OTOP3

Summary

OTOP3 (otopetrin 3, HGNC:19658) is a protein-coding gene on chromosome 17q25.1, encoding Proton channel OTOP3 (Q7RTS5). Proton-selective channel gated by extracellular protons.

Predicted to enable identical protein binding activity and 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 347741 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 129 total
• MANE Select transcript: NM_001272005

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19658
Approved symbol	OTOP3
Name	otopetrin 3
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182938
Ensembl biotype	protein_coding
OMIM	607828
Entrez	347741

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000328801, ENST00000956756

RefSeq mRNA: 2 — MANE Select: NM_001272005 NM_001272005, NM_178233

CCDS: CCDS86637

Canonical transcript exons

ENST00000328801 — 7 exons

Exon	Start	End
ENSE00002699352	74941393	74941809
ENSE00002704196	74949246	74949992
ENSE00002730201	74935898	74935940
ENSE00003552340	74943286	74943344
ENSE00003554947	74941901	74942037
ENSE00003585729	74943606	74943724
ENSE00003594730	74946661	74947475

Expression profiles

Bgee: expression breadth broad, 39 present calls, max score 96.54.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1663 / max 45.1213, expressed in 24 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162678	0.0859	17
162679	0.0628	13
208375	0.0090	6
162677	0.0086	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	96.54	gold quality
lower esophagus mucosa	UBERON:0035834	82.18	gold quality
esophagus mucosa	UBERON:0002469	81.05	gold quality
mucosa of transverse colon	UBERON:0004991	67.90	gold quality
skin of leg	UBERON:0001511	60.98	gold quality
esophagus	UBERON:0001043	54.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	53.77	gold quality
zone of skin	UBERON:0000014	52.17	gold quality
body of pancreas	UBERON:0001150	50.11	gold quality
pancreas	UBERON:0001264	48.22	gold quality
small intestine	UBERON:0002108	47.83	gold quality
small intestine Peyer’s patch	UBERON:0003454	44.16	gold quality
islet of Langerhans	UBERON:0000006	43.70	gold quality
tonsil	UBERON:0002372	42.67	gold quality
vagina	UBERON:0000996	42.38	gold quality
transverse colon	UBERON:0001157	42.00	gold quality
colonic epithelium	UBERON:0000397	41.12	gold quality
skin of abdomen	UBERON:0001416	40.30	gold quality
bone marrow cell	CL:0002092	40.18	gold quality
rectum	UBERON:0001052	39.99	gold quality
ectocervix	UBERON:0012249	39.83	gold quality
intestine	UBERON:0000160	39.48	gold quality
stromal cell of endometrium	CL:0002255	39.06	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	36.87	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
colon	UBERON:0001155	35.94	gold quality
sural nerve	UBERON:0015488	35.61	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
vermiform appendix	UBERON:0001154	35.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting OTOP3, 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-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-3670	97.88	64.39	763
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-6888-5P	95.89	63.78	831
HSA-MIR-6796-5P	95.37	66.08	1120
HSA-MIR-885-3P	95.14	63.08	448
HSA-MIR-6820-5P	94.04	61.13	161

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Otop3	ENSMUSG00000018862
rattus_norvegicus	Otop3	ENSRNOG00000053055
caenorhabditis_elegans		WBGENE00010403
caenorhabditis_elegans		WBGENE00017034
caenorhabditis_elegans		WBGENE00017449
caenorhabditis_elegans		WBGENE00018478
caenorhabditis_elegans		WBGENE00018479
caenorhabditis_elegans		WBGENE00018480

Paralogs (2): OTOP1 (ENSG00000163982), OTOP2 (ENSG00000183034)

Protein

Protein identifiers

Proton channel OTOP3 — Q7RTS5 (reviewed: Q7RTS5)

Alternative names: Otopetrin-3

All UniProt accessions (1): Q7RTS5

UniProt curated annotations — full annotation on UniProt →

Function. Proton-selective channel gated by extracellular protons.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane.

Activity regulation. Activated by extracellular acidification. Activated by Zn(2+) under non-acidic conditions.

Similarity. Belongs to the otopetrin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7RTS5-1	1	yes
Q7RTS5-2	2

RefSeq proteins (2): NP_001258934, NP_839947 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004878	Otopetrin	Family
IPR013087	Znf_C2H2_type	Domain

Pfam: PF03189

Catalyzed reactions (Rhea), 1 shown:

• H(+)(in) = H(+)(out) (RHEA:34979)

UniProt features (36 total): topological domain 13, transmembrane region 12, sequence variant 4, compositionally biased region 2, modified residue 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7RTS5-F1	76.95	0.39

Functional residue map

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

Post-translational modifications (2): 21, 23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 47 (showing top): BENPORATH_ES_WITH_H3K27ME3, CHX10_01, CEBPB_01, GOBP_MONOATOMIC_CATION_TRANSPORT, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, FREAC4_01, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, GOBP_TRANSMEMBRANE_TRANSPORT, KONDO_PROSTATE_CANCER_HCP_WITH_H3K27ME3, TUOMISTO_TUMOR_SUPPRESSION_BY_COL13A1_DN, TAATTA_CHX10_01, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_CHANNEL_ACTIVITY

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

GO Molecular Function (3): proton channel activity (GO:0015252), identical protein binding (GO:0042802), 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
protein binding	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
OTOP3	OC90	Q02509	604
OTOP3	ATP2B2	Q01814	545
OTOP3	TCTA	P57738	484
OTOP3	RGR	P47804	471
OTOP3	NR2C1	P13056	467
OTOP3	ATP2B4	P23634	441
OTOP3	OR51G2	Q8NGK0	441
OTOP3	CCDC78	A2IDD5	435
OTOP3	FDXR	P22570	421
OTOP3	SMPDL3A	Q92484	419
OTOP3	SLC26A4	O43511	379
OTOP3	OLFM1	Q99784	378
OTOP3	TMEM82	A0PJX8	370
OTOP3	CLDN23	Q96B33	370
OTOP3	RNF157	Q96PX1	356

IntAct

25 interactions, top by confidence:

A	B	Type	Score
OTOP3	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
OTOP3	COMT	psi-mi:“MI:0915”(physical association)	0.560
OTOP3	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
OTOP3	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
	OTOP3	psi-mi:“MI:0915”(physical association)	0.560
OTOP3	FAM210B	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	OTOP3	psi-mi:“MI:0915”(physical association)	0.560
COMT	OTOP3	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	OTOP3	psi-mi:“MI:0915”(physical association)	0.560
EBP	OTOP3	psi-mi:“MI:0915”(physical association)	0.560
OTOP3		psi-mi:“MI:0915”(physical association)	0.000
OTOP3	TMEM237	psi-mi:“MI:0915”(physical association)	0.000
OTOP3	SLC13A4	psi-mi:“MI:0915”(physical association)	0.000
OTOP3	FAM210B	psi-mi:“MI:0915”(physical association)	0.000
OTOP3	ZFYVE27	psi-mi:“MI:0915”(physical association)	0.000
OTOP3	EBP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): OTOP3 (Two-hybrid), OTOP3 (Two-hybrid), OTOP3 (Two-hybrid), OTOP3 (Two-hybrid), OTOP3 (Two-hybrid), OTOP3 (Two-hybrid), OTOP3 (Two-hybrid), OTOP3 (Two-hybrid), OTOP3 (Positive 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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	114
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1265 predictions. Top by Δscore:

Variant	Effect	Δscore
17:74935941:G:GC	donor_loss	1.0000
17:74935942:T:A	donor_loss	1.0000
17:74941391:A:AG	acceptor_gain	1.0000
17:74941392:G:GG	acceptor_gain	1.0000
17:74941805:GCGGG:G	donor_gain	1.0000
17:74941807:GGG:G	donor_gain	1.0000
17:74941808:GG:G	donor_gain	1.0000
17:74941808:GGG:G	donor_gain	1.0000
17:74941809:GG:G	donor_gain	1.0000
17:74941810:G:T	donor_loss	1.0000
17:74941811:T:A	donor_loss	1.0000
17:74943343:AGG:A	donor_loss	1.0000
17:74943345:G:C	donor_loss	1.0000
17:74943346:T:G	donor_loss	1.0000
17:74943600:CCCCA:C	acceptor_loss	1.0000
17:74943601:CCCA:C	acceptor_loss	1.0000
17:74943602:CCAGG:C	acceptor_loss	1.0000
17:74943603:CAGGT:C	acceptor_loss	1.0000
17:74943605:GGT:G	acceptor_gain	1.0000
17:74943721:ACAG:A	donor_loss	1.0000
17:74943725:G:GA	donor_loss	1.0000
17:74946656:CCCAG:C	acceptor_loss	1.0000
17:74946658:CAGGC:C	acceptor_loss	1.0000
17:74946659:A:AG	acceptor_gain	1.0000
17:74946659:A:AT	acceptor_loss	1.0000
17:74946659:AG:A	acceptor_gain	1.0000
17:74946660:G:GG	acceptor_gain	1.0000
17:74946660:G:GT	acceptor_loss	1.0000
17:74946660:GG:G	acceptor_gain	1.0000
17:74946660:GGCA:G	acceptor_gain	1.0000

AlphaMissense

3717 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:74947469:T:A	N538K	0.990
17:74947469:T:G	N538K	0.990
17:74949249:T:A	W542R	0.990
17:74949249:T:C	W542R	0.990
17:74943646:T:A	W243R	0.985
17:74943646:T:C	W243R	0.985
17:74941722:T:A	W135R	0.983
17:74941722:T:C	W135R	0.983
17:74947255:T:C	F467S	0.982
17:74946789:T:A	W312R	0.981
17:74946789:T:C	W312R	0.981
17:74947014:A:C	S387R	0.981
17:74947016:T:A	S387R	0.981
17:74947016:T:G	S387R	0.981
17:74949363:T:C	F580L	0.980
17:74949365:C:A	F580L	0.980
17:74949365:C:G	F580L	0.980
17:74949375:C:G	H584D	0.979
17:74947033:G:A	G393D	0.978
17:74947254:T:C	F467L	0.978
17:74947256:C:A	F467L	0.978
17:74947256:C:G	F467L	0.978
17:74949370:G:C	R582P	0.977
17:74943611:G:A	G231D	0.976
17:74949391:T:C	L589P	0.976
17:74949378:T:C	S585P	0.975
17:74946791:G:C	W312C	0.974
17:74946791:G:T	W312C	0.974
17:74947250:C:A	N465K	0.972
17:74947250:C:G	N465K	0.972

dbSNP variants (sampled 300 via entrez): RS1000289210 (17:74943524 GC>G), RS1000985564 (17:74947922 C>T), RS1001195486 (17:74943418 G>A,C), RS1001238217 (17:74943759 A>C,G), RS1001263818 (17:74938384 A>G), RS1001279395 (17:74949113 G>A), RS1001373396 (17:74948585 A>T), RS1001695350 (17:74938552 C>A), RS1001720468 (17:74943045 C>T), RS1002061665 (17:74934390 C>A,G,T), RS1002092710 (17:74934714 T>C), RS1002535037 (17:74943914 C>G,T), RS1003192755 (17:74946680 T>C), RS1003537094 (17:74942343 A>G), RS1003622483 (17:74935730 C>A,G,T)

Disease associations

OMIM: gene MIM:607828 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011369_37	Iron status biomarkers (ferritin levels)	1.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004459	ferritin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
arsenite	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
Folic Acid	increases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1GT	Abcam A-549 OTOP3 KO 1	Cancer cell line	Male
CVCL_B2PC	Abcam A-549 OTOP3 KO 2	Cancer cell line	Male

Clinical trials (associated diseases)

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