LGI4

protein-coding

leucine rich repeat LGI family member 4, the group of LGI family

Gene summary

Involved in regulation of myelination. Predicted to be located in extracellular region. Predicted to be active in obsolete extracellular space. Implicated in arthrogryposis multiplex congenita-1 and childhood absence epilepsy. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_139284.3

Inheritance

ClinVar variants

P:18U:88B:29

Top phenotype

Arthrogryposis multiplex congenita, neurogenic, with myelin defect

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr19:35,124,513-35,142,451

External References & Databases

Ensembl (ENSG00000153902)

Transcript & Mutation Effects

hg38 • Region Span ~17.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

arthrogryposis multiplex congenita 1, neurogenic, with myelin defectSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060486

Submitter: G2P

arthrogryposis multiplex congenita 1, neurogenic, with myelin defectSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060486

Submitter: PanelApp Australia

hypomyelination neuropathy-arthrogryposis syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017049

Submitter: Orphanet

arthrogryposis multiplex congenita 1, neurogenic, with myelin defectSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060486

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Arthrogryposis multiplex congenita, neurogenic, with myelin defectAR

Manifestation: Craniofacial; 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: 28318499

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LGI4 variants in ClinVar

9 Conditions Cataloged

Inborn genetic diseasesTotal: 81

not providedTotal: 27

Arthrogryposis multiplex congenita 1, neurogenic, with myelin defectTotal: 25

LGI4-related disorderTotal: 12

not specifiedTotal: 7

Fetal akinesia deformation sequence 1Total: 2

Arthrogryposis multiplex congenitaTotal: 2

Arthrogryposis multiplex congenita 2, neurogenic typeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_139284.3. 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			1 clinvar	17 clinvar	3 clinvar	21
missense	3 clinvar	4 clinvar	85 clinvar	7 clinvar	2 clinvar	101
nonsense	3 clinvar	3 clinvar	1 clinvar			7
start loss	1 clinvar					1
frameshift		4 clinvar				4
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	7	11	88	24	5	135

Highest pathogenic variant AF is 0.0001389345

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_139284.3	RefSeq	NP_644813.1	9	MANE Select
ENST00000310123.8	Ensembl	ENSP00000312273.3	9	MANE Select
ENST00000392225.7	Ensembl	ENSP00000376059.3	8	Standard
ENST00000587780.5	Ensembl	ENSP00000467044.2	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Developmental Biology
LGI-ADAM interactions

Biological Process

adult locomotory behavior
glial cell proliferation
myelination in peripheral nervous system
regulation of myelination
neuron maturation

Cellular Component

extracellular region
extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310123
Coding exons: 9
Length: 17939
Individuals with no LoFs: 125711
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125734
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.07	283	338	0.836	0.0000229	3334
Missense (PolyPhen)		72	98.121	0.73379		1062
Synonymous	0.895	143	157	0.909	0.0000113	1153
Loss of Function	2.58	7	19.2	0.364	8.24e-7	215

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000080	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00019	0.00016	rare
South Asian	0	0.0	absent
Other	0.00020	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of Schwann cell signaling pathway(s) that controls axon segregation and myelin formation (By similarity). {ECO:0000250|UniProtKB:Q8K1S1}.;

Recessive Scores

pRec: 0.120

Intolerance Scores

LoFtool: 0.237
RVIS EVS: 0
RVIS percentile EVS: 53.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.266

Gene Damage Prediction

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