Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.
Reference Guide
  /  
MLC1
Sign up free to test for 
MLC1
.
One login for 30+ lab companies.

MLC1

The MLC1 gene encodes a membrane protein essential in brain astrocytes and monocytes, playing a critical role in various cellular processes including ion transport and maintaining the blood-brain barrier. 

Mutations in MLC1 are linked to megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare neurological disorder marked by brain swelling and cysts, manifesting in early childhood with developmental delays and progressive neurological decline. 

The protein's interaction with the TRPV4 channel and its involvement in cellular morphology and signal transmission underscore its complex functionality in cellular health and disease.  Understanding MLC1's pathophysiology continues to be crucial for developing targeted therapies for MLC.

Understanding MLC1 [1., 2., 8.]

The MLC1 gene encodes a 377-amino acid membrane protein with eight predicted transmembrane domains.  The MLC1 protein is highly expressed in brain astrocytes (star-shaped glial cells that support and nourish neurons) and in circulating blood cells, particularly monocytes.  

Mutations in the MLC1 gene have been associated with megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare neurologic disorder in children.  These mutations hamper the normal trafficking and distribution of MLC1 in cell membranes, leading to enhanced degradation.  

MLC1 functionally cooperates with the TRPV4 cation channel, and pathological mutations can lead to dysregulation.  The exact function of MLC1 is not fully understood, but studies suggest its involvement in ion transport, cell volume regulation, and maintenance of the blood-brain barrier integrity.

In summary, the MLC1 gene encodes a membrane protein that is highly expressed in astrocytes and blood cells.  Mutations in MLC1 are associated with the rare leukodystrophy MLC, likely by disrupting the protein's trafficking and function, potentially through interactions with ion channels like TRPV4.

Role of MLC1 in Astrocyte Physiology

The physiological function of MLC1 extends beyond its classical association with megalencephalic leukoencephalopathy. 

There is strong scientific evidence supporting the critical role of MLC1 in regulating astrocyte morphology, function, and interactions with neighboring cells.  

For example, research indicates that MLC1 is present in distal astrocyte processes, also known as perisynaptic astrocyte processes (PAPs), which closely interact with excitatory synapses.

Loss of MLC1 affects glutamatergic synaptic transmission, resulting in reduced spontaneous release events and slower glutamate re-uptake.  [5.].

Additionally, altered MLC1 expression and localization leads to changes in cellular morphology and motility through actin remodeling.  MLC1 overexpression induces filopodia formation and suppresses motility, while knockdown of Mlc1 in mice promotes lamellipodia formation and increased membrane ruffling of astrocytes.  [4.]

MLC1 also acts as a negative regulator of actin branching.  Misallocation of pathogenic mutant MLC1 may disturb stable cell-cell communication and the homeostatic regulation of astrocytes in patients with MLC.  [4.]

MLC1-expressing perivascular astrocytes promote blood-brain barrier integrity. Mlc1 encodes an integral membrane protein that interacts with adhesion proteins like GlialCAM, chloride channels like CLCN2, and gap junction proteins like connexin 43.  [7.] 

Implications of MLC1 Dysfunction

Megalencephalic Leukoencephalopathy with Subcortical Cysts (MLC) [3., 6.]

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare genetic disorder characterized by cerebral white matter edema, macrocephaly, and the presence of subcortical cysts.  

It usually presents in infancy with an abnormally large head circumference and mild developmental delays.  Over time, patients with classic MLC experience slow neurological deterioration, including ataxia, spasticity, seizures, and cognitive decline. 

Brain MRI shows characteristic abnormalities, including swollen white matter and subcortical cysts.  Genetic testing reveals pathogenic variants in the MLC1 gene in approximately 75% of patients and the GLIALCAM gene in 20%.

Loss-of-function mutations in the MLC1 gene lead to folding defects and altered trafficking of the MLC1 protein, disrupting astrocyte function and brain ion and water homeostasis.

Pathogenic variants in GLIALCAM, which encodes a protein that interacts with MLC1, can also cause MLC.

There is currently no cure for MLC, and treatment is focused on managing symptoms as they arise, including physical therapy, anti-seizure medication, and preventing head trauma.  The prognosis varies, with some patients losing the ability to walk as teenagers, while others have milder courses.

Research into the molecular pathogenesis of MLC aims to identify potential treatments for this devastating disorder.

Genetic Alterations in the MLC1 Gene

The gene for the MLC1 protein may contain alterations or mutations that cause alterations of function of the MLC1 protein.  

Testing for genetic alterations in the form of SNPs is increasingly available and can shed light on an individual’s potential for health and disease.  

What is a SNP?

A SNP, or single nucleotide polymorphism, refers to a variation at a single position in a gene along its DNA sequence.  A gene encodes a protein, so an alteration in that gene programs the production of an altered protein.  

As a type of protein with great functionality in human health, alterations in genes for enzymes may confer a difference in function of that enzyme.  The function of that enzyme may be increased or decreased, depending on the altered protein produced.  

SNPs are the most common type of genetic variation in humans and can occur throughout the genome, influencing traits, susceptibility to diseases, and response to medications.

The completion of the Human Genome Project has significantly expanded opportunities for genetic testing by providing a comprehensive map of the human genome that facilitates the identification of genetic variations associated with various health conditions, including identifying SNPs that may cause alterations in protein structure and function.  

Genetic testing for SNPs enables the identification of alterations in genes, shedding light on their implications in health and disease susceptibility.

Laboratory Testing for MLC1

Genetic testing for single nucleotide polymorphisms (SNPs) typically involves obtaining a sample of DNA which can be extracted from blood, saliva, or cheek swabs. 

The sample may be taken in a lab, in the case of a blood sample.  Alternatively, a saliva or cheek swab sample may be taken from the comfort of home. 

Test Preparation

Prior to undergoing genetic testing, it's important to consult with a healthcare provider or genetic counselor to understand the purpose, potential outcomes, and implications of the test.  This consultation may involve discussing medical history, family history, and any specific concerns or questions. 

Additionally, individuals may be advised to refrain from eating, drinking, or chewing gum for a short period before providing a sample to ensure the accuracy of the test results.  Following sample collection, the DNA is processed in a laboratory where it undergoes analysis to identify specific genetic variations or SNPs. 

Once the testing is complete, individuals will typically receive their results along with interpretation and recommendations from a healthcare professional. 

It's crucial to approach genetic testing with proper understanding and consideration of its implications for one's health and well-being.

Patient-Centric Approaches

A patient-centered approach to SNP genetic testing emphasizes individualized medicine, tailoring healthcare decisions and interventions based on an individual's unique genetic makeup.

When that is combined with the individual’s health status and health history, preferences, and values, a truly individualized plan for care is possible. 

By integrating SNP testing into clinical practice, healthcare providers can offer personalized risk assessment, disease prevention strategies, and treatment plans that optimize patient outcomes and well-being. 

Genetic testing empowers a deeper understanding of genetic factors contributing to disease susceptibility, drug response variability, and overall health, empowering patients to actively participate in their care decisions. 

Furthermore, individualized medicine recognizes the importance of considering socioeconomic, cultural, and environmental factors alongside genetic information to deliver holistic and culturally sensitive care that aligns with patients' goals and preferences. 

Through collaborative decision-making and shared decision-making processes, patients and providers can make informed choices about SNP testing, treatment options, and lifestyle modifications, promoting patient autonomy, engagement, and satisfaction in their healthcare journey.

Genetic Panels and Combinations

Integrating multiple biomarkers into panels or combinations enhances the predictive power and clinical utility of pharmacogenomic testing.  

Biomarker panels comprising a variety of transporter proteins and enzymes including drug metabolizing enzymes offer comprehensive insights into individual drug response variability and treatment outcomes. 

Combining genetic SNP testing associated with drug transport, metabolism, and pharmacodynamics enables personalized medicine approaches tailored to individual patient characteristics and genetic profiles.

Order Genetic Testing

Click here to compare genetic test panels and order genetic testing for health-related SNPs. 

What's 
MLC1
?
If Your Levels Are High
Symptoms of High Levels
If Your Levels are Low
Symptoms of Low Levels

Hey providers! 👋 Join us for Fullscript Forward, a free virtual Health & Tech Summit on Friday, June 13, designed to help you level up your care with smarter tools, sharper insights, and cutting-edge strategies. Whether you're diving deeper into women’s health, optimizing supplement protocols, improving patient outcomes with adherence tools, or staying ahead with the latest in labs and diagnostics, this summit is built to support your clinical expertise and practice growth. Register Today!

Register Here
See References

[1.] Ambrosini E, Serafini B, Lanciotti A, Tosini F, Scialpi F, Psaila R, Raggi C, Di Girolamo F, Petrucci TC, Aloisi F. Biochemical characterization of MLC1 protein in astrocytes and its association with the dystrophin-glycoprotein complex. Mol Cell Neurosci. 2008 Mar;37(3):480-93. doi: 10.1016/j.mcn.2007.11.003. Epub 2007 Nov 17. PMID: 18165104.

[2.] Brignone MS, Lanciotti A, Camerini S, et al. MLC1 protein: a likely link between leukodystrophies and brain channelopathies. Frontiers in Cellular Neuroscience. 2015;09. doi:https://doi.org/10.3389/fncel.2015.00106

[3.] Hamilton EM, Pinar Tekturk, Cialdella F, et al. Megalencephalic leukoencephalopathy with subcortical cysts. 2018;90(16):e1395-e1403. doi:https://doi.org/10.1212/wnl.0000000000005334

[4.] Hwang J, Vu HM, Kim MS, Lim HH. Plasma membrane localization of MLC1 regulates cellular morphology and motility. Molecular Brain. 2019;12(1). doi:https://doi.org/10.1186/s13041-019-0540-6‌

[5.] Kater MSJ, Baumgart KF, Badia-Soteras A, Heistek TS, Carney KE, Timmerman AJ, van Weering JRT, Smit AB, van der Knaap MS, Mansvelder HD, Verheijen MHG, Min R. A novel role for MLC1 in regulating astrocyte-synapse interactions. Glia. 2023 Jul;71(7):1770-1785. doi: 10.1002/glia.24368. Epub 2023 Apr 1. PMID: 37002718.

[6.] Megalencephalic Leukoencephalopathy with subcortical Cysts (MLC). United Leukodystrophy Foundation. Accessed May 8, 2024. https://ulf.org/leukodystrophies/megalencephalic-leukoencephalopathy-with-subcortical-cysts-mlc/

[7.] Morales JE, De A, Miller AA, Chen Z, McCarty JH. Mlc1-Expressing Perivascular Astrocytes Promote Blood-Brain Barrier Integrity. The Journal of Neuroscience. Published online December 29, 2021:JN-RM-1918-21. doi:https://doi.org/10.1523/jneurosci.1918-21.2021

[8.] Petrini S, Minnone G, Coccetti M, Frank C, Aiello C, Cutarelli A, Ambrosini E, Lanciotti A, Brignone MS, D'Oria V, Strippoli R, De Benedetti F, Bertini E, Bracci-Laudiero L. Monocytes and macrophages as biomarkers for the diagnosis of megalencephalic leukoencephalopathy with subcortical cysts. Mol Cell Neurosci. 2013 Sep;56:307-21. doi: 10.1016/j.mcn.2013.07.001. Epub 2013 Jul 10. PMID: 23851226.

Test for

MLC1

No items found.
Order, track, and receive results from 30+ labs in one place.