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CBLN4 Gene

protein-coding   GIFtS: 50
GCID: GC20M054572

Cerebellin 4 Precursor

(Previous name: cerebellin precursor-like 1)
(Previous symbol: CBLNL1)
  See CBLN4-related disease
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Cerebellin 4 Precursor1 2
CBLNL11 2 3
Cerebellin Precursor-Like 11 2
Cerebellin-Like Glycoprotein 12 3
cerebellin-42

External Ids:    HGNC: 162311   Entrez Gene: 1406892   Ensembl: ENSG000000548037   OMIM: 6150295   UniProtKB: Q9NTU73   

Export aliases for CBLN4 gene to outside databases

Previous GC identifers: GC20M054005 GC20M051353


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CBLN4 Gene:
This gene encodes a member of a family of small secreted proteins containing C1Q domains. Members of this family
are involved in regulation of neurexin signalling during synapse development. The mouse homolog of the protein
encoded by this gene competes with netrin to bind to the deleted in colorectal cancer receptor. (provided by
RefSeq, Aug 2012)

GeneCards Summary for CBLN4 Gene:
CBLN4 (cerebellin 4 precursor) is a protein-coding gene. Diseases associated with CBLN4 include colorectal cancer. An important paralog of this gene is CBLN2.

UniProtKB/Swiss-Prot: CBLN4_HUMAN, Q9NTU7
Function: May be involved in synaptic functions in the CNS. May play a role in CBLN3 export from the endoplasmic
reticulum and secretion (By similarity)




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000020.10  NT_011362.11  NC_018931.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the CBLN4 gene promoter:
         TBP   Bach1   p53   Nkx2-5   Tal-1beta   GATA-1   Arnt   FAC1   Nkx6-1   ITF-2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidCBLN4 promoter sequence
   Search Chromatin IP Primers for CBLN4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CBLN4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20q13   Ensembl cytogenetic band:  20q13.2   HGNC cytogenetic band: 20q13

CBLN4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CBLN4 gene location

GeneLoc information about chromosome 20         GeneLoc Exon Structure

GeneLoc location for GC20M054572:  view genomic region     (about GC identifiers)

Start:
54,572,496 bp from pter      End:
54,580,528 bp from pter
Size:
8,033 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: CBLN4_HUMAN, Q9NTU7 (See protein sequence)
Recommended Name: Cerebellin-4 precursor  
Size: 201 amino acids; 21808 Da
Subunit: Homohexamer; disulfide-linked homotrimers. The trimers are assembled via the globular C1q domains. The
trimers associate via N-terminal cysteine residues to form disulfide-linked hexamers (By similarity). May form
oligomers with CBLN1, CBLN2 and CBLN3 prior to secretion (By similarity). Strongly interacts with DCC in a
NTN1-displaceable fashion (By similarity). Weakly binds to NRXN1 and NRXN2 long and short isoforms produced by
alternative promoter usage. Interaction with NRXN3 short isoform is hardly detectable; no interaction at all with
NRXN3 long isoform (By similarity)
Secondary accessions: A8K0S5

Explore the universe of human proteins at neXtProt for CBLN4: NX_Q9NTU7

Explore proteomics data for CBLN4 at MOPED

Post-translational modifications: 

  • Glycosylation2 at Asn29, Asn88

  • See CBLN4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_542184.1  
    ENSEMBL proteins: 
     ENSP00000064571  

    CBLN4 Human Recombinant Protein Products:

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    Cloud-Clone Corp. Proteins for CBLN4

     
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    antibodies-online proteins for CBLN4 (5 products) 

     
    antibodies-online peptides for CBLN4

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    antibodies-online kits for CBLN4 (4 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    2 InterPro protein domains:
     IPR008983 Tumour_necrosis_fac-like_dom
     IPR001073 C1q

    Graphical View of Domain Structure for InterPro Entry Q9NTU7

    ProtoNet protein and cluster: Q9NTU7

    1 Blocks protein domain: IPB001073 Complement C1q protein

    UniProtKB/Swiss-Prot: CBLN4_HUMAN, Q9NTU7
    Similarity: Contains 1 C1q domain


    Find genes that share domains with CBLN4           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: CBLN4_HUMAN, Q9NTU7
    Function: May be involved in synaptic functions in the CNS. May play a role in CBLN3 export from the endoplasmic
    reticulum and secretion (By similarity)

         Gene Ontology (GO): 1 molecular function term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005515protein binding ----
         
    Find genes that share ontologies with CBLN4           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for CBLN4:
     Synthetic lethal with Ras 

         1 MGI mutant phenotype (inferred from 2 alleles(MGI details for Cbln4):
     normal 

    Find genes that share phenotypes with CBLN4           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for CBLN4: Cbln4tm1Jim Cbln4tm1Lex

       genOway: Develop your customized and physiologically relevant rodent model for CBLN4

    miRNA
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    miRTarBase miRNAs that target CBLN4:
    hsa-mir-335-5p (MIRT017149)

    Block miRNA regulation of human, mouse, rat CBLN4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate CBLN4 (see all 13):
    hsa-miR-3910 hsa-miR-26a-2* hsa-miR-92a hsa-miR-367 hsa-miR-25 hsa-miR-32 hsa-miR-548aa hsa-miR-124
    SwitchGear 3'UTR luciferase reporter plasmidCBLN4 3' UTR sequence
    Inhib. RNA
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    CBLN4_HUMAN, Q9NTU7: Secreted (By similarity). Cell junction, synapse (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular3
    endoplasmic reticulum1

    Gene Ontology (GO): 3 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005615extracellular space IEA--
    GO:0030054cell junction IEA--
    GO:0045202synapse IEA--

    Find genes that share ontologies with CBLN4           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for CBLN4
    Interactions:

        Search GeneGlobe Interaction Network for CBLN4

    STRING Interaction Network Preview (showing 1 interactants - click image to see more details)

    1 Interacting protein for CBLN4 (Q9NTU73 ENSP000000645714) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CBLN3Q6UW013, ENSP000002674064I2D: score=1 STRING: ENSP00000267406
    About this table

    Gene Ontology (GO): 1 biological process term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0009306protein secretion IEA--

    Find genes that share ontologies with CBLN4           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for CBLN4



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for CBLN4 gene: 
    NM_080617.5  

    Unigene Cluster for CBLN4:

    Cerebellin 4 precursor
    Hs.126141  [show with all ESTs]
    Unigene Representative Sequence: BC047076
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000064571(uc002xxa.3)
    miRNA
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    Block miRNA regulation of human, mouse, rat CBLN4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate CBLN4 (see all 13):
    hsa-miR-3910 hsa-miR-26a-2* hsa-miR-92a hsa-miR-367 hsa-miR-25 hsa-miR-32 hsa-miR-548aa hsa-miR-124
    SwitchGear 3'UTR luciferase reporter plasmidCBLN4 3' UTR sequence
    Inhib. RNA
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    OriGene qPCR primer pairs and template standards for CBLN4
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    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat CBLN4
      QuantiTect SYBR Green Assays in human, mouse, rat CBLN4
      QuantiFast Probe-based Assays in human, mouse, rat CBLN4

    Additional mRNA sequence: BC047076.1 

    1 DOTS entry:

    DT.97797762 

    23 AceView cDNA sequences:

    BC069516 NM_080617 AY358527 BC069488 BC069402 BX093493 BC050026 BC047076 
    BF445600 BQ722274 AV722278 AA868507 BI668562 BX506987 BG704824 AW074518 
    CD244520 CA397204 AV721267 AI468259 BU781883 AL044686 BI669085 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    CBLN4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ACCACTTTAT
    CBLN4 Expression
    About this image


    CBLN4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 5) fully expand
     
     Kidney (Urinary System)    fully expand to see all 4 entries
             S-shaped Body Cells S-shaped Body
             Metanephros
     
     Testis (Reproductive System)    fully expand to see all 3 entries
             Pre-Sertoli Cells Testis Cord
             Seminiferous Tubules
     
     Neurons
             GABAergic Amacrine Cells Inner Nuclear Layer
     
     Eye (Sensory Organs)    fully expand to see all 2 entries
             GABAergic Amacrine Cells Inner Nuclear Layer
     
     Brain (Nervous System)
             Cerebellum
    CBLN4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    CBLN4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.126141
        Custom PCR Arrays for CBLN4
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    In Situ
    Assay Products:
     

     
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for CBLN4 gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Cbln41 , 5 cerebellin 4 precursor protein1, 5 88.89(n)1
    97.47(a)1
      2 (94.74 cM)5
    2289421  NM_175631.31  NP_783439.11 
     1720362335 
    chicken
    (Gallus gallus)
    Aves CBLN41 cerebellin 4 precursor 86.91(n)
    93.72(a)
      769254  NM_001079487.1  NP_001072955.1 
    lizard
    (Anolis carolinensis)
    Reptilia CBLN46
    cerebellin 4 precursor
    94(a)
    1 ↔ 1
    GL343217.1(2382025-2410836)
    African clawed frog
    (Xenopus laevis)
    Amphibia MGC644242 hypothetical protein MGC64424 78.79(n)    BC056851.1 
    zebrafish
    (Danio rerio)
    Actinopterygii cbln41 cerebellin 4 precursor 75.25(n)
    86.87(a)
      563847  NM_001110391.1  NP_001103861.1 


    ENSEMBL Gene Tree for CBLN4 (if available)
    TreeFam Gene Tree for CBLN4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for CBLN4 gene
    CBLN22  C1QL32  CBLN12  C1QTNF32  CAPRIN12  ENSG000002732942  C1QL22  CBLN32  
    CAPRIN22  C1QL12  C1QL42  
    4 SIMAP similar genes for CBLN4 using alignment to 1 protein entry:     CBLN4_HUMAN:
    CBLN2    CBLN1    CBLN3    CAPRIN2

    Find genes that share paralogs with CBLN4           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for CBLN4 (see all 202)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 20 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1861366541,2
    --54572008(+) TCCTAA/CGAAGA 1 -- ds50010--------
    rs1433491481,2
    --54572015(+) AAGAGA/GCCTGC 1 -- ds50010--------
    rs1467164521,2
    --54572062(+) AGAACG/TTTTCC 1 -- ds50010--------
    rs60145711,2
    C,F,A,H--54572086(+) TATGAG/AAATAT 1 -- ds500120Minor allele frequency- A:0.24NS EA NA WA CSA 1632
    rs1891780531,2
    --54572234(+) AGCTCA/GCAATT 1 -- ds50010--------
    rs598741711,2
    C,F--54572270(+) GTAAAG/TATTTC 1 -- ds50012Minor allele frequency- T:0.05NA EA 240
    rs1404212941,2
    C--54572271(+) TAAAGA/GTTTCC 1 -- ds50010--------
    rs1807022721,2
    --54572280(+) CCTATA/GTCAGC 1 -- ds50010--------
    rs1435815931,2
    --54572464(+) ACATAC/TTTCCA 1 -- ut310--------
    rs1859052401,2
    --54572484(+) GAAAAA/GAACAA 1 -- ut310--------

    HapMap Linkage Disequilibrium report for CBLN4 (54572496 - 54580528 bp)

    Structural Variations
          Database of Genomic Variants (DGV) variations for CBLN4: --
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing CBLN4
    DNA2.0 Custom Variant and Variant Library Synthesis for CBLN4

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 615029    OMIM disorders: --

    1 disease for CBLN4:    
    About MalaCards
    colorectal cancer


    Find genes that share disorders with CBLN4           About GenesLikeMe

    Genetic Association Database (GAD): CBLN4

    Export disorders for CBLN4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for CBLN4 gene, integrated from 10 sources (see all 17):
    (articles sorted by number of sources associating them with CBLN4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    2. Signal peptide prediction based on analysis of experimentally verified cleavage sites. (PubMed id 15340161)1, 2 Zhang Z. and Henzel W.J. (Protein Sci. 2004)
    3. The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. (PubMed id 12975309)1, 2 Clark H.F.... Gray A.M. (Genome Res. 2003)
    4. The DNA sequence and comparative analysis of human chromosome 20. (PubMed id 11780052)1, 2 Deloukas P....Rogers J. (Nature 2001)
    5. Precerebellin-related genes and precerebellin 1 peptide in the adrenal gland of the rat: expression pattern, localization, developmental regulation and effects on corticosteroidogenesis. (PubMed id 19212655)1, 9 Rucinski M....Malendowicz L.K. (Int. J. Mol. Med. 2009)
    6. The protein interaction landscape of the human CMGC kinase group. (PubMed id 23602568)1 Varjosalo M....Gstaiger M. (Cell Rep 2013)
    7. Glutamate receptor I'1 induces preferentially inhibitory presynaptic differentiation of cortical neurons by interacting with neurexins through cerebellin precursor protein subtypes. (PubMed id 22191730)1 Yasumura M....Mishina M. (J. Neurochem. 2012)
    8. The Cbln family of proteins interact with multiple signaling pathways. (PubMed id 22220752)1 Wei P....Morgan J.I. (J. Neurochem. 2012)
    9. Differential interactions of cerebellin precursor protein (Cbln) subtypes and neurexin variants for synapse formation of cortical neurons. (PubMed id 21356198)1 Joo J.Y....Mishina M. (Biochem. Biophys. Res. Commun. 2011)
    10. Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions. (PubMed id 21410790)1 Matsuda K. and Yuzaki M. (Eur. J. Neurosci. 2011)

    (in PubMed, OMIM, and NCBI Bookshelf)
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 140689 HGNC: 16231 AceView: CBLN4 Ensembl:ENSG00000054803 euGenes: HUgn140689
    ECgene: CBLN4 H-InvDB: CBLN4

    (According to HUGE)
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for CBLN4 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
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    IP news from LifeMap Sciences, Inc.)
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    Patent Information for CBLN4 gene:
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