MCOLN3
Mucolipin-3, a transient receptor potential channel involved in lysosomal function and autophagy
Gene Information Card
| Symbol | MCOLN3 |
|---|---|
| Full Name | mucolipin 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p22.3 |
| NCBI Gene ID | 55283 ncbi.nlm.nih.gov/gene/55283 |
| Ensembl ID | ENSG00000155755 |
| UniProt ID | Q8TDD5 |
| OMIM ID | 607400 |
| HGNC ID | 13357 |
| Aliases | TRPML3, ML3, MCOLN3 |
Description
MCOLN3 encodes mucolipin-3 (TRPML3), a member of the transient receptor potential (TRP) channel family localized to lysosomal and endosomal membranes. It functions as a non-selective cation channel permeable to Ca2+, Fe2+, and other ions, regulating lysosomal trafficking, autophagy, and iron homeostasis. Gain-of-function mutations cause hearing loss and pigmentation defects in mice, while human variants are linked to nonsyndromic hearing loss.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Nonsyndromic hearing loss (DFNA17-like) | Gain-of-function mutations in MCOLN3 lead to constitutive channel activity, disrupting lysosomal pH and autophagy in cochlear hair cells | ClinVar, OMIM |
| Age-related hearing loss | Altered MCOLN3 expression or function may contribute to progressive hearing loss | NCBI Gene, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Kidney | 8.2 | Low |
| Lung | 6.1 | Low |
| Brain | 4.3 | Low |
| Liver | 3.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | High expression in transfected cells |
| SH-SY5Y | 7.5 | Moderate expression |
| HeLa | 5.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1255G>A (p.Gly419Arg) | Missense | Rare | Gain-of-function; associated with hearing loss in mice |
| c.1610C>T (p.Thr537Ile) | Missense | Rare | Gain-of-function; reported in human hearing loss |
Mutation functional classification
Loss of Function (LOF)
Not well characterized; likely leads to impaired lysosomal ion homeostasis and autophagy defects.
Gain of Function (GOF)
Constitutive channel opening; causes lysosomal alkalinization, impaired autophagy, and hair cell degeneration.
Dominant Negative (DN)
Not reported for MCOLN3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Lysosomal ion homeostasis
• Autophagy
• TRP channel signaling
Protein Summary
Mucolipin-3 (TRPML3) is a 553-amino acid protein with six transmembrane domains and a large extracellular loop between S1 and S2. It forms homomultimeric channels in lysosomal membranes, regulating Ca2+ release from lysosomes, which is critical for lysosomal trafficking, fusion events, and autophagy. Gain-of-function mutations cause constitutive channel activity, leading to lysosomal dysfunction and cellular toxicity, particularly in sensory hair cells.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MCOLN3 Knockout HEK293 Cell Line | EDJ-KQ1625 | Human | 55283 | Details Get a Quote |
| MCOLN3 Knockout A-549 Cell Line | EDJ-KQ21324 | Human | 55283 | Details Get a Quote |
| MCOLN3 Knockout HCT 116 Cell Line | EDJ-KQ21325 | Human | 55283 | Details Get a Quote |
| MCOLN3 Knockout HeLa Cell Line | EDJ-KQ21326 | Human | 55283 | Details Get a Quote |
