LGI3

protein-coding

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

Gene summary

Predicted to be involved in regulation of exocytosis. Located in obsolete extracellular space. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_139278.4

Inheritance

ClinVar variants

P:13U:101B:13

Top phenotype

Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr8:22,146,830-22,157,084

External References & Databases

Ensembl (ENSG00000168481)

Transcript & Mutation Effects

hg38 • Region Span ~10.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder with muscle tone abnormalities and distal skeletal defectsLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859277

Submitter: Ambry Genetics

intellectual developmental disorder with muscle tone abnormalities and distal skeletal defectsLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0859277

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defectsAR

Manifestation: Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 35948005

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LGI3 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 90

not providedTotal: 22

Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defectsTotal: 11

Peripheral nerve hyperexcitability syndromeTotal: 9

LGI3-related disorderTotal: 8

Fetal anomalies with a likely genetic causeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_139278.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	6 clinvar	2 clinvar	10
missense	2 clinvar		95 clinvar	2 clinvar	3 clinvar	102
nonsense	2 clinvar	1 clinvar	2 clinvar			5
start loss						0
frameshift	3 clinvar	1 clinvar	1 clinvar			5
splice donor/acceptor (+/-2bp)	3 clinvar	1 clinvar	1 clinvar			5
Total	10	3	101	8	5	127

Highest pathogenic variant AF is 0.000021064918

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_139278.4	RefSeq	NP_644807.1	8	MANE Select
ENST00000306317.7	Ensembl	ENSP00000302297.2	8	MANE Select
ENST00000424267.6	Ensembl	ENSP00000399121.2	7	Standard
ENST00000424267.7	Ensembl	ENSP00000399121.2	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Developmental Biology
LGI-ADAM interactions

Biological Process

exocytosis
regulation of exocytosis

Molecular Function

catalytic activity

Cellular Component

extracellular region
synaptic vesicle
cell junction
neuron projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000306317
Coding exons: 8
Length: 10260
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125747
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.491	308	333	0.924	0.0000209	3515
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00013	0.00013	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May participate in the regulation of neuronal exocytosis. {ECO:0000250}.;

Recessive Scores

pRec: 0.125

Intolerance Scores

LoFtool: 0.262
RVIS EVS: -1.07
RVIS percentile EVS: 7.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.307

Gene Damage Prediction

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