LGI1

leucine rich glioma inactivated 1, the group of LGI family

Basic information

Region (hg38): 10:93757840-93806272

Previous symbols: [ "EPT" ]

Links

ENSG00000108231 ∙ NCBI:9211 ∙ OMIM:604619 ∙ HGNC:6572 ∙ Uniprot:O95970 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant epilepsy with auditory features (Limited), mode of inheritance: AD
• 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: CGD

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 ClinVar and linked to the LGI1 gene.

• Autosomal dominant epilepsy with auditory features (20 variants)
• Epilepsy, familial temporal lobe, 1 (4 variants)
• not provided (3 variants)
• Genitopatellar syndrome;Epilepsy, familial temporal lobe, 1 (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	96	1	100
missense	2	3	198	4		207
nonsense	15	2				17
start loss						0
frameshift	8	10				18
inframe indel			1			1
splice donor/acceptor (+/-2bp)		4	1			5
splice region		2	8	10	2	22
non coding			12	30	13	55
Total	25	19	215	130	14

Highest pathogenic variant AF is 0.00000657

Variants in LGI1

This is a list of pathogenic ClinVar variants found in the LGI1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-93757841-C-T		Epilepsy, familial temporal lobe, 1	Uncertain significance (Jun 14, 2016)
10-93757865-G-C		Epilepsy, familial temporal lobe, 1	Likely benign (Jun 14, 2016)
10-93757918-T-C		Epilepsy, familial temporal lobe, 1	Uncertain significance (Jun 14, 2016)
10-93757977-G-A		Epilepsy, familial temporal lobe, 1	Uncertain significance (Jan 13, 2018)
10-93758079-G-C		Epilepsy, familial temporal lobe, 1	Uncertain significance (Jan 13, 2018)
10-93758112-C-T		not specified	Likely benign (Jan 17, 2017)
10-93758145-A-G		Epilepsy, familial temporal lobe, 1 • not specified • Autosomal dominant epilepsy with auditory features • LGI1-related disorder	Conflicting classifications of pathogenicity (Jan 18, 2024)
10-93758148-G-T		Epilepsy, familial temporal lobe, 1	Likely pathogenic (Jan 01, 2019)
10-93758178-G-A		Inborn genetic diseases	Uncertain significance (Aug 17, 2021)
10-93758178-G-T		Autosomal dominant epilepsy with auditory features	Uncertain significance (Aug 17, 2023)
10-93758187-C-T		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
10-93758188-C-G		Autosomal dominant epilepsy with auditory features	Uncertain significance (May 06, 2022)
10-93758190-C-G		Inborn genetic diseases • Autosomal dominant epilepsy with auditory features	Conflicting classifications of pathogenicity (Apr 09, 2023)
10-93758191-T-G		Autosomal dominant epilepsy with auditory features	Uncertain significance (Sep 06, 2023)
10-93758197-G-A		Inborn genetic diseases	Uncertain significance (Sep 30, 2017)
10-93758197-G-C		Inborn genetic diseases	Uncertain significance (Nov 07, 2022)
10-93758199-A-G		Autosomal dominant epilepsy with auditory features	Uncertain significance (Jan 12, 2021)
10-93758200-T-C			Uncertain significance (Jul 11, 2022)
10-93758202-G-A		Autosomal dominant epilepsy with auditory features	Uncertain significance (Apr 08, 2022)
10-93758205-T-C		Inborn genetic diseases	Uncertain significance (May 31, 2017)
10-93758206-A-G		Inborn genetic diseases	Uncertain significance (May 26, 2024)
10-93758208-T-A		Autosomal dominant epilepsy with auditory features	Uncertain significance (Aug 09, 2022)
10-93758213-A-G		Autosomal dominant epilepsy with auditory features	Likely benign (Aug 30, 2023)
10-93758217-C-T		Autosomal dominant epilepsy with auditory features	Uncertain significance (Jan 19, 2022)
10-93758219-C-G		Autosomal dominant epilepsy with auditory features	Likely benign (Sep 10, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

• 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