Details for: FABP4

Gene ID: 2167

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: FABP4

Ensembl ID: ENSG00000170323

Description: fatty acid binding protein 4

Cell Significance Landscape

Associated with

Significant Cells

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

  • adipocyte CL0000136
    CSI 39.65
    rCSI 50.91%
    PRS 79.78
  • alveolar macrophage CL0000583
    CSI 38.3
    rCSI 63.09%
    PRS 90.63
  • endothelial cell of artery CL1000413
    CSI 24.78
    rCSI 36.31%
    PRS 91.4
  • alternatively activated macrophage CL0000890
    CSI 23.08
    rCSI 29.02%
    PRS 94.26
  • microcirculation associated smooth muscle cell CL0008035
    CSI 19.39
    rCSI 56.15%
    PRS 87.63
  • stromal cell CL0000499
    CSI 16.35
    rCSI 46%
    PRS 84.31
  • epicardial adipocyte CL1000309
    CSI 15.89
    rCSI 51.69%
    PRS 85.74
  • capillary endothelial cell CL0002144
    CSI 14.28
    rCSI 26.17%
    PRS 90.01
  • endothelial cell of lymphatic vessel CL0002138
    CSI 13.32
    rCSI 26.41%
    PRS 90.52
  • perivascular cell CL4033054
    CSI 12.52
    rCSI 17.11%
    PRS 91.81
  • tracheobronchial smooth muscle cell CL0019019
    CSI 10.38
    rCSI 18.31%
    PRS 91.54
  • fibroblast of lung CL0002553
    CSI 9.74
    rCSI 9.06%
    PRS 89.63
  • blood vessel endothelial cell CL0000071
    CSI 9.53
    rCSI 19.78%
    PRS 86.59
  • lung endothelial cell CL1001567
    CSI 7.96
    rCSI 18.55%
    PRS 94.74
  • vein endothelial cell CL0002543
    CSI 7.88
    rCSI 21.5%
    PRS 92.21
  • cardiac endothelial cell CL0010008
    CSI 7.88
    rCSI 31.78%
    PRS 89.14
  • mononuclear phagocyte CL0000113
    CSI 7.41
    rCSI 16.32%
    PRS 91.11
  • retinal blood vessel endothelial cell CL0002585
    CSI 7.27
    rCSI 11.61%
    PRS 91.25
  • type EC enteroendocrine cell CL0000577
    CSI 7.21
    rCSI 25.6%
    PRS 90.17
  • subcutaneous adipocyte CL0002521
    CSI 6.92
    rCSI 35.43%
    PRS 90.55
  • pancreatic stellate cell CL0002410
    CSI 6.62
    rCSI 38.51%
    PRS 90.36
  • elicited macrophage CL0000861
    CSI 6.35
    rCSI 5.83%
    PRS 93.5
  • mast cell CL0000097
    CSI 6.34
    rCSI 13.7%
    PRS 88.22
  • lung pericyte CL0009089
    CSI 6.31
    rCSI 16.65%
    PRS 92.71
  • pericyte CL0000669
    CSI 6.15
    rCSI 16.39%
    PRS 65.01
  • vein endothelial cell of respiratory system CL4033008
    CSI 6.1
    rCSI 41.9%
    PRS 92.14
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 6.09
    rCSI 7.99%
    PRS 95.09
  • vascular associated smooth muscle cell CL0000359
    CSI 5.5
    rCSI 17.85%
    PRS 86.6
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 5.47
    rCSI 6.61%
    PRS 93.63
  • metallothionein-positive alveolar macrophage CL4033042
    CSI 5.4
    rCSI 58.73%
    PRS 94.48
  • lung macrophage CL1001603
    CSI 4.96
    rCSI 11.08%
    PRS 93.25
  • endothelial cell of periportal hepatic sinusoid CL0019021
    CSI 3.81
    rCSI 17.5%
    PRS 90.79
  • lung interstitial macrophage CL4033043
    CSI 3.8
    rCSI 8.54%
    PRS 96.1
  • mesothelial cell CL0000077
    CSI 3.73
    rCSI 14.59%
    PRS 70.42
  • pulmonary artery endothelial cell CL1001568
    CSI 3.58
    rCSI 4.88%
    PRS 93.53
  • alveolar adventitial fibroblast CL4028006
    CSI 3.5
    rCSI 5.53%
    PRS 89.45
  • melanocyte of skin CL1000458
    CSI 3.18
    rCSI 4.34%
    PRS 58.32
  • basal cell of epidermis CL0002187
    CSI 2.94
    rCSI 5.21%
    PRS 59.1
  • endothelial cell of vascular tree CL0002139
    CSI 2.9
    rCSI 15.87%
    PRS 85.15
  • multi-ciliated epithelial cell CL0005012
    CSI 2.74
    rCSI 2.74%
    PRS 82.9
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 2.56
    rCSI 3.1%
    PRS 69.18
  • suprabasal keratinocyte CL4033013
    CSI 1.92
    rCSI 3.13%
    PRS 58.5
  • lung ciliated cell CL1000271
    CSI 1.52
    rCSI 1.76%
    PRS 82.7
  • cardiac blood vessel endothelial cell CL0010006
    CSI 1.48
    rCSI 10.47%
    PRS 82.07
  • intermediate monocyte CL0002393
    CSI 1.48
    rCSI 2.23%
    PRS 92.66
  • blood vessel smooth muscle cell CL0019018
    CSI 1.14
    rCSI 9.26%
    PRS 84.92
  • smooth muscle cell of the pulmonary artery CL0002591
    CSI 0.68
    rCSI 5.18%
    PRS 88.61

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.

Comma-separated if multiple.
Comma-separated if multiple.
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 [FABP4](/details-gene/2167) (Fatty Acid Binding Protein 4) is a protein-coding gene located on chromosome 8q21.13. As its name suggests, [FABP4](/details-gene/2167) is a member of the fatty acid-binding protein family and plays a central role in intracellular lipid transport and metabolism. **Overall**, its expression is most significant in [adipocyte](/details-cell/CL0000136), where it is a canonical marker involved in differentiation and lipid homeostasis. It also shows prominent expression in immune cells, particularly [alveolar macrophage](/details-cell/CL0000583), and various endothelial cell types, suggesting a multifaceted role at the interface of metabolism, immunity, and vascular biology. Clinically, it is associated with metabolic syndromes ([600434](https://omim.org/entry/600434)). ## Cellular Roles and Expression Landscape The expression profile of [FABP4](/details-gene/2167) highlights its dual function in metabolic and immune processes. **Overall**, it is most significantly expressed in [adipocyte](/details-cell/CL0000136) (CSI: 39.65) and [epicardial adipocyte](/details-cell/CL1000309) (CSI: 15.89), which is consistent with its established role in fat cell differentiation and triglyceride metabolism. The initial characterization and cloning of its cDNA was from human adipocytes [Link](https://doi.org/10.1021/bi00448a003). Beyond adipocytes, [FABP4](/details-gene/2167) exhibits very high significance in macrophage populations, including [alveolar macrophage](/details-cell/CL0000583) (CSI: 38.30) and [alternatively activated macrophage](/details-cell/CL0000890) (CSI: 23.08). This strong expression pattern points towards a critical role in modulating macrophage function, likely through the regulation of lipid-mediated signaling pathways that influence inflammation and pathogen response. A third prominent expression domain is the vasculature. [FABP4](/details-gene/2167) is significantly expressed in [endothelial cell of artery](/details-cell/CL1000413) (CSI: 24.78), [capillary endothelial cell](/details-cell/CL0002144) (CSI: 14.28), and [endothelial cell of lymphatic vessel](/details-cell/CL0002138) (CSI: 13.32), as well as associated [microcirculation associated smooth muscle cell](/details-cell/CL0008035) (CSI: 19.39). This suggests its involvement in fatty acid transport across the endothelial barrier and in the metabolic regulation of vascular tissues. ## Pathways and Molecular Function Functionally, [FABP4](/details-gene/2167) is primarily involved in lipid metabolism and transport. Gene Ontology annotations confirm its molecular function as [Fatty acid binding](/details-go/GO:0005504) and specifically [Long-chain fatty acid binding](/details-go/GO:0036041). Its biological activities are deeply connected to [Adipogenesis](/details-pathway/R-HSA-9843745) and the [Transcriptional regulation of white adipocyte differentiation](/details-pathway/R-HSA-381340), which aligns with its high expression in [adipocyte](/details-cell/CL0000136). The protein is localized to the [Cytoplasm](/details-go/GO:0005737), [Lipid droplet](/details-go/GO:0005811), and can also be found in the [Extracellular exosome](/details-go/GO:0070062), suggesting it may function both intracellularly and as a secreted adipokine. The gene's role in immune cells is supported by its involvement in processes like [Positive regulation of inflammatory response](/details-go/GO:0050729) and [Response to bacterium](/details-go/GO:0009617). This suggests that within macrophages, [FABP4](/details-gene/2167) may shuttle fatty acids that act as signaling molecules to regulate inflammatory pathways. Its participation in the cellular response to tumor necrosis factor ([GO:0071356](https://www.ebi.ac.uk/QuickGO/term/GO:0071356)) further strengthens its connection to inflammatory signaling. ## Research Directions The diverse expression pattern of [FABP4](/details-gene/2167) across metabolic, immune, and vascular cells presents several avenues for future investigation. Its role as a secreted protein from adipocytes and its high expression in macrophages positions it as a key link between obesity and chronic inflammation (metaflammation). **Testable Hypotheses:** 1. The high expression of [FABP4](/details-gene/2167) in [alveolar macrophage](/details-cell/CL0000583) suggests it is a critical mediator of lipid-dependent inflammatory responses in the lung. We hypothesize that [FABP4](/details-gene/2167) controls the availability of fatty acid substrates for the synthesis of pro-inflammatory eicosanoids in these cells during infection or injury. 2. Given its significant expression in arterial endothelial cells and its function in lipid transport, we hypothesize that endothelial [FABP4](/details-gene/2167) facilitates the transcytosis of fatty acids from the bloodstream into the subendothelial space, a key initiating step in the formation of atherosclerotic plaques. **Proposed Experimental Approach:** To test the first hypothesis regarding the role of [FABP4](/details-gene/2167) in lung inflammation, a conditional knockout mouse model could be employed, specifically deleting *Fabp4* in myeloid cells (e.g., using a Lyz2-Cre driver). These mice and their wild-type controls could be subjected to an inflammatory challenge, such as intranasal administration of lipopolysaccharide (LPS). The resulting inflammatory phenotype would be assessed by measuring cytokine and lipid mediator profiles in bronchoalveolar lavage fluid via ELISA and mass spectrometry. Furthermore, single-cell RNA sequencing of lung immune cells would reveal how the absence of [FABP4](/details-gene/2167) alters macrophage activation states and transcriptional programs in response to the inflammatory stimulus. **Therapeutic Potential:** [FABP4](/details-gene/2167) is a well-recognized target for metabolic diseases, as evidenced by research into small molecule inhibitors for type 2 diabetes [Link](https://doi.org/10.1016/j.bmcl.2004.06.057). Given its role in promoting inflammation and its link to atherosclerosis and other metabolic comorbidities, **inhibition** of [FABP4](/details-gene/2167) activity represents a promising therapeutic strategy. Targeting this protein could simultaneously ameliorate dyslipidemia and dampen the chronic low-grade inflammation that drives many cardiometabolic diseases. Because it is also secreted, strategies could involve either intracellular small molecule inhibitors or extracellular neutralizing antibodies.

Genular Protein ID: 2594913031

Symbol: FABP4_HUMAN

Name: Fatty acid-binding protein, adipocyte

UniProtKB Accession Codes:

P15090 Q6IBA1

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CPTAC 2 CTD 1 ChEBI 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 13 DrugCentral 1 EMBL 5 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 20 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GuidetoPHARMACOLOGY 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 PDB 243 PDBsum 243 PIR 1 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 2 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2481498

Title: Human adipocyte lipid-binding protein: purification of the protein and cloning of its complementary DNA.

PubMed ID: 2481498

DOI: 10.1021/bi00448a003

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: 22905912

Title: Resveratrol-induced changes of the human adipocyte secretion profile.

PubMed ID: 22905912

DOI: 10.1021/pr300539b

PubMed ID: 22223895

Title: Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.

PubMed ID: 22223895

DOI: 10.1074/mcp.m111.015131

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 16959974

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

PubMed ID: 16959974

DOI: 10.1126/science.1133427

PubMed ID: 15357969

Title: Discovery of inhibitors of human adipocyte fatty acid-binding protein, a potential type 2 diabetes target.

PubMed ID: 15357969

DOI: 10.1016/j.bmcl.2004.06.057

PubMed ID: 17077479

Title: Expression, purification, crystallization and structure of human adipocyte lipid-binding protein (aP2).

PubMed ID: 17077479

DOI: 10.1107/s1744309106038656

Sequence Information:

  • Length: 132
  • Mass: 14719
  • Checksum: 819D788FF4BF7235
  • Sequence:
    • MCDAFVGTWK LVSSENFDDY MKEVGVGFAT RKVAGMAKPN MIISVNGDVI TIKSESTFKN 
TEISFILGQE FDEVTADDRK VKSTITLDGG VLVHVQKWDG KSTTIKRKRE DDKLVVECVM 
KGVTSTRVYE RA