MLC1: Megalencephalic Leukoencephalopathy with Subcortical Cysts 1
A key gene in astrocytic volume regulation and myelin maintenance
Gene Information Card
| Symbol | MLC1 |
|---|---|
| Full Name | Megalencephalic Leukoencephalopathy with Subcortical Cysts 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 22q13.33 |
| NCBI Gene ID | 23209 ncbi.nlm.nih.gov/gene/23209 |
| Ensembl ID | ENSG00000100427 |
| UniProt ID | Q15049 |
| OMIM ID | 605908 |
| HGNC ID | 17082 |
| Aliases | KIAA0027, MLC, VLDLR |
Description
The MLC1 gene encodes a membrane protein predominantly expressed in astrocytes of the brain. It is involved in ion and water homeostasis, astrocyte volume regulation, and maintenance of myelin integrity. Mutations in MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare autosomal recessive leukodystrophy characterized by macrocephaly, motor deterioration, and cystic white matter changes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Megalencephalic Leukoencephalopathy with Subcortical Cysts (MLC) | Loss-of-function mutations in MLC1 disrupt astrocytic volume regulation and ion transport, leading to myelin vacuolation and cyst formation. | ClinVar, OMIM |
| Leukoencephalopathy, Megalencephalic, with or without Cysts | Same mechanism as MLC; allelic heterogeneity. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Cerebral cortex | 15.2 | Medium |
| Cerebellum | 10.8 | Medium |
| Spinal cord | 8.3 | Low |
| Heart | 1.2 | Not detected |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Astrocytes (primary) | 18.0 | High expression; key cell type |
| SH-SY5Y | 2.1 | Low neuronal expression |
| HEK293 | 0.8 | Not detected |
| U87MG | 14.5 | Glioblastoma cell line; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.135C>G (p.Cys45Trp) | Missense | Common in MLC | Loss of function; impaired protein trafficking |
| c.276G>A (p.Trp92Ter) | Nonsense | Rare | Loss of function; premature truncation |
| c.593T>C (p.Leu198Pro) | Missense | Rare | Loss of function; structural disruption |
| c.895C>T (p.Arg299Ter) | Nonsense | Rare | Loss of function; nonsense-mediated decay |
Mutation functional classification
Loss of Function (LOF)
Majority of MLC1 mutations result in loss of protein function, leading to impaired astrocytic volume regulation and myelin vacuolation.
Gain of Function (GOF)
No evidence of gain-of-function mutations in MLC1.
Dominant Negative (DN)
No dominant-negative effects reported; MLC1 is recessive.
View complete mutation data：
Gene Ontology (GO)
| • chloride channel activity (GO:0005254) | • protein binding (GO:0005515) |
| • plasma membrane (GO:0005886) | • integral component of membrane (GO:0016021) |
| • axon (GO:0030424) | • neuron projection (GO:0043005) |
| • myelin sheath (GO:0043209) | • transmembrane transport (GO:0055085) |
Pathways
• Ion transport by P-type ATPases (Reactome: R-HSA-936837)
• Astrocytic volume regulation (inferred)
Protein Summary
The MLC1 protein is a 377-amino acid membrane protein with eight transmembrane domains. It localizes to the plasma membrane of astrocytes, particularly at endfeet contacting blood vessels and at the nodes of Ranvier. MLC1 interacts with the Na+/K+ ATPase and the chloride channel ClC-2, contributing to ion and water homeostasis in the brain. Loss of MLC1 function leads to impaired astrocyte volume regulation, myelin vacuolation, and the clinical phenotype of megalencephalic leukoencephalopathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MLC1 Knockout HEK293 Cell Line | EDJ-KQ7893 | Human | 23209 | Details Get a Quote |
| MLC1 Knockout HeLa Cell Line | EDJ-KQ55705 | Human | 23209 | Details Get a Quote |
| MLC1 Knockout A-549 Cell Line | EDJ-KQ64202 | Human | 23209 | Details Get a Quote |
| MLC1 Knockout HCT 116 Cell Line | EDJ-KQ72647 | Human | 23209 | Details Get a Quote |
