Details for: PXDNL

Gene ID: 137902

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: PXDNL

Ensembl ID: ENSG00000147485

Description: peroxidasin like

Cell Significance Landscape

Associated with

Significant Cells

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

  • cardiac muscle cell CL0000746
    CSI 25.98
    rCSI 37.27%
    PRS 95.71
  • regular atrial cardiac myocyte CL0002129
    CSI 16.23
    rCSI 52.25%
    PRS 96.9
  • Mueller cell CL0000636
    CSI 10.03
    rCSI 22.88%
    PRS 96.68
  • regular ventricular cardiac myocyte CL0002131
    CSI 7.43
    rCSI 46.43%
    PRS 96.16
  • ependymal cell CL0000065
    CSI 6.82
    rCSI 13.85%
    PRS 92.35
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 6.77
    rCSI 11.37%
    PRS 95.85
  • cardiac endothelial cell CL0010008
    CSI 5.99
    rCSI 24.15%
    PRS 98.72
  • sncg GABAergic cortical interneuron CL4023015
    CSI 5.9
    rCSI 9.49%
    PRS 95.48
  • Schwann cell CL0002573
    CSI 5.74
    rCSI 16.31%
    PRS 97.35
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 5.37
    rCSI 6.68%
    PRS 94.95
  • inhibitory interneuron CL0000498
    CSI 5.16
    rCSI 11.91%
    PRS 95.74
  • fibroblast of cardiac tissue CL0002548
    CSI 4.95
    rCSI 23.72%
    PRS 98.86
  • astrocyte of the cerebral cortex CL0002605
    CSI 4.65
    rCSI 10.43%
    PRS 95.58
  • adipocyte CL0000136
    CSI 4.57
    rCSI 5.87%
    PRS 96.27
  • cerebellar granule cell CL0001031
    CSI 4.38
    rCSI 6.44%
    PRS 96.5
  • interneuron CL0000099
    CSI 4.04
    rCSI 8.11%
    PRS 97.16
  • fibroblast CL0000057
    CSI 3.91
    rCSI 11.24%
    PRS 93.63
  • epicardial adipocyte CL1000309
    CSI 3.79
    rCSI 12.35%
    PRS 97.45
  • retinal bipolar neuron CL0000748
    CSI 3.71
    rCSI 6.94%
    PRS 96.07
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.48
    rCSI 4.16%
    PRS 95.55
  • sst GABAergic cortical interneuron CL4023017
    CSI 3.36
    rCSI 4.33%
    PRS 96.12
  • renal beta-intercalated cell CL0002201
    CSI 3.35
    rCSI 7.99%
    PRS 98.45
  • vascular leptomeningeal cell CL4023051
    CSI 3.26
    rCSI 5.71%
    PRS 97.37
  • retinal ganglion cell CL0000740
    CSI 3.02
    rCSI 6.68%
    PRS 95.44
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 2.74
    rCSI 8.57%
    PRS 96.12
  • cerebral cortex endothelial cell CL1001602
    CSI 2.74
    rCSI 4.73%
    PRS 97.11
  • GABAergic neuron CL0000617
    CSI 2.68
    rCSI 8.97%
    PRS 93.07
  • endocardial cell CL0002350
    CSI 2.58
    rCSI 12.37%
    PRS 97.52
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 2.55
    rCSI 6.09%
    PRS 94.39
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 2.44
    rCSI 8.76%
    PRS 94.77
  • cardiac neuron CL0010022
    CSI 2.37
    rCSI 7.59%
    PRS 98.27
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 2.23
    rCSI 5.43%
    PRS 94.38
  • kidney connecting tubule epithelial cell CL1000768
    CSI 2.12
    rCSI 5.37%
    PRS 97.6
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 2.09
    rCSI 12.31%
    PRS 95.18
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.93
    rCSI 7.3%
    PRS 95.06
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.71
    rCSI 3.03%
    PRS 95.61
  • amacrine cell CL0000561
    CSI 1.71
    rCSI 4.95%
    PRS 95.76
  • flat midget bipolar cell CL4033033
    CSI 1.7
    rCSI 12.16%
    PRS 94.09
  • pulmonary alveolar type 1 cell CL0002062
    CSI 1.58
    rCSI 9.11%
    PRS 97.62
  • dopaminergic neuron CL0000700
    CSI 1.57
    rCSI 8.9%
    PRS 94.49
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.39
    rCSI 4.33%
    PRS 95.67
  • cardiac blood vessel endothelial cell CL0010006
    CSI 1.31
    rCSI 9.25%
    PRS 96.78
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 1.27
    rCSI 10.97%
    PRS 96.83
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 1.01
    rCSI 10.65%
    PRS 97.19
  • blood vessel smooth muscle cell CL0019018
    CSI 0.99
    rCSI 8.02%
    PRS 98.46
  • central nervous system neuron CL2000029
    CSI 0.94
    rCSI 6.9%
    PRS 96.04
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.43
    rCSI 10.39%
    PRS 93.31
  • direct pathway medium spiny neuron CL4023026
    CSI 0.41
    rCSI 9.89%
    PRS 93.66

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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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 [PXDNL](/gene/137902) (peroxidasin like) is a protein-coding gene located on chromosome 8q11.22-q11.23. It encodes a dual-function enzyme that exhibits both peroxidase and endonuclease activities. Functionally, [PXDNL](/gene/137902) is involved in cellular detoxification processes, particularly the catabolism of hydrogen peroxide and the broader response to oxidative stress. Expression data reveals its role as a highly significant and abundant protein in cardiac tissues, with its highest significance observed in [cardiac muscle cell](/details-cell/CL0000746), [regular atrial cardiac myocyte](/details-cell/CL0002129), and [regular ventricular cardiac myocyte](/details-cell/CL0002131). This cardiac-centric expression profile is consistent with its identification as a cardiac peroxidase, suggesting a crucial role in maintaining redox homeostasis in the heart. ## Cellular Roles and Expression Landscape The expression profile of [PXDNL](/gene/137902) firmly establishes it as a key gene in cardiovascular biology. **Overall**, it demonstrates the highest significance in [cardiac muscle cell](/details-cell/CL0000746) (CSI: 25.98), underscoring its importance in the fundamental contractile cells of the heart. This prominence is further supported by high significance in more specific subtypes, including [regular atrial cardiac myocyte](/details-cell/CL0002129) and [regular ventricular cardiac myocyte](/details-cell/CL0002131). The gene's activity extends to other components of the cardiac environment, such as [cardiac endothelial cell](/details-cell/CL0010008) and [fibroblast of cardiac tissue](/details-cell/CL0002548), indicating a broader role in the heart's cellular ecosystem. Beyond the heart, [PXDNL](/gene/137902) shows notable significance in specific neural and glial cell populations. It is a significant marker in [Mueller cell](/details-cell/CL0000636) of the retina, [ependymal cell](/details-cell/CL0000065) lining the cerebral ventricles, and various subtypes of inhibitory interneurons, including [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018). This pattern suggests specialized roles in maintaining homeostasis and managing oxidative stress within the central nervous system, particularly in high-metabolic-rate neural tissues. ## Pathways and Molecular Function The functional annotations for [PXDNL](/gene/137902) highlight its role as a critical enzyme in redox biology. Its involvement in biological processes such as [cellular oxidant detoxification](/details-go/GO:0098869), [hydrogen peroxide catabolic process](/details-go/GO:0042744), and [response to oxidative stress](/details-go/GO:0006979) is directly linked to its potent [peroxidase activity](/details-go/GO:0004601). This function, which relies on [heme binding](/details-go/GO:0020037), is particularly relevant in cardiomyocytes, which are susceptible to damage from reactive oxygen species generated during high metabolic activity. The protein has been specifically characterized as a novel cardiac peroxidase [Link](https://doi.org/10.1093/cvr/cvt256). Interestingly, [PXDNL](/gene/137902) also possesses [endonuclease activity](/details-go/GO:0004519). Research has identified it as the human PMR1 mRNA endonuclease, which is generated through alternative processing of the `PXDNL` gene product [Link](https://doi.org/10.1261/rna.031369.111). This endonuclease is capable of degrading specific mRNAs, suggesting a dual capacity for [PXDNL](/gene/137902) to regulate cellular function by controlling both protein expression (via mRNA decay) and redox state. The protein is found in the [endoplasmic reticulum](/details-go/GO:0005783), the [plasma membrane](/details-go/GO:0005886), and the [extracellular space](/details-go/GO:0005615), indicating it may act both within the cell and on its immediate environment. ## Research Directions The unique combination of high cardiac-specific expression and dual enzymatic functions positions [PXDNL](/gene/137902) as a compelling subject for further investigation, particularly in the context of cardiovascular disease. **Proposed Hypotheses:** 1. Given its high expression in [cardiac muscle cell](/details-cell/CL0000746) and its role in detoxifying reactive oxygen species, [PXDNL](/gene/137902) may be a critical protective factor against ischemia-reperfusion injury, where a sudden burst of oxidative stress causes significant tissue damage. Loss of [PXDNL](/gene/137902) function would be expected to exacerbate myocardial infarct size and worsen cardiac outcomes following a heart attack. 2. The significant expression of [PXDNL](/gene/137902) in retinal [Mueller cell](/details-cell/CL0000636) suggests a protective role in the eye. It is hypothesized that [PXDNL](/gene/137902) helps mitigate light-induced oxidative damage in the retina, and its dysregulation could contribute to the pathogenesis of degenerative retinal diseases like age-related macular degeneration. 3. The dual peroxidase and endonuclease functions of [PXDNL](/gene/137902) may be functionally coupled. We hypothesize that under conditions of cardiac stress, the peroxidase activity of [PXDNL](/gene/137902) locally alters the redox environment, which in turn modulates its PMR1 endonuclease activity to selectively degrade mRNAs encoding proteins involved in pathological remodeling. **Experimental Approach:** To test the first hypothesis regarding the role of [PXDNL](/gene/137902) in cardioprotection, a cardiomyocyte-specific knockout mouse model could be generated (e.g., *Pxdnl* flox/flox crossed with an αMHC-Cre driver line). These conditional knockout mice and their littermate controls would be subjected to a surgical model of left anterior descending (LAD) coronary artery ligation followed by reperfusion. The primary endpoints would include measuring infarct size via triphenyltetrazolium chloride (TTC) staining, assessing cardiac function using serial echocardiography, and quantifying markers of oxidative stress (e.g., 4-HNE, protein carbonylation) in heart tissue lysates. A significant increase in infarct size and a decline in cardiac function in the knockout mice would validate the protective role of [PXDNL](/gene/137902). **Therapeutic Potential:** Based on its protective, anti-oxidative function, [PXDNL](/gene/137902) represents a potential therapeutic target where **activation** or supplementation would be the desired outcome. Its high expression specificity for cardiac tissue suggests that therapies aimed at enhancing its activity could have minimal off-target effects. For conditions characterized by chronic cardiac oxidative stress, such as heart failure or diabetic cardiomyopathy, developing small-molecule activators of [PXDNL](/gene/137902) peroxidase activity could be a promising strategy. Alternatively, gene therapy approaches to overexpress [PXDNL](/gene/137902) specifically in the heart could offer a long-term benefit in preventing adverse cardiac remodeling.

Genular Protein ID: 111524387

Symbol: PXDNL_HUMAN

Name: Cardiac peroxidase

UniProtKB Accession Codes:

A1KZ92 B5ME43 B6CGZ3 H0YBM9 Q6ZMR2 Q96LH9

Database IDs:

AGR 1 AlphaFoldDB 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 8 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 10 Ensembl 1 ExpressionAtlas 1 GO 10 Gene3D 4 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 16 KEGG 1 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 5 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PeroxiBase 2 Pfam 5 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 RefSeq 1 SMART 5 SMR 1 STRING 1 SUPFAM 4 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 18929642

Title: Identification and characterization of VPO1, a new animal heme-containing peroxidase.

PubMed ID: 18929642

DOI: 10.1016/j.freeradbiomed.2008.09.009

PubMed ID: 16421571

Title: DNA sequence and analysis of human chromosome 8.

PubMed ID: 16421571

DOI: 10.1038/nature04406

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 12923263

Title: An endonuclease activity similar to Xenopus PMR1 catalyzes the degradation of normal and nonsense-containing human beta-globin mRNA in erythroid cells.

PubMed ID: 12923263

DOI: 10.1261/rna.5720303

PubMed ID: 22543864

Title: Identification of the human PMR1 mRNA endonuclease as an alternatively processed product of the gene for peroxidasin-like protein.

PubMed ID: 22543864

DOI: 10.1261/rna.031369.111

PubMed ID: 24253521

Title: Peroxidasin-like protein: a novel peroxidase homologue in the human heart.

PubMed ID: 24253521

DOI: 10.1093/cvr/cvt256

Sequence Information:

  • Length: 1463
  • Mass: 163686
  • Checksum: F6FE8200892CCCAE
  • Sequence:
    • MEPRLFCWTT LFLLAGWCLP GLPCPSRCLC FKSTVRCMHL MLDHIPQVPQ QTTVLDLRFN 
RIREIPGSAF KKLKNLNTLL LNNNHIRKIS RNAFEGLENL LYLYLYKNEI HALDKQTFKG 
LISLEHLYIH FNQLEMLQPE TFGDLLRLER LFLHNNKLSK IPAGSFSNLD SLKRLRLDSN 
ALVCDCDLMW LGELLQGFAQ HGHTQAAATC EYPRRLHGRA VASVTVEEFN CQSPRITFEP 
QDVEVPSGNT VYFTCRAEGN PKPEIIWIHN NHSLDLEDDT RLNVFDDGTL MIRNTRESDQ 
GVYQCMARNS AGEAKTQSAM LRYSSLPAKP SFVIQPQDTE VLIGTSTTLE CMATGHPHPL 
ITWTRDNGLE LDGSRHVATS SGLYLQNITQ RDHGRFTCHA NNSHGTVQAA ANIIVQAPPQ 
FTVTPKDQVV LEEHAVEWLC EADGNPPPVI VWTKTGGQLP VEGQHTVLSS GTLRIDRAAQ 
HDQGQYECQA VSSLGVKKVS VQLTVKPKAL AVFTQLPQDT SVEVGKNINI SCHAQGEPQP 
IITWNKEGVQ ITESGKFHVD DEGTLTIYDA GFPDQGRYEC VARNSFGLAV TNMFLTVTAI 
QGRQAGDDFV ESSILDAVQR VDSAINSTRR HLFSQKPHTS SDLLAQFHYP RDPLIVEMAR 
AGEIFEHTLQ LIRERVKQGL TVDLEGKEFR YNDLVSPRSL SLIANLSGCT ARRPLPNCSN 
RCFHAKYRAH DGTCNNLQQP TWGAALTAFA RLLQPAYRDG IRAPRGLGLP VGSRQPLPPP 
RLVATVWARA AAVTPDHSYT RMLMHWGWFL EHDLDHTVPA LSTARFSDGR PCSSVCTNDP 
PCFPMNTRHA DPRGTHAPCM LFARSSPACA SGRPSATVDS VYAREQINQQ TAYIDGSNVY 
GSSERESQAL RDPSVPRGLL KTGFPWPPSG KPLLPFSTGP PTECARQEQE SPCFLAGDHR 
ANEHLALAAM HTLWFREHNR MATELSALNP HWEGNTVYQE ARKIVGAELQ HITYSHWLPK 
VLGDPGTRML RGYRGYNPNV NAGIINSFAT AAFRFGHTLI NPILYRLNAT LGEISEGHLP 
FHKALFSPSR IIKEGGIDPV LRGLFGVAAK WRAPSYLLSP ELTQRLFSAA YSAAVDSAAT 
IIQRGRDHGI PPYVDFRVFC NLTSVKNFED LQNEIKDSEI RQKLRKLYGS PGDIDLWPAL 
MVEDLIPGTR VGPTLMCLFV TQFQRLRDGD RFWYENPGVF TPAQLTQLKQ ASLSRVLCDN 
GDSIQQVQAD VFVKAEYPQD YLNCSEIPKV DLRVWQDCCA DCRSRGQFRA VTQESQKKRS 
AQYSYPVDKD MELSHLRSRQ QDKIYVGEDA RNVTVLAKTK FSQDFSTFAA EIQETITALR 
EQINKLEARL RQAGCTDVRG VPRKAEERWM KEDCTHCICE SGQVTCVVEI CPPAPCPSPE 
LVKGTCCPVC RDRGMPSDSP EKR