Details for: NWD1

Gene ID: 284434

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: NWD1

Ensembl ID: ENSG00000188039

Description: NACHT and WD repeat domain containing 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • choroid plexus epithelial cell CL0000706
    CSI 23.17
    rCSI 37.94%
    PRS 97.28
  • ciliated epithelial cell CL0000067
    CSI 6.09
    rCSI 5.36%
    PRS 96.19
  • secretory cell CL0000151
    CSI 5.94
    rCSI 6.2%
    PRS 98.61
  • cerebral cortex endothelial cell CL1001602
    CSI 5.79
    rCSI 10.02%
    PRS 97.35
  • ciliated cell CL0000064
    CSI 5.15
    rCSI 8.35%
    PRS 96.36
  • squamous epithelial cell CL0000076
    CSI 5.01
    rCSI 11.88%
    PRS 96.45
  • multi-ciliated epithelial cell CL0005012
    CSI 4.26
    rCSI 4.25%
    PRS 97.04
  • astrocyte of the cerebral cortex CL0002605
    CSI 4
    rCSI 8.98%
    PRS 96.06
  • lung ciliated cell CL1000271
    CSI 3.94
    rCSI 4.56%
    PRS 97.17
  • retinal pigment epithelial cell CL0002586
    CSI 3.83
    rCSI 7.6%
    PRS 97.48
  • club cell CL0000158
    CSI 3.56
    rCSI 5.21%
    PRS 98.57
  • respiratory basal cell CL0002633
    CSI 3.23
    rCSI 3.34%
    PRS 99.09
  • respiratory suprabasal cell CL4033048
    CSI 3.06
    rCSI 3.93%
    PRS 99.18
  • conjunctival epithelial cell CL1000432
    CSI 2.86
    rCSI 4.36%
    PRS 98.18
  • ependymal cell CL0000065
    CSI 2.31
    rCSI 4.69%
    PRS 92.99
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.55
    rCSI 3.54%
    PRS 96.02
  • deuterosomal cell CL4033044
    CSI 1.26
    rCSI 4.26%
    PRS 95.91

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 [NWD1](/details-gene/284434) (NACHT and WD repeat domain containing 1) is a protein-coding gene that encodes a member of the NLR (NOD-like receptor) family of intracellular proteins. Functional annotations suggest it plays a key role in regulating transcriptional activity, including the [negative regulation of nf-kappab transcription factor activity](/details-cell/GO:0032088). Research has also implicated [NWD1](/details-gene/284434) in modulating androgen receptor signaling, linking it to the pathology of prostate cancer ([Link](https://doi.org/10.18632/oncotarget.1850)). **Overall**, its expression is most significant in specialized epithelial cells, with exceptionally high levels in the [choroid plexus epithelial cell](/details-cell/CL0000706) of the brain, as well as in various ciliated and secretory epithelial populations, suggesting a role in barrier function and inflammatory homeostasis. ## Cellular Roles and Expression Landscape The expression profile of [NWD1](/details-gene/284434) points to a specialized role in distinct epithelial and neural-associated cell types. **Overall**, the gene's significance is exceptionally high in the [choroid plexus epithelial cell](/details-cell/CL0000706) (CSI: 23.17), which forms the blood-cerebrospinal fluid barrier. This suggests a critical function in the central nervous system's unique immune environment. A second major theme is the gene's high significance across a range of ciliated cells, including [ciliated epithelial cell](/details-cell/CL0000067), [lung ciliated cell](/details-cell/CL1000271), and [multi-ciliated epithelial cell](/details-cell/CL0005012). This pattern implies a role in tissues reliant on mucociliary clearance, such as the respiratory tract. The gene is also a significant marker in other barrier or secretory epithelia, including [squamous epithelial cell](/details-cell/CL0000076), [secretory cell](/details-cell/CL0000151), and [club cell](/details-cell/CL0000158). Furthermore, its relevance extends to other CNS-associated cells like [astrocyte of the cerebral cortex](/details-cell/CL0002605) and [ependymal cell](/details-cell/CL0000065), reinforcing its potential importance in brain homeostasis. ## Pathways and Molecular Function [NWD1](/details-gene/284434) encodes a protein containing a NACHT domain, which is consistent with its annotated molecular function of [ATP binding](/details-cell/GO:0005524). Localized to the [cytosol](/details-cell/GO:0005829) and [nucleolus](/details-cell/GO:0005730), it appears to function as an intracellular signaling molecule involved in transcriptional control. This is strongly supported by its association with biological processes such as [positive regulation of gene expression](/details-cell/GO:0010628) and, more specifically, the [negative regulation of nf-kappab transcription factor activity](/details-cell/GO:0032088). The modulation of NF-kB, a master regulator of inflammation, is highly consistent with the high expression of [NWD1](/details-gene/284434) in barrier tissues like the choroid plexus and respiratory epithelium, which must tightly control immune responses to environmental stimuli. Additionally, published research has demonstrated that [NWD1](/details-gene/284434) can modulate androgen receptor signaling, revealing a role in hormone-dependent gene regulation relevant to prostate cancer ([Link](https://doi.org/10.18632/oncotarget.1850)). ## Research Directions The specific roles of [NWD1](/details-gene/284434) in non-cancerous tissues remain largely unexplored, presenting several avenues for future investigation. Its unique expression pattern and link to major signaling pathways lead to several testable hypotheses. **Proposed Hypotheses:** 1. In the respiratory system, [NWD1](/details-gene/284434) functions as a key regulator in [lung ciliated cells](/details-cell/CL1000271) to dampen NF-kB-driven inflammation in response to inhaled pathogens or irritants, thereby preserving ciliary function and tissue integrity. 2. Given its prominent expression in the choroid plexus, [NWD1](/details-gene/284434) is critical for maintaining the integrity of the blood-cerebrospinal fluid barrier by controlling inflammatory signaling within [choroid plexus epithelial cells](/details-cell/CL0000706) during neuroinflammation. 3. The mechanism by which [NWD1](/details-gene/284434) modulates androgen receptor (AR) activity involves its function as a scaffold or co-regulatory protein that influences the assembly of AR-associated transcriptional complexes in prostate cells. **Suggested Experimental Approach:** To test the first hypothesis regarding its role in respiratory epithelia, one could utilize an *in vitro* air-liquid interface (ALI) culture of primary human bronchial epithelial cells. Differentiated, ciliated cultures could be transduced with lentiviral vectors encoding shRNA to knock down [NWD1](/details-gene/284434). These knockdown cultures, along with non-targeting controls, would then be challenged with an inflammatory stimulus like lipopolysaccharide (LPS). The functional consequences could be measured by assessing NF-kB p65 nuclear translocation via immunofluorescence, quantifying pro-inflammatory cytokine secretion (e.g., IL-6, IL-8) by ELISA, and evaluating ciliary beat frequency using high-speed video microscopy. **Therapeutic Potential:** Based on evidence linking [NWD1](/details-gene/284434) to the modulation of androgen receptor signaling and its association with prostate cancer progression ([Link](https://doi.org/10.18632/oncotarget.1850)), the gene product represents a potential therapeutic target. The therapeutic strategy would likely involve **inhibition** to disrupt its pro-tumorigenic functions. As an intracellular protein, [NWD1](/details-gene/284434) is not a suitable target for antibody-based therapies. However, its NACHT domain, which functions as an ATPase, could represent a druggable pocket for the development of specific small molecule inhibitors to disrupt its activity in AR-dependent prostate cancers.

Genular Protein ID: 1569201176

Symbol: NWD1_HUMAN

Name: NACHT domain- and WD repeat-containing protein 1

UniProtKB Accession Codes:

Q149M9 C9J021 Q68CT3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 5 ExpressionAtlas 1 GO 5 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 6 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 2 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

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: 24681825

Title: The NLR-related protein NWD1 is associated with prostate cancer and modulates androgen receptor signaling.

PubMed ID: 24681825

DOI: 10.18632/oncotarget.1850

Sequence Information:

  • Length: 1564
  • Mass: 174552
  • Checksum: AB77411A1D6FBCFF
  • Sequence:
    • MQRGKPCRAL PTLKCQTFCQ RHGLMFEVVD LRWGIRNIEA TDHLTTELCL EEVDRCWKTS 
IGPAFVALIG DQYGPCLIPS RIDEKEWEVL RDHLTARPSD LELVARYFQR DENAFPPTYV 
LQAPGTGEAC EPEEATLTSV LRSGAQEARR LGLITQEQWQ HYHRSVIEWE IERSLLSSED 
REQGATVFLR EIQDLHKHIL EDCALRMVDR LADGCLDADA QNLLSSLKSH ITDMHPGVLK 
THRLPWSRDL VNPKNKTHAC YLKELGEQFV VRANHQVLTR LRELDTAGQE LAWLYQEIRH 
HLWQSSEVIQ TFCGRQELLA RLGQQLRHDD SKQHTPLVLF GPPGIGKTAL MCKLAEQMPR 
LLGHKTVTVL RLLGTSQMSS DARGLLKSIC FQVCLAYGLP LPPAQVLDAH TRVVQFFHTL 
LHTVSCRNFE SLVLLLDAMD DLDSVRHARR VPWLPLNCPP RVHLILSACS GALGVLDTLQ 
RVLLDPEAYW EVKPLSGNQG QQMIQLLLAA ARRTLSPVHT DLLWASLPEC GNPGRLRLAF 
EEARKWASFT VPVPLATTAE EATHQLCTRL EQTHGQLLVA HVLGYIVSSR HGLSEAELKD 
VLSLDDEVLQ DVYRDWTPPS KELLRFPPLL WVRLRRDLGY YLARRPVDGF TLLAIAHRQL 
VEVVRERYLS GSERAKRHGV LADFFSGTWS QGTKKLITLP LVGKPLNLDR KVAPQPLWFS 
HTVANLRKLK ELPYHLLHSG RLEELKQEVL GSMSWISCRG ISGGIEDLLD DFDLCAPHLD 
SPEVGLVREA LQLCRPAVEL RGMERSLLYT ELLARLHFFA TSHPALVGQL CQQAQSWFQL 
CAHPVLVPLG GFLQPPGGPL RATLSGCHKG ITAMAWGVEE KLLVIGTQDG IMAVWDMEEQ 
HVIHMLTGHT GEVRCVKIFA KGTLANSASK DYTLHLWNLL SGQEKFTIWD GGSKNPAEPQ 
IWNLHVDEAH KVVYSASGSK INAWNLETAE PVFHILGDAS DPWMCMAVLA SQATLLTVSR 
DGVVSLWSSA TGKLQGKQHM SSIKEETPTC AVSVQKQGKL VTGFSNGSIS LVSSKGDRLL 
EKLPDAVRFL VVSEDESLLA AGFGRSVRIF LADSRGFRRF MAMDLEHEDM VETAVFGTEN 
NLIITGSLDA LIQVWSLSEQ GTLLDILEGV GAPVSLLARG GALVASASPQ SSSFKVWDLS 
DAHRSRVPAP FLDRTGLTAV SHNGSYVYFP KIGDKNKVTI WDLAEGEEQD SLDTSSEIRC 
LEVAEQRKLL FTGLVSGVVL VFPLNSRQDV ICIPPPEARK AINCMSLSKC EDRLAIAYDN 
IVLVLDITSG DPCPVIDGPR YTFYTQLPET LSSVAILTDY RVVYSMTNGD LFLYECATSK 
AFPLETHRSR VACVEVSHKE QLVVSGSEDA LLCLWDLQAR KWKFEMSYTS SYCRGVQCAC 
FSKDDKYVYV GLKDRSILVW SVLDGTLLTV QFVHAVVNRI IPTTSGFIAP TRHGYLIREN 
FQCLSAKASP QDPLKNFKKA MWMVKSRQRE ELVAAAGAPQ DLESESAQGN ETKSNKCSQV 
CLIV