LGI4

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

Basic information

Region (hg38): 19:35124513-35142451

Links

ENSG00000153902 ∙ NCBI:163175 ∙ OMIM:608303 ∙ HGNC:18712 ∙ Uniprot:Q8N135 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypomyelination neuropathy-arthrogryposis syndrome (Supportive), mode of inheritance: AR
• arthrogryposis multiplex congenita 1, neurogenic, with myelin defect (Strong), mode of inheritance: AR
• arthrogryposis multiplex congenita 1, neurogenic, with myelin defect (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Arthrogryposis multiplex congenita, neurogenic, with myelin defect	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	Craniofacial; Musculoskeletal; Neurologic	28318499

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LGI4 gene.

• Arthrogryposis multiplex congenita 2, neurogenic type (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LGI4 gene is commonly pathogenic or not. These statistics are base on transcript: . Only rare variants are included in the table.

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				7	8	15
missense		1	47	5	2	55
nonsense		2				2
start loss	1					1
frameshift		3				3
splice donor/acceptor (+/-2bp)			1			1
Total	1	6	48	12	10

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LGI4	protein_coding	protein_coding	ENST00000310123	9	17939

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00715	0.990	125711	0	23	125734	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.07	283	338	0.836	0.0000229	3334
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000109	0.0000908
Ashkenazi Jewish	0.00	0.00
East Asian	0.000110	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000190	0.000158
Middle Eastern	0.000110	0.000109
South Asian	0.00	0.00
Other	0.000196	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of Schwann cell signaling pathway(s) that controls axon segregation and myelin formation (By similarity). {ECO:0000250|UniProtKB:Q8K1S1}.
• Pathway: Developmental Biology;LGI-ADAM interactions (Consensus)

Recessive Scores

• pRec: 0.120

Intolerance Scores

• loftool: 0.237
• rvis_EVS: 0
• rvis_percentile_EVS: 53.85

Haploinsufficiency Scores

• pHI: 0.0890
• hipred: N
• hipred_score: 0.199
• ghis: 0.596

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.266

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lgi4
• Phenotype: growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton 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); limbs/digits/tail 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)

Gene ontology

• Biological process: adult locomotory behavior;glial cell proliferation;myelination in peripheral nervous system;regulation of myelination;neuron maturation
• Cellular component: extracellular region;extracellular space