LGI1 (leucine rich glioma inactivated 1)

Gene

• Entrez ID: 9211
• Gene name: Leucine rich glioma inactivated 1
• Gene symbol: LGI1
• Synonyms (NCBI Gene): ADLTE, ADPAEF, ADPEAF, EPITEMPIN, EPT, ETL1, IB1099
• Chromosome: 10
• Chromosome location: 10q23.33
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28937874	A>C	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant, genic downstream transcript variant, intron variant
rs28939075	T>G	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant, genic downstream transcript variant, intron variant
rs104894167	T>C	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs146425212	A>C,G	Conflicting-interpretations-of-pathogenicity, benign	Coding sequence variant, missense variant, non coding transcript variant, synonymous variant
rs148862146	C>T	Conflicting-interpretations-of-pathogenicity, benign	Coding sequence variant, non coding transcript variant, synonymous variant
rs797044997	C>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs797044998	C>T	Pathogenic	Stop gained, coding sequence variant, intron variant, genic downstream transcript variant, non coding transcript variant
rs797044999	C>T	Pathogenic	Coding sequence variant, intron variant, genic downstream transcript variant, non coding transcript variant, missense variant
rs869025201	T>C	Pathogenic	Coding sequence variant, intron variant, genic downstream transcript variant, non coding transcript variant, missense variant
rs886039496	C>T	Pathogenic	Stop gained, coding sequence variant, intron variant, genic downstream transcript variant, non coding transcript variant
rs934556455	C>A,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant, intron variant, genic downstream transcript variant, non coding transcript variant, missense variant
rs1060502053	G>A	Pathogenic	Stop gained, non coding transcript variant, intron variant, genic downstream transcript variant, coding sequence variant
rs1060502054	C>T	Pathogenic	Stop gained, non coding transcript variant, coding sequence variant
rs1064794249	G>A	Likely-pathogenic	Non coding transcript variant, intron variant, genic downstream transcript variant, coding sequence variant, missense variant
rs1064797149	C>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1364913665	AT>-	Pathogenic	Frameshift variant, intron variant, non coding transcript variant, genic downstream transcript variant, coding sequence variant
rs1554907767	->AATAGTCAGAA	Pathogenic	Intron variant, non coding transcript variant, inframe indel, stop gained, coding sequence variant, genic downstream transcript variant
rs1554907787	T>G	Pathogenic	Intron variant, non coding transcript variant, stop gained, coding sequence variant, genic downstream transcript variant
rs1564851314	G>T	Likely-pathogenic	Splice acceptor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1108339	hsa-miR-1269	CLIP-seq
MIRT1108340	hsa-miR-1269b	CLIP-seq
MIRT1108341	hsa-miR-1288	CLIP-seq
MIRT1108342	hsa-miR-3654	CLIP-seq
MIRT1108343	hsa-miR-378	CLIP-seq
MIRT1108344	hsa-miR-378b	CLIP-seq
MIRT1108345	hsa-miR-378c	CLIP-seq
MIRT1108346	hsa-miR-378d	CLIP-seq
MIRT1108347	hsa-miR-378e	CLIP-seq
MIRT1108348	hsa-miR-378f	CLIP-seq
MIRT1108349	hsa-miR-378h	CLIP-seq
MIRT1108350	hsa-miR-378i	CLIP-seq
MIRT1108351	hsa-miR-422a	CLIP-seq
MIRT1108352	hsa-miR-4477b	CLIP-seq
MIRT1108353	hsa-miR-4515	CLIP-seq
MIRT1108354	hsa-miR-4520a-3p	CLIP-seq
MIRT1108355	hsa-miR-4638-3p	CLIP-seq
MIRT1108356	hsa-miR-4740-5p	CLIP-seq
MIRT1108357	hsa-miR-499-3p	CLIP-seq
MIRT1108358	hsa-miR-499a-3p	CLIP-seq
MIRT2260819	hsa-miR-889	CLIP-seq
MIRT2430724	hsa-miR-30a	CLIP-seq
MIRT2430725	hsa-miR-30b	CLIP-seq
MIRT2430726	hsa-miR-30c	CLIP-seq
MIRT2430727	hsa-miR-30d	CLIP-seq
MIRT2430728	hsa-miR-30e	CLIP-seq
MIRT2430729	hsa-miR-4495	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005102	Function	Signaling receptor binding	IPI	20463223
GO:0005102	Function	Signaling receptor binding	IPI	20463223
GO:0005515	Function	Protein binding	IPI	20463223, 27066583
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IDA	17067999
GO:0005615	Component	Extracellular space	IDA	17067999
GO:0005615	Component	Extracellular space	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	ISS
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005794	Component	Golgi apparatus	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0007399	Process	Nervous system development	TAS	9879993
GO:0007411	Process	Axon guidance	IMP	20463223
GO:0030307	Process	Positive regulation of cell growth	IMP	20463223
GO:0030425	Component	Dendrite	IEA
GO:0031175	Process	Neuron projection development	IMP	20463223
GO:0043083	Component	Synaptic cleft	IEA
GO:0043194	Component	Axon initial segment	IEA
GO:0045202	Component	Synapse	IEA
GO:0048018	Function	Receptor ligand activity	ISS
GO:0050806	Process	Positive regulation of synaptic transmission	IEA
GO:0050806	Process	Positive regulation of synaptic transmission	ISS
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0099645	Process	Neurotransmitter receptor localization to postsynaptic specialization membrane	IEA

Other IDs

• MIM: 604619
• HGNC: 6572
• e!Ensembl: ENSG00000108231

Protein

• UniProt ID: O95970
• Protein name: Leucine-rich glioma-inactivated protein 1 (Epitempin-1)
• Protein 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
• PDB: 5Y2Z, 5Y30, 5Y31, 8HPY, 8HQ1, 8HQ2, 8Y6B
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13855	LRR_8	69 → 127	Leucine rich repeat	Repeat
  PF13855	LRR_8	115 → 175	Leucine rich repeat	Repeat
  PF03736	EPTP	225 → 266	EPTP domain	Repeat
  PF03736	EPTP	271 → 312	EPTP domain	Repeat
  PF03736	EPTP	317 → 363	EPTP domain	Repeat
  PF03736	EPTP	366 → 414	EPTP domain	Repeat
  PF03736	EPTP	419 → 461	EPTP domain	Repeat
  PF03736	EPTP	464 → 505	EPTP domain	Repeat
  PF03736	EPTP	510 → 550	EPTP domain	Repeat

• Tissue specificity: TISSUE SPECIFICITY: Predominantly expressed in neural tissues, especially in brain. Expression is reduced in low-grade brain tumors and significantly reduced or absent in malignant gliomas. {ECO:0000269|PubMed:16518856}.; TISSUE SPECIFICITY: [Isoform 1]:
• Sequence:

  MESERSKRMGNACIPLKRIAYFLCLLSALLLTEGKKPAKPKCPAVCTCTKDNALCENARS
  IPRTVPPDVISLSFVRSGFTEISEGSFLFTPSLQLLLFTSNSFDVISDDAFIGLPHLEYL
  FIENNNIKSISRHTFRGLKSLIHLSLANNNLQTLPKDIFKGLDSLTNVDLRGNSFNCDCK
  LKWLVEWLGHTNATVEDIYCEGPPEYKKRKINSLSSKDFDCIITEFAKSQDLPYQSLSID
  TFSYLNDEYVVIAQPFTGKCIFLEWDHVEKTFRNYDNITGTSTVVCKPIVIETQLYVIVA
  QLFGGSHIYKRDSFANKFIKIQDIEILKIRKPNDIETFKIENNWYFVVADSSKAGFTTIY
  KWNGNGFYSHQSLHAWYRDTDVEYLEIVRTPQTLRTPHLILSSSSQRPVIYQWNKATQLF
  TNQTDIPNMEDVYAVKHFSVKGDVYICLTRFIGDSKVMKWGGSSFQDIQRMPSRGSMVFQ
  PLQINNYQYAILGSDYSFTQVYNWDAEKAKFVKFQELNVQAPRSFTHVSINKRNFLFASS
  FKGNTQIYKHVIVDLSA

• Sequence length: 557

Pathways

Reactome:

LGI-ADAM interactions

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Autosomal dominant epilepsy with auditory features	Likely pathogenic; Pathogenic	rs2134020777, rs2133975489, rs2134017952, rs2134021516, rs2134026513, rs2134026684, rs1027289865, rs2134017940, rs2134027169, rs104894166, rs119488099, rs797044999, rs797044998, rs2492919720, rs2059988348, rs2492903992, rs148862146, rs2492860700, rs1060502054, rs1060502053, rs1064794249, rs1554907835, rs1554907787, rs1554907767, rs1564845068, rs1564851314, rs1589776148, rs1364913665	RCV002242881 RCV002242924 RCV002242806 RCV002242849 RCV002242923 RCV001929947 RCV001939695 RCV001956161 RCV001940095 RCV003595853 RCV002227996 RCV003595879 RCV003595878 RCV002824342 RCV003596947 RCV003596856 RCV003597027 RCV003762640 RCV002230371 RCV002230817 RCV003595993 RCV002231763 RCV002231762 RCV002233483 RCV002233713 RCV002233238 RCV002234945 RCV002234247
Epilepsy, familial temporal lobe, 1	Likely pathogenic; Pathogenic	rs2059593242, rs1027289865, rs2134026964, rs2134026453, rs869025201, rs28937874, rs2134020917, rs1589762127, rs104894166, rs28939075, rs2134001459, rs104894167, rs119488099, rs119488100, rs797044999, rs797044998, rs2492801872, rs2492905831, rs2492905676, rs1364913665, rs2059583625, rs2059586444	RCV001330013 RCV003228039 RCV002077370 RCV002244147 RCV000207482 RCV000005763 RCV000005764 RCV000005765 RCV000005766 RCV000005768 RCV000005769 RCV000005770 RCV000005771 RCV000005772 RCV000192478 RCV000193378 RCV003388897 RCV003448527 RCV003494072 RCV002487662 RCV001262511 RCV001291524
Genitopatellar syndrome	Pathogenic	rs2134026964	RCV002077370
LGI1-related disorder	Likely pathogenic; Pathogenic	rs119488099, rs2492904557	RCV003407283 RCV003403044
Seizure	Likely pathogenic; Pathogenic	rs797044999, rs886039496, rs1370527260, rs1364913665	RCV004546453 RCV004577328 RCV003384292 RCV006261988

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Autosomal dominant epilepsy	Uncertain significance	rs2492919581	RCV003156202
Bilateral tonic-clonic seizure	Uncertain significance	rs1554906737	RCV000626875
Cholangiocarcinoma	Benign	rs12255855	RCV005918164
Gastric cancer	Benign	rs12255855	RCV005918163
Intellectual disability	Likely benign; Uncertain significance	rs2059988321, rs2059948035	RCV001252304 RCV001257684

Associations from Text Mining
Disease Name	Relationship Type	References
Aphasia	Associate	19064878
Autoimmune Diseases of the Nervous System	Associate	36621173, 37217310
Autosomal Dominant Lateral Temporal Lobe Epilepsy	Associate	12023020, 12446220, 15079011, 15660777, 15946341, 16707245, 18711109, 19064878, 19780791, 22323750, 24177143
Bohring syndrome	Associate	12023020
Brain Neoplasms	Associate	18575738
Developmental Disabilities	Associate	26993267
Drug Resistant Epilepsy	Associate	19552651
Encephalitis	Associate	30253786, 32849520, 35115410, 36973076, 37217310, 37644514
Epilepsies Partial	Associate	20659151, 31327507
Epilepsy	Associate	15660777, 15946341, 16707245, 19835947, 20863412, 21504429, 24177143, 31020005
Epilepsy Generalized	Associate	15079011
Epilepsy Idiopathic Generalized	Associate	15079011
Epilepsy Temporal Lobe	Associate	12023020, 14510822, 15009222, 19552651, 20863412, 21479274, 21504429, 22496201, 23621105, 25243798, 28633043, 29034879
Facial Asymmetry	Associate	30253786
Frontotemporal Dementia	Associate	19552651
Glioma	Inhibit	15047712
Glioma	Associate	19835947
Hearing Disorders	Associate	15079011, 19064878, 22323750
Immunologic Deficiency Syndromes	Associate	29788256
Limbic Encephalitis	Associate	29272336
Lipodystrophy Familial Partial	Associate	21479274
Neoplasm Metastasis	Inhibit	15047712
Neoplasm Metastasis	Associate	19835947
Neoplasms	Associate	19835947
Nerve Degeneration	Associate	33843981
Neurologic Manifestations	Associate	15660777
Paraneoplastic Syndromes Nervous System	Associate	33843981
Seizures	Associate	15009222, 15946341, 16707245, 19780791, 21504429, 29272336, 33453592
Status Epilepticus	Associate	19552651
Temporal epilepsy familial	Associate	15079011, 15660777
Warts	Associate	31892232