OTOP2

protein-coding

otopetrin 2

Gene summary

Predicted to enable proton channel activity. Predicted to be involved in proton transmembrane transport. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_178160.3

Inheritance

—

ClinVar variants

U:92B:9

Top phenotype

Meniere disease

gnomAD constraint

pLI —, LoF o/e 0.97

Max pathogenic AF

—

Genomic locus

chr17:74,922,950-74,933,912

External References & Databases

Ensembl (ENSG00000183034)

Transcript & Mutation Effects

hg38 • Region Span ~11.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to OTOP2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 96

not providedTotal: 3

Meniere diseaseTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_178160.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense			92 clinvar	5 clinvar	2 clinvar	99
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	92	7	2	101

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_178160.3	RefSeq	NP_835454.1	6	MANE Select
ENST00000331427.9	Ensembl	ENSP00000332528.4	6	MANE Select
ENST00000580223.2	Ensembl	ENSP00000463837.2	3	Standard
ENST00000857247.1	Ensembl	ENSP00000527306.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proton transmembrane transport

Molecular Function

proton channel activity

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000331427
Coding exons: 6
Length: 9638
Individuals with no LoFs: 125654
Homozygous LoFs: 0
Heterozygous LoFs: 94
Defined: 125748
p: 0.000374

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.306	334	350	0.954	0.0000204	3634
Missense (PolyPhen)		102	112.36	0.90781		1221
Synonymous	0.662	145	156	0.932	0.00000999	1190
Loss of Function	0.108	21	21.5	0.975	0.00000119	201

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00081	0.00080	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00060	0.00060	rare
East Asian	0.00044	0.00044	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00046	0.00045	rare
South Asian	0.00023	0.00023	rare
Other	0.00082	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Proton-selective channel that specifically transports protons into cells. Proton-selective channel activity is probably required in cell types that use changes in intracellular pH for cell signaling or to regulate biochemical or developmental processes. {ECO:0000250|UniProtKB:Q80SX5}.;

Intolerance Scores

LoFtool: 0.823
RVIS EVS: -0.26
RVIS percentile EVS: 34.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.167

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium