OTOP2
Chr 17otopetrin 2
Proton-selective ion channel open at neutral pH. Active at neutral and alkaline extracellular pH, likely participates in some alkali-related physiological activities
Clinical Summary— OTOP2
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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.40LOEUF
pLI 0.000
Z-score 0.11
OE 0.97 (0.69–1.40)
Highly tolerant — LoF variants common in population
Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.31Z-score
OE missense 0.95 (0.87–1.04)
334 obs / 350.1 exp
Mild missense constraint
Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.97 (0.69–1.40)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.87–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 21 / 21.5Missense obs/exp: 334 / 350.1Syn Z: 0.66
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
OTOP2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
OTOPETRIN 2; OTOP2
MIM #607827 · *
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
Non-invasive diagnosis of esophageal cancer by a simplified circulating cell-free DNA methylation assay targeting OTOP2 and KCNA3: a double-blinded, multicenter, prospective study.
Bian Y et al.·J Hematol Oncol
2024Clinical trial
Rare Coding Variants in Patients with Non-Syndromic Vestibular Dysfunction.
Sumalde AAM et al.·Genes (Basel)
2023Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Determination of the Immunomodulatory Role of OTOP2 in Colon Adenocarcinoma.
Lu C et al.·J Cancer
2024Open Access
Genome-wide methylation profiling identified methylated KCNA3 and OTOP2 as promising diagnostic markers for esophageal squamous cell carcinoma.
Bian Y et al.·Chin Med J (Engl)
2024Open Access
OTOP2, Inversely Modulated by miR-3148, Inhibits CRC Cell Migration, Proliferation and Epithelial-Mesenchymal Transition: Evidence from Bioinformatics Data Mining and Experimental Verification.
Guo S et al.·Cancer Manag Res
2022Open Access
Wild-type p53 regulates OTOP2 transcription through DNA loop alteration of the promoter in colorectal cancer.
Qu H et al.·FEBS Open Bio
2019Open Access
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
Structural motifs for subtype-specific pH-sensitive gating of vertebrate otopetrin proton channels
Teng B et al.·Elife
2022
Correction: Non-invasive diagnosis of esophageal cancer by a simplified circulating cell-free DNA methylation assay targeting OTOP2 and KCNA3: a double-blinded, multicenter, prospective study
Bian Y et al.·J Hematol Oncol
2024
CFTR High Expresser BEST4+ cells are pH-sensing neuropod cells: new implications for intestinal physiology and Cystic Fibrosis disease.
Dos Reis DC et al.·Am J Physiol Cell Physiol
2025
Structural mechanism of proton conduction in otopetrin proton channel.
Gan N et al.·Nat Commun
2024Functional
CFTR High Expresser BEST4+ cells are pH-sensing neuropod cells: new implications for intestinal physiology and Cystic Fibrosis disease.
Dos Reis DC et al.·bioRxiv
2025
Single-cell atlas in the living fossil Yangtze sturgeon provides insight into the evolution of fish.
Chen Y et al.·Genome Biol
2025
Top 6 full-text resultsSearch PubTator3 ↗
External Resources
Links to major genomics databases and tools