRNOG00000081416
rattus_norvegicus	Or4c105	ENSRNOG00000084716
rattus_norvegicus	Or4c105b	ENSRNOG00000089765

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 4C46 — A6NHA9 (reviewed: A6NHA9)

All UniProt accessions (1): A6NHA9

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_001004703* (*=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-A6NHA9-F1	88.47	0.54

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): 95–177

Glycosylation sites (1): 6

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, 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, chr11q11, REACTOME_OLFACTORY_SIGNALING_PATHWAY, REACTOME_SENSORY_PERCEPTION, 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

206 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OR4C46	ZNF530	Q6P9A1	507
OR4C46	DGCR2	P98153	447
OR4C46	ACOT6	Q3I5F7	377
OR4C46	CFAP65	Q6ZU64	372
OR4C46	TEKT5	Q96M29	370
OR4C46	ADGRF4	Q8IZF3	369
OR4C46	SAP30BP	Q9UHR5	355
OR4C46	FAM117B	Q6P1L5	349
OR4C46	FASTKD5	Q7L8L6	349
OR4C46	LRRC73	Q5JTD7	336
OR4C46	ARHGAP33	O14559	324
OR4C46	GPR153	Q6NV75	324
OR4C46	FAM3D	Q96BQ1	323
OR4C46	SDAD1	Q9NVU7	323
OR4C46	TTC39B	Q5VTQ0	321

IntAct

0 interactions, top by confidence:

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

331 predictions. Top by Δscore:

Variant	Effect	Δscore
11:54603589:GT:G	donor_gain	0.6800
11:54603141:A:AG	acceptor_gain	0.6700
11:54603567:G:GT	donor_gain	0.6700
11:54603651:A:AG	donor_gain	0.6700
11:54603200:A:G	donor_gain	0.6300
11:54603239:T:G	acceptor_gain	0.6300
11:54603680:G:GT	donor_gain	0.6200
11:54603148:A:AG	acceptor_gain	0.5900
11:54603195:GCA:G	donor_gain	0.5800
11:54603496:T:TA	acceptor_gain	0.5800
11:54603936:A:G	donor_gain	0.5800
11:54603359:T:A	acceptor_gain	0.5700
11:54603676:TGCAG:T	donor_gain	0.5600
11:54603140:C:G	acceptor_gain	0.5500
11:54603435:A:AG	acceptor_gain	0.5500
11:54603648:GCC:G	donor_gain	0.5500
11:54603191:T:G	donor_gain	0.5400
11:54603325:G:GT	donor_gain	0.5400
11:54603142:T:G	acceptor_gain	0.5300
11:54603495:G:GA	donor_gain	0.5300
11:54603303:C:T	donor_gain	0.5100
11:54603435:ACT:A	acceptor_gain	0.5000
11:54603716:G:GT	donor_gain	0.5000
11:54603192:G:GG	donor_gain	0.4900
11:54603193:A:AG	donor_gain	0.4900
11:54603215:C:G	donor_gain	0.4900
11:54603493:TCCTA:T	donor_gain	0.4900
11:54603827:T:G	donor_gain	0.4800
11:54603880:A:G	donor_gain	0.4800
11:54603096:A:AA	donor_gain	0.4700

AlphaMissense

2050 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:54603969:A:C	F10L	0.742
11:54603969:A:T	F10L	0.742
11:54603971:A:G	F10L	0.742
11:54603501:G:C	F166L	0.736
11:54603501:G:T	F166L	0.736
11:54603503:A:G	F166L	0.736
11:54603474:A:C	F175L	0.692
11:54603474:A:T	F175L	0.692
11:54603476:A:G	F175L	0.692
11:54603699:A:C	F100L	0.616
11:54603699:A:T	F100L	0.616
11:54603701:A:G	F100L	0.616
11:54603252:A:C	F249L	0.566
11:54603252:A:T	F249L	0.566
11:54603254:A:G	F249L	0.566

dbSNP variants (sampled 300 via entrez): RS1000309059 (11:54605189 C>A,G), RS1001906325 (11:54604223 T>A,C), RS1003581688 (11:54602972 T>A), RS1003705814 (11:54605905 G>C), RS1005651838 (11:54603001 T>A,C), RS1006433037 (11:54605570 C>T), RS1006921188 (11:54604392 G>A), RS1007690264 (11:54604716 C>G), RS1008243899 (11:54604599 G>T), RS1008438705 (11:54603978 C>T), RS1010216281 (11:54604002 T>C), RS1012108445 (11:54602806 C>A,T), RS1012239553 (11:54602674 C>A,T), RS1012689006 (11:54605210 T>C,G), RS1012762881 (11:54605869 A>C,G,T)

Disease associations

OMIM: gene MIM:614273 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002223_29	HDL cholesterol	2.000000e-10
GCST004232_70	HDL cholesterol levels	5.000000e-09
GCST005580_48	Intraocular pressure	1.000000e-12
GCST005580_56	Intraocular pressure	3.000000e-12
GCST009725_43	Intraocular pressure	2.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004695	intraocular pressure measurement

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
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Cadmium	decreases expression	1
Catechin	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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