Details for: CDKL2

Gene ID: 8999

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: CDKL2

Ensembl ID: ENSG00000138769

Description: cyclin dependent kinase like 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 9.4
    rCSI 24.3%
    PRS 86.2
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 6.89
    rCSI 9.77%
    PRS 86.91
  • VIP GABAergic cortical interneuron CL4023016
    CSI 4.94
    rCSI 5.9%
    PRS 75.78
  • choroid plexus epithelial cell CL0000706
    CSI 4.78
    rCSI 7.84%
    PRS 81.85
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 4.34
    rCSI 7.29%
    PRS 75.73
  • retinal bipolar neuron CL0000748
    CSI 3.72
    rCSI 6.97%
    PRS 80.53
  • sst GABAergic cortical interneuron CL4023017
    CSI 3.72
    rCSI 4.79%
    PRS 76.92
  • retinal cone cell CL0000573
    CSI 3.49
    rCSI 5.62%
    PRS 81.53
  • interneuron CL0000099
    CSI 3.41
    rCSI 6.86%
    PRS 83.03
  • sncg GABAergic cortical interneuron CL4023015
    CSI 3.35
    rCSI 5.38%
    PRS 76.82
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.26
    rCSI 4.06%
    PRS 73.61
  • pulmonary alveolar type 2 cell CL0002063
    CSI 3.11
    rCSI 4.82%
    PRS 90.72
  • rod bipolar cell CL0000751
    CSI 2.98
    rCSI 5.36%
    PRS 84.27
  • renal alpha-intercalated cell CL0005011
    CSI 2.8
    rCSI 3.74%
    PRS 92.82
  • ciliated epithelial cell CL0000067
    CSI 2.79
    rCSI 2.45%
    PRS 80.62
  • cerebral cortex neuron CL0010012
    CSI 2.48
    rCSI 10.1%
    PRS 82.19
  • retina horizontal cell CL0000745
    CSI 2.4
    rCSI 3.65%
    PRS 86.35
  • ependymal cell CL0000065
    CSI 2.33
    rCSI 4.73%
    PRS 71.34
  • retinal ganglion cell CL0000740
    CSI 2.25
    rCSI 4.97%
    PRS 78.46
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.14
    rCSI 3.79%
    PRS 75.19
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 2.13
    rCSI 6.65%
    PRS 78.99
  • kidney connecting tubule epithelial cell CL1000768
    CSI 2.05
    rCSI 5.21%
    PRS 82.66
  • parietal epithelial cell CL1000452
    CSI 1.86
    rCSI 4.96%
    PRS 83.63
  • epithelial cell of proximal tubule CL0002306
    CSI 1.8
    rCSI 4.39%
    PRS 82.61
  • direct pathway medium spiny neuron CL4023026
    CSI 1.78
    rCSI 42.68%
    PRS 73.5
  • lung ciliated cell CL1000271
    CSI 1.77
    rCSI 2.05%
    PRS 83.67
  • OFF midget ganglion cell CL4033047
    CSI 1.72
    rCSI 35.11%
    PRS 81.41
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.69
    rCSI 40.81%
    PRS 73.76
  • ON midget ganglion cell CL4033046
    CSI 1.66
    rCSI 33.77%
    PRS 80.64
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.65
    rCSI 5.93%
    PRS 73.72
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.59
    rCSI 9.38%
    PRS 76.25
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.41
    rCSI 3.44%
    PRS 73.51
  • ON parasol ganglion cell CL4033052
    CSI 1.31
    rCSI 18.61%
    PRS 81.76
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.23
    rCSI 2.95%
    PRS 78.7
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 1.12
    rCSI 3.68%
    PRS 77.71
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.07
    rCSI 4.03%
    PRS 75.98
  • amacrine cell CL0000561
    CSI 1.03
    rCSI 2.98%
    PRS 80.78
  • neural progenitor cell CL0011020
    CSI 1.02
    rCSI 4.49%
    PRS 78.86
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.01
    rCSI 3.16%
    PRS 77.13
  • central nervous system neuron CL2000029
    CSI 0.95
    rCSI 6.96%
    PRS 80.51
  • GABAergic neuron CL0000617
    CSI 0.81
    rCSI 2.7%
    PRS 75.81

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 [CDKL2](/details-gene/8999) (Cyclin Dependent Kinase Like 2) is a protein-coding gene located on chromosome 4q21.1 that encodes a serine/threonine-protein kinase. Functionally, it is involved in fundamental cellular processes including `[protein phosphorylation](/details-cell/GO:0006468)`, `[regulation of cell cycle](/details-cell/GO:0051726)`, and `[signal transduction](/details-cell/GO:0007165)`. Expression data reveals a highly specific role for [CDKL2](/details-gene/8999) in distinct and specialized cell populations. **Overall**, it exhibits its highest significance in epithelial cells of the kidney nephron, particularly the `[kidney loop of Henle thin ascending limb epithelial cell](/details-cell/CL1001107)` and `[kidney loop of Henle thin descending limb epithelial cell](/details-cell/CL1001111)`. Additionally, it shows marked expression in various neuronal subtypes, including multiple classes of GABAergic cortical interneurons and retinal cells, suggesting a dual role in both renal physiology and neural circuit function. ## Cellular Roles and Expression Landscape The expression profile of [CDKL2](/details-gene/8999) points to a specialized function rather than a ubiquitous housekeeping role. The **Overall** context shows its most significant expression is concentrated in two main biological systems: the kidney and the central nervous system. Its role as a defining marker is most prominent in the kidney, where it has exceptionally high significance in the `[kidney loop of Henle thin ascending limb epithelial cell](/details-cell/CL1001107)` (CSI: 9.40) and the `[kidney loop of Henle thin descending limb epithelial cell](/details-cell/CL1001111)` (CSI: 6.89). This suggests a critical function in the unique physiological processes of this nephron segment, which is primarily responsible for generating the kidney's interstitial osmotic gradient. Its significance in `[renal alpha-intercalated cell](/details-cell/CL0005011)` further supports a role in renal homeostasis. In the nervous system, [CDKL2](/details-gene/8999) is highly significant across a spectrum of inhibitory interneurons, including `[VIP GABAergic cortical interneuron](/details-cell/CL4023016)`, `[lamp5 GABAergic cortical interneuron](/details-cell/CL4023011)`, `[sst GABAergic cortical interneuron](/details-cell/CL4023017)`, and `[pvalb GABAergic cortical interneuron](/details-cell/CL4023018)`. This pattern suggests it may be involved in regulating common pathways that define the function or development of these diverse inhibitory neurons. Its expression in retinal cells, such as `[retinal bipolar neuron](/details-cell/CL0000748)` and `[retinal cone cell](/details-cell/CL0000573)`, further implicates it in specialized neural signaling. Beyond these systems, [CDKL2](/details-gene/8999) is also a marker for other specialized epithelial cells, including `[choroid plexus epithelial cell](/details-cell/CL0000706)`, `[pulmonary alveolar type 2 cell](/details-cell/CL0002063)`, and `[ciliated epithelial cell](/details-cell/CL0000067)`, hinting at a broader involvement in epithelial cell biology, potentially related to transport or secretion. ## Pathways and Molecular Function The molecular functions of [CDKL2](/details-gene/8999) are centered on its kinase activity, as annotated by its involvement in `[cyclin-dependent protein serine/threonine kinase activity](/details-cell/GO:0004693)` and `[ATP binding](/details-cell/GO:0005524)`. These core functions enable its participation in broader biological processes like `[protein phosphorylation](/details-cell/GO:0006468)` and `[signal transduction](/details-cell/GO:0007165)`. Its localization to the `[cytoplasm](/details-cell/GO:0005737)` and `[nucleus](/details-cell/GO:0005634)` suggests it can phosphorylate substrates in multiple cellular compartments, influencing a wide range of cellular activities from gene expression to cytoplasmic signaling. The annotated role in `[regulation of cell cycle](/details-cell/GO:0051726)` and its localization to the `[centrosome](/details-cell/GO:0005813)` are particularly noteworthy. This is consistent with findings that the CDKL kinase family has evolved functions related to cilia ([Link](https://doi.org/10.1016/j.celrep.2017.12.083)), structures which are anchored by the basal body, a centrosome-derived organelle. This connection strongly aligns with the gene's high expression in `[ciliated epithelial cell](/details-cell/CL0000067)` and in kidney epithelial cells, which possess primary cilia critical for flow-sensing and signaling. ## Research Directions The specific expression pattern and known functions of [CDKL2](/details-gene/8999) suggest several avenues for future investigation. Its kinase activity makes it a potentially druggable target, and understanding its precise roles could have clinical implications. **Proposed Hypotheses:** 1. Given its exceptionally high and specific expression in the thin limbs of the loop of Henle, [CDKL2](/details-gene/8999) may be a master regulator of water and solute transport. It could phosphorylate and modulate the activity or trafficking of key channel proteins (e.g., aquaporins, chloride channels) essential for creating the kidney's concentration gradient. 2. The consistent high expression of [CDKL2](/details-gene/8999) across multiple, functionally distinct classes of cortical GABAergic interneurons suggests it is not a marker of a single subtype but rather controls a fundamental process common to these cells, such as the regulation of synaptic plasticity, neurotransmitter release, or the maintenance of their inhibitory tone. 3. Based on its centrosomal localization (`[GO:0005813](/details-cell/GO:0005813)`) and high expression in ciliated cell types, [CDKL2](/details-gene/8999) likely plays a crucial role in the formation, maintenance, or signaling function of primary cilia in epithelial cells of the kidney and choroid plexus. **Key Experimental Approach:** To test the hypothesis regarding its role in ciliary biology (Hypothesis 3), a robust experimental plan could be implemented. CRISPR-Cas9-mediated knockout of [CDKL2](/details-gene/8999) could be performed in a well-established renal epithelial cell line that readily forms primary cilia, such as mouse inner medullary collecting duct (mIMCD-3) cells. Following knockout confirmation, ciliary structure and function would be assessed. Cilia formation, length, and morphology could be quantified via immunofluorescence microscopy using antibodies against ciliary markers like acetylated α-tubulin and Arl13b. Ciliary function could be interrogated by measuring the cellular response to stimuli that activate cilia-dependent signaling pathways, such as the Sonic Hedgehog (Shh) pathway. A failure to form proper cilia or a blunted response to Shh pathway agonists in knockout cells compared to wild-type controls would provide strong evidence for [CDKL2](/details-gene/8999)'s essential role in ciliary function. **Therapeutic Potential:** As a protein kinase, [CDKL2](/details-gene/8999) is a tractable therapeutic target for small molecule inhibitors. Its highly restricted expression pattern is advantageous, as targeting it would likely result in fewer off-target effects compared to a ubiquitously expressed kinase. If dysfunction of [CDKL2](/details-gene/8999) were linked to specific channelopathies, ciliopathies, or neurological disorders affecting interneuron function, developing a modulator of its kinase activity could be a viable therapeutic strategy. Given its role in fundamental processes, inhibition would be the most likely approach to counter any gain-of-function mutations or pathological hyperactivity.

Genular Protein ID: 3880967034

Symbol: CDKL2_HUMAN

Name: Serine/threonine-protein kinase KKIAMRE

UniProtKB Accession Codes:

Q92772 B2R695

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CPTAC 2 CTD 1 ChEBI 12 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 DrugCentral 1 EC 3 EMBL 5 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 11 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 3 Rhea 6 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: 9000130

Title: Molecular cloning of the epidermal growth factor-stimulated protein kinase p56 KKIAMRE.

PubMed ID: 9000130

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: 29420175

Title: CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function.

PubMed ID: 29420175

DOI: 10.1016/j.celrep.2017.12.083

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

Sequence Information:

  • Length: 493
  • Mass: 56019
  • Checksum: 5CC20A91CBF89EFE
  • Sequence:
    • MEKYENLGLV GEGSYGMVMK CRNKDTGRIV AIKKFLESDD DKMVKKIAMR EIKLLKQLRH 
ENLVNLLEVC KKKKRWYLVF EFVDHTILDD LELFPNGLDY QVVQKYLFQI INGIGFCHSH 
NIIHRDIKPE NILVSQSGVV KLCDFGFART LAAPGEVYTD YVATRWYRAP ELLVGDVKYG 
KAVDVWAIGC LVTEMFMGEP LFPGDSDIDQ LYHIMMCLGN LIPRHQELFN KNPVFAGVRL 
PEIKEREPLE RRYPKLSEVV IDLAKKCLHI DPDKRPFCAE LLHHDFFQMD GFAERFSQEL 
QLKVQKDARN VSLSKKSQNR KKEKEKDDSL VEERKTLVVQ DTNADPKIKD YKLFKIKGSK 
IDGEKAEKGN RASNASCLHD SRTSHNKIVP STSLKDCSNV SVDHTRNPSV AIPPLTHNLS 
AVAPSINSGM GTETIPIQGY RVDEKTKKCS IPFVKPNRHS PSGIYNINVT TLVSGPPLSD 
DSGADLPQME HQH

Genular Protein ID: 1240773223

Symbol: J3KNE8_HUMAN

Name: N/A

UniProtKB Accession Codes:

J3KNE8

Database IDs:

ARBA 12 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChEBI 11 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 2 EMBL 4 Ensembl 2 ExpressionAtlas 1 GO 5 Gene3D 1 GeneTree 1 HGNC 1 InterPro 5 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PANTHER 2 PROSITE 4 PROSITE-ProRule 1 PeptideAtlas 2 Pfam 1 PhylomeDB 1 Proteomes 2 RefSeq 2 Rhea 6 SAM 1 SMART 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: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

Sequence Information:

  • Length: 570
  • Mass: 64840
  • Checksum: 8BC3ED5C80F7DB77
  • Sequence:
    • MEKYENLGLV GEGSYGMVMK CRNKDTGRIV AIKKFLESDD DKMVKKIAMR EIKLLKQLRH 
ENLVNLLEVC KKKKRWYLVF EFVDHTILDD LELFPNGLDY QVVQKYLFQI INGIGFCHSH 
NIIHRDIKPE NILVSQSGVV KLCDFGFART LAAPGEVYTD YVATRWYRAP ELLVGDVKYG 
KAVDVWAIGC LVTEMFMGEP LFPGDSDIDQ LYHIMMCLGN LIPRHQELFN KNPVFAGVRL 
PEIKEREPLE RRYPKLSEVV IDLAKKCLHI DPDKRPFCAE LLHHDFFQMD GFAERFSQEL 
QLKVQKDARN VSLSKKSQNR KKEKEKDDSL VEERKTLVVQ DTNADPKIKD YKLFKIKGSK 
IDGEKAEKGN RASNASCLHD SRTSHNKIVP STSLKDCSNV SVDHTRNPSV AIPPLTHNLS 
AVAPSINSGM GTETIPIQGY RVDEKTKKCS IPFVKPNRHS PSGIYNINVT TLVSSEKNLF 
WASKKRREYS RTDVRLPELN YNHLPELRAL GGIARNSRLT KKESKILSES RIPSLAAIDL 
HTPSITLHQV SGPPLSDDSG ADLPQMEHQH

Genular Protein ID: 4002699490

Symbol: B4DH08_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DH08

Database IDs:

ARBA 12 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChEBI 11 DNASU 1 DisGeNET 1 EC 2 EMBL 2 GO 4 Gene3D 1 InterPro 5 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 4 PROSITE-ProRule 1 Pfam 1 RefSeq 2 Rhea 6 SAM 1 SMART 1 SUPFAM 1

Sequence Information:

  • Length: 570
  • Mass: 64868
  • Checksum: 9CF3E36C99F7DB77
  • Sequence:
    • MEKYENLGLV GEGSYGMVMK CRNKDTGRIV AIKKFLESDD DKMVKKIAMR EIKLLKQLRH 
ENLVNLLEVC KKKKRWYLVF EFVDHTILDD LELFPNGLDY QVVQKYLFQI INGIGFCHSH 
NIIHRDIKPE NILVSQSGVV KLCDFGFART LAAPGEVYTD YVATRWYRAP ELLVGDVKYG 
KAVDVWAIGC LVTEMFMGEP LFPGDSDIDQ LYHIMMCLGN LIPRHQELFN KNPVFAGVRL 
PEIKEREPLE RRYPKLSEVV IDLAKKCLHI DPDKRPFCAE LLHHDFFQMD GFAERFSQEL 
QLKVQKDARN VSLSKKSQNR KKEKEKDDSL VEERKTLVVQ DTNADPKIKD YKLFKIKGSK 
IDGEKAEKGN RASNASCLHD SRTSHNKIVP STSLKDCSNV SVDHTRNPSV AIPPLTHNLS 
AVAPSINSGM GTETIPIQGY RVDEKTKRCS IPFVKPNRHS PSGIYNINVT TLVSSEKNLF 
WASKKRREYS RTDVRLPELN YNHLPELRAL GGIARNSRLT KKESKILSES RIPSLAAIDL 
HTPSITLHQV SGPPLSDDSG ADLPQMEHQH