MCOLN3

Chr 1

mucolipin TRP cation channel 3

Also known as: TRP-ML3, TRPML3

NCBI Gene: 55283ENSG00000055732UniProt: Q8TDD5

This gene encodes one of members of the mucolipin cation channel proteins. Mutation studies of the highly similar protein in mice have shown that the protein is found in cochlea hair cells, and mutant mice show early-onset hearing loss and balance problems. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

Research Assistant →
0
Active trials
8
Pubs (1 yr)
16
P/LP submissions
0%
P/LP missense
0.94
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— MCOLN3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 65 VUS of 94 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.82
OE 0.65 (0.46–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.62Z-score
OE missense 0.90 (0.81–0.99)
260 obs / 289.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.65 (0.46–0.94)
0≤0.351.4
Missense OE0.90 (0.81–0.99)
0≤0.61.4
Synonymous OE0.82
0≤1.21.6
LoF obs/exp: 21 / 32.1Missense obs/exp: 260 / 289.8Syn Z: 1.43
DN
0.78top 25%
GOF
0.81top 10%
LOF
0.1895th %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

94 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic2
VUS65
Likely Benign2
14
Pathogenic
2
Likely Pathogenic
65
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
2
0
2
VUS
0
63
2
0
65
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Total06418183

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

View in ClinVar →

Protein Context — Lollipop Plot

MCOLN3 · 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.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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