Details for: STARD4

Gene ID: 134429

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: STARD4

Ensembl ID: ENSG00000164211

Description: StAR related lipid transfer domain containing 4

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • epithelial cell of lower respiratory tract CL0002632
    CSI 24.63
    rCSI 19.09%
    PRS 92.04
  • elicited macrophage CL0000861
    CSI 7.25
    rCSI 6.66%
    PRS 93.98
  • lung secretory cell CL1000272
    CSI 6.68
    rCSI 16.54%
    PRS 89.8
  • Kupffer cell CL0000091
    CSI 4.22
    rCSI 9.66%
    PRS 90.29
  • club cell CL0000158
    CSI 3.81
    rCSI 5.58%
    PRS 84.64
  • cerebral cortex neuron CL0010012
    CSI 3.39
    rCSI 13.81%
    PRS 82.01
  • retinal pigment epithelial cell CL0002586
    CSI 3.24
    rCSI 6.42%
    PRS 85.7
  • melanocyte CL0000148
    CSI 3.2
    rCSI 2.37%
    PRS 85.28
  • goblet cell CL0000160
    CSI 2.91
    rCSI 2.75%
    PRS 87.11
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.75
    rCSI 6.17%
    PRS 76.08
  • pulmonary capillary endothelial cell CL4028001
    CSI 2.71
    rCSI 5.17%
    PRS 94.99
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.71
    rCSI 3.23%
    PRS 75.66
  • group 3 innate lymphoid cell CL0001071
    CSI 2.62
    rCSI 1.97%
    PRS 92.75
  • cardiac muscle cell CL0000746
    CSI 2.61
    rCSI 3.75%
    PRS 81.3
  • enterocyte CL0000584
    CSI 2.6
    rCSI 4.19%
    PRS 86.35
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 2.53
    rCSI 3.32%
    PRS 95.6
  • stem cell CL0000034
    CSI 2.52
    rCSI 2.43%
    PRS 85.02
  • type B pancreatic cell CL0000169
    CSI 2.37
    rCSI 5.25%
    PRS 89.32
  • cerebral cortex endothelial cell CL1001602
    CSI 2.32
    rCSI 4.01%
    PRS 83.64
  • peripheral nervous system neuron CL2000032
    CSI 2.26
    rCSI 3.07%
    PRS 82.87
  • blood vessel endothelial cell CL0000071
    CSI 2.18
    rCSI 4.52%
    PRS 87.56
  • colon epithelial cell CL0011108
    CSI 2.15
    rCSI 2.25%
    PRS 86.95
  • retinal ganglion cell CL0000740
    CSI 2.11
    rCSI 4.67%
    PRS 78.32
  • retinal bipolar neuron CL0000748
    CSI 2.04
    rCSI 3.81%
    PRS 80.41
  • BEST4+ enteroycte CL4030026
    CSI 2.01
    rCSI 2.5%
    PRS 89.23
  • granulocyte CL0000094
    CSI 2.01
    rCSI 3.07%
    PRS 93.81
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.01
    rCSI 2.49%
    PRS 73.45
  • colonocyte CL1000347
    CSI 1.98
    rCSI 2.84%
    PRS 87.73
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.95
    rCSI 3.45%
    PRS 75.07
  • M cell of gut CL0000682
    CSI 1.94
    rCSI 2.07%
    PRS 91.59
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.92
    rCSI 1.48%
    PRS 92.39
  • glioblast CL0000030
    CSI 1.86
    rCSI 2.97%
    PRS 81.82
  • intestine goblet cell CL0019031
    CSI 1.8
    rCSI 1.59%
    PRS 86.84
  • placental villous trophoblast CL2000060
    CSI 1.79
    rCSI 2.76%
    PRS 87.68
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.77
    rCSI 42.75%
    PRS 73.63
  • direct pathway medium spiny neuron CL4023026
    CSI 1.74
    rCSI 41.66%
    PRS 73.37
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 1.71
    rCSI 3.11%
    PRS 82.75
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.7
    rCSI 2.18%
    PRS 85.92
  • small intestine goblet cell CL1000495
    CSI 1.64
    rCSI 3.6%
    PRS 91.96
  • ON midget ganglion cell CL4033046
    CSI 1.57
    rCSI 31.94%
    PRS 80.5
  • enteroendocrine cell CL0000164
    CSI 1.55
    rCSI 2.12%
    PRS 87.96
  • innate lymphoid cell CL0001065
    CSI 1.48
    rCSI 3.05%
    PRS 84.12
  • lung macrophage CL1001603
    CSI 1.42
    rCSI 3.16%
    PRS 93.75
  • retinal blood vessel endothelial cell CL0002585
    CSI 1.41
    rCSI 2.25%
    PRS 91.81
  • ON parasol ganglion cell CL4033052
    CSI 1.18
    rCSI 16.67%
    PRS 81.57
  • OFF midget ganglion cell CL4033047
    CSI 1.12
    rCSI 22.75%
    PRS 81.25
  • colon goblet cell CL0009039
    CSI 1.1
    rCSI 2.6%
    PRS 91.3
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.95
    rCSI 2.3%
    PRS 73.37
  • endothelial cell of placenta CL0009092
    CSI 0.83
    rCSI 4.09%
    PRS 93.43
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.78
    rCSI 2.44%
    PRS 76.99
  • type EC enteroendocrine cell CL0000577
    CSI 0.72
    rCSI 2.57%
    PRS 90.71
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.64
    rCSI 2.29%
    PRS 73.59
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.63
    rCSI 2.37%
    PRS 75.87
  • pancreatic stellate cell CL0002410
    CSI 0.57
    rCSI 3.29%
    PRS 91.02
  • central nervous system neuron CL2000029
    CSI 0.47
    rCSI 3.42%
    PRS 80.38
  • group 2 innate lymphoid cell CL0001069
    CSI 0.35
    rCSI 1.9%
    PRS 97.42

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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Legend:
  • Query Gene
  • 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 Analyzed for its expression specificity (CSI Z-SCORE), [STARD4](/details-gene/134429) is revealed not as a cell-specific marker but as a broadly expressed gene essential for intracellular cholesterol transport. Its consistent presence across diverse cell types, coupled with its core function in lipid metabolism, suggests it plays a fundamental housekeeping role in maintaining cellular cholesterol homeostasis rather than defining a specific cellular identity. ## Cellular Roles and Expression Landscape The expression profile of [STARD4](/details-gene/134429), when evaluated for specificity, indicates a ubiquitous rather than a cell-type-defining role. The **Overall** analysis shows consistently low **CSI (Z-SCORE)** values (0.00) and non-significant p-values (p > 0.3) across a wide array of functionally distinct cells. This includes cell types from various tissues such as [epithelial cell of lower respiratory tract](/details-cell/CL0002632), [Kupffer cell](/details-cell/CL0000091) in the liver, [cerebral cortex neuron](/details-cell/CL0010012), and [cardiac muscle cell](/details-cell/CL0000746). This lack of statistical specificity suggests that while [STARD4](/details-gene/134429) is present and functional in these cells, its expression level is not uniquely elevated to distinguish them from other cell populations. Instead, its broad expression pattern is consistent with a housekeeping function critical for the viability and function of most, if not all, cell types. This is strongly supported by its known role as an intracellular cholesterol transporter, a process fundamental to membrane integrity, steroid synthesis, and cellular signaling in virtually all vertebrate cells (PubMed: [18403318](https://pubmed.ncbi.nlm.nih.gov/18403318/)). The diverse list of "Top Expressed Cells" should therefore be interpreted not as sites of specific enrichment, but as evidence of the gene's widespread necessity. ## Pathways and Molecular Function The functional annotations for [STARD4](/details-gene/134429) align perfectly with its broad expression profile, reinforcing its role as a key facilitator of a fundamental metabolic process. Gene Ontology (GO) analysis highlights its involvement in '[intracellular cholesterol transport](/details-ontology/GO:0032367)', '[cholesterol import](/details-ontology/GO:0070508)', and '[cholesterol binding](/details-ontology/GO:0015485)'. These functions are crucial for moving cholesterol from the endoplasmic reticulum to other cellular compartments, such as lipid droplets for storage or mitochondria for steroidogenesis (PubMed: [18403318](https://pubmed.ncbi.nlm.nih.gov/18403318/)). Its localization to the '[cytosol](/details-ontology/GO:0005829)' and '[endoplasmic reticulum](/details-ontology/GO:0005783)' is consistent with its function as a soluble lipid transfer protein. Furthermore, its participation in Reactome pathways such as '[Metabolism of lipids](/details-pathway/R-HSA-556833)' and '[Metabolism of steroids](/details-pathway/R-HSA-8957322)' underscores its integral position within the cell's core metabolic network. This central role in a universal process explains why a specificity-based analysis (CSI Z-SCORE) does not identify it as a marker for any single cell type; rather, its function is a common requirement shared by many. ## Research Directions The ubiquitous expression of [STARD4](/details-gene/134429) suggests its regulation and function are likely critical under conditions of metabolic stress or in tissues with high lipid flux. While it may not serve as a specific cell marker, its functional importance could be highly context-dependent. ### Testable Hypotheses: 1. **Hypothesis:** The expression of [STARD4](/details-gene/134429) is upregulated as a compensatory response to cellular cholesterol overload, serving to sequester excess free cholesterol into less toxic cholesteryl esters. * **Experimental Approach:** Treat cell lines with high cholesterol demands, such as macrophages (RAW 264.7) or hepatocytes (HepG2), with acetylated LDL to induce a foam cell-like phenotype. Quantify [STARD4](/details-gene/134429) mRNA and protein levels via qPCR and Western blot, respectively. Functional consequences can be assessed by measuring the rate of cholesteryl ester formation using radiolabeled oleate. 2. **Hypothesis:** Although broadly expressed, the function of [STARD4](/details-gene/134429) is non-redundant and essential in steroidogenic tissues, where cholesterol transport is a rate-limiting step for hormone production. * **Experimental Approach:** Utilize CRISPR/Cas9 to knock out [STARD4](/details-gene/134429) in a human adrenal carcinoma cell line (e.g., H295R). Stimulate steroidogenesis with forskolin and measure the output of key steroid hormones like cortisol and DHEA-S using ELISA or mass spectrometry. A significant reduction in hormone production post-knockout would confirm its non-redundant role. 3. **Hypothesis:** In the central nervous system, where cells like [astrocytes](/details-cell/CL0002605) and [neurons](/details-cell/CL0010012) require precise cholesterol regulation for synaptogenesis and membrane health, disruption of [STARD4](/details-gene/134429) will lead to impaired neuronal function and increased susceptibility to lipid-induced stress. * **Experimental Approach:** Generate a conditional knockout mouse model to ablate [STARD4](/details-gene/134429) specifically in neural cells. Assess the mice for behavioral deficits, analyze synaptic density and morphology in the hippocampus via immunohistochemistry, and measure levels of neurodegeneration markers (e.g., Fluoro-Jade staining) following a high-fat diet challenge. ### Therapeutic Potential: Given its fundamental role in cholesterol metabolism, [STARD4](/details-gene/134429) represents a potential therapeutic target in diseases of lipid dysregulation. Systemic targeting may be challenging due to its ubiquitous expression. However, modulating its activity could be beneficial in localized contexts. For example, enhancing [STARD4](/details-gene/134429) expression or activity in macrophages within atherosclerotic plaques could promote cholesterol efflux and reduce foam cell formation. Conversely, inhibiting its function in certain cancers that exhibit hyperactive steroid hormone signaling could represent a novel anti-neoplastic strategy. Future therapeutic development would likely require tissue-specific delivery mechanisms to mitigate off-target effects.

Genular Protein ID: 3033473855

Symbol: STAR4_HUMAN

Name: StAR-related lipid transfer protein 4

UniProtKB Accession Codes:

Q96DR4 Q86TN9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChEBI 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 3 ExpressionAtlas 1 GO 11 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 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 PDB 2 PDBsum 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 7 Rhea 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissLipids 2 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12011452

Title: The cholesterol-regulated StarD4 gene encodes a StAR-related lipid transfer protein with two closely related homologues, StarD5 and StarD6.

PubMed ID: 12011452

DOI: 10.1073/pnas.052143799

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

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: 18403318

Title: Intracellular cholesterol transporter StarD4 binds free cholesterol and increases cholesteryl ester formation.

PubMed ID: 18403318

DOI: 10.1194/jlr.m700537-jlr200

Sequence Information:

  • Length: 205
  • Mass: 23517
  • Checksum: 59A8D4B95BFAE27F
  • Sequence:
    • MEGLSDVASF ATKLKNTLIQ YHSIEEDKWR VAKKTKDVTV WRKPSEEFNG YLYKAQGVID 
DLVYSIIDHI RPGPCRLDWD SLMTSLDILE NFEENCCVMR YTTAGQLWNI ISPREFVDFS 
YTVGYKEGLL SCGISLDWDE KRPEFVRGYN HPCGWFCVPL KDNPNQSLLT GYIQTDLRGM 
IPQSAVDTAM ASTLTNFYGD LRKAL

Genular Protein ID: 2002732111

Symbol: B0AZS2_HUMAN

Name: N/A

UniProtKB Accession Codes:

B0AZS2

Database IDs:

ARBA 2 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 6 GO 7 Gene3D 1 InterPro 4 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 2 PeptideAtlas 1 Pfam 1 RefSeq 4 SUPFAM 1

Citations:

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

Sequence Information:

  • Length: 107
  • Mass: 12163
  • Checksum: BD5D18B73C177423
  • Sequence:
    • MRYTTAGQLW NIISPREFVD FSYTVGYKEG LLSCGISLDW DEKRPEFVRG YNHPCGWFCV 
PLKDNPNQSL LTGYIQTDLR GMIPQSAVDT AMASTLTNFY GDLRKAL