Leucine-rich, glioma inactivated 1, also known as LGI1, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
which in humans is encoded by the ''LGI1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
It may be a
metastasis suppressor.
Function
The leucine-rich glioma inactivated -1 gene is rearranged as a result of translocations in
glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nons ...
cell lines. The protein contains a hydrophobic segment representing a putative transmembrane domain with the amino terminus located outside the cell. It also contains leucine-rich repeats with conserved cysteine-rich flanking sequences. This gene is predominantly expressed in neural tissues and its expression is reduced in low grade brain tumors and significantly reduced or absent in malignant gliomas.
Clinical significance
Since its earliest discovery, the LGI1 gene has been implicated in the control of cancer
metastasis
Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...
and in a predisposition to
epilepsy
Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...
. Following genetic linkage studies placing the hereditary form of
autosomal dominant partial epilepsy with auditory features (
ADPEAF) on chromosome region 10q24
mutation analysis of affected members in these families
demonstrated LGI1 was a major cause of the disease.
More recently, LGI1 has been shown to be the major target of human autoantibodies
which immunoprecipitate voltage-gated potassium channel complexes from mammalian brain tissue. LGI1 antibodies are found in patients with
limbic encephalitis
Limbic encephalitis is a form of encephalitis, a disease characterized by inflammation of the brain. Limbic encephalitis is caused by autoimmunity: an abnormal state where the body produces antibodies against itself. Some cases are associated with ...
and in patients with
faciobrachial dystonic seizures (
FBDS). FBDS are a recently described form of epilepsy which is characterized by frequent, brief seizures which affect the arm and face. They appear to be preferentially responsive to immunotherapy over anti-epileptic drugs.
Interactions
LGI1 has been shown to
interact with
ADAM22,
[ and ]DLG4
PSD-95 (postsynaptic density protein 95) also known as SAP-90 (synapse-associated protein 90) is a protein that in humans is encoded by the ''DLG4'' (discs large homolog 4) gene.
PSD-95 is a member of the membrane-associated guanylate kinase (MA ...
.
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Autosomal Dominant Partial Epilepsy with Auditory Features