Details for: PEX5L

Gene ID: 51555

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: PEX5L

Ensembl ID: ENSG00000114757

Description: peroxisomal biogenesis factor 5 like

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • VIP GABAergic cortical interneuron CL4023016
    CSI 49.29
    rCSI 58.88%
    PRS 98.44
  • sncg GABAergic cortical interneuron CL4023015
    CSI 41.32
    rCSI 66.46%
    PRS 98.33
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 40.11
    rCSI 49.9%
    PRS 98.21
  • sst GABAergic cortical interneuron CL4023017
    CSI 39.84
    rCSI 51.36%
    PRS 98.77
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 35.2
    rCSI 59.09%
    PRS 98.58
  • retinal cone cell CL0000573
    CSI 29.39
    rCSI 47.3%
    PRS 98.3
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 28
    rCSI 60.73%
    PRS 97.6
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 25.98
    rCSI 62.14%
    PRS 97.93
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 24.22
    rCSI 58.86%
    PRS 97.88
  • ependymal cell CL0000065
    CSI 23.91
    rCSI 48.53%
    PRS 96.74
  • retina horizontal cell CL0000745
    CSI 23.87
    rCSI 36.39%
    PRS 99.4
  • oligodendrocyte CL0000128
    CSI 23.32
    rCSI 68.92%
    PRS 98.62
  • neuron CL0000540
    CSI 20.31
    rCSI 54.1%
    PRS 97.44
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 20.31
    rCSI 66.76%
    PRS 97.65
  • retinal ganglion cell CL0000740
    CSI 20.05
    rCSI 44.3%
    PRS 98.45
  • glutamatergic neuron CL0000679
    CSI 19.44
    rCSI 39.95%
    PRS 97.08
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 19.31
    rCSI 35.09%
    PRS 98.92
  • inhibitory interneuron CL0000498
    CSI 18.61
    rCSI 42.95%
    PRS 98.6
  • L6b glutamatergic cortical neuron CL4023038
    CSI 17.87
    rCSI 55.86%
    PRS 98.46
  • vascular leptomeningeal cell CL4023051
    CSI 17.86
    rCSI 31.31%
    PRS 99.21
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 17.77
    rCSI 63.96%
    PRS 98.15
  • Schwann cell CL0002573
    CSI 17.24
    rCSI 49.01%
    PRS 99.29
  • cerebral cortex neuron CL0010012
    CSI 16.88
    rCSI 68.78%
    PRS 98.45
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 16.45
    rCSI 62.18%
    PRS 98.12
  • mesothelial cell CL0000077
    CSI 16.41
    rCSI 64.17%
    PRS 98.34
  • S cone cell CL0003050
    CSI 15.93
    rCSI 70%
    PRS 98.99
  • cerebellar granule cell CL0001031
    CSI 15.9
    rCSI 23.37%
    PRS 98.78
  • adipocyte CL0000136
    CSI 15.72
    rCSI 20.19%
    PRS 98.83
  • melanocyte CL0000148
    CSI 15.45
    rCSI 11.44%
    PRS 99.27
  • retinal bipolar neuron CL0000748
    CSI 15.32
    rCSI 28.69%
    PRS 98.54
  • interneuron CL0000099
    CSI 15.14
    rCSI 30.4%
    PRS 99.11
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 14.94
    rCSI 46.72%
    PRS 98.64
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 14.92
    rCSI 17.23%
    PRS 98.93
  • GABAergic amacrine cell CL4030027
    CSI 12.74
    rCSI 43.64%
    PRS 97.72
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 12.54
    rCSI 22.15%
    PRS 98.48
  • neural cell CL0002319
    CSI 12.43
    rCSI 46.89%
    PRS 97.46
  • cerebral cortex endothelial cell CL1001602
    CSI 12.22
    rCSI 21.13%
    PRS 99.07
  • serotonergic neuron CL0000850
    CSI 11.32
    rCSI 50.58%
    PRS 97
  • glial cell CL0000125
    CSI 11.18
    rCSI 42.56%
    PRS 98.38
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 10.85
    rCSI 63.89%
    PRS 98.25
  • Mueller cell CL0000636
    CSI 10.68
    rCSI 24.37%
    PRS 98.84
  • GABAergic neuron CL0000617
    CSI 10.53
    rCSI 35.27%
    PRS 96.86
  • astrocyte of the cerebral cortex CL0002605
    CSI 10.23
    rCSI 22.93%
    PRS 98.61
  • Bergmann glial cell CL0000644
    CSI 9.96
    rCSI 13.63%
    PRS 98.89
  • neural progenitor cell CL0011020
    CSI 7.74
    rCSI 34.05%
    PRS 96.73
  • neuroendocrine cell CL0000165
    CSI 7.73
    rCSI 29.88%
    PRS 99.62
  • retinal rod cell CL0000604
    CSI 7.39
    rCSI 13.02%
    PRS 98.68
  • enteroendocrine cell CL0000164
    CSI 6.82
    rCSI 9.32%
    PRS 98.97
  • dopaminergic neuron CL0000700
    CSI 6.66
    rCSI 37.65%
    PRS 98.1
  • amacrine cell CL0000561
    CSI 6.39
    rCSI 18.52%
    PRS 98.64
  • lung neuroendocrine cell CL1000223
    CSI 6.27
    rCSI 9.28%
    PRS 99.37
  • central nervous system neuron CL2000029
    CSI 5.96
    rCSI 43.84%
    PRS 98.74
  • H2 horizontal cell CL0004218
    CSI 5.36
    rCSI 26.63%
    PRS 98.83
  • Cajal-Retzius cell CL0000695
    CSI 4.72
    rCSI 36.99%
    PRS 99.7
  • basket cell CL0000118
    CSI 4.69
    rCSI 29.4%
    PRS 95.79
  • enteroendocrine cell of small intestine CL0009006
    CSI 4.39
    rCSI 9.66%
    PRS 99.56
  • regular ventricular cardiac myocyte CL0002131
    CSI 3.88
    rCSI 24.21%
    PRS 98.65
  • macroglial cell CL0000126
    CSI 3.87
    rCSI 9.94%
    PRS 99.18
  • ON parasol ganglion cell CL4033052
    CSI 3.63
    rCSI 51.54%
    PRS 98.48
  • diffuse bipolar 1 cell CL4033027
    CSI 3.53
    rCSI 26.5%
    PRS 97.5
  • OFF midget ganglion cell CL4033047
    CSI 2.85
    rCSI 57.94%
    PRS 98.42
  • ON midget ganglion cell CL4033046
    CSI 2.82
    rCSI 57.52%
    PRS 98.33
  • H1 horizontal cell CL0004217
    CSI 2.3
    rCSI 9.11%
    PRS 98.66
  • type B pancreatic cell CL0000169
    CSI 1.92
    rCSI 4.25%
    PRS 99.35
  • neuroplacodal cell CL0000032
    CSI 1.86
    rCSI 17.22%
    PRS 98.76
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.8
    rCSI 43.55%
    PRS 97.35
  • direct pathway medium spiny neuron CL4023026
    CSI 1.8
    rCSI 43%
    PRS 97.36

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 [PEX5L](/details-gene/51555) (Peroxisomal Biogenesis Factor 5 Like) is a protein-coding gene located on chromosome 3q26.33. As its name suggests, it is a paralog of the PEX5 protein and is fundamentally involved in the import of proteins into the peroxisome matrix. Functionally, it acts as a receptor for proteins containing a Peroxisome Targeting Signal 1 (PTS1), binding to them in the [cytosol](/details-cell/GO:0005829) and docking at the [peroxisomal membrane](/details-cell/GO:0005778) to facilitate their translocation. Expression data reveals a remarkably specific and significant role for [PEX5L](/details-gene/51555) within the central nervous system. **Overall**, it shows the highest significance in various subtypes of GABAergic cortical interneurons, glutamatergic neurons, retinal cells, and oligodendrocytes, suggesting it is a crucial component for maintaining the specialized metabolic functions of these high-energy-demand neural cell types. ## Cellular Roles and Expression Landscape The expression profile of [PEX5L](/details-gene/51555) highlights its specialized function within the nervous system. The gene demonstrates particularly high significance in inhibitory interneurons, including [VIP GABAergic cortical interneurons](/details-cell/CL4023016) (CSI: 49.29), [sncg GABAergic cortical interneurons](/details-cell/CL4023015) (CSI: 41.32), and [pvalb GABAergic cortical interneurons](/details-cell/CL4023018) (CSI: 40.11). This pattern suggests a critical role in supporting the unique metabolic and signaling requirements of these cells, which are essential for regulating cortical circuit activity. In addition to interneurons, [PEX5L](/details-gene/51555) is also a significant gene in various excitatory [neurons](/details-cell/CL0000540), such as [L2/3 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4030059) (CSI: 28.00), and glial cells, most notably [oligodendrocytes](/details-cell/CL0000128) (CSI: 23.32). Its prominence in [oligodendrocytes](/details-cell/CL0000128) is consistent with the critical role of peroxisomes in lipid metabolism, particularly the synthesis of plasmalogens, which are essential components of the myelin sheath. Furthermore, its high significance in multiple retinal cell types, including [retinal cone cells](/details-cell/CL0000573) (CSI: 29.39) and [retina horizontal cells](/details-cell/CL0000745) (CSI: 23.87), underscores its importance in the highly metabolically active environment of the retina. The broad but specific expression across these functionally diverse neural cells points to a fundamental role for [PEX5L](/details-gene/51555)-mediated peroxisomal function in maintaining neural health and circuit integrity. ## Pathways and Molecular Function The functional annotations for [PEX5L](/details-gene/51555) are centered on peroxisomal biology. The gene product is directly involved in '[Protein import into peroxisome matrix, docking](/details-cell/GO:0016560)' by acting as a receptor that recognizes the C-terminal PTS1 on cargo proteins. This is confirmed by its molecular function of '[Peroxisome matrix targeting signal-1 binding](/details-cell/GO:0005052)', a role that was experimentally investigated for PEX5-related proteins ([Link](https://pubmed.ncbi.nlm.nih.gov/11463335/)). Peroxisomes are vital organelles for cellular metabolism, responsible for beta-oxidation of very long-chain fatty acids, synthesis of ether lipids (plasmalogens), and detoxification of reactive oxygen species. The high expression of [PEX5L](/details-gene/51555) in [neurons](/details-cell/CL0000540) and [oligodendrocytes](/details-cell/CL0000128) is directly aligned with these functions, as these cells have high demands for lipid metabolism (for myelination and membrane integrity) and are particularly vulnerable to oxidative stress. Additionally, its annotation for '[Regulation of camp-mediated signaling](/details-cell/GO:0043949)' and '[Small gtpase binding](/details-cell/GO:0031267)' suggests that [PEX5L](/details-gene/51555) may have broader roles, potentially linking peroxisomal status to intracellular signaling cascades that are crucial for neuronal function. ## Research Directions The specific and high-level expression of [PEX5L](/details-gene/51555) in the central nervous system, coupled with its core function in peroxisomal biogenesis, suggests that its dysregulation could be implicated in neurological disorders. While the provided data does not cover a disease context, the gene's functional and cellular profile allows for the formulation of several testable hypotheses. 1. **Hypothesis 1:** Given the critical role of peroxisomes in lipid metabolism and the high significance of [PEX5L](/details-gene/51555) in [oligodendrocytes](/details-cell/CL0000128), haploinsufficiency or pathogenic variants in [PEX5L](/details-gene/51555) may contribute to demyelinating diseases, such as multiple sclerosis or leukodystrophies, by impairing plasmalogen synthesis and compromising myelin sheath integrity. 2. **Hypothesis 2:** The distinctively high expression of [PEX5L](/details-gene/51555) across multiple subtypes of GABAergic interneurons suggests it supports the high metabolic demand required for sustained inhibitory neurotransmission. Its disruption could therefore lead to an excitatory/inhibitory imbalance, contributing to the pathophysiology of disorders like epilepsy or schizophrenia. **Experimental Approach:** To test the first hypothesis, a compelling experiment would be to generate a conditional knockout mouse model where [PEX5L](/details-gene/51555) is specifically deleted in [oligodendrocyte](/details-cell/CL0000128) precursor cells (e.g., using an *Olig2-Cre* or *PDGFRa-CreERT2* driver line). The resulting phenotype could be analyzed through a multi-modal approach: electron microscopy to assess myelin sheath thickness and integrity, lipidomics/mass spectrometry on brain tissue to quantify changes in plasmalogen levels, and behavioral tests (e.g., rotarod) to evaluate motor coordination deficits characteristic of demyelination. **Therapeutic Potential:** As an intracellular receptor involved in organelle biogenesis, [PEX5L](/details-gene/51555) is not a conventional drug target for small molecule inhibition or antibody-based therapies. Its function is essential for cellular health, and direct inhibition would likely be toxic. However, if mutations in [PEX5L](/details-gene/51555) are linked to severe peroxisomal biogenesis disorders, it could be a candidate for gene-replacement therapies. More immediately, its cell-type-specific expression suggests that its mRNA or protein levels could serve as a sensitive biomarker for monitoring the health of [oligodendrocytes](/details-cell/CL0000128) or specific neuronal populations in the context of neurodegenerative or demyelinating diseases.

Genular Protein ID: 2403664369

Symbol: PEX5R_HUMAN

Name: PEX5-related protein

UniProtKB Accession Codes:

Q8IYB4 B7Z2A5 B7Z305 B7Z318 B7Z5Z5 B7Z8P2 E7EUV8 E7EUZ0 E9PEC1 E9PH97 Q9NQD1 Q9P2U3 Q9P2U4

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 8 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 13 Ensembl 9 ExpressionAtlas 1 GO 8 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 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 8 RNAct 1 RefSeq 17 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16641997

Title: The DNA sequence, annotation and analysis of human chromosome 3.

PubMed ID: 16641997

DOI: 10.1038/nature04728

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: 11463335

Title: Identification of PEX5p-related novel peroxisome-targeting signal 1 (PTS1)-binding proteins in mammals.

PubMed ID: 11463335

DOI: 10.1042/0264-6021:3570635

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: 626
  • Mass: 69697
  • Checksum: 07109ABE1B2314C1
  • Sequence:
    • MYQGHMQKSK EQGYGKLSSD EDLEIIVDQK QGKGSRAADK AVAMVMKEIP REESAEEKPL 
LTMTSQLVNE QQESRPLLSP SIDDFLCETK SEAIARPVTS NTAVLTTGLD LLDLSEPVSQ 
TQTKAKKSEP SSKTSSLKKK ADGSDLISTD AEQRGQPLRV PETSSLDLDI QTQLEKWDDV 
KFHGDRNTKG HPMAERKSSS SRTGSKELLW SSEHRSQPEL SGGKSALNSE SASELELVAP 
TQARLTKEHR WGSALLSRNH SLEEEFERAK AAVESDTEFW DKMQAEWEEM ARRNWISENQ 
EAQNQVTISA SEKGYYFHTE NPFKDWPGAF EEGLKRLKEG DLPVTILFME AAILQDPGDA 
EAWQFLGITQ AENENEQAAI VALQRCLELQ PNNLKALMAL AVSYTNTGHQ QDACDALKNW 
IKQNPKYKYL VKSKKGSPGL TRRMSKSPVD SSVLEGVKEL YLEAAHQNGD MIDPDLQTGL 
GVLFHLSGEF NRAIDAFNAA LTVRPEDYSL WNRLGATLAN GDRSEEAVEA YTRALEIQPG 
FIRSRYNLGI SCINLGAYRE AVSNFLTALS LQRKSRNQQQ VPHPAISGNI WAALRIALSL 
MDQPELFQAA NLGDLDVLLR AFNLDP