Details for: STARD8

Gene ID: 9754

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: STARD8

Ensembl ID: ENSG00000130052

Description: StAR related lipid transfer domain containing 8

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 4.2
    rCSI 10.95%
    PRS 96.93
  • Kupffer cell CL0000091
    CSI 3.61
    rCSI 8.25%
    PRS 96.51
  • pulmonary capillary endothelial cell CL4028001
    CSI 3.34
    rCSI 6.36%
    PRS 97.99
  • blood vessel endothelial cell CL0000071
    CSI 2.72
    rCSI 5.64%
    PRS 94.88
  • cerebral cortex endothelial cell CL1001602
    CSI 2.53
    rCSI 4.38%
    PRS 93.08
  • cardiac endothelial cell CL0010008
    CSI 1.77
    rCSI 7.12%
    PRS 96.1
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 0.98
    rCSI 1.19%
    PRS 80.19

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

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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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 [STARD8](/details-gene/9754) (StAR related lipid transfer domain containing 8) is a protein-coding gene located on the X chromosome that functions as a GTPase-activating protein (GAP) for Rho family proteins, including RhoA and Cdc42. Its molecular activities are centrally involved in the regulation of the actin cytoskeleton, cell morphology, and signal transduction. **Overall**, expression data highlight [STARD8](/details-gene/9754) as a significant gene in tissue-resident macrophage populations, such as [Kupffer cell](/details-cell/CL0000091)s, and various types of endothelial cells, including [pulmonary capillary endothelial cell](/details-cell/CL4028001)s. Research indicates it functions as a tumor suppressor, with its downregulation being implicated in cancer progression ([Link](https://doi.org/10.1038/sj.onc.1210244)). The gene is associated with a clinical phenotype cataloged under OMIM [300689](https://omim.org/entry/300689). ## Cellular Roles and Expression Landscape The expression profile of [STARD8](/details-gene/9754) suggests a prominent role in both the innate immune system and the vasculature. The gene shows its highest significance in macrophage populations, particularly [kidney interstitial alternatively activated macrophage](/details-cell/CL1000695) (CSI: 4.20) and the liver-resident [Kupffer cell](/details-cell/CL0000091) (CSI: 3.61). This strong expression pattern in tissue-resident phagocytes points towards a role in regulating key macrophage functions such as migration, phagocytosis, and tissue surveillance, which are heavily dependent on dynamic cytoskeletal rearrangement. Concurrently, [STARD8](/details-gene/9754) is highly significant across multiple endothelial cell types, including [pulmonary capillary endothelial cell](/details-cell/CL4028001) (CSI: 3.34), [blood vessel endothelial cell](/details-cell/CL0000071) (CSI: 2.72), [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 2.53), and [cardiac endothelial cell](/details-cell/CL0010008) (CSI: 1.77). This widespread expression in the endothelium is consistent with its function in regulating cell-cell junctions and adhesion, processes critical for maintaining vascular barrier integrity. Moderate significance is also observed in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 0.98), suggesting a potential secondary role in adaptive immune memory. ## Pathways and Molecular Function The functional annotations for [STARD8](/details-gene/9754) converge on its role as a key negative regulator of Rho GTPase signaling. As a protein with [Gtpase activator activity](/details-go/GO:0005096), it promotes the hydrolysis of GTP to GDP on Rho proteins, thereby inactivating them. This activity is central to several Reactome pathways, including the [Rho gtpase cycle](/details-pathway/R-HSA-9012999), [Rhoa gtpase cycle](/details-pathway/R-HSA-8980692), and [Cdc42 gtpase cycle](/details-pathway/R-HSA-9013148). These signaling cascades are fundamental to [Actin cytoskeleton organization](/details-go/GO:0030036), which is critical for cell shape, motility, and adhesion. Consistent with this function, [STARD8](/details-gene/9754) protein localizes to the [focal adhesion](/details-go/GO:0005925), a cellular structure crucial for cell-matrix interactions and mechanosensing ([Link](https://doi.org/10.1016/j.bbrc.2007.10.052)). Its involvement in these processes aligns with its high expression in motile macrophages and endothelial cells, which require precise spatiotemporal control of their cytoskeleton to perform their physiological functions. The protein also possesses a [Lipid binding](/details-go/GO:0008289) domain, characteristic of the StAR-related lipid transfer (START) protein family, although its specific role in lipid transport remains an area of active investigation. ## Research Directions Given that [STARD8](/details-gene/9754), also known as Deleted in Liver Cancer 3 (DLC3), has established roles as a tumor suppressor and a regulator of the cytoskeleton, several research avenues emerge. **Proposed Hypotheses:** 1. **Hypothesis 1:** Based on its high significance in macrophages and its function as a Rho/Cdc42 GAP, [STARD8](/details-gene/9754) is a critical regulator of macrophage polarization. Its activity may be required to resolve pro-inflammatory (M1) phenotypes by controlling the cytoskeletal organization necessary for phagocytosis and motility, with its loss promoting a more stationary, unresolved inflammatory state. 2. **Hypothesis 2:** In endothelial cells, [STARD8](/details-gene/9754) is essential for maintaining vascular barrier integrity by stabilizing focal adhesions and adherens junctions through negative regulation of RhoA. Downregulation of [STARD8](/details-gene/9754) during inflammation could contribute to increased vascular permeability and leukocyte extravasation. 3. **Hypothesis 3:** The tumor suppressor function of [STARD8](/details-gene/9754) in liver cancer ([Link](https://doi.org/10.1038/sj.onc.1210244)) is primarily mediated by its ability to enforce contact inhibition. Its loss allows cancer cells to overcome density-dependent growth arrest by dysregulating RhoA-mediated cytoskeletal tension at cell-cell junctions. **Experimental Approach to Test Hypothesis 1:** To test the role of [STARD8](/details-gene/9754) in macrophage polarization, one could utilize a CRISPR-Cas9 knockout or siRNA-mediated knockdown approach in primary human monocytes or a murine macrophage cell line like RAW 264.7. Control and [STARD8](/details-gene/9754)-deficient cells would be polarized towards M1 (LPS/IFN-γ) and M2 (IL-4/IL-13) phenotypes. The impact on polarization could be assessed by measuring the expression of canonical M1/M2 marker genes (e.g., *iNOS*, *Arg1*) via qPCR, analyzing cytokine secretion (e.g., TNF-α, IL-10) using ELISA, and evaluating functional changes in phagocytic capacity using fluorescently labeled zymosan particles. These functional readouts could be directly correlated with RhoA/Cdc42 activity levels using G-LISA or pull-down assays. **Therapeutic Potential:** The existing literature strongly suggests that [STARD8](/details-gene/9754) functions as a tumor suppressor, particularly in liver cancer where its expression is often diminished ([Link](https://doi.org/10.1038/sj.onc.1210244)). Therefore, therapeutic strategies would likely focus on **activation** or restoration of its function rather than inhibition. The development of small molecules that stabilize [STARD8](/details-gene/9754) protein or enhance its GAP activity could represent a novel therapeutic strategy to restore contact inhibition and suppress tumor growth. Alternatively, gene therapy approaches aimed at re-introducing [STARD8](/details-gene/9754) expression in tumor cells could be explored as a potential treatment for cancers characterized by its loss.

Genular Protein ID: 2980139488

Symbol: STAR8_HUMAN

Name: StAR-related lipid transfer protein 8

UniProtKB Accession Codes:

Q92502 A8K6T2 D3DVT9 Q5JST0 Q68DG7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 3 ExpressionAtlas 1 GO 6 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 3 RefSeq 4 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8724849

Title: Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1.

PubMed ID: 8724849

DOI: 10.1093/dnares/3.1.17

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 17976533

Title: START-GAP3/DLC3 is a GAP for RhoA and Cdc42 and is localized in focal adhesions regulating cell morphology.

PubMed ID: 17976533

DOI: 10.1016/j.bbrc.2007.10.052

PubMed ID: 17297465

Title: Deleted in liver cancer 3 (DLC-3), a novel Rho GTPase-activating protein, is downregulated in cancer and inhibits tumor cell growth.

PubMed ID: 17297465

DOI: 10.1038/sj.onc.1210244

PubMed ID: 17517630

Title: Oncogenic inhibition by a deleted in liver cancer gene requires cooperation between tensin binding and Rho-specific GTPase-activating protein activities.

PubMed ID: 17517630

DOI: 10.1073/pnas.0703033104

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 1023
  • Mass: 112601
  • Checksum: F93804B352450DE2
  • Sequence:
    • MTLNNCASMK LEVHFQSKQN EDSEEEEQCT ISSHWAFQQE SKCWSPMGSS DLLAPPSPGL 
PATSSCESVL TELSATSLPV ITVSLPPEPA DLPLPGRAPS SSDRPLLSPT QGQEGPQDKA 
KKRHRNRSFL KHLESLRRKE KSGSQQAEPK HSPATSEKVS KASSFRSCRG FLSAGFYRAK 
NWAATSAGGS GANTRKAWEA WPVASFRHPQ WTHRGDCLVH VPGDHKPGTF PRSLSIESLC 
PEDGHRLADW QPGRRWGCEG RRGSCGSTGS HASTYDNLPE LYPAEPVMVG AEAEDEDDEE 
SGGSYAHLDD ILQHVWGLQQ RVELWSRAMY PDLGPGDEEE EEATSSVEIA TVEVKCQAEA 
LSQMEVPAHG ESPAWAQAEV QPAVLAPAQA PAEAEPVAQE EAEAPAPAPA PAPAQDSEQE 
AHSGGEPTFA SSLSVEEGHS ISDTVASSSE LDSSGNSMNE AEAAGPLAGL QASMPRERRD 
SGVGASLTRP CRKLRWHSFQ NSHRPSLNSE SLEINRQFAG QINLLHKGSL LRLTAFMEKY 
TVPHKQGWVW SMPKFMRRNK TPDYRGQHVF GVPPLIHVQR TGQPLPQSIQ QAMRYLRSQC 
LDQVGIFRKS GVKSRIQNLR QMNETSPDNV CYEGQSAYDV ADLLKQYFRD LPEPIFTSKL 
TTTFLQIYQL LPKDQWLAAA QAATLLLPDE NREVLQTLLY FLSDIASAEE NQMTAGNLAV 
CLAPSIFHLN VSKKDSPSPR IKSKRSLIGR PGPRDLSDNM AATQGLSHMI SDCKKLFQVP 
QDMVLQLCSS YSAAELSPPG PALAELRQAQ AAGVSLSLYM EENIQDLLRD AAERFKGWMS 
VPGPQHTELA CRKAPDGHPL RLWKASTEVA APPAVVLHRV LRERALWDED LLRAQVLEAL 
MPGVELYHYV TDSMAPHPCR DFVVLRMWRS DLPRGGCLLV SQSLDPEQPV PESGVRALML 
TSQYLMEPCG LGRSRLTHIC RADLRGRSPD WYNKVFGHLC AMEVAKIRDS FPTLQAAGPE 
TKL