OR6C6

Summary

OR6C6 (olfactory receptor family 6 subfamily C member 6, HGNC:31293) is a protein-coding gene on chromosome 12q13.2, encoding Olfactory receptor 6C6 (A6NF89). Odorant receptor. It is a selective cancer dependency (DepMap: 12.9% 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 283365 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 48 total
• Cancer dependency (DepMap): dependent in 12.9% of screened cell lines
• MANE Select transcript: NM_001005493

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31293
Approved symbol	OR6C6
Name	olfactory receptor family 6 subfamily C member 6
Location	12q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188324
Ensembl biotype	protein_coding
Entrez	283365

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000358433

RefSeq mRNA: 1 — MANE Select: NM_001005493 NM_001005493

CCDS: CCDS31817

Canonical transcript exons

ENST00000358433 — 2 exons

Exon	Start	End
ENSE00001403093	55293988	55295257
ENSE00003813727	55296319	55296569

Expression profiles

Bgee: expression breadth tissue_specific, 1 present calls, max score 73.92.

Top tissues by expression

123 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	73.92	silver quality
granulocyte	CL:0000094	38.74	gold quality
bone marrow cell	CL:0002092	38.14	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
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	34.80	gold quality
bone marrow	UBERON:0002371	33.92	gold quality
muscle tissue	UBERON:0002385	33.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
liver	UBERON:0002107	31.04	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
blood	UBERON:0000178	30.20	gold quality
descending thoracic aorta	UBERON:0002345	30.05	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
right uterine tube	UBERON:0001302	29.71	gold quality
right lobe of liver	UBERON:0001114	29.52	gold quality
leukocyte	CL:0000738	29.51	gold quality
vermiform appendix	UBERON:0001154	29.30	gold quality
adrenal tissue	UBERON:0018303	29.25	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
monocyte	CL:0000576	29.00	gold quality
urinary bladder	UBERON:0001255	28.81	gold quality
right coronary artery	UBERON:0001625	28.24	gold quality
duodenum	UBERON:0002114	28.14	gold quality
smooth muscle tissue	UBERON:0001135	27.75	gold quality
placenta	UBERON:0001987	27.65	gold quality
lymph node	UBERON:0000029	27.57	gold quality
pancreas	UBERON:0001264	27.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.12

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.9% of screened cell lines.

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Or6c6	ENSMUSG00000095075
mus_musculus	Or6c6c	ENSMUSG00000095401
rattus_norvegicus		ENSRNOG00000072157
rattus_norvegicus		ENSRNOG00000082680
rattus_norvegicus	Or6c6b	ENSRNOG00000084318
rattus_norvegicus	Or6c6i	ENSRNOG00000085043
rattus_norvegicus	Olr951	ENSRNOG00000091024

Paralogs (18): OR6F1 (ENSG00000169214), OR2AP1 (ENSG00000179615), OR6C4 (ENSG00000179626), OR6C2 (ENSG00000179695), OR6T1 (ENSG00000181499), OR6S1 (ENSG00000181803), OR6C70 (ENSG00000184954), OR6C76 (ENSG00000185821), OR6C75 (ENSG00000187857), OR6M1 (ENSG00000196099), OR6C74 (ENSG00000197706), OR6C68 (ENSG00000205327), OR6C65 (ENSG00000205328), OR6C3 (ENSG00000205329), OR6C1 (ENSG00000205330), OR6X1 (ENSG00000221931), OR6V1 (ENSG00000225781), OR6J1 (ENSG00000255804)

Protein

Protein identifiers

Olfactory receptor 6C6 — A6NF89 (reviewed: A6NF89)

All UniProt accessions (2): A0A126GW15, A6NF89

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_001005493* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000725	Olfact_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR047132	Olfact_rcpt_6C-like	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-A6NF89-F1	89.64	0.71

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): 3

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, GOBP_DETECTION_OF_CHEMICAL_STIMULUS, GOMF_MOLECULAR_TRANSDUCER_ACTIVITY, KONDO_PROSTATE_CANCER_WITH_H3K27ME3

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 (3): lipid droplet (GO:0005811), 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
intracellular membraneless organelle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

190 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OR6C6	PRODH2	Q9UF12	520
OR6C6	ZNF630	Q2M218	433
OR6C6	TRIM9	Q9C026	399
OR6C6	ITIH2	P19823	378
OR6C6	CFAP47	Q6ZTR5	370
OR6C6	ITIH6	Q6UXX5	368
OR6C6	MOGS	Q13724	368
OR6C6	GPKOW	Q92917	356
OR6C6	NT5DC1	Q5TFE4	326
OR6C6	SSTR3	P32745	326
OR6C6	INTS6L	Q5JSJ4	321
OR6C6	PRODH	O43272	308
OR6C6	KCTD21	Q4G0X4	296
OR6C6	MCTP2	Q6DN12	281
OR6C6	GLT8D1	Q68CQ7	270
OR6C6	SSX3	Q99909	270

IntAct

0 interactions, top by confidence:

BioGRID (1): NUCKS1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A6NCV1, A6NF89, A6NJZ3, A6NL08, A6NM76, O95221, P0C7N1, P0C7N5, P37070, P37071, P37072, Q15617, Q60886, Q6IEU7, Q8N127, Q8NGE1, Q8NGG0, Q8NGG8, Q8NGP8, Q8NGP9, Q8NGR8, Q8NGS9, Q8NGT0, Q8NGT1, Q8NGX3, Q8NH01, Q8NH10, Q8NH51, Q8NH69, Q8VEW5, Q8VF65, Q8VF66, Q8VF76, Q8VFD0, Q8VFD3, Q8VFK2, Q8VG02, Q8VG03, Q8VG04, Q8VG07

Diamond homologs: A0A3B3IT45, A4D2G3, A6NF89, A6NGY5, A6NL08, A6NL26, A6NMU1, A6NND4, O88628, P0C629, P0C646, P0C7N1, P0C7T3, P23266, P23273, P23274, P30954, Q13606, Q60888, Q62007, Q6IF63, Q6IFG1, Q6W049, Q8NGA6, Q8NGF0, Q8NGF1, Q8NGF3, Q8NGG8, Q8NGH5, Q8NGH6, Q8NGH7, Q8NGH8, Q8NGH9, Q8NGI0, Q8NGI1, Q8NGI2, Q8NGI3, Q8NGI7, Q8NGJ2, Q8NGJ3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

272 predictions. Top by Δscore:

Variant	Effect	Δscore
12:55295030:T:TA	donor_gain	0.9100
12:55294917:CCGG:C	acceptor_gain	0.8500
12:55294919:G:T	acceptor_gain	0.8100
12:55295024:A:AC	donor_gain	0.7800
12:55294918:C:T	acceptor_gain	0.7600
12:55294920:G:GC	acceptor_gain	0.7600
12:55295031:C:A	donor_gain	0.7600
12:55295047:A:AC	donor_gain	0.7400
12:55295048:C:CC	donor_gain	0.7400
12:55294918:CGG:C	acceptor_gain	0.7300
12:55295027:A:AC	donor_gain	0.7200
12:55295028:C:CC	donor_gain	0.7200
12:55295012:A:AC	donor_gain	0.7000
12:55295013:C:CC	donor_gain	0.7000
12:55295029:T:C	donor_gain	0.7000
12:55294916:CCCGG:C	acceptor_gain	0.6900
12:55295061:A:AC	donor_gain	0.6800
12:55295062:C:CC	donor_gain	0.6800
12:55295159:A:AC	donor_gain	0.6800
12:55295044:A:AC	donor_gain	0.6700
12:55295070:T:TA	donor_gain	0.6700
12:55294915:TCCCG:T	acceptor_gain	0.6600
12:55295010:A:T	donor_gain	0.6300
12:55294920:G:C	acceptor_gain	0.6100
12:55294760:A:T	acceptor_gain	0.6000
12:55295049:G:C	donor_gain	0.6000
12:55294361:C:CC	acceptor_gain	0.5600
12:55294928:A:C	acceptor_gain	0.5600
12:55295132:G:C	acceptor_gain	0.5600
12:55294543:C:CC	acceptor_gain	0.5400

AlphaMissense

2066 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:55294477:G:C	S252R	0.929
12:55294477:G:T	S252R	0.929
12:55294479:T:G	S252R	0.929
12:55295203:G:C	F10L	0.918
12:55295203:G:T	F10L	0.918
12:55295205:A:G	F10L	0.918
12:55294903:A:C	F110L	0.917
12:55294903:A:T	F110L	0.917
12:55294905:A:G	F110L	0.917
12:55295125:G:C	S36R	0.904
12:55295125:G:T	S36R	0.904
12:55295127:T:G	S36R	0.904
12:55294735:A:C	F166L	0.903
12:55294735:A:T	F166L	0.903
12:55294737:A:G	F166L	0.903
12:55294708:A:C	F175L	0.901
12:55294708:A:T	F175L	0.901
12:55294710:A:G	F175L	0.901
12:55294874:C:G	R120P	0.854
12:55294525:A:C	F236L	0.838
12:55294525:A:T	F236L	0.838
12:55294527:A:G	F236L	0.838
12:55294794:A:G	W147R	0.834
12:55294794:A:T	W147R	0.834
12:55295030:T:A	E68V	0.833
12:55294798:G:C	S145R	0.827
12:55294798:G:T	S145R	0.827
12:55294800:T:G	S145R	0.827
12:55295204:A:G	F10S	0.822
12:55294381:A:C	N284K	0.818

dbSNP variants (sampled 300 via entrez): RS1000365809 (12:55293676 G>C), RS1001602851 (12:55298456 G>A), RS1002378954 (12:55294545 G>A), RS1003255420 (12:55297335 C>G,T), RS1004184207 (12:55294166 G>A,T), RS1004276113 (12:55294517 C>T), RS1006174801 (12:55296169 T>C), RS1006225574 (12:55295870 A>C), RS1007210576 (12:55297822 G>A,T), RS1007726125 (12:55296558 T>C), RS1007908341 (12:55295475 T>C), RS1007957567 (12:55295667 C>A,G), RS1009022299 (12:55296942 A>G), RS1009111799 (12:55296348 T>C), RS1009281791 (12:55297798 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002238_5	Contrast sensitivity	5.000000e-06
GCST010002_217	Refractive error	6.000000e-174

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005419	contrast sensitivity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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