Details for: DYRK4

Gene ID: 8798

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: DYRK4

Ensembl ID: ENSG00000010219

Description: dual specificity tyrosine phosphorylation regulated kinase 4

Cell Significance Landscape

Associated with

Significant Cells

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

  • intestine goblet cell CL0019031
    CSI 5.4
    rCSI 4.79%
    PRS 70.12
  • small intestine goblet cell CL1000495
    CSI 4.49
    rCSI 9.83%
    PRS 78.73
  • epithelial cell of lung CL0000082
    CSI 3.74
    rCSI 3.1%
    PRS 72.5
  • early lymphoid progenitor CL0000936
    CSI 3.38
    rCSI 2.97%
    PRS 77.71
  • common myeloid progenitor CL0000049
    CSI 3.31
    rCSI 2.68%
    PRS 74.28
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.26
    rCSI 5.75%
    PRS 52.44
  • immature B cell CL0000816
    CSI 3.23
    rCSI 2.4%
    PRS 84.46
  • retinal cone cell CL0000573
    CSI 3.03
    rCSI 4.88%
    PRS 61.63
  • goblet cell CL0000160
    CSI 3.02
    rCSI 2.85%
    PRS 71.48
  • rod bipolar cell CL0000751
    CSI 2.88
    rCSI 5.17%
    PRS 65.34
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.79
    rCSI 2.52%
    PRS 69.63
  • mucus secreting cell CL0000319
    CSI 2.75
    rCSI 4.37%
    PRS 82.12
  • OFF-bipolar cell CL0000750
    CSI 2.75
    rCSI 3.75%
    PRS 76.1
  • stem cell CL0000034
    CSI 2.74
    rCSI 2.64%
    PRS 64.23
  • interstitial cell of Cajal CL0002088
    CSI 2.7
    rCSI 3.44%
    PRS 77.86
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.5
    rCSI 1.75%
    PRS 75.31
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.48
    rCSI 1.92%
    PRS 75.55
  • hematopoietic stem cell CL0000037
    CSI 2.32
    rCSI 1.54%
    PRS 75.08
  • mesodermal cell CL0000222
    CSI 2.19
    rCSI 2.63%
    PRS 70.27
  • chondrocyte CL0000138
    CSI 2.19
    rCSI 3.48%
    PRS 64.7
  • ciliated epithelial cell CL0000067
    CSI 2.13
    rCSI 1.87%
    PRS 60.48
  • transit amplifying cell of colon CL0009011
    CSI 2
    rCSI 2.35%
    PRS 74.29
  • neural crest cell CL0011012
    CSI 1.96
    rCSI 1.55%
    PRS 59.59
  • granulocyte monocyte progenitor cell CL0000557
    CSI 1.94
    rCSI 1.68%
    PRS 76.92
  • intestinal epithelial cell CL0002563
    CSI 1.94
    rCSI 2.02%
    PRS 69.91
  • common dendritic progenitor CL0001029
    CSI 1.87
    rCSI 2.35%
    PRS 82.04
  • club cell CL0000158
    CSI 1.76
    rCSI 2.58%
    PRS 67.12
  • mesenchymal cell CL0008019
    CSI 1.75
    rCSI 4.46%
    PRS 65.77
  • colon goblet cell CL0009039
    CSI 1.69
    rCSI 4.02%
    PRS 79.48
  • Hofbauer cell CL3000001
    CSI 1.63
    rCSI 3.08%
    PRS 81.83
  • retina horizontal cell CL0000745
    CSI 1.53
    rCSI 2.33%
    PRS 68.71
  • enteric smooth muscle cell CL0002504
    CSI 1.35
    rCSI 1.93%
    PRS 73.75
  • duct epithelial cell CL0000068
    CSI 1.31
    rCSI 1.92%
    PRS 77.14
  • melanocyte of skin CL1000458
    CSI 1.29
    rCSI 1.76%
    PRS 39.94
  • stromal cell CL0000499
    CSI 0.94
    rCSI 2.66%
    PRS 67.79
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.86
    rCSI 2.49%
    PRS 72.63

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 [DYRK4](/details-gene/8798) (dual specificity tyrosine phosphorylation regulated kinase 4) is a protein-coding gene located on chromosome 12p13.32. It encodes a member of the DYRK family of dual-specificity kinases that can phosphorylate substrates on serine, threonine, and tyrosine residues. Functional annotations indicate its core roles in [protein phosphorylation](/details-cell/GO:0006468), [ATP binding](/details-cell/GO:0005524), and [protein binding](/details-cell/GO:0005515), with localization to the [cytoplasm](/details-cell/GO:0005737) and [nucleus](/details-cell/GO:0005634). **Overall**, expression data highlight its significant role in highly specialized secretory cells, particularly [intestine goblet cell](/details-cell/CL0019031)s, as well as in various progenitor cell populations, including [early lymphoid progenitor](/details-cell/CL0000936)s and [common myeloid progenitor](/details-cell/CL0000049)s, suggesting a function in both terminal cell differentiation and lineage commitment. ## Cellular Roles and Expression Landscape The expression profile of [DYRK4](/details-gene/8798) reveals its importance across several distinct biological systems. The most significant expression is observed in secretory epithelial cells of the intestine, including [intestine goblet cell](/details-cell/CL0019031) (CSI: 5.40) and [small intestine goblet cell](/details-cell/CL1000495) (CSI: 4.49), as well as [epithelial cell of lung](/details-cell/CL0000082) (CSI: 3.74). This strong association with mucus-secreting lineages suggests a potential role for [DYRK4](/details-gene/8798) in the regulation of secretory pathways, cell maturation, or maintenance of the mucosal barrier. A second major functional context for [DYRK4](/details-gene/8798) appears to be in the regulation of progenitor and stem cell populations. The gene is a significant marker in several hematopoietic progenitors, such as [early lymphoid progenitor](/details-cell/CL0000936) (CSI: 3.38), [common myeloid progenitor](/details-cell/CL0000049) (CSI: 3.31), and [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 2.79). This pattern is consistent with a role for its kinase activity in mediating cell fate decisions during hematopoiesis. Finally, a notable pattern of expression is seen in specialized neuronal cell types of the retina, including [retinal cone cell](/details-cell/CL0000573) (CSI: 3.03) and [rod bipolar cell](/details-cell/CL0000751) (CSI: 2.88). This suggests a specialized function in retinal development or signal transduction. The broad but specific expression pattern across secretory, progenitor, and neuronal cells indicates that [DYRK4](/details-gene/8798) may be a context-dependent regulator of diverse cellular processes. ## Pathways and Molecular Function [DYRK4](/details-gene/8798) is a kinase, and its molecular functions are centered on catalytic activity. Gene Ontology annotations confirm its ability to act as a [protein serine/threonine kinase](/details-cell/GO:0004674) and a [protein tyrosine kinase](/details-cell/GO:0004713), defining it as a dual-specificity kinase. Its requirement for [ATP binding](/details-cell/GO:0005524) and [metal ion binding](/details-cell/GO:0046872) is characteristic of protein kinases. The kinase is primarily located within the [cytoplasm](/details-cell/GO:0005737) and [nucleus](/details-cell/GO:0005634), suggesting it can phosphorylate targets in both compartments to regulate signaling cascades, gene expression, or cytoskeletal dynamics. Research indicates that different splice variants of [DYRK4](/details-gene/8798) can exhibit distinct subcellular localizations and catalytic activities, adding a layer of regulatory complexity ([Link](https://doi.org/10.1074/jbc.m110.157909)). Although previously described as testis-specific ([Link](https://doi.org/10.1016/j.mce.2006.12.041)), the current data reveals a broader functional landscape. ## Research Directions The diverse expression profile of [DYRK4](/details-gene/8798) suggests it plays multiple, context-specific roles. Its prominence in both progenitor cells and terminally differentiated secretory cells warrants further investigation. **Proposed Hypotheses:** 1. Given its exceptionally high significance in [intestine goblet cell](/details-cell/CL0019031)s, [DYRK4](/details-gene/8798) likely plays a critical role in the terminal differentiation or secretory function of these cells, possibly by phosphorylating key regulators of mucin granule biogenesis or exocytosis. 2. The consistent expression of [DYRK4](/details-gene/8798) across multiple hematopoietic progenitor lineages ([early lymphoid progenitor](/details-cell/CL0000936), [common myeloid progenitor](/details-cell/CL0000049)) suggests that it functions as a signaling node that influences lineage commitment. Its activity level may bias differentiation towards one lineage over another. **Key Experimental Approach:** To test the hypothesis regarding its role in goblet cells, a compelling approach would be to use a human intestinal organoid model. * **Experiment:** Generate [DYRK4](/details-gene/8798) knockout (KO) and kinase-dead mutant organoids using CRISPR-Cas9. Compare these to wild-type organoids. Assess goblet cell differentiation by quantifying the number of Alcian blue-positive cells and measuring the expression of goblet cell markers like *MUC2* and *TFF3* via qRT-PCR and immunofluorescence. To test secretory function, stimulate the organoids with an agonist like carbachol and measure secreted mucin levels in the supernatant using an enzyme-linked immunosorbent assay (ELISA). **Therapeutic Potential:** As a protein kinase, [DYRK4](/details-gene/8798) is a structurally suitable candidate for small molecule inhibitor development. However, its expression in critical cell populations, including hematopoietic progenitors and intestinal epithelial cells, raises significant safety concerns for systemic therapies, which could lead to myelosuppression or impaired gut barrier function. Therefore, its therapeutic potential may be limited to diseases where a clear pathogenic, gain-of-function role is established in a specific cell type, such as certain cancers. In such a scenario, developing highly specific inhibitors or targeted delivery systems would be essential to mitigate on-target, off-tissue toxicity.

Genular Protein ID: 1868102776

Symbol: DYRK4_HUMAN

Name: Dual specificity tyrosine-phosphorylation-regulated kinase 4

UniProtKB Accession Codes:

Q9NR20 A8K8F7 Q8NEF2 Q92631

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 19 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 4 EMBL 5 Ensembl 2 ExpressionAtlas 1 GO 10 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 1 Rhea 9 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11062477

Title: Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23.

PubMed ID: 11062477

DOI: 10.1038/81664

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: 9748265

Title: Sequence characteristics, subcellular localization, and substrate specificity of DYRK-related kinases, a novel family of dual specificity protein kinases.

PubMed ID: 9748265

DOI: 10.1074/jbc.273.40.25893

PubMed ID: 17292540

Title: The expression of the testis-specific Dyrk4 kinase is highly restricted to step 8 spermatids but is not required for male fertility in mice.

PubMed ID: 17292540

DOI: 10.1016/j.mce.2006.12.041

PubMed ID: 21127067

Title: Splice variants of the dual specificity tyrosine phosphorylation-regulated kinase 4 (DYRK4) differ in their subcellular localization and catalytic activity.

PubMed ID: 21127067

DOI: 10.1074/jbc.m110.157909

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

Sequence Information:

  • Length: 520
  • Mass: 59608
  • Checksum: 33FECD8249DDB223
  • Sequence:
    • MPASELKASE IPFHPSIKTQ DPKAEEKSPK KQKVTLTAAE ALKLFKNQLS PYEQSEILGY 
AELWFLGLEA KKLDTAPEKF SKTSFDDEHG FYLKVLHDHI AYRYEVLETI GKGSFGQVAK 
CLDHKNNELV ALKIIRNKKR FHQQALMELK ILEALRKKDK DNTYNVVHMK DFFYFRNHFC 
ITFELLGINL YELMKNNNFQ GFSLSIVRRF TLSVLKCLQM LSVEKIIHCD LKPENIVLYQ 
KGQASVKVID FGSSCYEHQK VYTYIQSRFY RSPEVILGHP YDVAIDMWSL GCITAELYTG 
YPLFPGENEV EQLACIMEVL GLPPAGFIQT ASRRQTFFDS KGFPKNITNN RGKKRYPDSK 
DLTMVLKTYD TSFLDFLRRC LVWEPSLRMT PDQALKHAWI HQSRNLKPQP RPQTLRKSNS 
FFPSETRKDK VQGCHHSSRK ADEITKETTE KTKDSPTKHV QHSGDQQDCL QHGADTVQLP 
QLVDAPKKSE AAVGAEVSMT SPGQSKNFSL KNTNVLPPIV

Genular Protein ID: 3316185404

Symbol: B4E1A4_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4E1A4

Database IDs:

ARBA 6 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 5 Gene3D 1 InterPro 3 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 1 RefSeq 1 SAM 1 SMR 1 SUPFAM 1

Sequence Information:

  • Length: 233
  • Mass: 26300
  • Checksum: 7BB4A385E91391CB
  • Sequence:
    • MWSLGCITAE LYTGYPLFPG ENEVEQLACI MEVLGLPPAG FIQTASRRQT FFDSKGFPKN 
ITNNRGKKRY PDSKDLTMVL KTYDTSFLDF LRRCLVWEPS LRMTPDQALK HAWIHQSRNL 
KPQPRPQTLR KSNSFFPSET RKDKVQGCHH SSRKDEITKE TTEKTKDSPT KHVQHSGDQQ 
DCLQHGADTV QLPQLVDAPK KSEAAVGAEV SMTSPGQSKN FSLKNTNVLP PIV

Genular Protein ID: 3521716462

Symbol: D3JEN2_HUMAN

Name: N/A

UniProtKB Accession Codes:

D3JEN2

Database IDs:

ARBA 6 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 2 Gene3D 1 InterPro 3 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 1 RefSeq 1 SAM 1 SMART 1 SMR 1 SUPFAM 1

Sequence Information:

  • Length: 254
  • Mass: 28688
  • Checksum: 2B99D84367AFE681
  • Sequence:
    • SRFYRSPEVI LGHPYDVAID MWSLGCITAE LYTGYPLFPG ENEVEQLACI MEVLGLPPAG 
FIQTASRRQT FFDSKGFPKN ITNNRGKKRY PDSKDLTMVL KTYDTSFLDF LRRCLVWEPS 
LRMTPDQALK HAWIHQSRNL KPQPRPQTLR KSNSFFPSET RKDKVQGCHH SSRKADEITK 
ETTEKTKDSP TKHVQHSGDQ QDCLQHGADT VQLPQLVDAP KKSEAAVGAE VSMTSPGQSK 
NFSLKNTNVL PPIV