Details for: KRBA2

Gene ID: 124751

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: KRBA2

Ensembl ID: ENSG00000184619

Description: KRAB-A domain containing 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • lung neuroendocrine cell CL1000223
    CSI 6.13
    rCSI 9.06%
    PRS 98.48
  • alveolar adventitial fibroblast CL4028006
    CSI 5.8
    rCSI 9.15%
    PRS 99.51
  • secretory cell CL0000151
    CSI 3.91
    rCSI 4.08%
    PRS 98.98
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 3.67
    rCSI 4.23%
    PRS 97.44
  • natural killer cell CL0000623
    CSI 3.3
    rCSI 6.4%
    PRS 97.47
  • choroid plexus epithelial cell CL0000706
    CSI 3.12
    rCSI 5.12%
    PRS 97.78
  • retinal rod cell CL0000604
    CSI 2.69
    rCSI 4.75%
    PRS 97.68
  • cardiac muscle cell CL0000746
    CSI 2.37
    rCSI 3.4%
    PRS 97.11
  • retinal pigment epithelial cell CL0002586
    CSI 2.34
    rCSI 4.64%
    PRS 98.15
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.06
    rCSI 4.62%
    PRS 96.92
  • mast cell CL0000097
    CSI 2.03
    rCSI 4.38%
    PRS 94.76
  • retinal cone cell CL0000573
    CSI 2.02
    rCSI 3.25%
    PRS 97.05
  • kidney connecting tubule epithelial cell CL1000768
    CSI 2.01
    rCSI 5.09%
    PRS 98.38
  • vein endothelial cell CL0002543
    CSI 1.96
    rCSI 5.35%
    PRS 99.24
  • innate lymphoid cell CL0001065
    CSI 1.78
    rCSI 3.68%
    PRS 95.99
  • S cone cell CL0003050
    CSI 1.67
    rCSI 7.33%
    PRS 97.79
  • neural progenitor cell CL0011020
    CSI 1.44
    rCSI 6.33%
    PRS 95.09
  • pulmonary alveolar type 1 cell CL0002062
    CSI 0.9
    rCSI 5.18%
    PRS 98.42

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 [KRBA2](/details-gene/124751), or KRAB-A domain containing 2, is a protein-coding gene located on chromosome 17p13.1. As its name implies, it contains a Krüppel-associated box (KRAB) domain, a well-characterized transcriptional repressor motif. Functional annotations suggest its involvement in the [regulation of dna-templated transcription](/details-go/GO:0006355) and [nucleic acid binding](/details-go/GO:0003676), consistent with its role as a transcription factor. **Overall**, expression data indicate that [KRBA2](/details-gene/124751) is a significant gene in a diverse range of specialized cell types, showing the highest significance in [lung neuroendocrine cell](/details-cell/CL1000223)s, [alveolar adventitial fibroblast](/details-cell/CL4028006)s, and various immune cells, suggesting it may play a role in maintaining distinct cellular identities across multiple tissues. ## Cellular Roles and Expression Landscape The expression profile of [KRBA2](/details-gene/124751) suggests a broad but specific functional landscape. **Overall**, its most significant expression is observed in [lung neuroendocrine cell](/details-cell/CL1000223)s (CSI: 6.13) and [alveolar adventitial fibroblast](/details-cell/CL4028006)s (CSI: 5.80), indicating a potentially crucial role in the lung, both in specialized secretory cells and in the structural fibroblast compartment. The gene's significance extends to several other distinct cellular contexts: * **Neural and Sensory Tissues:** High significance is noted in cells of the nervous system and sensory organs, including [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338), [choroid plexus epithelial cell](/details-cell/CL0000706), [retinal rod cell](/details-cell/CL0000604), and [astrocyte of the cerebral cortex](/details-cell/CL0002605). This pattern suggests a role in the development or maintenance of specialized neural cell functions. * **Immune System:** [KRBA2](/details-gene/124751) is also a significant marker in several innate immune cell populations, such as the [natural killer cell](/details-cell/CL0000623) (CSI: 3.30), [mast cell](/details-cell/CL0000097), and [innate lymphoid cell](/details-cell/CL0001065). This is consistent with a function in regulating the transcriptional programs that define these immune cell lineages. * **Epithelial and Mesenchymal Cells:** The gene is also prominent in diverse cell types like [secretory cell](/details-cell/CL0000151)s, [cardiac muscle cell](/details-cell/CL0000746)s, and [kidney connecting tubule epithelial cell](/details-cell/CL1000768)s, highlighting its widespread, yet cell-type-specific, importance. ## Pathways and Molecular Function The function of [KRBA2](/details-gene/124751) is primarily linked to transcriptional control. Gene Ontology annotations indicate its involvement in biological processes such as [regulation of dna-templated transcription](/details-go/GO:0006355) and [dna integration](/details-go/GO:0015074). Its molecular functions are annotated as [nucleic acid binding](/details-go/GO:0003676) and [protein binding](/details-go/GO:0005515). The presence of a KRAB domain strongly suggests that [KRBA2](/details-gene/124751) functions as a transcriptional repressor, likely by recruiting co-repressor complexes to specific DNA loci. This regulatory role is consistent with its specific expression pattern, where it may be responsible for silencing inappropriate gene expression to maintain the specialized identity of cells like [lung neuroendocrine cell](/details-cell/CL1000223)s or [natural killer cell](/details-cell/CL0000623)s. Its characterization has been supported by large-scale cDNA and genome sequencing projects [[Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1101/gr.2596504)]. ## Research Directions The diverse expression profile of [KRBA2](/details-gene/124751) points to several avenues for future research into its role in cellular specification and disease. **Proposed Hypotheses:** 1. Given its top-ranking significance in [lung neuroendocrine cell](/details-cell/CL1000223)s, [KRBA2](/details-gene/124751) may function as a master transcriptional repressor that establishes or maintains the neuroendocrine lineage in the lung. Its dysregulation could therefore be a contributing factor to the pathogenesis of neuroendocrine tumors, such as small-cell lung cancer. 2. The high significance of [KRBA2](/details-gene/124751) in [alveolar adventitial fibroblast](/details-cell/CL4028006)s suggests a potential role in regulating fibroblast identity and function. It may be involved in repressing pro-fibrotic genes in a healthy state, with its downregulation potentially contributing to pathological conditions like pulmonary fibrosis. 3. The consistent expression in multiple innate immune cells, including [natural killer cell](/details-cell/CL0000623)s and [innate lymphoid cell](/details-cell/CL0001065)s, suggests that [KRBA2](/details-gene/124751) is involved in regulating innate immune effector functions, possibly by repressing genes associated with adaptive immunity or other hematopoietic lineages. **Experimental Approach:** To test the hypothesis that [KRBA2](/details-gene/124751) is essential for maintaining the neuroendocrine cell state, one could perform a CRISPR-Cas9-mediated knockout of the gene in a human lung neuroendocrine cell line. The impact on cellular identity could be assessed by RNA-sequencing to identify genome-wide transcriptional changes and by quantitative PCR and immunoblotting to measure changes in key neuroendocrine markers (e.g., Chromogranin A, Synaptophysin) and markers of other cell lineages. A loss of the neuroendocrine phenotype upon [KRBA2](/details-gene/124751) deletion would provide strong evidence for its role as a key lineage-defining factor. **Therapeutic Potential:** As an intracellular transcription factor, [KRBA2](/details-gene/124751) presents a challenging direct target for conventional small-molecule therapies. However, if its dysregulation is causally linked to diseases such as neuroendocrine cancers, understanding its downstream targets and repressive mechanisms could unveil more druggable nodes in the pathways it controls. For example, if [KRBA2](/details-gene/124751) represses an oncogenic pathway, strategies aimed at restoring its function or expression could have therapeutic value. Conversely, if it is overexpressed and contributes to pathology, targeting its protein-protein interactions with co-repressors may be a viable, albeit complex, therapeutic strategy.

Genular Protein ID: 710015568

Symbol: KRBA2_HUMAN

Name: KRAB-A domain-containing protein 2

UniProtKB Accession Codes:

Q6ZNG9 Q8IYY0

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 2 Ensembl 1 ExpressionAtlas 1 GO 3 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

Sequence Information:

  • Length: 492
  • Mass: 56205
  • Checksum: D84C1502A38DCCAF
  • Sequence:
    • MPSFLVPSLV SSPVLLKLLF SPGPKTIWSL WQQPMLFQEA TAFENMTKDW NYLEGSQKDC 
YRDTMLDSYE NTVPQGSFLQ LSMMPQRAGN DPPGVSNASE MEMEISNMRE KFLMSVTKLV 
ESKSYNSKVF SKEKYFQTIK EVKEAKEKGK KSSRDYRRAA KYDVISVQGT EKLIEATHGE 
RDRIRYYVHK EELFDILHDT HLSIGHGGRT RMLKELQGKY GNVTKEVIVL YLTLCKQCHQ 
KNPVPKRGLA PKPMTFKDID STCQVEILDM QSSADGEFKF ILYYQDHSTK FIILRPLRTK 
QAHEVVSVLL DIFTILGTPS VLDSDSGVEF TNQVVHELNE LWPDLKIVSG KYHPGQSQGS 
LEGASRDVKN MISTWMQSNH SCHWAKGLRF MQMVRNQAFD VSLQQSPFEA MFGYKAKFGL 
YSSNLPRETV ATLQTEEELE IAEEQLENSL WIRQEERAEI GADRSDMDDD MDPTPEASEP 
STSQGTSGLL CW

Genular Protein ID: 303705152

Symbol: A8MX02_HUMAN

Name: N/A

UniProtKB Accession Codes:

A8MX02

Database IDs:

AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DisGeNET 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 GO 2 Gene3D 1 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 4 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 PANTHER 2 PROSITE 2 PeptideAtlas 2 Proteomes 2 RefSeq 2 SAM 1 SMR 1 SUPFAM 1 UCSC 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: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

Sequence Information:

  • Length: 410
  • Mass: 46799
  • Checksum: AB7221B0E26E5859
  • Sequence:
    • MMPQRAGNDP PGVSNASEME MEISNMREKF LMSVTKLVES KSYNSKVFSK EKYFQTIKEV 
KEAKEKGKKS SRDYRRAAKY DVISVQGTEK LIEATHGERD RIRYYVHKEE LFDILHDTHL 
SIGHGGRTRM LKELQGKYGN VTKEVIVLYL TLCKQCHQKN PVPKRGLAPK PMTFKDIDST 
CQVEILDMQS SADGEFKFIL YYQDHSTKFI ILRPLRTKQA HEVVSVLLDI FTILGTPSVL 
DSDSGVEFTN QVVHELNELW PDLKIVSGKY HPGQSQGSLE GASRDVKNMI STWMQSNHSC 
HWAKGLRFMQ MVRNQAFDVS LQQSPFEAMF GYKAKFGLYS SNLPRETVAT LQTEEELEIA 
EEQLENSLWI RQEERAEIGA DRSDMDDDMD PTPEASEPST SQGTSGLLCW