LGI1

Protein identityUniProt · HPA

UniProt accession

O95970

Gene

LGI1

Ensembl

ENSG00000108231

Chromosome

10

Canonical length

557 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted secreted proteins

Secretome location

Secreted in brain

OverviewNCBI Gene

This gene encodes a member of the secreted leucine-rich repeat (LRR) superfamily and shares homology with members of the SLIT protein family. The encoded protein may regulate the activity of voltage-gated potassium channels and may be involved in neuronal growth regulation and cell survival. This gene is rearranged as a result of translocations in glioblastoma cell lines, and it is frequently down-regulated or rearranged in malignant gliomas. Mutations in this gene result in autosomal dominant lateral temporal epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

Canonical amino-acid sequenceUniProt

557 residues, UniProt reviewed canonical sequence.

>O95970|LGI1
     1  MESERSKRMG NACIPLKRIA YFLCLLSALL LTEGKKPAKP KCPAVCTCTK DNALCENARS
    61  IPRTVPPDVI SLSFVRSGFT EISEGSFLFT PSLQLLLFTS NSFDVISDDA FIGLPHLEYL
   121  FIENNNIKSI SRHTFRGLKS LIHLSLANNN LQTLPKDIFK GLDSLTNVDL RGNSFNCDCK
   181  LKWLVEWLGH TNATVEDIYC EGPPEYKKRK INSLSSKDFD CIITEFAKSQ DLPYQSLSID
   241  TFSYLNDEYV VIAQPFTGKC IFLEWDHVEK TFRNYDNITG TSTVVCKPIV IETQLYVIVA
   301  QLFGGSHIYK RDSFANKFIK IQDIEILKIR KPNDIETFKI ENNWYFVVAD SSKAGFTTIY
   361  KWNGNGFYSH QSLHAWYRDT DVEYLEIVRT PQTLRTPHLI LSSSSQRPVI YQWNKATQLF
   421  TNQTDIPNME DVYAVKHFSV KGDVYICLTR FIGDSKVMKW GGSSFQDIQR MPSRGSMVFQ
   481  PLQINNYQYA ILGSDYSFTQ VYNWDAEKAK FVKFQELNVQ APRSFTHVSI NKRNFLFASS
   541  FKGNTQIYKH VIVDLSA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LGI1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

69 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LGI1.

Disease | AllUniProt

Conditions LGI1 is implicated in, by any mechanism.

• Epilepsy, familial temporal lobe, 1 (ETL1) MIM:600512

Disease | GeneticClinVar

73 pathogenic / likely-pathogenic of 568 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal dominant epilepsy with auditory features
• Epilepsy, familial temporal lobe, 1
• Developmental and epileptic encephalopathy 121
• Inborn genetic diseases
• Seizure

Disease | AutoantibodyPubMed

Conditions in which antibodies against LGI1 are reported. Each links to that disease's full target list.

• Encephalitis 107
• Limbic Encephalitis 81
• Hashimoto Disease 51
• Seizures 44
• Autoimmune Diseases of the Nervous System 28
• Epilepsy 15
• Brain Diseases 9
• Neoplasm Recurrence, Local 6
• Pain 4
• Psychotic Disorders 4
• Peripheral Nervous System Diseases 3
• Thymoma 3

Showing 12 of 23 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for LGI1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.19

gnomAD pLI

1

gnomAD missense Z

2.78

DepMap mean gene effect

-0.1

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• axon guidance
• nervous system development
• neuron projection development
• neurotransmitter receptor localization to postsynaptic specialization membrane
• positive regulation of cell growth
• positive regulation of synaptic transmission

Molecular functions

• receptor ligand activity
• signaling receptor binding

Cellular components

• axon initial segment
• cytoplasm
• dendrite
• endoplasmic reticulum
• extracellular region
• extracellular space
• glutamatergic synapse
• Golgi apparatus
• synaptic cleft

Protein domainsUniProt · Pfam · InterPro

• Cysteine-rich flanking region, C-terminal
• Leucine-rich repeat
• Leucine-rich repeat, typical subtype
• Leucine-rich glioma-inactivated , EPTP repeat
• EAR
• Leucine-rich repeat domain superfamily
• Leucine-rich glioma-inactivated/LGI-related
• EPTP domain
• Leucine rich repeat

KeywordsUniProt

• Cytoplasm
• Endoplasmic reticulum
• Epilepsy
• Glycoprotein
• Golgi apparatus
• Leucine-rich repeat
• Repeat
• Secreted
• Signal
• Synapse

InteractionsUniProt · HPA

Protein binding partners of LGI1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• KCNA4
• KCNAB1
• ADAM11
• ADAM22
• DLG4