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    LGI4 leucine rich repeat LGI family member 4 [ Homo sapiens (human) ]

    Gene ID: 163175, updated on 10-Dec-2024

    Summary

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    Official Symbol
    LGI4provided by HGNC
    Official Full Name
    leucine rich repeat LGI family member 4provided by HGNC
    Primary source
    HGNC:HGNC:18712
    See related
    Ensembl:ENSG00000153902 MIM:608303; AllianceGenome:HGNC:18712
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    AMC1; LGIL3; AMCNMY
    Summary
    Involved in regulation of myelination. Predicted to be located in extracellular region. Predicted to be active in extracellular space. Implicated in arthrogryposis multiplex congenita-1 and childhood absence epilepsy. [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Broad expression in fat (RPKM 15.0), brain (RPKM 9.1) and 21 other tissues See more
    Orthologs
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    Genomic context

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    See LGI4 in Genome Data Viewer
    Location:
    19q13.12; 19q13.11
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (35124513..35135059, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (37669192..37679738, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (35615417..35625963, complement)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene HPN antisense RNA 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:35581426-35581963 Neighboring gene hepatitis A virus cellular receptor 1-like Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:35600165-35600765 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:35613161-35614050 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:35614051-35614938 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14456 Neighboring gene FXYD domain containing ion transport regulator 3 Neighboring gene microRNA 6887 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:35632134-35632696 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:35633820-35634380 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:35634381-35634942 Neighboring gene FXYD domain containing ion transport regulator 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:35642007-35642406 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr19:35643105-35643656 Neighboring gene FXYD domain containing ion transport regulator 7 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:35644606-35645470

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Characterizing the molecular etiology of arthrogryposis multiplex congenita in patients with LGI4 mutations. Booth DG, et al. Glia, 2021 Nov. PMID 34288120
    2. Positive association between benign familial infantile convulsions and LGI4. Ishii A, et al. Brain Dev, 2010 Aug. PMID 19815358
    3. Loss-of-Function Mutations in LGI4, a Secreted Ligand Involved in Schwann Cell Myelination, Are Responsible for Arthrogryposis Multiplex Congenita. Xue S, et al. Am J Hum Genet, 2017 Apr 6. PMID 28318499, Free PMC Article
    4. Intratumoral heterogeneity of ADAM23 promotes tumor growth and metastasis through LGI4 and nitric oxide signals. Costa ET, et al. Oncogene, 2015 Mar 5. PMID 24662834
    5. Genotypic association of exonic LGI4 polymorphisms and childhood absence epilepsy. Gu W, et al. Neurogenetics, 2004 Feb. PMID 14505228

    See all (14) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Characterizing the molecular etiology of arthrogryposis multiplex congenita in patients with LGI4 mutations.
      Title: Characterizing the molecular etiology of arthrogryposis multiplex congenita in patients with LGI4 mutations.
    2. in four unrelated multiplex families presenting with severe arthrogryposis multiplex congenital, identified biallelic loss-of-function mutations in LGI4; functional tests showed these germline mutations caused aberrant splicing of the endogenous LGI4 transcript and in a cell-based assay impaired the secretion of truncated LGI4 protein
      Title: Loss-of-Function Mutations in LGI4, a Secreted Ligand Involved in Schwann Cell Myelination, Are Responsible for Arthrogryposis Multiplex Congenita.
    3. Intratumoral heterogeneity of ADAM23 promotes tumor growth and metastasis through LGI4 and nitric oxide signals.
      Title: Intratumoral heterogeneity of ADAM23 promotes tumor growth and metastasis through LGI4 and nitric oxide signals.
    4. The positive genotypic association between benign familial infantile convulsions (BFIC)and c.1722G/A polymorphism suggests that LGI4 might contribute to the susceptibility to BFIC.
      Title: Positive association between benign familial infantile convulsions and LGI4.
    5. Schwann cells are the principal cellular source of Lgi4 in the developing nerve; transgenic Lgi4 binds directly to Adam22 without a requirement for additional membrane associated factors.
      Title: Adam22 is a major neuronal receptor for Lgi4-mediated Schwann cell signaling.
    6. Observational study of gene-disease association. (HuGE Navigator)
      Title: Positive association between benign familial infantile convulsions and LGI4.
    7. Screening of the LGI4 coding region in BFIC and childhood absence epilepsy (CAE) revealed several frequent exonic polymorphisms.
      Title: Genotypic association of exonic LGI4 polymorphisms and childhood absence epilepsy.
    8. has seven copies of the EPTP repeat, a unifying protein sequence motif of a heterogenous group of proteins linked to epileptic diseases. The EPTP repeat probably forms a beta-propeller structure.
      Title: The novel EPTP repeat defines a superfamily of proteins implicated in epileptic disorders.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Arthrogryposis multiplex congenita 1, neurogenic, with myelin defect
    MedGen: C4479539 OMIM: 617468 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    involved_in adult locomotory behavior IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in glial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in myelination in peripheral nervous system IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in neuron maturation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of myelination IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    leucine-rich repeat LGI family member 4
    Names
    LGI1-like protein 3
    leucine-rich glioma-inactivated gene 4
    leucine-rich glioma-inactivated protein 4

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_139284.3 → NP_644813.1  leucine-rich repeat LGI family member 4 precursor

      See identical proteins and their annotated locations for NP_644813.1

      Status: VALIDATED

      Source sequence(s)
      AJ487519, AJ487959, BC140008, BU740724
      Consensus CDS
      CCDS12444.1
      UniProtKB/Swiss-Prot
      B2RN53, B9EGS7, Q5M8T1, Q8N135
      Related
      ENSP00000312273.3, ENST00000310123.8
      Conserved Domains (5) summary
      TIGR00864
      Location:131 → 206
      PCC; polycystin cation channel protein
      sd00031
      Location:54 → 77
      LRR_1; leucine-rich repeat [structural motif]
      sd00033
      Location:167 → 205
      LRR_RI; leucine-rich repeat [structural motif]
      pfam03736
      Location:396 → 438
      EPTP; EPTP domain
      pfam13855
      Location:76 → 136
      LRR_8; Leucine rich repeat

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      35124513..35135059 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017026428.1 → XP_016881917.1  leucine-rich repeat LGI family member 4 isoform X1

      UniProtKB/TrEMBL
      Q658V8
      Related
      ENST00000493050.5
      Conserved Domains (1) summary
      pfam03736
      Location:224 → 266
      EPTP; EPTP domain

    2. XM_017026429.1 → XP_016881918.1  leucine-rich repeat LGI family member 4 isoform X1

      UniProtKB/TrEMBL
      Q658V8
      Conserved Domains (1) summary
      pfam03736
      Location:224 → 266
      EPTP; EPTP domain

    3. XM_047438343.1 → XP_047294299.1  leucine-rich repeat LGI family member 4 isoform X1

      UniProtKB/TrEMBL
      Q658V8

    4. XM_017026430.2 → XP_016881919.1  leucine-rich repeat LGI family member 4 isoform X1

      UniProtKB/TrEMBL
      Q658V8
      Conserved Domains (1) summary
      pfam03736
      Location:224 → 266
      EPTP; EPTP domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      37669192..37679738 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054320081.1 → XP_054176056.1  leucine-rich repeat LGI family member 4 isoform X1

      UniProtKB/TrEMBL
      Q658V8

    2. XM_054320083.1 → XP_054176058.1  leucine-rich repeat LGI family member 4 isoform X1

      UniProtKB/TrEMBL
      Q658V8

    3. XM_054320082.1 → XP_054176057.1  leucine-rich repeat LGI family member 4 isoform X1

      UniProtKB/TrEMBL
      Q658V8

    4. XM_054320084.1 → XP_054176059.1  leucine-rich repeat LGI family member 4 isoform X1

      UniProtKB/TrEMBL
      Q658V8
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8N135.1 GenPept UniProtKB/Swiss-Prot:Q8N135

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