Details for: INSL4

Gene ID: 3641

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: INSL4

Ensembl ID: ENSG00000120211

Description: insulin like 4

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • placental villous trophoblast CL2000060
    CSI 3.45
    rCSI 5.33%
    PRS 99.87
  • syncytiotrophoblast cell CL0000525
    CSI 2.43
    rCSI 6.99%
    PRS 99.55

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [INSL4](/details-gene/3641) (Insulin Like 4) is a protein-coding gene located on chromosome 9p24.1. It encodes a member of the insulin gene superfamily, a secreted peptide hormone primarily expressed in the placenta. Functionally, [INSL4](/details-gene/3641) is involved in cell-cell signaling and hormone activity, with a specific role in promoting the proliferation of trophoblast cells during pregnancy, as first described in its cloning ([Link](https://doi.org/10.1006/geno.1995.9980)). Its high expression in placental cell types underscores its specialized function in embryonic and placental development ([Link](https://doi.org/10.1002/(sici)1098-2795(199810)51:2<123::aid-mrd1>3.0.co;2-s)). The protein is associated with the OMIM entry [600910](https://omim.org/entry/600910). ## Cellular Roles and Expression Landscape The expression profile of [INSL4](/details-gene/3641) demonstrates a highly specialized role confined to placental tissue. **Overall**, the gene shows its most significant expression in cells critical for placental function and fetal development. * **Primary Expression Context:** [INSL4](/details-gene/3641) is a defining marker for key placental cell types, exhibiting the highest significance in [placental villous trophoblast](/details-cell/CL2000060) (CSI: 3.45) and [syncytiotrophoblast cell](/details-cell/CL0000525) (CSI: 2.43). These cells form the interface between maternal and fetal circulation and are essential for nutrient exchange, hormone production, and maintaining pregnancy. The specific and high expression in these cells suggests that [INSL4](/details-gene/3641) is a crucial workhorse in placental biology. * **Functional Specificity:** The localization to trophoblastic tissues indicates that the primary function of [INSL4](/details-gene/3641) is likely restricted to the maternal-fetal unit during gestation. Research has confirmed the presence of the translated peptide in human placenta, reinforcing its role as a locally acting hormone ([Link](https://doi.org/10.1210/jcem.82.9.4359)). ## Pathways and Molecular Function The functional annotations for [INSL4](/details-gene/3641) are consistent with its role as a secreted signaling peptide in the placenta. As an extracellular protein ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)), it participates in several key biological processes and molecular functions: * **Biological Process:** [INSL4](/details-gene/3641) is annotated for involvement in [cell-cell signaling](/details-go/GO:0007267) and [signal transduction](/details-go/GO:0007165). Most notably, it is implicated in the [positive regulation of chorionic trophoblast cell proliferation](/details-go/GO:1901384), which directly aligns with its specific expression in these cells and is critical for placental growth and vascular remodeling. * **Molecular Function:** Its function as a hormone is highlighted by annotations for [hormone activity](/details-go/GO:0005179) and [signaling receptor binding](/details-go/GO:0005102). Specifically, its potential to engage with the insulin signaling pathway is suggested by its annotation for [insulin-like growth factor receptor binding](/details-go/GO:0005159), implying a role in modulating metabolic or growth signals at the maternal-fetal interface. ## Research Directions The highly specific expression and function of [INSL4](/details-gene/3641) in the placenta make it a key molecule for understanding the regulation of pregnancy and a potential factor in placental pathologies. **Proposed Hypotheses:** 1. Given its established role in promoting trophoblast proliferation ([GO:1901384](https://www.ebi.ac.uk/QuickGO/term/GO:1901384)), dysregulated expression of [INSL4](/details-gene/3641) may contribute to pregnancy complications characterized by abnormal placental development, such as preeclampsia or intrauterine growth restriction (IUGR). Overexpression could lead to abnormal invasion, while underexpression could impair placental growth. 2. As a member of the insulin superfamily, [INSL4](/details-gene/3641) may exert endocrine or paracrine effects on maternal metabolism to support fetal nutrient demands. It could potentially modulate maternal insulin sensitivity or glucose uptake in peripheral tissues, and its misregulation could contribute to the development of gestational diabetes. **Experimental Approach:** To test the hypothesis that [INSL4](/details-gene/3641) is critical for proper placental function (Hypothesis 1), a multi-faceted approach using human placental explants or trophoblast cell lines (e.g., BeWo) could be employed. One could use lentiviral vectors to stably overexpress or shRNA to knock down [INSL4](/details-gene/3641) expression. The functional consequences would be assessed using proliferation assays (e.g., Ki-67 staining), migration and invasion assays (e.g., transwell Matrigel invasion assays), and analysis of key signaling pathways (e.g., PI3K/AKT, MAPK) via western blotting. This would directly link [INSL4](/details-gene/3641) levels to the cellular behaviors underlying healthy placental development. **Therapeutic Potential:** Due to its specific expression in the placenta, [INSL4](/details-gene/3641) presents an intriguing but challenging therapeutic target. It is unlikely to be a target for systemic therapies like cancer due to its restricted expression. However, it could serve as a valuable biomarker in maternal circulation for monitoring placental health and detecting pathologies like preeclampsia early. As a secreted peptide, recombinant [INSL4](/details-gene/3641) could be explored as a potential therapeutic agent itself, administered to treat conditions of placental insufficiency. Conversely, for conditions involving trophoblast over-invasion, a monoclonal antibody designed to neutralize circulating [INSL4](/details-gene/3641) could be a potential strategy, although the therapeutic window during pregnancy would be extremely narrow and require careful consideration.

Genular Protein ID: 2028027322

Symbol: INSL4_HUMAN

Name: Early placenta insulin-like peptide

UniProtKB Accession Codes:

Q14641 A8K678 Q5W127

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 GO 6 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 1 STRING 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8666396

Title: Cloning of a new member of the insulin gene superfamily (INSL4) expressed in human placenta.

PubMed ID: 8666396

DOI: 10.1006/geno.1995.9980

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 15340161

Title: Signal peptide prediction based on analysis of experimentally verified cleavage sites.

PubMed ID: 15340161

DOI: 10.1110/ps.04682504

PubMed ID: 9284764

Title: Identification of pro-EPIL and EPIL peptides translated from insulin-like 4 (INSL4) mRNA in human placenta.

PubMed ID: 9284764

DOI: 10.1210/jcem.82.9.4359

PubMed ID: 9740319

Title: Insulin-like 4 (INSL4) gene expression in human embryonic and trophoblastic tissues.

PubMed ID: 9740319

DOI: 10.1002/(sici)1098-2795(199810)51:2&lt;123::aid-mrd1&gt;3.0.co;2-s

PubMed ID: 12414911

Title: Transcriptional expression of genes involved in cell invasion and migration by normal and tumoral trophoblast cells.

PubMed ID: 12414911

DOI: 10.1210/jc.2002-021093

Sequence Information:

  • Length: 139
  • Mass: 15445
  • Checksum: 47FB61F6F86C1342
  • Sequence:
    • MASLFRSYLP AIWLLLSQLL RESLAAELRG CGPRFGKHLL SYCPMPEKTF TTTPGGWLLE 
SGRPKEMVST SNNKDGQALG TTSEFIPNLS PELKKPLSEG QPSLKKIILS RKKRSGRHRF 
DPFCCEVICD DGTSVKLCT