Details for: FBXO27

Gene ID: 126433

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: FBXO27

Ensembl ID: ENSG00000161243

Description: F-box protein 27

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • interneuron CL0000099
    CSI 3.61
    rCSI 7.25%
    PRS 94.92
  • cerebellar granule cell CL0001031
    CSI 3.2
    rCSI 4.71%
    PRS 94.61
  • ependymal cell CL0000065
    CSI 2.55
    rCSI 5.17%
    PRS 87.6
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.34
    rCSI 3.01%
    PRS 92.49
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.28
    rCSI 2.73%
    PRS 91.93
  • placental villous trophoblast CL2000060
    CSI 2.26
    rCSI 3.5%
    PRS 96.29
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.12
    rCSI 2.63%
    PRS 90.52
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.97
    rCSI 3.48%
    PRS 91.82
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.96
    rCSI 3.29%
    PRS 92.06
  • dendritic cell, human CL0001056
    CSI 1.94
    rCSI 2.98%
    PRS 99
  • cardiac muscle cell CL0000746
    CSI 1.63
    rCSI 2.35%
    PRS 92.93
  • amacrine cell CL0000561
    CSI 1.54
    rCSI 4.45%
    PRS 93
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.1
    rCSI 2.67%
    PRS 90.55
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.8
    rCSI 3.03%
    PRS 91.8
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.77
    rCSI 2.41%
    PRS 93.33
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.45
    rCSI 2.64%
    PRS 91.98

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 [FBXO27](/details-gene/126433) is a protein-coding gene that encodes F-box only protein 27, a component of the Skp1-Cullin-F-box (SCF) E3 ubiquitin ligase complex. Functionally, it is involved in protein ubiquitination and subsequent proteasomal degradation, playing a role in processes such as the ER-associated degradation (ERAD) pathway and antigen processing. Expression data highlights its significant role across a diverse range of cell types, with particularly high significance in the central nervous system, where it is a prominent marker for various neuronal subtypes including [interneuron](/details-cell/CL0000099)s and [cerebellar granule cell](/details-cell/CL0001031)s. It is also notably expressed in specialized cells such as [placental villous trophoblast](/details-cell/CL2000060) and [dendritic cell, human](/details-cell/CL0001056), suggesting context-specific roles in development and immunity. ## Cellular Roles and Expression Landscape The expression profile of [FBXO27](/details-gene/126433) indicates a critical, albeit widespread, function in terminally differentiated cells with high metabolic or signaling activity. **Overall**, the gene shows the highest significance in the nervous system. It is a defining marker for multiple classes of inhibitory neurons, including general [interneuron](/details-cell/CL0000099)s (CSI: 3.61) and specific subtypes such as [sst GABAergic cortical interneuron](/details-cell/CL4023017), [VIP GABAergic cortical interneuron](/details-cell/CL4023016), and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018). Its high significance in [cerebellar granule cell](/details-cell/CL0001031)s (CSI: 3.20) further underscores its importance in neuronal function and maintenance. Beyond the nervous system, [FBXO27](/details-gene/126433) is significantly expressed in other specialized cell types. Its high CSI score in [ependymal cell](/details-cell/CL0000065)s, which line the ventricular system of the brain, and [placental villous trophoblast](/details-cell/CL2000060)s suggests a role in cellular barriers and feto-maternal exchange. Furthermore, its expression in [cardiac muscle cell](/details-cell/CL0000746)s is consistent with a role in the high-rate protein turnover required in contractile tissues. The presence of [dendritic cell, human](/details-cell/CL0001056) among the top expressed cell types points towards a specialized function in the immune system, particularly in antigen presentation. ## Pathways and Molecular Function The molecular function of [FBXO27](/details-gene/126433) is centered on its role as a substrate-recognition component of the [SCF ubiquitin ligase complex](/details-cell/GO:0019005). This is supported by its annotated activities in [ubiquitin protein ligase activity](/details-cell/GO:0061630) and [SCF-dependent proteasomal ubiquitin-dependent protein catabolic process](/details-cell/GO:0031146). These functions place [FBXO27](/details-gene/126433) as a key regulator of protein homeostasis through targeted degradation. Consistent with its expression in [dendritic cell, human](/details-cell/CL0001056)s, [FBXO27](/details-gene/126433) is implicated in the [immune system](/details-cell/R-HSA-168256). Specifically, it is involved in [antigen processing: ubiquitination & proteasome degradation](/details-cell/R-HSA-983168) and [class I MHC mediated antigen processing & presentation](/details-cell/R-HSA-983169). This suggests that [FBXO27](/details-gene/126433) helps determine which cellular proteins are degraded into peptides for presentation on MHC class I molecules, a critical step in the adaptive immune response against infected or malignant cells. Its broader involvement in the [metabolism of proteins](/details-cell/R-HSA-392499) and the [ERAD pathway](/details-cell/GO:0036503) aligns with its high expression in metabolically active cells like neurons and cardiomyocytes, where quality control of proteins is essential. One study has highlighted the diversity in tissue expression and substrate binding among a lectin family of ubiquitin ligases including [FBXO27](/details-gene/126433) [Link](https://doi.org/10.1074/jbc.m709508200). ## Research Directions The diverse expression pattern of [FBXO27](/details-gene/126433) across neuronal, immune, and muscle cells, coupled with its core function as an E3 ligase, suggests it regulates distinct sets of protein substrates in a cell-type-specific manner. Future research should focus on identifying these substrates to unravel its specific roles in health and disease. **Proposed Hypotheses:** 1. In the central nervous system, [FBXO27](/details-gene/126433) likely targets key synaptic proteins (e.g., receptors, scaffolding proteins, ion channels) for degradation within various [interneuron](/details-cell/CL0000099) subtypes, thereby acting as a critical regulator of synaptic plasticity and the maintenance of inhibitory tone in cortical circuits. 2. In [dendritic cell, human](/details-cell/CL0001056)s, [FBXO27](/details-gene/126433) functions as a selective E3 ligase that modulates the immunopeptidome by targeting specific self-proteins or viral antigens for processing and presentation via the MHC class I pathway, thus shaping the T-cell response. **Experimental Approach:** To test the second hypothesis regarding its role in antigen presentation, a compelling experiment would be to use CRISPR-Cas9 to knock out [FBXO27](/details-gene/126433) in a human monocyte-derived dendritic cell line (e.g., MUTZ-3). These knockout and wild-type cells could then be pulsed with a known model antigen (e.g., a viral protein). Subsequently, MHC class I-associated peptides would be isolated by immunoprecipitation and analyzed by quantitative mass spectrometry (immunopeptidomics). A significant alteration in the repertoire or abundance of presented peptides in the knockout cells would provide direct evidence for the role of [FBXO27](/details-gene/126433) in shaping the antigenic landscape. **Therapeutic Potential:** As an E3 ubiquitin ligase, [FBXO27](/details-gene/126433) is a member of a druggable class of enzymes. Its role in antigen presentation makes it a potential target for immunomodulation. For cancer immunotherapy, inhibiting [FBXO27](/details-gene/126433) could theoretically alter the tumor immunopeptidome, potentially increasing the presentation of neoantigens and enhancing T-cell-mediated tumor destruction. Conversely, in the context of autoimmune disease, specific activators or "molecular glues" could be developed to enhance the degradation of proteins involved in presenting self-antigens. However, its widespread and high expression in the CNS and cardiac tissue presents a significant challenge, suggesting that any therapeutic strategy would require highly targeted delivery to avoid severe off-target effects.

Genular Protein ID: 1067038038

Symbol: FBX27_HUMAN

Name: F-box only protein 27

UniProtKB Accession Codes:

Q8NI29 Q96C87

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 6 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 2 RefSeq 1 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: 12383498

Title: A new subfamily of structurally related human F-box proteins.

PubMed ID: 12383498

DOI: 10.1016/s0378-1119(02)00867-3

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: 18203720

Title: Diversity in tissue expression, substrate binding, and SCF complex formation for a lectin family of ubiquitin ligases.

PubMed ID: 18203720

DOI: 10.1074/jbc.m709508200

Sequence Information:

  • Length: 283
  • Mass: 31623
  • Checksum: 0A66E26971320B5F
  • Sequence:
    • MGASVSRGRA ARVPAPEPEP EEALDLSQLP PELLLVVLSH VPPRTLLGRC RQVCRGWRAL 
VDGQALWLLI LARDHGATGR ALLHLARSCQ SPARNARPCP LGRFCARRPI GRNLIRNPCG 
QEGLRKWMVQ HGGDGWVVEE NRTTVPGAPS QTCFVTSFSW CCKKQVLDLE EEGLWPELLD 
SGRIEICVSD WWGARHDSGC MYRLLVQLLD ANQTVLDKFS AVPDPIPQWN NNACLHVTHV 
FSNIKMGVRF VSFEHRGQDT QFWAGHYGAR VTNSSVIVRV RLS