LGI3

leucine rich repeat LGI family member 3, the group of LGI family

Basic information

Region (hg38): 8:22146830-22157084

Links

ENSG00000168481 ∙ NCBI:203190 ∙ OMIM:608302 ∙ HGNC:18711 ∙ Uniprot:Q8N145 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects (Limited), mode of inheritance: AR
• intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects	AR	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	Musculoskeletal; Neurologic	35948005

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LGI3 gene.

• Peripheral nerve hyperexcitability syndrome (9 variants)
• Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects (5 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LGI3 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				1	2	3
missense	2		41	2	3	48
nonsense	2	1				3
start loss						0
frameshift	3					3
inframe indel						0
splice donor/acceptor (+/-2bp)	2		2			4
splice region						0
non coding						0
Total	9	1	43	3	5

Highest pathogenic variant AF is 0.0000131

Variants in LGI3

This is a list of pathogenic ClinVar variants found in the LGI3 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-22148197-A-T		not specified	Uncertain significance (Mar 05, 2024)
8-22148215-C-G		not specified	Uncertain significance (Apr 19, 2024)
8-22148221-G-A			Uncertain significance (Jun 14, 2024)
8-22148279-C-T		not specified	Uncertain significance (Sep 22, 2023)
8-22148297-G-A		not specified	Uncertain significance (Nov 22, 2021)
8-22148311-C-T		not specified	Uncertain significance (Jul 12, 2023)
8-22148360-G-T		not specified	Uncertain significance (Jan 04, 2022)
8-22148444-G-A		not specified	Uncertain significance (Nov 16, 2022)
8-22148444-G-T		not specified	Uncertain significance (Feb 10, 2023)
8-22148479-A-G		not specified	Uncertain significance (Dec 22, 2023)
8-22148485-C-T		Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects	Uncertain significance (Jun 17, 2021)
8-22148533-G-A		not specified	Uncertain significance (May 27, 2022)
8-22148610-G-A		LGI3-related disorder	Likely benign (Jun 13, 2019)
8-22148641-C-T		not specified	Uncertain significance (Jul 26, 2021)
8-22148657-C-T			Benign (Jul 31, 2018)
8-22148681-C-G		not specified	Uncertain significance (Jun 10, 2022)
8-22148687-G-A		not specified	Uncertain significance (Aug 04, 2023)
8-22148689-CA-C		Peripheral nerve hyperexcitability syndrome • Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects	Pathogenic (Jun 28, 2022)
8-22148693-G-T		not specified	Uncertain significance (Jun 09, 2022)
8-22148730-C-A			Uncertain significance (May 13, 2023)
8-22148734-C-T		not specified	Uncertain significance (Jun 29, 2022)
8-22148774-C-T			Uncertain significance (Apr 09, 2024)
8-22148800-C-T		not specified	Uncertain significance (May 20, 2024)
8-22148816-C-T		Peripheral nerve hyperexcitability syndrome • Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects	Pathogenic (Jun 28, 2022)
8-22148831-C-T		not specified	Uncertain significance (Dec 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LGI3	protein_coding	protein_coding	ENST00000306317	8	10260

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000178	0.994	125724	0	23	125747	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.491	308	333	0.924	0.0000209	3515
Missense in Polyphen		91	112.52	0.80878		1248
Synonymous	-0.223	149	146	1.02	0.00000900	1140
Loss of Function	2.44	12	25.2	0.475	0.00000133	252

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000275	0.000275
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000548	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.0000548	0.0000544
South Asian	0.000131	0.000131
Other	0.000173	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May participate in the regulation of neuronal exocytosis. {ECO:0000250}.
• Pathway: Developmental Biology;LGI-ADAM interactions (Consensus)

Recessive Scores

• pRec: 0.125

Intolerance Scores

• loftool: 0.262
• rvis_EVS: -1.07
• rvis_percentile_EVS: 7.43

Haploinsufficiency Scores

• pHI: 0.203
• hipred: N
• hipred_score: 0.334
• ghis: 0.612

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lgi3

Gene ontology

• Biological process: exocytosis;regulation of exocytosis
• Cellular component: extracellular region;synaptic vesicle;cell junction;neuron projection
• Molecular function: catalytic activity