LGI4 (Leucine Rich Repeat LGI Family Member 4)
A key regulator of peripheral nerve myelination and Schwann cell function
Gene Information Card
| Symbol | LGI4 |
|---|---|
| Full Name | Leucine Rich Repeat LGI Family Member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.12 |
| NCBI Gene ID | 163175 ncbi.nlm.nih.gov/gene/163175 |
| Ensembl ID | ENSG00000153902 |
| UniProt ID | Q8IYW5 |
| OMIM ID | 608303 |
| HGNC ID | 18712 |
| Aliases | KIAA1909, LGI4, MGC138290 |
Description
LGI4 (Leucine Rich Repeat LGI Family Member 4) is a protein-coding gene that encodes a secreted protein belonging to the leucine-rich repeat (LRR) superfamily. The protein is essential for peripheral nerve myelination, specifically mediating the interaction between Schwann cells and axons. LGI4 binds to the ADAM22 receptor on Schwann cells to promote myelination and is critical for proper nerve conduction and motor function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary motor and sensory neuropathy (HMSN) / Charcot-Marie-Tooth disease | Loss-of-function mutations in LGI4 disrupt Schwann cell-axon interaction, impairing myelination of peripheral nerves. | ClinVar, OMIM |
| Arthrogryposis multiplex congenita (AMC) with peripheral neuropathy | Biallelic LGI4 mutations lead to severe congenital neuropathy and joint contractures. | OMIM, PubMed |
| Peripheral nerve hypomyelination | LGI4 deficiency results in reduced myelin thickness and abnormal nerve conduction. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Peripheral nerve | 12.5 | Medium |
| Brain | 8.2 | Low |
| Spinal cord | 6.0 | Low |
| Testis | 3.1 | Low |
| Skeletal muscle | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Schwann cells (primary) | 15.0 | High expression; key for myelination |
| HEK293 | 0.5 | Low expression |
| SH-SY5Y | 1.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1072C>T (p.Arg358*) | Nonsense | Rare | Loss of function; truncated protein |
| c.1246G>A (p.Gly416Arg) | Missense | Rare | Loss of function; impaired ADAM22 binding |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein production |
Mutation functional classification
Loss of Function (LOF)
Most LGI4 mutations are loss-of-function, leading to reduced or absent protein activity, impairing Schwann cell myelination and causing peripheral neuropathy.
Gain of Function (GOF)
No gain-of-function mutations have been reported for LGI4.
Dominant Negative (DN)
No dominant-negative mutations have been described for LGI4.
View complete mutation data：
Gene Ontology (GO)
| • extracellular region (GO:0005576) | • protein binding (GO:0005515) |
| • axon ensheathment (GO:0008366) | • myelination (GO:0042552) |
| • chemical synaptic transmission (GO:0007268) |
Pathways
• LGI4-ADAM22 signaling in peripheral nerve myelination
• Neuregulin-ErbB signaling pathway (indirect)
Protein Summary
The LGI4 protein is a secreted glycoprotein containing leucine-rich repeats (LRRs) and a C-terminal domain. It is primarily expressed in Schwann cells and acts as a ligand for the ADAM22 receptor on the Schwann cell surface. Binding of LGI4 to ADAM22 triggers intracellular signaling that promotes myelination of peripheral axons. Loss of LGI4 function leads to severe hypomyelination and peripheral neuropathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LGI4 Knockout HEK293 Cell Line | EDJ-KQ14062 | Human | 163175 | Details Get a Quote |
| LGI4 Knockout HeLa Cell Line | EDJ-KQ58854 | Human | 163175 | Details Get a Quote |
| LGI4 Knockout A-549 Cell Line | EDJ-KQ67343 | Human | 163175 | Details Get a Quote |
| LGI4 Knockout HCT 116 Cell Line | EDJ-KQ75737 | Human | 163175 | Details Get a Quote |
