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INSL4 Gene

protein-coding   GIFtS: 48
GCID: GC09P005231

Insulin-Like 4 (Placenta)

  See INSL4-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
Insulin-Like 4 (Placenta)1 2     Early Placenta Insulin-Like Peptide2
Insulin-Like Peptide 42 3     Early Placenta Insulin-Like Peptide (EPIL)2
EPIL2 3     Placentin3
PLACENTIN2     

External Ids:    HGNC: 60871   Entrez Gene: 36412   Ensembl: ENSG000001202117   OMIM: 6009105   UniProtKB: Q146413   

Export aliases for INSL4 gene to outside databases

Previous GC identifers: GC09P005385 GC09P005212 GC09P005221 GC09P005266


(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 INSL4 Gene:
INSL4 encodes the insulin-like 4 protein, a member of the insulin superfamily. INSL4 encodes a precursor that
undergoes post-translational cleavage to produce 3 polypeptide chains, A-C, that form tertiary structures
composed of either all three chains, or just the A and B chains. Expression of INSL4 products occurs within the
early placental cytotrophoblast and syncytiotrophoblast. (provided by RefSeq, Jul 2008)

GeneCards Summary for INSL4 Gene:
INSL4 (insulin-like 4 (placenta)) is a protein-coding gene. Diseases associated with INSL4 include placenta accreta. GO annotations related to this gene include insulin-like growth factor receptor binding and receptor binding.

UniProtKB/Swiss-Prot: INSL4_HUMAN, Q14641
Function: May play an important role in trophoblast development and in the regulation of bone formation

Gene Wiki entry for INSL4 Gene


(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_000009.11  NC_018920.2  NT_008413.19  
Regulatory elements:
   Regulatory transcription factor binding sites in the INSL4 gene promoter:
         LHX3b/Lhx3b   LHX3a/Lhx3a   Pax-4a   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidINSL4 promoter sequence
   Search Chromatin IP Primers for INSL4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat INSL4


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

Entrez Gene cytogenetic band: 9p24   Ensembl cytogenetic band:  9p24.1   HGNC cytogenetic band: 9p24

INSL4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
INSL4 gene location

GeneLoc information about chromosome 9         GeneLoc Exon Structure

GeneLoc location for GC09P005231:  view genomic region     (about GC identifiers)

Start:
5,231,419 bp from pter      End:
5,235,304 bp from pter
Size:
3,886 bases      Orientation:
plus 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: INSL4_HUMAN, Q14641 (See protein sequence)
Recommended Name: Early placenta insulin-like peptide precursor  
Size: 139 amino acids; 15445 Da
Developmental stage: Highly expressed in the early placenta. Expression of epil peptides in the villous
cytotrophoblast is different from that displayed by the syncytiotrophoblast. In fetal tissues it was identified
in the perichondrium of all four limbs, vertebrae, and ribs. It was abundant in interbone ligaments
Secondary accessions: A8K678 Q5W127

Explore the universe of human proteins at neXtProt for INSL4: NX_Q14641

Explore proteomics data for INSL4 at MOPED


See INSL4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_002186.1  
ENSEMBL proteins: 
 ENSP00000239316  

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(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:
 IPR022421 Relaxin
 IPR023258 Placentin

Graphical View of Domain Structure for InterPro Entry Q14641

ProtoNet protein and cluster: Q14641

1 Blocks protein domain: IPB004825 Insulin/IGF/relaxin

UniProtKB/Swiss-Prot: INSL4_HUMAN, Q14641
Similarity: Belongs to the insulin family


Find genes that share domains with INSL4           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: INSL4_HUMAN, Q14641
Function: May play an important role in trophoblast development and in the regulation of bone formation

     Genatlas biochemistry entry for INSL4:
insulin-like 4,growth factor expressed in placenta and uterus

     Gene Ontology (GO): 3 molecular function terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0005102receptor binding TAS8702754
GO:0005159insulin-like growth factor receptor binding TAS8666396
GO:0005179hormone activity IEA--
     
Find genes that share ontologies with INSL4           About GenesLikeMe


Animal Models:
   genOway: Develop your customized and physiologically relevant rodent model for INSL4

miRNA
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hsa-mir-26b-5p (MIRT030220)

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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
INSL4_HUMAN, Q14641: Secreted (By similarity)
Subcellular locations from COMPARTMENTS: 

CompartmentConfidence
extracellular4

Gene Ontology (GO): 2 cellular component terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0005576extracellular region ----
GO:0005615extracellular space TAS8702754

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(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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Interactions:

    GeneGlobe Interaction Network for INSL4

Gene Ontology (GO): 5 biological process terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0007165signal transduction TAS8702754
GO:0007267cell-cell signaling TAS8702754
GO:0007275multicellular organismal development TAS8702754
GO:0007565female pregnancy TAS8702754
GO:0008283cell proliferation TAS8702754

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(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 compounds at ApexBio 

Browse Tocris compounds for INSL4

1 Novoseek inferred chemical compound relationship for INSL4 gene    About this table
Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
tyrosine 0 1 8702754 (1)



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(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 INSL4 gene: 
NM_002195.1  

Unigene Cluster for INSL4:

Insulin-like 4 (placenta)
Hs.418506  [show with all ESTs]
Unigene Representative Sequence: AL574010
1 Ensembl transcript including schematic representation, and UCSC links where relevant:
ENST00000239316(uc003ziy.3)
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Additional mRNA sequence: 

AK291543.1 BC026254.1 L34838.1 

2 DOTS entries:

DT.100747192  DT.314754 

Selected AceView cDNA sequences (see all 47):

CR601901 CF527906 BX102762 AU136752 N69496 BQ007399 AI088100 AI148843 
BX371720 AL574010 BQ004108 AL550042 CF528060 BC026254 BV178729 AI128289 
L34838 CF528405 BV167944 AA777897 R75761 NM_002195 AI784163 BQ011259 

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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INSL4 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>2/3
CGAP TAG: ACAAAAAAAA
INSL4 Expression
About this image

INSL4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

INSL4 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.418506

UniProtKB/Swiss-Prot: INSL4_HUMAN, Q14641
Tissue specificity: Expressed in placenta, uterus and in fetal perichondrium. Expression levels were increased in
both early placentas and molar pregnancies and were reduced in choriocarcinoma cells

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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 human and chimp.

Orthologs for INSL4 gene from 1 species (see representative species )    About this table
Organism Taxonomic
classification
Gene Description Human
Similarity
Orthology
Type
Details
chimpanzee
(Pan troglodytes)
Mammalia INSL41 insulin-like 4 (placenta) 98.56(n)
97.84(a)
  736816  NM_001177814.1  NP_001171285.1 


ENSEMBL Gene Tree for INSL4 (if available)
TreeFam Gene Tree for INSL4 (if available)

(Paralogs according to 1HomoloGene,
2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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Paralogs for INSL4 gene

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1 Pseudogenes.org Pseudogene for INSL4
PGOHUM00000235954


(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 INSL4 (see all 186)    About this table                                 

Genomic DataTranscription Related DataAllele Frequencies
SNP IDValidClinical
significance
Chr 9 posSequence#AA
Chg
TypeMore#Allele
freq
PopTotal
sample
More
----------
rs727016911,2
C,F--5229419(+) CCCATT/ACCCTT 1 -- us2k12Minor allele frequency- A:0.13NA 122
rs121152491,2
C,F,H--5229426(+) ccttaT/Cgattt 1 -- us2k15Minor allele frequency- C:0.10NS EA WA 538
rs780537601,2
C--5229440(+) CCGATA/GGGAGG 1 -- us2k10--------
rs783566991,2
C,F--5229457(+) TATCCC/TAGACC 1 -- us2k11Minor allele frequency- T:0.04WA 118
rs1144328811,2
F--5229523(+) ACCTCC/TCTTGA 1 -- us2k11Minor allele frequency- T:0.01WA 118
rs1120431171,2
F--5229556(+) AATTAC/TAGTAA 1 -- us2k11Minor allele frequency- T:0.50CSA 2
rs592242111,2
C,F--5229637(+) TCCTTA/GTGGGA 1 -- us2k12Minor allele frequency- G:0.06WA 120
rs1446250031,2
C--5229791(+) ATTCCA/TACCCG 1 -- us2k10--------
rs1511418251,2
--5229796(+) TACCCA/GTCAAT 1 -- us2k10--------
rs580347041,2
C,F--5229798(+) CCCGTC/TAATTT 1 -- us2k12Minor allele frequency- T:0.08WA 120

HapMap Linkage Disequilibrium report for INSL4 (5231419 - 5235304 bp)

Structural Variations
     Database of Genomic Variants (DGV) 9 variations for INSL4:    About this table    
Variant IDTypeSubtypePubMed ID
nsv831495CNV Loss17160897
dgv8017n71CNV Loss21882294
nsv525777CNV Loss19592680
nsv892145CNV Gain21882294
nsv892136CNV Gain21882294
nsv466100CNV Gain19166990
nsv527495CNV Gain19592680
nsv892141CNV Gain21882294
nsv892144CNV Gain21882294

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 600910    OMIM disorders: --

1 disease for INSL4:    
About MalaCards
placenta accreta


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4 Novoseek inferred disease relationships for INSL4 gene    About this table

Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
breast cancer 5.13 7 18035692 (5), 11861376 (1), 16322324 (1)
metastasis 0.842 2 18035692 (1), 12414911 (1)
tumors 0 3 16322324 (2), 12414911 (1)
cancer 0 3 16322324 (2), 18035692 (1)

Genetic Association Database (GAD): INSL4

Export disorders for INSL4 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 INSL4 gene, integrated from 10 sources (see all 30):
(articles sorted by number of sources associating them with INSL4)
    Utopia: connect your pdf to the dynamic
world of online information

  1. Cloning of a new member of the insulin gene superfamily (INSL4) expressed in human placenta. (PubMed id 8666396)1, 2, 3, 9 Chassin D.... Bellet D. (Genomics 1995)
  2. Identification of pro-EPIL and EPIL peptides translated from insulin- like 4 (INSL4) mRNA in human placenta. (PubMed id 9284764)1, 2, 9 Bellet D.... Bidart J.-M. (J. Clin. Endocrinol. Metab. 1997)
  3. Insulin-like 4 (INSL4) gene expression in human embryonic and trophoblastic tissues. (PubMed id 9740319)1, 2, 9 Laurent A.... Vidaud M. (Mol. Reprod. Dev. 1998)
  4. The INSL4 gene maps close to WI-5527 at 9p24.1--&gt;p23.3 clustered with two relaxin genes and outside the critical region for the monosomy 9p syndrome. (PubMed id 9730618)1, 3, 9 Veitia R....McElreavey K. (Cytogenet. Cell Genet. 1998)
  5. Transcriptional expression of genes involved in cell invasion and migration by normal and tumoral trophoblast cells. (PubMed id 12414911)1, 2, 9 Janneau J.-L.... Bellet D. (J. Clin. Endocrinol. Metab. 2002)
  6. A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population. (PubMed id 19915573)1, 4 Asano K....Kubo M. (Nat. Genet. 2009)
  7. DNA sequence and analysis of human chromosome 9. (PubMed id 15164053)1, 2 Humphray S.J.... Dunham I. (Nature 2004)
  8. 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)
  9. 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)
  10. Early placental insulin-like protein (INSL4 or EPIL) in placental and fetal membrane growth. (PubMed id 15958731)1, 9 Millar L....Bryant-Greenwood G. (Biol. Reprod. 2005)

(in PubMed, OMIM, and NCBI Bookshelf)
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 ANDOR
Aliases
Disorders
Free Text  

  Query String
PubMed
OMIM
NCBI Bookshelf
  (Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 3641 HGNC: 6087 AceView: INSL4 Ensembl:ENSG00000120211 euGenes: HUgn3641
ECgene: INSL4 H-InvDB: INSL4

(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 INSL4 Pharmacogenomics, SNPs, Pathways

(Patent information from GeneIP,
Licensable technologies from WIS Yeda, Salk, Tufts,
IP news from LifeMap Sciences, Inc.)
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Patent Information for INSL4 gene:
Search GeneIP for patents involving INSL4

GeneCards and IP:
Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
Advanced Cell Diagnostics, Animal models from genOway)
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 OriGene Antibodies for INSL4   OriGene RNAi products in human, mouse, rat for INSL4  
 OriGene qPCR primer pairs and template standards for INSL4   OriGene Protein Over-expression Lysate for INSL4  
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 OriGene Custom Antibody Services for INSL4   OriGene Custom Protein Services for INSL4  

 
 
 Block miRNA regulation of human, mouse, rat INSL4 using miScript Target Protectors SeqTarget long-range PCR primers for resequencing INSL4
 DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat INSL4 Predesigned siRNA for gene silencing in human, mouse, rat INSL4
 QuantiFast Probe-based Assays in human, mouse, rat INSL4 QuantiTect SYBR Green Assays in human, mouse, rat INSL4
 Custom PCR Arrays for INSL4 Search Chromatin IP Primers for INSL4
 Pre-validated RT2 qPCR Primer Assay in human, mouse / rat INSL4  GeneGlobe Interaction Network for INSL4
 Regulatory tfbs in INSL4 promoter
 GenScript Custom Purified and Recombinant Proteins Services for INSL4 GenScript cDNA clones with any tag delivered in your preferred vector for INSL4
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 Vector-based siRNA and miRNA, Ready for Transfection Gene Mutant Library, Variants up to 10^11
 Plasmid Preparation Custom Peptide Services
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 Search Tocris compounds for INSL4
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 Search www.enzolifesciences.com for proteins, assays, substrates, inhibitors & antibodies

 Novus Tissue Slides
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 See all of Abcam's Antibodies, Kits and Proteins for INSL4
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 Browse ESI BIO Cell Lines and PureStem Progenitors for INSL4
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 Browse SwitchGear 3'UTR luciferase reporter plasmids for INSL4
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 Search ThermoFisher Antibodies for INSL4
 Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat INSL4
 Browse compounds at ApexBio
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  Search eBioscience for proteins for INSL4
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  eBioscience FlowRNA Probe Sets
 genOway: Develop your customized and physiologically relevant rodent model for INSL4
 antibodies-online antibodies for INSL4 (14 products)
 antibodies-online kits for INSL4 (2 products)
  Search antibodies-online for peptides for INSL4
 antibodies-online proteins for INSL4 (7 products)
       
GeneCards Homepage - Last full update: 7 May 2014 - Incrementals: 9 May 2014 , 2 Jun 2014 , 26 Jun 2014 , 30 Jun 2014 , 21 Aug 2014 , 8 Sep 2014 , 7 Oct 2014

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