OR6C65

Summary

OR6C65 (olfactory receptor family 6 subfamily C member 65, HGNC:31295) is a protein-coding gene on chromosome 12q13.2, encoding Olfactory receptor 6C65 (A6NJZ3). 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 403282 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_001005518

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31295
Approved symbol	OR6C65
Name	olfactory receptor family 6 subfamily C member 65
Location	12q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205328
Ensembl biotype	protein_coding
Entrez	403282

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000379665

RefSeq mRNA: 1 — MANE Select: NM_001005518 NM_001005518

CCDS: CCDS31821

Canonical transcript exons

ENST00000379665 — 1 exons

Exon	Start	End
ENSE00004472039	55400529	55401467

Expression profiles

Bgee: expression breadth tissue_specific, 3 present calls, max score 98.91.

Top tissues by expression

128 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	98.91	gold quality
granulocyte	CL:0000094	37.35	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
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
liver	UBERON:0002107	28.32	gold quality
leukocyte	CL:0000738	28.16	gold quality
duodenum	UBERON:0002114	28.14	gold quality
monocyte	CL:0000576	27.58	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
urinary bladder	UBERON:0001255	26.80	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.16	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	25.28	gold quality
endometrium	UBERON:0001295	24.90	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.47

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Or6c65	ENSMUSG00000049894
rattus_norvegicus	Or6c66b	ENSRNOG00000002333

Paralogs (18): OR6F1 (ENSG00000169214), OR2AP1 (ENSG00000179615), OR6C4 (ENSG00000179626), OR6C2 (ENSG00000179695), OR6T1 (ENSG00000181499), OR6S1 (ENSG00000181803), OR6C70 (ENSG00000184954), OR6C76 (ENSG00000185821), OR6C75 (ENSG00000187857), OR6C6 (ENSG00000188324), OR6M1 (ENSG00000196099), OR6C74 (ENSG00000197706), OR6C68 (ENSG00000205327), OR6C3 (ENSG00000205329), OR6C1 (ENSG00000205330), OR6X1 (ENSG00000221931), OR6V1 (ENSG00000225781), OR6J1 (ENSG00000255804)

Protein

Protein identifiers

Olfactory receptor 6C65 — A6NJZ3 (reviewed: A6NJZ3)

All UniProt accessions (2): A6NJZ3, A0A126GW71

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_001005518* (*=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 (20 total): topological domain 8, transmembrane region 7, glycosylation site 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NJZ3-F1	89.71	0.65

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 3, 93

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, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, 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

148 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OR6C65	ITIH6	Q6UXX5	667
OR6C65	INTS6L	Q5JSJ4	621
OR6C65	GLT8D1	Q68CQ7	581
OR6C65	HTATSF1	O43719	507
OR6C65	NT5DC1	Q5TFE4	480
OR6C65	KCTD21	Q4G0X4	447
OR6C65	PRODH2	Q9UF12	445
OR6C65	ZNF630	Q2M218	370
OR6C65	TRIM9	Q9C026	348
OR6C65	CEP152	O94986	325
OR6C65	ITIH2	P19823	321
OR6C65	MXRA5	Q9NR99	311
OR6C65	SUMF1	Q8NBK3	311
OR6C65	MAN1B1	Q9UKM7	311
OR6C65	CFAP47	Q6ZTR5	307

IntAct

0 interactions, top by confidence:

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: A6NCV1, A6NDL8, A6NF89, A6NIJ9, A6NJZ3, A6NL08, A6NL26, A6NM76, O76001, O76002, O76100, O95007, P0C623, P0C626, P23266, P23267, P23272, P23274, P30953, P30955, P34985, P58173, P59922, P70526, Q13606, Q5TZ20, Q60882, Q60890, Q6UXT6, Q7TQQ0, Q7Z3T1, Q8N146, Q8N148, Q8N162, Q8N628, Q8NGA1, Q8NGC5, Q8NGE1, Q8NGE2, Q8NGE5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

106 predictions. Top by Δscore:

Variant	Effect	Δscore
12:55400589:TTAC:T	donor_gain	0.7700
12:55400601:A:AG	donor_gain	0.7600
12:55400635:GT:G	donor_gain	0.7600
12:55400595:GTT:G	donor_gain	0.6800
12:55400633:GAGT:G	donor_gain	0.6800
12:55400596:T:G	donor_gain	0.6500
12:55400578:A:G	donor_gain	0.6400
12:55400596:T:TA	donor_gain	0.6400
12:55400589:T:G	donor_gain	0.6200
12:55400637:G:GG	donor_gain	0.6000
12:55400632:TGAGT:T	donor_gain	0.5800
12:55400633:GAGTG:G	donor_gain	0.5800
12:55401177:A:AG	acceptor_gain	0.5500
12:55400634:AGTGT:A	donor_loss	0.5400
12:55400635:GTGTA:G	donor_loss	0.5400
12:55400636:TG:T	donor_loss	0.5400
12:55400637:G:GT	donor_loss	0.5400
12:55400638:TAAGT:T	donor_loss	0.5400
12:55400639:A:AC	donor_loss	0.5400
12:55400640:A:AC	donor_loss	0.5400
12:55400641:G:C	donor_loss	0.5300
12:55400634:AGT:A	donor_gain	0.5200
12:55400635:GTG:G	donor_gain	0.5200
12:55400636:TGT:T	donor_gain	0.5200
12:55400940:GTCT:G	donor_gain	0.5100
12:55401225:A:T	donor_gain	0.5100
12:55401073:T:G	acceptor_gain	0.5000
12:55400597:T:TA	donor_gain	0.4900
12:55401263:G:GA	donor_gain	0.4800
12:55400637:GTA:G	donor_gain	0.4500

AlphaMissense

2072 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:55401024:T:C	F166L	0.756
12:55401026:T:A	F166L	0.756
12:55401026:T:G	F166L	0.756
12:55400556:T:C	F10L	0.755
12:55400558:C:A	F10L	0.755
12:55400558:C:G	F10L	0.755
12:55401234:T:C	F236L	0.726
12:55401236:T:A	F236L	0.726
12:55401236:T:G	F236L	0.726
12:55401051:T:C	F175L	0.706
12:55401053:C:A	F175L	0.706
12:55401053:C:G	F175L	0.706
12:55400856:T:C	F110L	0.692
12:55400858:T:A	F110L	0.692
12:55400858:T:G	F110L	0.692
12:55401291:T:C	F255L	0.625
12:55401293:T:A	F255L	0.625
12:55401293:T:G	F255L	0.625
12:55401384:T:C	F286L	0.606
12:55401386:T:A	F286L	0.606
12:55401386:T:G	F286L	0.606
12:55400739:T:C	F71L	0.602
12:55400741:T:A	F71L	0.602
12:55400741:T:G	F71L	0.602
12:55400703:T:C	F59L	0.598
12:55400705:C:A	F59L	0.598
12:55400705:C:G	F59L	0.598
12:55400718:T:C	F64L	0.593
12:55400720:C:A	F64L	0.593
12:55400720:C:G	F64L	0.593

dbSNP variants (sampled 300 via entrez): RS1002022550 (12:55401586 A>G), RS1002051583 (12:55401895 A>G), RS1002516158 (12:55399486 C>T), RS1003452013 (12:55398827 C>T), RS1003523447 (12:55400592 C>T), RS1003721322 (12:55400347 A>T), RS1003967908 (12:55401825 T>A), RS1003973014 (12:55400098 G>A), RS1004325028 (12:55401592 A>G), RS1005016195 (12:55401914 A>G), RS1006056649 (12:55400219 A>G), RS1006749030 (12:55399729 T>A,C), RS1007356599 (12:55399554 C>G,T), RS1008323067 (12:55399177 T>A), RS1009800810 (12:55401052 T>A)

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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
maleic acid	increases expression	1
Benzo(a)pyrene	increases methylation	1
Methapyrilene	increases methylation	1

Clinical trials (associated diseases)

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