LGI4 (leucine rich repeat LGI family member 4)

Gene

• Entrez ID: 163175
• Gene name: Leucine rich repeat LGI family member 4
• Gene symbol: LGI4
• Synonyms (NCBI Gene): AMC1, AMCNMY, LGIL3
• Chromosome: 19
• Chromosome location: 19q13.12|19q13.11

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs201728190	C>G	Likely-pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant
rs755500591	C>G,T	Pathogenic	Coding sequence variant, missense variant
rs775997446	C>A,G,T	Pathogenic	Missense variant, coding sequence variant, stop gained
rs779232987	C>T	Pathogenic	Missense variant, coding sequence variant
rs1064797093	C>G	Pathogenic	Intron variant
rs1064797094	A>T	Pathogenic	Coding sequence variant, missense variant
rs1064797095	C>A,T	Pathogenic	Intron variant
rs1201430967	A>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1207534366	A>C,G	Pathogenic	Initiator codon variant, upstream transcript variant, missense variant, genic upstream transcript variant
rs1366269616	G>A	Pathogenic	Stop gained, coding sequence variant
rs1555733773	C>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1555734932	A>C	Likely-pathogenic	5 prime UTR variant, upstream transcript variant, coding sequence variant, missense variant, genic upstream transcript variant
rs1600470099	C>-	Likely-pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1108476	hsa-miR-198	CLIP-seq
MIRT1108477	hsa-miR-2964a-5p	CLIP-seq
MIRT1108478	hsa-miR-3684	CLIP-seq
MIRT2260864	hsa-miR-1250	CLIP-seq
MIRT2260865	hsa-miR-3649	CLIP-seq
MIRT2260866	hsa-miR-3929	CLIP-seq
MIRT2260867	hsa-miR-4419b	CLIP-seq
MIRT2260868	hsa-miR-4478	CLIP-seq
MIRT2260869	hsa-miR-4505	CLIP-seq
MIRT2260870	hsa-miR-4712-5p	CLIP-seq
MIRT2260871	hsa-miR-770-5p	CLIP-seq
MIRT2452988	hsa-miR-922	CLIP-seq
MIRT2683880	hsa-miR-4431	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IEA
GO:0008344	Process	Adult locomotory behavior	IEA
GO:0014009	Process	Glial cell proliferation	IEA
GO:0014044	Process	Schwann cell development	IEA
GO:0021782	Process	Glial cell development	IEA
GO:0022011	Process	Myelination in peripheral nervous system	IBA
GO:0022011	Process	Myelination in peripheral nervous system	IEA
GO:0031641	Process	Regulation of myelination	IEA
GO:0031641	Process	Regulation of myelination	IMP	28318499
GO:0042063	Process	Gliogenesis	IEA
GO:0042551	Process	Neuron maturation	IBA
GO:0042551	Process	Neuron maturation	IEA
GO:0042552	Process	Myelination	IEA

Other IDs

• MIM: 608303
• HGNC: 18712
• e!Ensembl: ENSG00000153902

Protein

• UniProt ID: Q8N135
• Protein name: Leucine-rich repeat LGI family member 4 (LGI1-like protein 3) (Leucine-rich glioma-inactivated protein 4)
• Protein function: Component of Schwann cell signaling pathway(s) that controls axon segregation and myelin formation (By similarity).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13855	LRR_8	52 → 112	Leucine rich repeat	Repeat
  PF13855	LRR_8	101 → 160	Leucine rich repeat	Repeat
  PF03736	EPTP	212 → 251	EPTP domain	Repeat
  PF03736	EPTP	351 → 393	EPTP domain	Repeat
  PF03736	EPTP	396 → 438	EPTP domain	Repeat

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed, with highest expression in brain. {ECO:0000269|PubMed:12023020}.
• Sequence:

  MGGAGILLLLLAGAGVVVAWRPPKGKCPLRCSCSKDSALCEGSPDLPVSFSPTLLSLSLV
  RTGVTQLKAGSFLRIPSLHLLLFTSNSFSVIEDDAFAGLSHLQYLFIEDNEIGSISKNAL
  RGLRSLTHLSLANNHLETLPRFLFRGLDTLTHVDLRGNPFQCDCRVLWLLQWMPTVNASV
  GTGACAGPASLSHMQLHHLDPKTFKCRAIELSWFQTVGESALSVEPFSYQGEPHIVLAQP
  FAGRCLILSWDYSLQRFRPEEELPAASVVSCKPLVLGPSLFVLAARLWGGSQLWARPSPG
  LRLAPTQTLAPRRLLRPNDAELLWLEGQPCFVVADASKAGSTTLLCRDGPGFYPHQSLHA
  WHRDTDAEALELDGRPHLLLASASQRPVLFHWTGGRFERRTDIPEAEDVYATRHFQAGGD
  VFLCLTRYIGDSMVMRWDGSMFRLLQQLPSRGAHVFQPLLIARDQLAILGSDFAFSQVLR
  LEPDKGLLEPLQELGPPALVAPRAFAHITMAGRRFLFAACFKGPTQIYQHHEIDLSA

• Sequence length: 537

Pathways

Reactome:

LGI-ADAM interactions

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Arthrogryposis multiplex congenita	Likely pathogenic	rs1201430967	RCV000855466	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Arthrogryposis multiplex congenita 1, neurogenic, with myelin defect	Likely pathogenic; Pathogenic	rs2065139570, rs2513330090, rs2513320717, rs779232987, rs775997446, rs1064797093, rs1064797094, rs1064797095, rs755500591, rs1366269616, rs1555734932, rs1600470099, rs2065136111, rs2065190797	RCV001844373 RCV003146992 RCV003153025 RCV000487489 RCV000487492 RCV000487486 RCV000487490 RCV000487493 RCV000487487 RCV000664223 RCV000664224 RCV000984971 RCV001251121 RCV001251122	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Arthrogryposis multiplex congenita 2, neurogenic type	Pathogenic	rs1207534366	RCV000766216	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Fetal akinesia deformation sequence 1	Likely pathogenic	rs1201430967	RCV000855466	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HODGKINS LYMPHOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LGI4-related disorder	Benign; Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PENA-SHOKEIR SYNDROME TYPE I	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arthrogryposis	Arthrogryposis multiplex congenita	GENOMICS_ENGLAND_DG	16341215, 28318499		★☆☆☆☆ Found in Text Mining only
Arthrogryposis	Arthrogryposis multiplex congenita	BEFREE	28318499, 31513940		★☆☆☆☆ Found in Text Mining only
Arthrogryposis	Arthrogryposis	Pubtator	28318499, 33820833	Associate	★☆☆☆☆ Found in Text Mining only
Arthrogryposis	Arthrogryposis multiplex congenita	HPO_DG			★☆☆☆☆ Found in Text Mining only
ARTHROGRYPOSIS MULTIPLEX CONGENITA, NEUROGENIC TYPE (disorder)	Neurogenic arthrogryposis multiplex congenita	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
ARTHROGRYPOSIS MULTIPLEX CONGENITA, NEUROGENIC, WITH MYELIN DEFECT	Arthrogryposis Multiplex Congenita, Neurogenic, With Myelin Defect	GENOMICS_ENGLAND_DG	16341215		★☆☆☆☆ Found in Text Mining only
ARTHROGRYPOSIS MULTIPLEX CONGENITA, NEUROGENIC, WITH MYELIN DEFECT	Arthrogryposis Multiplex Congenita, Neurogenic, With Myelin Defect	UNIPROT_DG	28318499		★☆☆☆☆ Found in Text Mining only
ARTHROGRYPOSIS MULTIPLEX CONGENITA, NEUROGENIC, WITH MYELIN DEFECT	Arthrogryposis Multiplex Congenita, Neurogenic, With Myelin Defect	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
ARTHROGRYPOSIS MULTIPLEX CONGENITA, NEUROGENIC, WITH MYELIN DEFECT	Arthrogryposis Multiplex Congenita, Neurogenic, With Myelin Defect	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Autosomal Dominant Lateral Temporal Lobe Epilepsy	Temporal lobe epilepsy	BEFREE	15079010		★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	12023020	Associate	★☆☆☆☆ Found in Text Mining only
Congenital Camptodactyly	Congenital Camptodactyly	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Congenital Camptodactyly	Congenital Camptodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital clubfoot	Congenital Clubfoot	HPO_DG			★☆☆☆☆ Found in Text Mining only
Demyelinating Diseases	Demyelinating diseases	Pubtator	28318499	Associate	★☆☆☆☆ Found in Text Mining only
Distal arthrogryposis syndrome	Distal arthrogryposis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	19815358		★☆☆☆☆ Found in Text Mining only
Esotropia	Esotropia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Familial benign neonatal epilepsy	Benign Epilepsy	BEFREE	14505228, 19815358		★☆☆☆☆ Found in Text Mining only
Flexion contracture - elbow	Elbow flexion contracture	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	24662834		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	GENOMICS_ENGLAND_DG	16341215		★☆☆☆☆ Found in Text Mining only
Hip Contracture	Hip Contracture	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypomyelination neuropathy-arthrogryposis syndrome	Hypomyelination Neuropathy-Arthrogryposis Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Idiopathic generalized epilepsy	Epilepsy	BEFREE	14505228		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	GENOMICS_ENGLAND_DG	16341215		★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pena-Shokeir syndrome type I	Pena Shokeir syndrome	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	27814717	Associate	★☆☆☆☆ Found in Text Mining only
Vertical Talus	Vertical Talus	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only