OTOP3
protein-codingotopetrin 3
Gene summary
Predicted to enable identical protein binding activity and 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
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.1 kbGenCC 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 OTOP3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001272005.2. 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 | 4 | 4 | ||||
| missense | 117 | 8 | 125 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 117 | 12 | 0 | 129 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001258934.1 | 7 | MANE Select | |
| Ensembl | ENSP00000328090.5 | 7 | MANE Select | |
| RefSeq | NP_839947.1 | 7 | Standard | |
| Ensembl | ENSP00000626815.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- proton transmembrane transport
Molecular Function
- nucleic acid binding
- proton channel activity
Cellular Component
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000328801
- Coding exons
- 7
- Length
- 14274
- Individuals with no LoFs
- 125452
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 295
- Defined
- 125748
- p
- 0.00118
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.20 | 436 | 371 | 1.18 | 0.0000231 | 3772 |
| Missense (PolyPhen) | 151 | 133.81 | 1.1285 | 1472 | ||
| Synonymous | 0.527 | 155 | 164 | 0.948 | 0.0000106 | 1299 |
| Loss of Function | 0.984 | 19 | 24.2 | 0.784 | 0.00000134 | 236 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0011 | 0.0011 | notable |
| Latino/Admixed American | 0.0015 | 0.0015 | notable |
| Ashkenazi Jewish | 0.0028 | 0.0028 | notable |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.0011 | 0.0011 | notable |
| South Asian | 0.0018 | 0.0018 | notable |
| Other | 0.0011 | 0.00098 | notable |
dbNSFP Gene Annotations
Source:
- 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:Q80UF9}.;
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- LoFtool
- 0.781
- RVIS EVS
- 0.92
- RVIS percentile EVS
- 89.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0680
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |