On this page
MLC1
modulator of VRAC current 1
The MLC1 gene provides instructions for a protein primarily found in the brain, where it is thought to be involved in fluid balance and cell adhesion. The MLC1 gene encodes a protein called modulator of VRAC current 1, which is found predominantly in brain cells, specifically astroglial cells.
MLC1 is located on the long (q) arm of chromosome 22, at band 22q13.33. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 22 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The MLC1 gene, also known as modulator of VRAC current 1, is essential for proper brain development and function. It provides genetic instructions for a protein expressed mainly in the brain, but also in the spleen and white blood cells.
Within the brain, the MLC1 protein is located in astroglial cells, which are a specialised type of glial cell that supports and protects neurons. Abnormalities in the MLC1 gene are primarily associated with megalencephalic leukoencephalopathy with subcortical cysts, a rare inherited neurological disorder.
What the gene does
The MLC1 protein functions at the junctions between neighbouring astroglial cells in the brain. While its exact role at these cell junctions is still being investigated, research suggests it may control the movement of fluids into cells or influence the strength of cell-to-cell attachment, a process known as cell adhesion.
Furthermore, studies indicate that the MLC1 protein could be involved in transporting molecules across critical protective barriers in the brain, such as the blood-brain barrier and the brain-cerebrospinal fluid barrier. These barriers regulate which substances can enter the brain's delicate nerve tissue, safeguarding its health and function.
Video: Genetics 101
Chromosome location
The MLC1 gene is located on chromosome 22, specifically at position 22q13.33. This gene's precise location on the long arm of chromosome 22 helps in understanding its genetic context and how changes in this region can impact health.
Protein structure
The MLC1 protein consists of 377 amino acids. It contains a Disordered region located at amino acid positions 1-36. The specific functions of other potential domains within the protein are still under investigation.
Key variants
Variants within the MLC1 gene can alter the protein's structure or function, leading to its association with inherited conditions. These genetic changes can range from single nucleotide substitutions to larger deletions or insertions, each potentially affecting the protein's ability to perform its normal cellular roles.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.135del | p.Cys46fs | Pathogenic | ★★☆☆ | Megalencephalic leukoencephalopathy with subcortical cysts |
c.177+1del | - | Pathogenic/Likely pathogenic | ★★☆☆ | Megalencephalic leukoencephalopathy with subcortical cysts |
c.359C>T | p.Ala120Val | Pathogenic/Likely pathogenic | ★★☆☆ | Megalencephalic leukoencephalopathy with subcortical cysts |
c.597+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Megalencephalic leukoencephalopathy with subcortical cysts |
c.736del | p.Ser246fs | Pathogenic | ★★☆☆ | Megalencephalic leukoencephalopathy with subcortical cysts 1 |
c.772-1G>C | - | Pathogenic | ★★☆☆ | Megalencephalic leukoencephalopathy with subcortical cysts 1 |
c.849del | p.Ile283_Met284insTer | Pathogenic/Likely pathogenic | ★★☆☆ | Megalencephalic leukoencephalopathy with subcortical cysts |
c.894+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Megalencephalic leukoencephalopathy with subcortical cysts 1 |
c.908_918delinsGCA | p.Val303fs | Pathogenic | ★★☆☆ | Inborn genetic diseases |
c.976T>C | p.Cys326Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Megalencephalic leukoencephalopathy with subcortical cysts |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the MLC1 gene are a primary cause of Megalencephalic leukoencephalopathy with subcortical cysts. This condition affects brain development and function, often leading to problems with movement, balance, and in some cases, recurrent seizures. It accounts for a significant proportion of cases of this specific leukoencephalopathy.
UK clinical status
The MLC1 gene is included in several NHS England Genomic Medicine Service clinical panels, indicating its recognised clinical importance within the UK. It is categorised as 'green' in panels such as DDG2P, Early onset or syndromic epilepsy, Foetal anomalies (R21), Inherited white matter disorders, Intellectual disability, and White matter disorders and cerebral calcification - childhood onset, signifying that there is strong evidence for its association with disease.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the MLC1 gene?
The MLC1 gene produces a protein primarily found in astroglial cells of the brain. It is believed to be involved in regulating fluid movement into cells and maintaining the connections between neighbouring brain cells, which are crucial for normal brain function.
Which condition is most commonly associated with MLC1 gene variants?
Variants in the MLC1 gene are most commonly associated with Megalencephalic leukoencephalopathy with subcortical cysts. This is an inherited neurological disorder that impacts brain development and function, often causing issues with movement.
Where is the MLC1 protein found in the body?
The MLC1 protein is primarily found in the brain, specifically within astroglial cells. It is also detected in other tissues such as the spleen and white blood cells, though its main function is understood to be within the central nervous system.
References
- Capdevila-Nortes X, López-Hernández T, Apaja PM. Insights into MLC pathogenesis: GlialCAM is an MLC1 chaperone required for proper activation of volume-regulated anion currents. Human molecular genetics. 2013. PMID: 23793458
- López-Hernández T, Sirisi S, Capdevila-Nortes X. Molecular mechanisms of MLC1 and GLIALCAM mutations in megalencephalic leukoencephalopathy with subcortical cysts. Human molecular genetics. 2011. PMID: 21624973
- Montagna G, Teijido O, Eymard-Pierre E. Vacuolating megalencephalic leukoencephalopathy with subcortical cysts: functional studies of novel variants in MLC1. Human mutation. 2006. PMID: 16470554
- Ilja Boor PK, de Groot K, Mejaski-Bosnjak V. Megalencephalic leukoencephalopathy with subcortical cysts: an update and extended mutation analysis of MLC1. Human mutation. 2006. PMID: 16652334
- Boor PK, de Groot K, Waisfisz Q. MLC1: a novel protein in distal astroglial processes. Journal of neuropathology and experimental neurology. 2005. PMID: 15892299