Details for: KAZALD1

Gene ID: 81621

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: KAZALD1

Ensembl ID: ENSG00000107821

Description: Kazal type serine peptidase inhibitor domain 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • goblet cell CL0000160
    CSI 3.5
    rCSI 3.31%
    PRS 98.84
  • intestine goblet cell CL0019031
    CSI 3.27
    rCSI 2.9%
    PRS 98.69
  • mucous neck cell CL0000651
    CSI 3.26
    rCSI 4.7%
    PRS 99.03
  • mucus secreting cell CL0000319
    CSI 3.24
    rCSI 5.15%
    PRS 99.54
  • foveolar cell of stomach CL0002179
    CSI 2.54
    rCSI 5.41%
    PRS 99.08
  • microcirculation associated smooth muscle cell CL0008035
    CSI 2.21
    rCSI 6.39%
    PRS 98.98
  • colon goblet cell CL0009039
    CSI 1.98
    rCSI 4.72%
    PRS 99.19
  • mesenchymal cell CL0008019
    CSI 1.13
    rCSI 2.88%
    PRS 98.76

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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  • 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 [KAZALD1](/details-gene/81621), or Kazal type serine peptidase inhibitor domain 1, is a protein-coding gene located on chromosome 10q24.31. The gene encodes a secreted protein belonging to the Kazal-type serine protease inhibitor family, first identified through large-scale cDNA sequencing and bioinformatics initiatives ([Link](https://doi.org/10.1101/gr.1293003), [Link](https://doi.org/10.1038/ng1285)). Its expression is highly specific to mucus-secreting epithelial cells, particularly [goblet cells](/details-cell/CL0000160) in the intestine and stomach. Functional annotations suggest its involvement in the organization of the extracellular matrix ([GO:0030198](https://www.ebi.ac.uk/QuickGO/term/GO:0030198)) and the regulation of cell growth ([GO:0001558](https://www.ebi.ac.uk/QuickGO/term/GO:0001558)), potentially through its capacity to bind insulin-like growth factors ([GO:0005520](https://www.ebi.ac.uk/QuickGO/term/GO:0005520)). ## Cellular Roles and Expression Landscape The expression profile of [KAZALD1](/details-gene/81621) strongly indicates a specialized role in mucosal biology and secretory functions. **Overall**, the gene shows the highest significance in cells responsible for producing and secreting mucus. It is a top marker for [goblet cells](/details-cell/CL0000160) (CSI: 3.50), specifically [intestine goblet cells](/details-cell/CL0019031) (CSI: 3.27) and [colon goblet cells](/details-cell/CL0009039) (CSI: 1.98), as well as [mucous neck cells](/details-cell/CL0000651) (CSI: 3.26) and [foveolar cells of the stomach](/details-cell/CL0002179) (CSI: 2.54). This restricted expression pattern across various gastrointestinal secretory cells highlights [KAZALD1](/details-gene/81621) as a key component of the mucosal barrier. Interestingly, significant expression is also noted in certain stromal cell types, including [microcirculation associated smooth muscle cells](/details-cell/CL0008035) (CSI: 2.21) and [mesenchymal cells](/details-cell/CL0008019) (CSI: 1.13). This suggests that in addition to its function in the epithelial layer, [KAZALD1](/details-gene/81621) may also play a role in the underlying connective tissue, possibly contributing to tissue homeostasis and structure. ## Pathways and Molecular Function Functionally, [KAZALD1](/details-gene/81621) is annotated as an extracellular protein ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)) primarily located in the interstitial matrix ([GO:0005614](https://www.ebi.ac.uk/QuickGO/term/GO:0005614)). Its molecular activities appear to be regulatory and structural. The gene's involvement in extracellular matrix organization ([GO:0030198](https://www.ebi.ac.uk/QuickGO/term/GO:0030198)) is consistent with its secretion by [goblet cells](/details-cell/CL0000160), where it may help structure the mucus layer or the basement membrane. Furthermore, [KAZALD1](/details-gene/81621) is implicated in fundamental cellular processes such as cell differentiation ([GO:0030154](https://www.ebi.ac.uk/QuickGO/term/GO:0030154)) and the regulation of cell growth ([GO:0001558](https://www.ebi.ac.uk/QuickGO/term/GO:0001558)). A specific molecular function attributed to the protein is insulin-like growth factor (IGF) binding ([GO:0005520](https://www.ebi.ac.uk/QuickGO/term/GO:0005520)). This suggests a potential mechanism where [KAZALD1](/details-gene/81621) modulates local growth factor signaling within the epithelial niche, thereby influencing the proliferation and maturation of surrounding cells. ## Research Directions The specific expression of [KAZALD1](/details-gene/81621) in mucosal and stromal cells, combined with its putative functions, opens several avenues for future investigation, particularly concerning gastrointestinal health and disease. **Proposed Hypotheses:** 1. As a secreted protease inhibitor expressed by [goblet cells](/details-cell/CL0000160), [KAZALD1](/details-gene/81621) plays a direct role in maintaining the integrity of the gastrointestinal mucosal barrier by protecting key structural proteins, such as mucins, from enzymatic degradation by luminal or host-derived proteases. 2. Given its IGF-binding capacity ([GO:0005520](https://www.ebi.ac.uk/QuickGO/term/GO:0005520)), [KAZALD1](/details-gene/81621) acts as a local modulator of the IGF signaling axis in the intestinal crypt, regulating the balance between epithelial cell proliferation and differentiation into secretory lineages. Dysregulation of this function could contribute to inflammatory bowel diseases or gastrointestinal cancers. **Experimental Approach:** To test the hypothesis that [KAZALD1](/details-gene/81621) modulates epithelial homeostasis via IGF signaling, a study using intestinal organoid models would be highly informative. CRISPR-Cas9 could be used to generate [KAZALD1](/details-gene/81621) knockout human intestinal organoids. The proliferation rates and differentiation status of these knockout organoids could be compared to wild-type controls, both at baseline and following stimulation with IGF-1. Readouts would include quantifying cell proliferation via EdU incorporation and assessing the number of differentiated [goblet cells](/details-cell/CL0000160) through immunofluorescence for MUC2. Changes in downstream IGF signaling pathways (e.g., phosphorylation of AKT and ERK) could be measured by Western blot. **Therapeutic Potential:** As a secreted protein, [KAZALD1](/details-gene/81621) is a potentially accessible therapeutic target. If its overexpression is linked to pathological conditions, such as fibrosis or tumor growth (by modulating the extracellular matrix or growth factor signaling), it could be targeted for inhibition using neutralizing antibodies. Conversely, if loss of [KAZALD1](/details-gene/81621) function is found to compromise mucosal barrier integrity, as in inflammatory bowel disease, supplementation with a recombinant form of the protein could represent a novel therapeutic strategy to restore barrier function.

Genular Protein ID: 1505525798

Symbol: KAZD1_HUMAN

Name: Kazal-type serine protease inhibitor domain-containing protein 1

UniProtKB Accession Codes:

Q96I82 D3DR74 Q6ZMB1 Q9BQ73

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 Ensembl 1 GO 8 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 11 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIRSF 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 4 SMART 3 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

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: 15340161

Title: Signal peptide prediction based on analysis of experimentally verified cleavage sites.

PubMed ID: 15340161

DOI: 10.1110/ps.04682504

Sequence Information:

  • Length: 304
  • Mass: 32945
  • Checksum: D6259658B62E99CD
  • Sequence:
    • MLPPPRPAAA LALPVLLLLL VVLTPPPTGA RPSPGPDYLR RGWMRLLAEG EGCAPCRPEE 
CAAPRGCLAG RVRDACGCCW ECANLEGQLC DLDPSAHFYG HCGEQLECRL DTGGDLSRGE 
VPEPLCACRS QSPLCGSDGH TYSQICRLQE AARARPDANL TVAHPGPCES GPQIVSHPYD 
TWNVTGQDVI FGCEVFAYPM ASIEWRKDGL DIQLPGDDPH ISVQFRGGPQ RFEVTGWLQI 
QAVRPSDEGT YRCLGRNALG QVEAPASLTV LTPDQLNSTG IPQLRSLNLV PEEEAESEEN 
DDYY