OR4M1

Summary

OR4M1 (olfactory receptor family 4 subfamily M member 1, HGNC:14735) is a protein-coding gene on chromosome 14q11.2, encoding Olfactory receptor 4M1 (Q8NGD0). Olfactory receptor that acts as a receptor of Asprosin hormone, potentially at the surface of hepatocytes and may help to promote hepatocyte glucose release.

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 441670 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (No Known Disease Relationship, GenCC)
• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_001005500

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14735
Approved symbol	OR4M1
Name	olfactory receptor family 4 subfamily M member 1
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000176299
Ensembl biotype	protein_coding
OMIM	619939
Entrez	441670

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000315957, ENST00000641200, ENST00000641705, ENST00000641808

RefSeq mRNA: 1 — MANE Select: NM_001005500 NM_001005500

CCDS: CCDS32021

Canonical transcript exons

ENST00000641200 — 2 exons

Exon	Start	End
ENSE00003813149	19780294	19783696
ENSE00003813155	19773504	19773593

Expression profiles

Bgee: expression breadth tissue_specific, 6 present calls, max score 81.69.

Top tissues by expression

113 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	81.69	gold quality
sural nerve	UBERON:0015488	46.05	gold quality
right testis	UBERON:0004534	43.81	gold quality
testis	UBERON:0000473	42.79	gold quality
left testis	UBERON:0004533	42.51	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	35.00	gold quality
bone marrow	UBERON:0002371	33.67	silver quality
monocyte	CL:0000576	32.33	gold quality
muscle tissue	UBERON:0002385	32.25	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
leukocyte	CL:0000738	31.90	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
vermiform appendix	UBERON:0001154	29.23	gold quality
liver	UBERON:0002107	29.11	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
adrenal tissue	UBERON:0018303	28.94	gold quality
tonsil	UBERON:0002372	28.75	gold quality
duodenum	UBERON:0002114	28.14	gold quality
urinary bladder	UBERON:0001255	28.06	gold quality
lymph node	UBERON:0000029	27.57	gold quality
islet of Langerhans	UBERON:0000006	26.89	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
calcaneal tendon	UBERON:0003701	25.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.77

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Asprosin is a key regulatory factor for preserving the homeostasis of energy metabolism. Asprosin promotes hepatic glucose release in the liver and appetite stimulation in the hypothalamus through activation of the cAMP signaling circuitry through interacting with its G protein-coupled receptor, called OR4M1. In this review, we discuss the current literature on asprosin and its receptor, OR4M1. (PMID:35707591)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Or4m1	ENSMUSG00000045306
rattus_norvegicus	Or4m1	ENSRNOG00000012545

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 4M1 — Q8NGD0 (reviewed: Q8NGD0)

Alternative names: Olfactory receptor OR14-7

All UniProt accessions (2): A0A126GWC3, Q8NGD0

UniProt curated annotations — full annotation on UniProt →

Function. Olfactory receptor that acts as a receptor of Asprosin hormone, potentially at the surface of hepatocytes and may help to promote hepatocyte glucose release.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in the testis and olfactory bulb.

Miscellaneous. The human olfactory receptor 4M1 (Q8NGD0) is not the one to one ortholog of mouse Or4m1 (Q8VFT4).

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

RefSeq proteins (1): NP_001005500* (*=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 variant 2, chain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NGD0-F1	89.70	0.68

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: 17 (showing top): GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, KEGG_OLFACTORY_TRANSDUCTION, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, 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

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

160 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OR4M1	POTEM	A6NI47	540
OR4M1	FBN1	P35555	456
OR4M1	POTEG	Q6S5H5	419
OR4M1	OR1J2	Q8NGS2	407
OR4M1	OR2C1	O95371	403
OR4M1	OR4K2	Q8NGD2	393
OR4M1	OR4Q3	Q8NH05	390
OR4M1	OR4N2	Q8NGD1	388
OR4M1	OR2L13	Q8N349	363
OR4M1	OR51G1	Q8NGK1	344
OR4M1	OR11H2	Q8NH07	307
OR4M1	CCDC91	Q7Z6B0	301
OR4M1	OR4K5	Q8NGD3	299
OR4M1	OR4X1	Q8NH49	288
OR4M1	OR4K1	Q8NGD4	282

IntAct

2 interactions, top by confidence:

A	B	Type	Score
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350

BioGRID (1): OR4M1 (Affinity Capture-MS)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

165 predictions. Top by Δscore:

Variant	Effect	Δscore
14:19780444:G:GT	donor_gain	0.7500
14:19780386:G:GT	donor_gain	0.6600
14:19780643:T:A	acceptor_gain	0.6300
14:19780386:G:T	donor_gain	0.5900
14:19780445:A:T	donor_gain	0.5700
14:19780390:TCC:T	donor_gain	0.5600
14:19780349:GAC:G	donor_gain	0.5500
14:19780350:ACA:A	donor_gain	0.5500
14:19780351:C:G	donor_gain	0.5100
14:19781012:CTCAG:C	donor_loss	0.5100
14:19781013:TCAG:T	donor_loss	0.5100
14:19781014:CAGGT:C	donor_loss	0.5100
14:19781015:AG:A	donor_loss	0.5100
14:19781016:GGT:G	donor_loss	0.5100
14:19781017:G:GA	donor_loss	0.5100
14:19781018:T:A	donor_loss	0.5100
14:19781190:ACATT:A	acceptor_gain	0.5100
14:19780553:A:AG	acceptor_gain	0.4800
14:19780554:G:GG	acceptor_gain	0.4800
14:19781190:A:AG	acceptor_gain	0.4800
14:19781191:C:G	acceptor_gain	0.4700
14:19780589:G:GT	donor_gain	0.4400
14:19780759:C:G	donor_gain	0.4400
14:19780987:T:TA	acceptor_gain	0.4400
14:19781019:G:GT	donor_loss	0.4400
14:19780385:G:GT	donor_gain	0.4300
14:19780756:T:TA	donor_gain	0.4300
14:19780473:C:T	donor_gain	0.4200
14:19780554:GCCC:G	acceptor_gain	0.4100
14:19781192:ATT:A	acceptor_gain	0.4100

AlphaMissense

2050 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:19780676:G:A	M118I	0.987
14:19780676:G:C	M118I	0.987
14:19780676:G:T	M118I	0.987
14:19780687:G:C	R122P	0.978
14:19781177:T:A	N285K	0.977
14:19781177:T:G	N285K	0.977
14:19781079:T:C	F253L	0.975
14:19781081:T:A	F253L	0.975
14:19781081:T:G	F253L	0.975
14:19780950:T:C	C210R	0.973
14:19780356:T:C	F12L	0.972
14:19780358:T:A	F12L	0.972
14:19780358:T:G	F12L	0.972
14:19780854:T:C	F178L	0.972
14:19780856:C:A	F178L	0.972
14:19780856:C:G	F178L	0.972
14:19780357:T:C	F12S	0.971
14:19780695:G:C	A125P	0.968
14:19780929:A:C	S203R	0.968
14:19780931:T:A	S203R	0.968
14:19780931:T:G	S203R	0.968
14:19780684:A:C	D121A	0.967
14:19780926:A:C	S202R	0.967
14:19780928:T:A	S202R	0.967
14:19780928:T:G	S202R	0.967
14:19780684:A:T	D121V	0.966
14:19780686:C:A	R122S	0.966
14:19781161:T:A	I280K	0.966
14:19780510:T:C	L63S	0.964
14:19780357:T:G	F12C	0.961

dbSNP variants (sampled 300 via entrez): RS1000323154 (14:19777698 T>C), RS1000673882 (14:19777192 A>G), RS1000978366 (14:19775778 C>G,T), RS1001505290 (14:19776332 C>A,G,T), RS1002017835 (14:19784115 A>G), RS1002059769 (14:19776795 G>A,C,T), RS1002615780 (14:19782532 C>G,T), RS1002913093 (14:19782850 A>G), RS1003059489 (14:19774931 A>C,G,T), RS1003506615 (14:19772544 A>C,G), RS1004702968 (14:19780407 G>A,C), RS1004806505 (14:19783641 A>T), RS1004857571 (14:19784089 C>T), RS1005452638 (14:19775849 A>C), RS1005859559 (14:19782511 A>G)

Disease associations

OMIM: gene MIM:619939 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (1): Tourette syndrome (MONDO:0007661)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

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
Benzo(a)pyrene	increases methylation	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome