LGI1
leucine rich glioma inactivated 1, the group of LGI family
Basic information
Region (hg38): 10:93757840-93806272
Previous symbols: [ "EPT" ]
Links
Phenotypes
GenCC
Source:
- epilepsy, familial temporal lobe, 1 (Strong), mode of inheritance: AD
- autosomal dominant epilepsy with auditory features (Supportive), mode of inheritance: AD
- autosomal dominant epilepsy with auditory features (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Epilepsy, familial temporal lobe, 1 | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Neurologic | 8773604; 11906506; 12205652; 11810107; 15079010; 15079011; 17562837; 19064878; 20301709; 21444903; 21504429; 22496201 |
ClinVar
This is a list of variants' phenotypes submitted to
- Autosomal_dominant_epilepsy_with_auditory_features (378 variants)
- not_provided (134 variants)
- Inborn_genetic_diseases (71 variants)
- Epilepsy,_familial_temporal_lobe,_1 (58 variants)
- not_specified (19 variants)
- LGI1-related_disorder (6 variants)
- Seizure (4 variants)
- Intellectual_disability (2 variants)
- Autosomal_dominant_epilepsy (1 variants)
- Bilateral_tonic-clonic_seizure (1 variants)
- Genitopatellar_syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the LGI1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005097.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 126 | 130 | ||||
| missense | 241 | 14 | 267 | |||
| nonsense | 15 | 18 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 12 | 13 | 26 | |||
| splice donor/acceptor (+/-2bp) | 10 | |||||
| Total | 34 | 31 | 246 | 141 | 0 |
Highest pathogenic variant AF is 0.0000018598654
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| LGI1 | protein_coding | protein_coding | ENST00000371418 | 8 | 40351 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.000858 | 125730 | 0 | 3 | 125733 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.78 | 158 | 292 | 0.542 | 0.0000154 | 3682 |
| Missense in Polyphen | 30 | 117.61 | 0.25509 | 1574 | ||
| Synonymous | 0.698 | 103 | 112 | 0.916 | 0.00000660 | 1034 |
| Loss of Function | 4.43 | 1 | 24.8 | 0.0403 | 0.00000123 | 320 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000177 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Regulates voltage-gated potassium channels assembled from KCNA1, KCNA4 and KCNAB1. It slows down channel inactivation by precluding channel closure mediated by the KCNAB1 subunit. Ligand for ADAM22 that positively regulates synaptic transmission mediated by AMPA-type glutamate receptors (By similarity). Plays a role in suppressing the production of MMP1/3 through the phosphatidylinositol 3-kinase/ERK pathway. May play a role in the control of neuroblastoma cell survival. {ECO:0000250, ECO:0000269|PubMed:15047712, ECO:0000269|PubMed:16518856}.;
- Disease
- DISEASE: Epilepsy, familial temporal lobe, 1 (ETL1) [MIM:600512]: A focal form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe. Seizures are usually accompanied by sensory symptoms, most often auditory in nature. {ECO:0000269|PubMed:11810107, ECO:0000269|PubMed:12205652, ECO:0000269|PubMed:12601709, ECO:0000269|PubMed:12771268, ECO:0000269|PubMed:15079010, ECO:0000269|PubMed:17067999, ECO:0000269|PubMed:17296837, ECO:0000269|PubMed:17562837, ECO:0000269|PubMed:18625862, ECO:0000269|PubMed:19552651}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Developmental Biology;LGI-ADAM interactions
(Consensus)
Recessive Scores
- pRec
- 0.326
Intolerance Scores
- loftool
- rvis_EVS
- -0.71
- rvis_percentile_EVS
- 14.4
Haploinsufficiency Scores
- pHI
- 0.638
- hipred
- Y
- hipred_score
- 0.786
- ghis
- 0.640
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.784
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Lgi1
- Phenotype
- adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); pigmentation phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- lgi1b
- Affected structure
- tectal ventricle
- Phenotype tag
- abnormal
- Phenotype quality
- hydrocephalic
Gene ontology
- Biological process
- nervous system development;axon guidance;cell population proliferation;positive regulation of cell growth;neuron projection development;positive regulation of synaptic transmission;protein homooligomerization;neurotransmitter receptor localization to postsynaptic specialization membrane
- Cellular component
- extracellular region;extracellular space;membrane;cell junction;synaptic cleft;glutamatergic synapse
- Molecular function
- signaling receptor binding;protein binding