Details for: NFKBID

Gene ID: 84807

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: NFKBID

Ensembl ID: ENSG00000167604

Description: NFKB inhibitor delta

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • plasmablast CL0000980
    CSI 21.43
    rCSI 16.86%
    PRS 87.66
  • endothelial cell of lymphatic vessel CL0002138
    CSI 19.41
    rCSI 38.48%
    PRS 87.61
  • memory T cell CL0000813
    CSI 13.8
    rCSI 26.58%
    PRS 96.69
  • CD14-positive monocyte CL0001054
    CSI 9.97
    rCSI 12.42%
    PRS 91.24
  • small pre-B-II cell CL0000954
    CSI 9.62
    rCSI 9.25%
    PRS 93.98
  • inflammatory macrophage CL0000863
    CSI 9.44
    rCSI 16.14%
    PRS 95.16
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 8.57
    rCSI 11.23%
    PRS 92.43
  • dendritic cell, human CL0001056
    CSI 8.06
    rCSI 12.38%
    PRS 90.64
  • early lymphoid progenitor CL0000936
    CSI 7.19
    rCSI 6.32%
    PRS 88.05
  • mononuclear phagocyte CL0000113
    CSI 6.67
    rCSI 14.69%
    PRS 86.89
  • blood vessel endothelial cell CL0000071
    CSI 6.58
    rCSI 13.65%
    PRS 80.64
  • class switched memory B cell CL0000972
    CSI 6
    rCSI 4.48%
    PRS 93.44
  • alpha-beta T cell CL0000789
    CSI 5.22
    rCSI 6.12%
    PRS 94.38
  • colon macrophage CL0009038
    CSI 4.85
    rCSI 22.42%
    PRS 93.26
  • myeloid leukocyte CL0000766
    CSI 4.43
    rCSI 4.09%
    PRS 84.88
  • monocyte CL0000576
    CSI 4.39
    rCSI 7.93%
    PRS 86.92
  • dendritic cell CL0000451
    CSI 4.27
    rCSI 5.26%
    PRS 85.64
  • precursor B cell CL0000817
    CSI 4.17
    rCSI 3.65%
    PRS 89.79
  • immature B cell CL0000816
    CSI 4.15
    rCSI 3.08%
    PRS 92.32
  • unswitched memory B cell CL0000970
    CSI 3.96
    rCSI 3.33%
    PRS 94.08
  • memory B cell CL0000787
    CSI 3.83
    rCSI 3.78%
    PRS 93.09
  • group 3 innate lymphoid cell CL0001071
    CSI 3.8
    rCSI 2.85%
    PRS 88.8
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.75
    rCSI 2.62%
    PRS 86.87
  • hematopoietic stem cell CL0000037
    CSI 3.57
    rCSI 2.38%
    PRS 85.87
  • elicited macrophage CL0000861
    CSI 3.29
    rCSI 3.02%
    PRS 90.2
  • lung interstitial macrophage CL4033043
    CSI 2.99
    rCSI 6.71%
    PRS 93.21
  • granulocyte CL0000094
    CSI 2.89
    rCSI 4.41%
    PRS 89.65
  • pro-B cell CL0000826
    CSI 2.88
    rCSI 2.39%
    PRS 85.81
  • fraction A pre-pro B cell CL0002045
    CSI 2.86
    rCSI 3.27%
    PRS 91.85
  • erythrocyte CL0000232
    CSI 2.79
    rCSI 6.33%
    PRS 83.48
  • lung macrophage CL1001603
    CSI 2.49
    rCSI 5.57%
    PRS 89.81
  • activated type II NK T cell CL0000931
    CSI 2.46
    rCSI 2.77%
    PRS 94.06
  • Kupffer cell CL0000091
    CSI 2.44
    rCSI 5.58%
    PRS 84.4
  • promyelocyte CL0000836
    CSI 2.42
    rCSI 3.49%
    PRS 88.09
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 2.29
    rCSI 5.97%
    PRS 84.59
  • mast cell CL0000097
    CSI 2.25
    rCSI 4.85%
    PRS 86.57
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 2.21
    rCSI 2.64%
    PRS 95.5
  • keratinocyte CL0000312
    CSI 2.15
    rCSI 1.8%
    PRS 85.59
  • basophil CL0000767
    CSI 2.14
    rCSI 4.53%
    PRS 92.36
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 2.11
    rCSI 2.55%
    PRS 90.19
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.1
    rCSI 1.62%
    PRS 86.65
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.02
    rCSI 1.75%
    PRS 86.99
  • alternatively activated macrophage CL0000890
    CSI 1.91
    rCSI 2.4%
    PRS 91.38
  • mature B cell CL0000785
    CSI 1.9
    rCSI 1.65%
    PRS 91.53
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.9
    rCSI 1.83%
    PRS 82.95
  • myeloid dendritic cell CL0000782
    CSI 1.89
    rCSI 2.74%
    PRS 93.92
  • T-helper 17 cell CL0000899
    CSI 1.87
    rCSI 1.49%
    PRS 96.55
  • common myeloid progenitor CL0000049
    CSI 1.77
    rCSI 1.43%
    PRS 85.56
  • tissue-resident macrophage CL0000864
    CSI 1.76
    rCSI 8.22%
    PRS 92.81
  • IgA plasma cell CL0000987
    CSI 1.66
    rCSI 1.7%
    PRS 89.19
  • T-helper 1 cell CL0000545
    CSI 1.65
    rCSI 2.98%
    PRS 95.24
  • intermediate monocyte CL0002393
    CSI 1.65
    rCSI 2.49%
    PRS 88.4
  • transitional stage B cell CL0000818
    CSI 1.56
    rCSI 5.1%
    PRS 95.44
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 1.48
    rCSI 2.53%
    PRS 93.59
  • large pre-B-II cell CL0000957
    CSI 1.45
    rCSI 4.13%
    PRS 87.49
  • alveolar macrophage CL0000583
    CSI 1.44
    rCSI 2.37%
    PRS 86.95
  • common dendritic progenitor CL0001029
    CSI 1.43
    rCSI 1.8%
    PRS 90.68
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.43
    rCSI 1.29%
    PRS 82.08
  • Langerhans cell CL0000453
    CSI 1.43
    rCSI 2.18%
    PRS 92.48
  • Hofbauer cell CL3000001
    CSI 1.43
    rCSI 2.69%
    PRS 90.29
  • common lymphoid progenitor CL0000051
    CSI 1.37
    rCSI 1.83%
    PRS 95.21
  • germinal center B cell CL0000844
    CSI 1.16
    rCSI 3.47%
    PRS 91.2
  • promonocyte CL0000559
    CSI 1.13
    rCSI 1.93%
    PRS 88.33
  • B-2 B cell CL0000822
    CSI 1.09
    rCSI 23.02%
    PRS 94.5
  • CD8-alpha-alpha-positive, alpha-beta intraepithelial T cell CL0000915
    CSI 0.66
    rCSI 3.01%
    PRS 95.5
  • group 2 innate lymphoid cell CL0001069
    CSI 0.59
    rCSI 3.22%
    PRS 96.13

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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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 [NFKBID](/details-gene/84807) (NFKB inhibitor delta) is a protein-coding gene located on chromosome 19q13.12 that functions as a negative regulator of the NF-kappa-B signaling pathway. As an inhibitor, it plays a crucial role in modulating gene expression, particularly in the context of inflammation and immune cell function. Expression data indicate that [NFKBID](/details-gene/84807) is highly significant in various immune cell populations, with its most prominent expression observed in terminally differentiated B cells, such as [plasmablast](/details-cell/CL0000980), as well as in [endothelial cell of lymphatic vessel](/details-cell/CL0002138), [memory T cell](/details-cell/CL0000813), and multiple myeloid lineages, suggesting a broad role in orchestrating immune homeostasis and response. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [NFKBID](/details-gene/84807) highlights its significant role within the hematopoietic and vascular systems, particularly in cells central to both innate and adaptive immunity. The gene shows its highest significance in the B lymphocyte lineage, specifically in [plasmablast](/details-cell/CL0000980) (CSI: 21.43), with notable expression also found in earlier developmental stages like [small pre-B-II cell](/details-cell/CL0000954) and in [class switched memory B cell](/details-cell/CL0000972). This pattern suggests a potential role for [NFKBID](/details-gene/84807) in regulating the final stages of B cell differentiation and antibody production. In the T cell compartment, [NFKBID](/details-gene/84807) is a key marker for [memory T cell](/details-cell/CL0000813) (CSI: 13.80) and [alpha-beta T cell](/details-cell/CL0000789), which is consistent with early studies identifying it as a T lymphocyte activation gene ([Link](https://doi.org/10.1016/j.ygeno.2003.12.019)). Its function is further implicated in myeloid cell biology, with high significance in [CD14-positive monocyte](/details-cell/CL0001054), [inflammatory macrophage](/details-cell/CL0000863), and [dendritic cell, human](/details-cell/CL0001056). This widespread expression across key immune effector cells underscores its function as a critical modulator of immune responses. Beyond immune cells, [NFKBID](/details-gene/84807) shows remarkably high significance in [endothelial cell of lymphatic vessel](/details-cell/CL0002138) (CSI: 19.41), indicating a potential function in lymphatic vessel biology, possibly related to immune cell trafficking or inflammatory signaling within the lymphatic system. ## Pathways and Molecular Function The functions of [NFKBID](/details-gene/84807) are primarily centered on the regulation of transcription and immune signaling. Its annotated localization to the [nucleus](/details-cell/GO:0005634) is consistent with its primary role as a regulator of gene expression ([GO:0010468](https://www.ebi.ac.uk/QuickGO/term/GO:0010468)) through its ability to bind other proteins ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)), namely components of the NF-kappa-B complex. This regulatory function is integral to several key biological processes: * **Inflammatory response** ([GO:0006954](https://www.ebi.ac.uk/QuickGO/term/GO:0006954)): By inhibiting NF-kappa-B, a master regulator of inflammation, [NFKBID](/details-gene/84807) likely acts as a feedback brake to prevent excessive or prolonged inflammatory reactions. This is consistent with its high expression in monocytes and macrophages. * **T cell signaling**: The gene is involved in the T cell receptor signaling pathway ([GO:0050852](https://www.ebi.ac.uk/QuickGO/term/GO:0050852)) and the positive regulation of t-helper 17 cell differentiation ([GO:2000321](https://www.ebi.ac.uk/QuickGO/term/GO:2000321)). This aligns with its high CSI in [memory T cell](/details-cell/CL0000813) and suggests a role in fine-tuning T cell activation, differentiation, and the establishment of immune memory. ## Research Directions The expression profile and functional annotations of [NFKBID](/details-gene/84807) suggest it is a pivotal negative regulator in the immune system. Based on the available data, several testable hypotheses can be proposed. 1. **Hypothesis 1:** Given its peak expression in [plasmablast](/details-cell/CL0000980), [NFKBID](/details-gene/84807) is essential for the terminal differentiation of B cells into antibody-secreting cells by modulating NF-kappa-B activity thresholds required for this transition. Its upregulation may serve to terminate the proliferation signal and enable the final maturation program. 2. **Hypothesis 2:** In [endothelial cell of lymphatic vessel](/details-cell/CL0002138), [NFKBID](/details-gene/84807) functions to maintain lymphatic vessel integrity and quiescence during homeostasis. During inflammation, its downregulation may be a required step to permit vessel activation, permeability changes, and immune cell trafficking. **Experimental Approach:** To test the role of [NFKBID](/details-gene/84807) in B cell differentiation (Hypothesis 1), one could utilize a CRISPR-Cas9-based knockout strategy in primary human naive B cells. Control and knockout cells could be stimulated *in vitro* with CD40L and cytokines (e.g., IL-21) to drive plasmablast differentiation. The outcome could be measured by quantifying the generation of CD27+CD38++ plasmablasts via flow cytometry, assessing immunoglobulin secretion levels using ELISA, and performing RNA-seq to determine how the loss of [NFKBID](/details-gene/84807) alters the transcriptional programs governing B cell fate. **Therapeutic Potential:** As a natural inhibitor of the pro-inflammatory and pro-survival NF-kappa-B pathway, [NFKBID](/details-gene/84807) represents a potential target for therapeutic **activation** or enhancement. In autoimmune diseases or certain B-cell malignancies characterized by hyperactive NF-kappa-B signaling, strategies to increase the functional activity or expression of [NFKBID](/details-gene/84807) could be beneficial. Due to its intracellular location in the [nucleus](/details-cell/GO:0005634), therapeutic development would likely focus on small molecules that stabilize the protein or mimic its inhibitory function rather than on antibody-based approaches.

Genular Protein ID: 126506334

Symbol: IKBD_HUMAN

Name: NF-kappa-B inhibitor delta

UniProtKB Accession Codes:

Q8NI38 Q8NI39 Q9BRG9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 ExpressionAtlas 1 GO 5 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 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 2 RNAct 1 RefSeq 5 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: 15177553

Title: T lymphocyte activation gene identification by coregulated expression on DNA microarrays.

PubMed ID: 15177553

DOI: 10.1016/j.ygeno.2003.12.019

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

Sequence Information:

  • Length: 313
  • Mass: 33481
  • Checksum: B986234830428320
  • Sequence:
    • MEAGPWRVSA PPSGPPQFPA VVPGPSLEVA RAHMLALGPQ QLLAQDEEGD TLLHLFAARG 
LRWAAYAAAE VLQVYRRLDI REHKGKTPLL VAAAANQPLI VEDLLNLGAE PNAADHQGRS 
VLHVAATYGL PGVLLAVLNS GVQVDLEARD FEGLTPLHTA ILALNVAMRP SDLCPRVLST 
QARDRLDCVH MLLQMGANHT SQEIKSNKTV LHLAVQAANP TLVQLLLELP RGDLRTFVNM 
KAHGNTALHM AAALPPGPAQ EAIVRHLLAA GADPTLRNLE NEQPVHLLRP GPGPEGLRQL 
LKRSRVAPPG LSS