OTOP2

Summary

OTOP2 (otopetrin 2, HGNC:19657) is a protein-coding gene on chromosome 17q25.1, encoding Proton channel OTOP2 (Q7RTS6). Proton-selective ion channel open at neutral pH.

Predicted to enable proton channel activity. Predicted to be involved in proton transmembrane transport. Predicted to be located in plasma membrane. Predicted to be active in membrane.

Source: NCBI Gene 92736 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 103 total — 1 likely-pathogenic
• MANE Select transcript: NM_178160

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19657
Approved symbol	OTOP2
Name	otopetrin 2
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000183034
Ensembl biotype	protein_coding
OMIM	607827
Entrez	92736

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000331427, ENST00000580223, ENST00000584711, ENST00000857247, ENST00000857248, ENST00000962901

RefSeq mRNA: 1 — MANE Select: NM_178160 NM_178160

CCDS: CCDS11708

Canonical transcript exons

ENST00000331427 — 7 exons

Exon	Start	End
ENSE00001310938	74927223	74927281
ENSE00001319201	74930279	74931153
ENSE00001321689	74927665	74927798
ENSE00002688169	74933375	74933912
ENSE00003475573	74924600	74924945
ENSE00003485076	74925556	74925692
ENSE00003897568	74924273	74924333

Expression profiles

Bgee: expression breadth broad, 37 present calls, max score 95.53.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0114 / max 8.3302, expressed in 5 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
208374	0.0114	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	95.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.01	gold quality
rectum	UBERON:0001052	78.35	gold quality
transverse colon	UBERON:0001157	75.27	gold quality
lower esophagus mucosa	UBERON:0035834	67.42	gold quality
esophagus mucosa	UBERON:0002469	66.80	gold quality
left testis	UBERON:0004533	64.43	gold quality
testis	UBERON:0000473	64.27	gold quality
right testis	UBERON:0004534	63.14	gold quality
colonic epithelium	UBERON:0000397	58.84	silver quality
colon	UBERON:0001155	57.70	gold quality
intestine	UBERON:0000160	56.42	gold quality
small intestine Peyer’s patch	UBERON:0003454	53.31	gold quality
small intestine	UBERON:0002108	53.24	gold quality
duodenum	UBERON:0002114	52.82	gold quality
skin of leg	UBERON:0001511	48.12	gold quality
esophagus	UBERON:0001043	46.95	gold quality
smooth muscle tissue	UBERON:0001135	46.86	gold quality
zone of skin	UBERON:0000014	43.49	gold quality
leukocyte	CL:0000738	42.14	gold quality
monocyte	CL:0000576	41.65	gold quality
body of uterus	UBERON:0009853	40.80	gold quality
granulocyte	CL:0000094	40.78	gold quality
muscle layer of sigmoid colon	UBERON:0035805	38.49	gold quality
bone marrow cell	CL:0002092	38.04	gold quality
myometrium	UBERON:0001296	37.95	gold quality
muscle tissue	UBERON:0002385	37.40	gold quality
skin of abdomen	UBERON:0001416	37.04	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	1421.26
E-ANND-3	no	2.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting OTOP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-619-3P	98.38	65.58	693
HSA-MIR-4450	98.26	68.35	725
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-6777-3P	95.35	64.30	699

Literature-anchored findings (GeneRIF, showing 1)

• The OTOP2 is down-regulated in cancerous tissues and that elevated OTOP2 effectively suppresses tumor proliferation in vitro. (PMID:30652071)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	otop2	ENSDARG00000006522
mus_musculus	Otop2	ENSMUSG00000050201
rattus_norvegicus	Otop2	ENSRNOG00000028121
caenorhabditis_elegans		WBGENE00010403
caenorhabditis_elegans		WBGENE00017034
caenorhabditis_elegans		WBGENE00017449
caenorhabditis_elegans		WBGENE00018478
caenorhabditis_elegans		WBGENE00018479
caenorhabditis_elegans		WBGENE00018480

Paralogs (2): OTOP1 (ENSG00000163982), OTOP3 (ENSG00000182938)

Protein

Protein identifiers

Proton channel OTOP2 — Q7RTS6 (reviewed: Q7RTS6)

Alternative names: Otopetrin-2

All UniProt accessions (2): Q7RTS6, A0A6E1ZAN8

UniProt curated annotations — full annotation on UniProt →

Function. Proton-selective ion channel open at neutral pH. Active at neutral and alkaline extracellular pH, likely participates in some alkali-related physiological activities.

Subcellular location. Cell membrane.

Activity regulation. Active at neutral and alkaline extracellular pH, acid extracellular pH appears to inhibit the channel. Insensitive to activation by Zn(2+).

Similarity. Belongs to the otopetrin family.

RefSeq proteins (1): NP_835454* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004878	Otopetrin	Family

Pfam: PF03189

Catalyzed reactions (Rhea), 1 shown:

• H(+)(in) = H(+)(out) (RHEA:34979)

UniProt features (16 total): transmembrane region 12, sequence variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7RTS6-F1	78.55	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 57 (showing top): BENPORATH_ES_WITH_H3K27ME3, LFA1_Q6, GOBP_MONOATOMIC_CATION_TRANSPORT, CCANNAGRKGGC_UNKNOWN, GATA3_01, TGACATY_UNKNOWN, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, GOBP_TRANSMEMBRANE_TRANSPORT, GATA_Q6, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, YKACATTT_UNKNOWN, TCANNTGAY_SREBP1_01, GOMF_TRANSPORTER_ACTIVITY

GO Biological Process (3): proton transmembrane transport (GO:1902600), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (2): proton channel activity (GO:0015252), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic cation transmembrane transport	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
monoatomic cation channel activity	1
proton transmembrane transporter activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

350 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OTOP2	BEST4	Q8NFU0	741
OTOP2	OC90	Q02509	599
OTOP2	GUCA2B	Q16661	545
OTOP2	ATP2B2	Q01814	539
OTOP2	TMEM82	A0PJX8	465
OTOP2	TMEM128	Q5BJH2	453
OTOP2	ATP2B4	P23634	441
OTOP2	TMIGD1	Q6UXZ0	436
OTOP2	HID1	Q8IV36	406
OTOP2	MS4A12	Q9NXJ0	399
OTOP2	C6orf163	Q5TEZ5	396
OTOP2	SLC26A4	O43511	379
OTOP2	OR1D5	P58170	374
OTOP2	CFAP107	Q8N1D5	374
OTOP2	OTOL1	A6NHN0	372

IntAct

18 interactions, top by confidence:

A	B	Type	Score
OTOP2	FATE1	psi-mi:“MI:0915”(physical association)	0.600
OTOP2	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
OTOP2	MANBAL	psi-mi:“MI:0915”(physical association)	0.560
GJA8	OTOP2	psi-mi:“MI:0915”(physical association)	0.560
CD79A	OTOP2	psi-mi:“MI:0915”(physical association)	0.560
AGO2	NDUFA4	psi-mi:“MI:0914”(association)	0.350
OTOP2	FATE1	psi-mi:“MI:0915”(physical association)	0.000
OTOP2	TMEM237	psi-mi:“MI:0915”(physical association)	0.000
OTOP2	GJA8	psi-mi:“MI:0915”(physical association)	0.000
OTOP2	CD79A	psi-mi:“MI:0915”(physical association)	0.000
OTOP2	MANBAL	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): OTOP2 (Two-hybrid), OTOP2 (Two-hybrid), OTOP2 (Two-hybrid), OTOP2 (Two-hybrid), OTOP2 (Two-hybrid), S (Reconstituted Complex), OTOP2 (Negative Genetic)

ESM2 similar proteins: A1L504, A2A6C4, A5D7M7, A6NH21, A8WCG0, B0BNG2, D3ZI76, E9PY61, J3QMI4, O15554, O75908, O77759, O89109, P0C8N6, P51811, Q14DK4, Q1HG43, Q3TD49, Q496Z4, Q49LS0, Q49LS1, Q49LS5, Q49LS8, Q5GH56, Q5GH64, Q5GH72, Q5PQL3, Q5T1A1, Q5XK03, Q60850, Q6PRD1, Q7RTS5, Q7RTS6, Q7TN58, Q7TN60, Q7TQ65, Q7Z403, Q7Z404, Q80SX5, Q80UF9

Diamond homologs: A9JTM7, Q7RTS5, Q7RTS6, Q80SX5, Q80UF9, Q7M734, Q7RTM1, Q7ZWK8, Q80VM9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	92
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3024556	NM_173477.5(USH1G):c.1382+2_1382+3del	Likely pathogenic

SpliceAI

898 predictions. Top by Δscore:

Variant	Effect	Δscore
17:74924915:G:T	donor_gain	1.0000
17:74925689:CCAG:C	donor_loss	1.0000
17:74925690:CAG:C	donor_loss	1.0000
17:74925691:AG:A	donor_loss	1.0000
17:74925692:GG:G	donor_loss	1.0000
17:74925693:GT:G	donor_loss	1.0000
17:74927336:A:T	donor_gain	1.0000
17:74930274:A:AG	acceptor_gain	1.0000
17:74930278:GA:G	acceptor_gain	1.0000
17:74931154:G:GG	donor_gain	1.0000
17:74933372:C:G	acceptor_gain	1.0000
17:74933373:A:AG	acceptor_gain	1.0000
17:74933374:G:GA	acceptor_gain	1.0000
17:74933374:GCT:G	acceptor_gain	1.0000
17:74933374:GCTGT:G	acceptor_gain	1.0000
17:74924329:GCCAG:G	donor_gain	0.9900
17:74924331:CAGGT:C	donor_loss	0.9900
17:74924332:AGGT:A	donor_loss	0.9900
17:74924334:G:A	donor_loss	0.9900
17:74924335:T:A	donor_loss	0.9900
17:74924596:ACAGT:A	acceptor_gain	0.9900
17:74924597:CA:C	acceptor_loss	0.9900
17:74924598:A:AG	acceptor_gain	0.9900
17:74924598:AG:A	acceptor_loss	0.9900
17:74924598:AGT:A	acceptor_gain	0.9900
17:74924599:G:GA	acceptor_gain	0.9900
17:74924599:GT:G	acceptor_gain	0.9900
17:74924599:GTG:G	acceptor_gain	0.9900
17:74924599:GTGAT:G	acceptor_gain	0.9900
17:74924860:G:GT	donor_gain	0.9900

AlphaMissense

3669 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:74930662:A:C	S343R	0.993
17:74930664:C:A	S343R	0.993
17:74930664:C:G	S343R	0.993
17:74933378:T:A	W508R	0.992
17:74933378:T:C	W508R	0.992
17:74930672:G:A	G346D	0.986
17:74930893:T:C	F420L	0.986
17:74930895:T:A	F420L	0.986
17:74930895:T:G	F420L	0.986
17:74933520:T:C	L555P	0.986
17:74930894:T:C	F420S	0.985
17:74931147:T:A	N504K	0.983
17:74931147:T:G	N504K	0.983
17:74933393:T:C	F513L	0.983
17:74933395:C:A	F513L	0.983
17:74933395:C:G	F513L	0.983
17:74925579:T:C	C113R	0.982
17:74933516:A:C	S554R	0.982
17:74933518:C:A	S554R	0.982
17:74933518:C:G	S554R	0.982
17:74933507:G:C	A551P	0.981
17:74925570:T:C	F110L	0.979
17:74925572:T:A	F110L	0.979
17:74925572:T:G	F110L	0.979
17:74933453:T:A	W533R	0.979
17:74933453:T:C	W533R	0.979
17:74930363:T:C	L243P	0.978
17:74933499:G:C	R548P	0.978
17:74930889:C:A	N418K	0.977
17:74930889:C:G	N418K	0.977

dbSNP variants (sampled 300 via entrez): RS1000011247 (17:74924109 A>G), RS1000280562 (17:74933052 C>T), RS1000565359 (17:74923095 G>A), RS1000596602 (17:74923310 G>A,C), RS1000714053 (17:74932794 C>G), RS1000720394 (17:74927439 T>C), RS1000743489 (17:74927165 C>A,T), RS1001205708 (17:74929626 G>A,C), RS1001722902 (17:74933260 G>A), RS1001873828 (17:74922397 C>T), RS1001959732 (17:74928995 C>T), RS1002024117 (17:74927403 G>A), RS1002061665 (17:74934390 C>A,G,T), RS1002074401 (17:74932690 T>C), RS1002104211 (17:74932349 G>A)

Disease associations

OMIM: gene MIM:607827 | disease phenotypes: MIM:276900, MIM:156000

GenCC curated gene-disease

Mondo (2): Usher syndrome (MONDO:0019501), Meniere disease (MONDO:0007972)

Orphanet (2): Usher syndrome (Orphanet:886), NON RARE IN EUROPE: Menière disease (Orphanet:45360)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005580_308	Intraocular pressure	4.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008575	Meniere Disease	C09.218.568.217.500
D052245	Usher Syndromes	C09.218.458.341.186.500.500; C09.218.458.341.887.886; C10.597.751.418.341.186.500.500; C10.597.751.418.341.887.886; C10.597.751.941.162.625.500; C11.768.585.658.500.813; C11.966.075.375.500; C16.131.077.299.500; C16.320.290.684.500; C23.888.592.763.393.341.887.886

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Diazinon	increases methylation	1
Estradiol	increases expression	1
Methapyrilene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01574313	PHASE4	COMPLETED	Effect of Stellate Ganglion Block on Meniere’s Disease
NCT02529475	PHASE4	TERMINATED	Evaluation of Inner Ear and Brain Structures With Contrast-enhanced MRI in Healthy Subjects (HYDROPS)
NCT04815187	PHASE4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT03664674	PHASE3	COMPLETED	Phase 3 Study of OTO-104 in Subjects With Unilateral Meniere’s Disease
NCT04677972	PHASE3	COMPLETED	SPI-1005 for the Treatment of Meniere’s Disease
NCT05851508	PHASE3	RECRUITING	The Effecttiveness of Intratympanic Methylprednisolon Injections Compared to Placebo in the Treatment of Vertigo Attacks in Meniere’s Disease
NCT02065011	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Determine the Long-Term Safety, Tolerability and Biological Activity of SAR421869 in Patients With Usher Syndrome Type 1B
NCT05420350	PHASE2	UNKNOWN	Lamotrigine and Bupropion for Meniere’s Disease
NCT06544434	PHASE2	RECRUITING	Laser Acupuncture for Meniere Disease
NCT04674735	PHASE1	WITHDRAWN	Safety of APSLXR in Patients Presenting Vertigo of Vestibular Origin or Meniere’s Disease
NCT01505062	PHASE1/PHASE2	TERMINATED	Study of SAR421869 in Participants With Retinitis Pigmentosa Associated With Usher Syndrome Type 1B
NCT04355689	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy of NPI-001 Tablets for RP Associated With Usher Syndrome
NCT06789445	PHASE1/PHASE2	RECRUITING	A Study to Investigate the Safety of OpCT-001 in Adults Who Have Primary Photoreceptor Disease (CLARICO)
NCT00004345	Not specified	TERMINATED	Study of Dietary N-3 Fatty Acids in Patients With Retinitis Pigmentosa and Usher Syndrome
NCT00016471	Not specified	COMPLETED	A Genetic Analysis of Usher Syndrome in Ashkenazi Jews
NCT00106743	Not specified	COMPLETED	Natural History and Genetic Studies of Usher Syndrome
NCT01954953	Not specified	UNKNOWN	Clinical and Genetic Examination of Usher Syndrome Patients’ Cohort in Europe
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT03319524	Not specified	COMPLETED	Clinical and Genetic Testing of Patients With Usher Syndrome
NCT03901391	Not specified	COMPLETED	Prospective Open Clinical and Genetic Study of Patients With Retinitis Pigmentosa
NCT03990727	Not specified	UNKNOWN	Phenotype Correlates Genotype of Inherited Retina Dystrophies, Retinitis Pigmentosa, Con>Rod Dystrophies.
NCT04665726	Not specified	RECRUITING	Natural History Study of Usher Syndrome ( Light4Deaf )
NCT04906135	Not specified	COMPLETED	Auditory Neural Function in Implanted Patients With Usher Syndrome
NCT05355415	Not specified	RECRUITING	Adaptive Optics Imaging of Outer Retinal Diseases
NCT07278843	Not specified	RECRUITING	Natural History of Photoreceptor Degeneration in USH1B: Clinical Parameters and Validation of Functional Vision Tests in MYO7A
NCT07548944	Not specified	RECRUITING	Observational Study to Investigate the Short-term Effects of Transcorneal Electrical Stimulation on Visual Performance
NCT04218123	PHASE2/PHASE3	COMPLETED	Assessing the Efficacy of a Serotonin and Norepinephrine Reuptake Inhibitor for Improving Meniere’s Disease Outcomes
NCT04766853	PHASE1/PHASE2	COMPLETED	Verification of the Efficacy/safety of the Intratympanic Drug Delivery for Hearing Loss
NCT04794842	EARLY_PHASE1	UNKNOWN	Comparing Topical Tetracaine Drops to Topical Focal Phenol for Local Anesthesia During Intratympanic Steroid Injection
NCT00599560	Not specified	COMPLETED	Vasopressin and V2 Receptor in Meniere’s Disease
NCT02371798	Not specified	WITHDRAWN	Unilateral Meniere Disease: Can Double Dose Gadolinium and Delayed Imaging Make the Diagnosis?
NCT03520322	Not specified	TERMINATED	A Study of a Mastoid Device in Subjects With Ménière’s Disease
NCT03795675	Not specified	ACTIVE_NOT_RECRUITING	CI Following VS Removal or Labyrinthectomy
NCT04370366	Not specified	RECRUITING	Imaging of Endolymphatic Hydrops at 7T MRI
NCT04569175	Not specified	COMPLETED	Non Enhanced Labyrinth Imaging for the Detection of Endolymphatic Hydrops in Meniere’s Disease NELI Study
NCT04686695	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation Treatment on Meniere Disease
NCT04835688	Not specified	UNKNOWN	Ventilation Tube Insertion for Unilateral Menière’s Disease
NCT04902963	Not specified	COMPLETED	What is the Tympanic Membrane Healing Time After Insertion of a Gelfoam PE Tube?
NCT04935970	Not specified	UNKNOWN	Metabolic Disorders and Vertigo