Details for: SERPINB8

Gene ID: 5271

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: SERPINB8

Ensembl ID: ENSG00000166401

Description: serpin family B member 8

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • granulocyte monocyte progenitor cell CL0000557
    CSI 8.02
    rCSI 6.94%
    PRS 97.13
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.87
    rCSI 2.71%
    PRS 97.61
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 3.81
    rCSI 4.99%
    PRS 98.93
  • keratinocyte CL0000312
    CSI 3.79
    rCSI 3.17%
    PRS 95.62
  • promyelocyte CL0000836
    CSI 3.6
    rCSI 5.19%
    PRS 96.83
  • common myeloid progenitor CL0000049
    CSI 3.37
    rCSI 2.73%
    PRS 97.03
  • myeloid leukocyte CL0000766
    CSI 3.12
    rCSI 2.87%
    PRS 97.12
  • conjunctival epithelial cell CL1000432
    CSI 2.88
    rCSI 4.39%
    PRS 95.21
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.83
    rCSI 2.18%
    PRS 97.96
  • elicited macrophage CL0000861
    CSI 2.72
    rCSI 2.5%
    PRS 98.34
  • basal cell CL0000646
    CSI 2.23
    rCSI 2.98%
    PRS 94.22
  • alternatively activated macrophage CL0000890
    CSI 2.21
    rCSI 2.78%
    PRS 98.72
  • club cell CL0000158
    CSI 2.04
    rCSI 2.99%
    PRS 93.98
  • promonocyte CL0000559
    CSI 1.9
    rCSI 3.25%
    PRS 96.99
  • intermediate monocyte CL0002393
    CSI 1.71
    rCSI 2.59%
    PRS 98.23
  • lung macrophage CL1001603
    CSI 1.5
    rCSI 3.34%
    PRS 98.46

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)

Loading network (please wait)...

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 Analyzed for its expression specificity (CSI Z-Score), [SERPINB8](/details-gene/5271) (serpin family B member 8) does not appear to be a defining marker for any specific cell type. The data indicate that it is broadly expressed at basal levels across diverse cell lineages, including myeloid and epithelial cells. Functionally, it is known as a serine-type endopeptidase inhibitor. Its clinical relevance is most clearly established in dermatology, where loss-of-function mutations are linked to exfoliative ichthyosis with impaired intercellular adhesion, as reported by Pohler et al. (2016) ([DOI: 10.1016/j.ajhg.2016.06.004](https://doi.org/10.1016/j.ajhg.2016.06.004)). ## Cellular Roles and Expression Landscape The expression profile of [SERPINB8](/details-gene/5271), when evaluated for cell-type specificity, reveals a notable lack of enrichment in any particular cell population. In the **Overall** context, the CSI (Z-SCORE) is 0.00 with non-significant p-values (p > 0.5) for all top-listed cell types. This strongly suggests that its transcript levels do not significantly deviate from the average gene expression within these cells, and therefore, it cannot be considered a specific biomarker. Despite the lack of specificity, its presence is consistently detected in a range of cells. These include various stages of myeloid development, such as [granulocyte monocyte progenitor cell](/details-cell/CL0000557)s and [promyelocyte](/details-cell/CL0000836)s, as well as mature immune cells like [CD14-positive, CD16-positive monocyte](/details-cell/CL0002397)s and [plasmacytoid dendritic cell, human](/details-cell/CL0001058). The gene is also expressed in multiple epithelial cell types, including [keratinocyte](/details-cell/CL0000312), [conjunctival epithelial cell](/details-cell/CL1000432), and [club cell](/details-cell/CL0000158). This broad but non-specific expression pattern is consistent with a role in a fundamental biological process common to many cell types rather than a specialized cellular function. The documented expression in [keratinocyte](/details-cell/CL0000312)s directly correlates with its known role in skin integrity, where mutations lead to severe adhesion defects ([DOI: 10.1016/j.ajhg.2016.06.004](https://doi.org/10.1016/j.ajhg.2016.06.004)). ## Pathways and Molecular Function The functional annotations for [SERPINB8](/details-gene/5271) align with its observed broad expression and its role as a regulator of proteolysis. Its primary molecular function is serine-type endopeptidase inhibitor activity ([GO:0004867](/https://www.ebi.ac.uk/QuickGO/term/GO:0004867)), a crucial mechanism for controlling enzymatic cascades in various biological settings. The gene's involvement in epithelial cell-cell adhesion ([GO:0090136](/https://www.ebi.ac.uk/QuickGO/term/GO:0090136)) provides a direct molecular basis for the exfoliative ichthyosis phenotype observed in patients with mutations. This suggests [SERPINB8](/details-gene/5271) protects key adhesion proteins in the skin from proteolytic degradation. Furthermore, its annotation to hemostasis ([R-HSA-109582](https://reactome.org/content/detail/R-HSA-109582)) and dissolution of fibrin clot ([R-HSA-75205](https://reactome.org/content/detail/R-HSA-75205)) is consistent with its expression in myeloid cells, which are key players in wound healing and coagulation. Its presence in the [extracellular space](/https://www.ebi.ac.uk/QuickGO/term/GO:0005615) and [cytosol](/https://www.ebi.ac.uk/QuickGO/term/GO:0005829) suggests it may function both inside and outside the cell to regulate protease activity. ## Research Directions While the provided data indicate [SERPINB8](/details-gene/5271) is not a specific cell marker under homeostatic conditions, its functional importance, particularly in skin, suggests its role may be dynamically regulated by cellular context and stress. ### Testable Hypotheses: 1. **Hypothesis:** The expression of [SERPINB8](/details-gene/5271) is significantly upregulated in [keratinocyte](/details-cell/CL0000312)s and other epidermal cells as a protective response to mechanical stress or inflammatory signals. This upregulation may be critical for reinforcing cell-cell junctions by inhibiting proteases that target adhesion molecules like desmogleins. * **Experimental Approach:** Utilize single-cell RNA sequencing and immunofluorescence on human skin explants or 3D skin equivalents subjected to mechanical stretching or treatment with pro-inflammatory cytokines (e.g., TNF-α, IL-1β). Quantify changes in [SERPINB8](/details-gene/5271) transcript and protein levels, and correlate its localization with cell adhesion structures. 2. **Hypothesis:** In myeloid cells like [monocyte](/details-cell/CL0002397)s, [SERPINB8](/details-gene/5271) acts as a local regulator of the coagulation cascade during inflammation. Its expression and secretion may be induced during monocyte activation or differentiation into macrophages to modulate fibrinolysis at sites of tissue injury or infection. * **Experimental Approach:** Isolate primary human monocytes and differentiate them into macrophages *in vitro*. Use qRT-PCR and ELISA to measure [SERPINB8](/details-gene/5271) expression and secretion following stimulation with lipopolysaccharide (LPS). Assess the functional impact by measuring the rate of fibrin clot dissolution in the presence of conditioned media from these cells. 3. **Hypothesis:** The broad, low-specificity expression of [SERPINB8](/details-gene/5271) across many cell types suggests functional redundancy with other SERPINB family members. The severe skin-specific phenotype from its loss-of-function mutations arises because it has a non-redundant, critical target protease in [keratinocyte](/details-cell/CL0000312)s that other serpins cannot effectively inhibit. * **Experimental Approach:** Use CRISPR-Cas9 to systematically knock out [SERPINB8](/details-gene/5271) and other co-expressed SERPINB members (e.g., SERPINB3, SERPINB4) in a keratinocyte cell line. Perform proteomics-based activity-based protein profiling (ABPP) to identify the specific proteases that become hyperactive upon [SERPINB8](/details-gene/5271) loss, thereby revealing its unique target. ### Therapeutic Potential: The most immediate therapeutic application lies in treating exfoliative ichthyosis ([OMIM: 601697](https://omim.org/entry/601697)) caused by [SERPINB8](/details-gene/5271) deficiency. Strategies could include the development of topical protein replacement therapies or gene-based therapies to restore its function in the epidermis. Its role in hemostasis is less defined, but further research into its specific protease targets could potentially uncover roles in modulating thrombosis or bleeding, though this remains speculative.

Genular Protein ID: 2495925437

Symbol: SPB8_HUMAN

Name: Serpin B8

UniProtKB Accession Codes:

P50452 B4DTW2 Q7Z2V6 Q8N178

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 4 ExpressionAtlas 1 GO 8 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MEROPS 1 MIM 3 MalaCards 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 1 RefSeq 4 SABIO-RK 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8530382

Title: Molecular cloning, expression, and partial characterization of two novel members of the ovalbumin family of serine proteinase inhibitors.

PubMed ID: 8530382

DOI: 10.1074/jbc.270.50.29854

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 16177791

Title: DNA sequence and analysis of human chromosome 18.

PubMed ID: 16177791

DOI: 10.1038/nature03983

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: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 27476651

Title: Loss-of-function mutations in SERPINB8 linked to exfoliative ichthyosis with impaired mechanical stability of intercellular adhesions.

PubMed ID: 27476651

DOI: 10.1016/j.ajhg.2016.06.004

Sequence Information:

  • Length: 374
  • Mass: 42767
  • Checksum: 7235A033519AC612
  • Sequence:
    • MDDLCEANGT FAISLFKILG EEDNSRNVFF SPMSISSALA MVFMGAKGST AAQMSQALCL 
YKDGDIHRGF QSLLSEVNRT GTQYLLRTAN RLFGEKTCDF LPDFKEYCQK FYQAELEELS 
FAEDTEECRK HINDWVAEKT EGKISEVLDA GTVDPLTKLV LVNAIYFKGK WNEQFDRKYT 
RGMLFKTNEE KKTVQMMFKE AKFKMGYADE VHTQVLELPY VEEELSMVIL LPDDNTDLAV 
VEKALTYEKF KAWTNSEKLT KSKVQVFLPR LKLEESYDLE PFLRRLGMID AFDEAKADFS 
GMSTEKNVPL SKVAHKCFVE VNEEGTEAAA ATAVVRNSRC SRMEPRFCAD HPFLFFIRHH 
KTNCILFCGR FSSP

Genular Protein ID: 2578140797

Symbol: A0A1B0GU38_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A1B0GU38

Database IDs:

AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 GO 2 Gene3D 2 GeneTree 1 HGNC 1 InterPro 5 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 1 RefSeq 2 RuleBase 1 SMART 2 SMR 1 SUPFAM 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16177791

Title: DNA sequence and analysis of human chromosome 18.

PubMed ID: 16177791

DOI: 10.1038/nature03983

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

Sequence Information:

  • Length: 259
  • Mass: 29515
  • Checksum: 32FE6A23C2D03CD3
  • Sequence:
    • MDDLCEANGT FAISLFKILG EEDNSRNVFF SPMSISSALA MVFMGAKGST AAQMSQALCL 
YKDGDIHRGF QSLLSEVNRT GTQYLLRTAN RLFGEKTCDF LPDFKEYCQK FYQAELEELS 
FAEDTEECRK HINDWVAEKT EGKISEVLDA GTVDPLTKLV LVNAIYFKGK WNEQFDRKYT 
RGMLFKTNEE KKTVQMMFKE AKFKMGYADE VHTQVLELPY VEEELSMVIL LPDDNTDLAV 
DTLRSTSFFC DILANIIST