OTOP3

Chr 17

otopetrin 3

NCBI Gene: 347741ENSG00000182938UniProt: Q7RTS5

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. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
13
Pathogenic / LP
151
ClinVar variants
2
Pubs (1 yr)
-1.2
Missense Z
1.15
LOEUF
Clinical Summary— OTOP3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 125 VUS of 151 total submissions
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.15LOEUF
pLI 0.000
Z-score 0.98
OE 0.78 (0.55–1.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.20Z-score
OE missense 1.18 (1.09–1.27)
436 obs / 371.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.78 (0.55–1.15)
0≤0.351.4
Missense OE1.18 (1.09–1.27)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 19 / 24.2Missense obs/exp: 436 / 371.0Syn Z: 0.53
GOFDN
DN
0.6649th %ile
GOF
0.77top 25%
LOF
0.3648th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

151 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic1
VUS125
Likely Benign13
12
Pathogenic
1
Likely Pathogenic
125
VUS
13
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
1
0
1
VUS
0
121
4
0
125
Likely Benign
0
9
0
4
13
Benign
0
0
0
0
0
Total0130174151

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

OTOP3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

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
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
OTOP3 functions as an oncogenic regulator of ferroptosis-mediated colorectal cancer progression.
Lee YJ et al.·Genes Genomics
2025
Activation of mouse Otop3 proton channels by Zn2.
Fujii T et al.·Biochem Biophys Res Commun
2023Functional
Structures of the otopetrin proton channels Otop1 and Otop3.
Saotome K et al.·Nat Struct Mol Biol
2019Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients