Details for: DOK6

Gene ID: 220164

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: DOK6

Ensembl ID: ENSG00000206052

Description: docking protein 6

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • retinal bipolar neuron CL0000748
    CSI 49.28
    rCSI 92.3%
    PRS 98.47
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 47.68
    rCSI 59.32%
    PRS 98.13
  • rod bipolar cell CL0000751
    CSI 43.03
    rCSI 77.33%
    PRS 98.97
  • VIP GABAergic cortical interneuron CL4023016
    CSI 40.46
    rCSI 48.33%
    PRS 98.37
  • sncg GABAergic cortical interneuron CL4023015
    CSI 38.13
    rCSI 61.32%
    PRS 98.29
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 34.78
    rCSI 58.38%
    PRS 98.51
  • sst GABAergic cortical interneuron CL4023017
    CSI 29.55
    rCSI 38.09%
    PRS 98.69
  • ependymal cell CL0000065
    CSI 25.23
    rCSI 51.19%
    PRS 96.64
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 23.29
    rCSI 26.9%
    PRS 98.87
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 22.16
    rCSI 53.85%
    PRS 97.77
  • astrocyte CL0000127
    CSI 21.07
    rCSI 44.88%
    PRS 97.09
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 20.97
    rCSI 37.04%
    PRS 98.41
  • progenitor cell CL0011026
    CSI 20.52
    rCSI 43.63%
    PRS 98.81
  • peripheral nervous system neuron CL2000032
    CSI 19.99
    rCSI 27.23%
    PRS 99.09
  • neuron CL0000540
    CSI 19.69
    rCSI 52.45%
    PRS 97.33
  • retinal ganglion cell CL0000740
    CSI 19.31
    rCSI 42.65%
    PRS 98.4
  • ON-bipolar cell CL0000749
    CSI 19.3
    rCSI 28.69%
    PRS 99.12
  • L6b glutamatergic cortical neuron CL4023038
    CSI 18.67
    rCSI 58.36%
    PRS 98.38
  • glioblast CL0000030
    CSI 18.54
    rCSI 29.57%
    PRS 98.75
  • interneuron CL0000099
    CSI 18.17
    rCSI 36.47%
    PRS 99.04
  • stromal cell CL0000499
    CSI 17.61
    rCSI 49.55%
    PRS 99.36
  • adipocyte CL0000136
    CSI 17.31
    rCSI 22.22%
    PRS 98.76
  • fibroblast of lung CL0002553
    CSI 17.22
    rCSI 16.02%
    PRS 99.88
  • neural cell CL0002319
    CSI 17.15
    rCSI 64.71%
    PRS 97.3
  • cerebral cortex neuron CL0010012
    CSI 17.14
    rCSI 69.86%
    PRS 98.35
  • retina horizontal cell CL0000745
    CSI 16.63
    rCSI 25.36%
    PRS 99.37
  • OFF-bipolar cell CL0000750
    CSI 16.63
    rCSI 22.74%
    PRS 99.1
  • cerebral cortex endothelial cell CL1001602
    CSI 15.98
    rCSI 27.64%
    PRS 99.03
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 15.93
    rCSI 57.34%
    PRS 98.05
  • vascular leptomeningeal cell CL4023051
    CSI 15.83
    rCSI 27.75%
    PRS 99.14
  • diffuse bipolar 6 cell CL4033032
    CSI 15.36
    rCSI 80.76%
    PRS 97.38
  • renal interstitial pericyte CL1001318
    CSI 15.18
    rCSI 41.83%
    PRS 99.63
  • OFFx cell CL4033036
    CSI 15.17
    rCSI 71.35%
    PRS 97.45
  • epithelial cell of proximal tubule CL0002306
    CSI 14.89
    rCSI 36.37%
    PRS 98.35
  • alveolar type 1 fibroblast cell CL4028004
    CSI 14.45
    rCSI 15.82%
    PRS 99.88
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 14.15
    rCSI 46.49%
    PRS 97.57
  • hepatic stellate cell CL0000632
    CSI 13.87
    rCSI 51.96%
    PRS 99.4
  • GABAergic amacrine cell CL4030027
    CSI 13.85
    rCSI 47.45%
    PRS 97.56
  • astrocyte of the cerebral cortex CL0002605
    CSI 13.31
    rCSI 29.84%
    PRS 98.5
  • neural crest cell CL0011012
    CSI 13.22
    rCSI 10.45%
    PRS 99.48
  • cardiac muscle cell CL0000746
    CSI 13.21
    rCSI 18.96%
    PRS 98.42
  • invaginating midget bipolar cell CL4033034
    CSI 13.15
    rCSI 77.64%
    PRS 97.82
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 13.04
    rCSI 28.29%
    PRS 97.49
  • inhibitory interneuron CL0000498
    CSI 12.7
    rCSI 29.32%
    PRS 98.52
  • myofibroblast cell CL0000186
    CSI 12.36
    rCSI 17.11%
    PRS 99.55
  • interstitial cell of Cajal CL0002088
    CSI 12.23
    rCSI 15.56%
    PRS 99.88
  • glycinergic amacrine cell CL4030028
    CSI 12.08
    rCSI 31.47%
    PRS 98.35
  • H2 horizontal cell CL0004218
    CSI 11.69
    rCSI 58.1%
    PRS 98.76
  • cardiac neuron CL0010022
    CSI 11.47
    rCSI 36.7%
    PRS 99.49
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 11.28
    rCSI 14.48%
    PRS 99.27
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 11.06
    rCSI 20.1%
    PRS 98.83
  • diffuse bipolar 3a cell CL4033029
    CSI 10.91
    rCSI 74.25%
    PRS 97.8
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 10.87
    rCSI 33.99%
    PRS 98.57
  • Mueller cell CL0000636
    CSI 10.48
    rCSI 23.91%
    PRS 98.82
  • alveolar adventitial fibroblast CL4028006
    CSI 10.42
    rCSI 16.46%
    PRS 99.83
  • Schwann cell CL0002573
    CSI 10.25
    rCSI 29.13%
    PRS 99.19
  • amacrine cell CL0000561
    CSI 10.01
    rCSI 29.01%
    PRS 98.52
  • choroid plexus epithelial cell CL0000706
    CSI 9.99
    rCSI 16.36%
    PRS 98.74
  • flat midget bipolar cell CL4033033
    CSI 9.96
    rCSI 71.18%
    PRS 97.65
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 9.9
    rCSI 58.27%
    PRS 98.16
  • cerebellar granule cell CL0001031
    CSI 9.75
    rCSI 14.33%
    PRS 98.73
  • chondrocyte CL0000138
    CSI 9.33
    rCSI 14.84%
    PRS 98.71
  • diffuse bipolar 3b cell CL4033030
    CSI 8.5
    rCSI 56.41%
    PRS 98.02
  • tracheobronchial smooth muscle cell CL0019019
    CSI 8.42
    rCSI 14.85%
    PRS 99.75
  • diffuse bipolar 1 cell CL4033027
    CSI 8.16
    rCSI 61.37%
    PRS 97.29
  • fibroblast of cardiac tissue CL0002548
    CSI 8.04
    rCSI 38.49%
    PRS 99.87
  • glutamatergic neuron CL0000679
    CSI 7.92
    rCSI 16.27%
    PRS 96.96
  • retinal pigment epithelial cell CL0002586
    CSI 7.9
    rCSI 15.69%
    PRS 99.04
  • diffuse bipolar 2 cell CL4033028
    CSI 7.66
    rCSI 59.32%
    PRS 97.81
  • lung pericyte CL0009089
    CSI 7.62
    rCSI 20.1%
    PRS 99.8
  • central nervous system neuron CL2000029
    CSI 7.25
    rCSI 53.26%
    PRS 98.68
  • dopaminergic neuron CL0000700
    CSI 6.95
    rCSI 39.25%
    PRS 98
  • endothelial cell of vascular tree CL0002139
    CSI 6.63
    rCSI 36.25%
    PRS 98.59
  • glial cell CL0000125
    CSI 6.61
    rCSI 25.15%
    PRS 98.33
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 6.3
    rCSI 15.08%
    PRS 97.84
  • diffuse bipolar 4 cell CL4033031
    CSI 6.18
    rCSI 70.79%
    PRS 96.24
  • neural progenitor cell CL0011020
    CSI 5.99
    rCSI 26.35%
    PRS 96.6
  • GABAergic neuron CL0000617
    CSI 5.96
    rCSI 19.97%
    PRS 96.78
  • medium spiny neuron CL1001474
    CSI 5.93
    rCSI 51.09%
    PRS 98.51
  • serotonergic neuron CL0000850
    CSI 5.65
    rCSI 25.25%
    PRS 96.81
  • regular atrial cardiac myocyte CL0002129
    CSI 5.19
    rCSI 16.72%
    PRS 98.9
  • cerebellar neuron CL1001611
    CSI 4.78
    rCSI 42.11%
    PRS 97.44
  • mesenchymal cell CL0008019
    CSI 4.14
    rCSI 10.51%
    PRS 99.49
  • cerebral cortex pyramidal neuron CL4023111
    CSI 4.04
    rCSI 24.86%
    PRS 99.63
  • ON parasol ganglion cell CL4033052
    CSI 3.92
    rCSI 55.69%
    PRS 98.37
  • parietal epithelial cell CL1000452
    CSI 3.7
    rCSI 9.89%
    PRS 99.24
  • regular ventricular cardiac myocyte CL0002131
    CSI 3.03
    rCSI 18.96%
    PRS 98.6
  • midbrain dopaminergic neuron CL2000097
    CSI 2.87
    rCSI 18.4%
    PRS 98.47
  • OFF midget ganglion cell CL4033047
    CSI 2.79
    rCSI 56.8%
    PRS 98.32
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.74
    rCSI 10.35%
    PRS 98.03
  • mesangial cell CL0000650
    CSI 2.68
    rCSI 10.94%
    PRS 99.89
  • ON midget ganglion cell CL4033046
    CSI 2.66
    rCSI 54.25%
    PRS 98.23
  • cone retinal bipolar cell CL0000752
    CSI 2.55
    rCSI 33.34%
    PRS 98.78
  • direct pathway medium spiny neuron CL4023026
    CSI 2.53
    rCSI 60.51%
    PRS 97.2
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.5
    rCSI 60.31%
    PRS 97.2
  • H1 horizontal cell CL0004217
    CSI 2.46
    rCSI 9.75%
    PRS 98.55
  • starburst amacrine cell CL0004232
    CSI 2.3
    rCSI 19.37%
    PRS 97.19
  • enteroglial cell CL4040002
    CSI 2.19
    rCSI 11.51%
    PRS 99.38
  • neuroendocrine cell CL0000165
    CSI 2.08
    rCSI 8.04%
    PRS 99.59
  • blood vessel smooth muscle cell CL0019018
    CSI 1.67
    rCSI 13.59%
    PRS 99.66

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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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 [DOK6](/details-gene/220164), or Docking protein 6, is a protein-coding gene located on chromosome 18q22.2. As a member of the DOK family of intracellular adaptors, it functions primarily in signal transduction pathways downstream of receptor tyrosine kinases. Functional annotations link [DOK6](/details-gene/220164) to critical processes in neurodevelopment, including [Axon guidance](/details-cell/R-HSA-422475), [Ret signaling](/details-cell/R-HSA-8853659), and the positive regulation of the MAPK cascade. Its expression profile is highly specific to the nervous system, with significant expression observed in diverse neuronal populations such as [retinal bipolar neurons](/details-cell/CL0000748), various subtypes of cortical GABAergic interneurons, and developing [neuroblasts](/details-cell/CL0000338). Experimental evidence confirms its role in promoting neurite outgrowth, highlighting its importance in establishing neuronal connectivity [[Link](https://doi.org/10.1074/jbc.m403726200)]. ## Cellular Roles and Expression Landscape **Overall**, the expression of [DOK6](/details-gene/220164) is predominantly and highly localized to the central nervous system, where it marks a wide array of both developing and mature cell types. The gene shows its highest significance in specialized [neurons](/details-cell/CL0000540) of the retina, including [retinal bipolar neuron](/details-cell/CL0000748) (CSI: 49.28) and [rod bipolar cell](/details-cell/CL0000751) (CSI: 43.03), suggesting a crucial function in visual information processing pathways. Concurrently, it is a key marker for multiple distinct subtypes of cortical inhibitory interneurons, such as [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 47.68), [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 40.46), and [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 29.55). Its high significance is also noted in excitatory [neurons](/details-cell/CL0000540), specifically [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040) (CSI: 22.16). Beyond mature neuronal circuits, [DOK6](/details-gene/220164) is significantly expressed in neural progenitor populations, including [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338) (CSI: 23.29) and [progenitor cell](/details-cell/CL0011026) (CSI: 20.52). Its presence in supportive glial cells like [astrocytes](/details-cell/CL0000127) (CSI: 21.07) and [ependymal cells](/details-cell/CL0000065) (CSI: 25.23) further indicates a broad, yet specific, role within the neural tissue environment. This expression pattern, spanning diverse neuronal and developmental cell types, underscores its fundamental role in nervous system construction and function. ## Pathways and Molecular Function The molecular functions of [DOK6](/details-gene/220164) are centered on its role as a cytoplasmic adaptor protein that facilitates intracellular signaling cascades. Its involvement in the [Cell surface receptor protein tyrosine kinase signaling pathway](/details-cell/GO:0007169) and [Ras protein signal transduction](/details-cell/GO:0007265) provides a mechanism for its biological effects. These activities are integral to broader developmental programs, as reflected by its annotation in pathways such as [Nervous system development](/details-cell/R-HSA-9675108) and [Axon guidance](/details-cell/R-HSA-422475). The gene's function is particularly tied to the [Ret signaling](/details-cell/R-HSA-8853659) pathway. This connection is experimentally supported by research demonstrating that [DOK6](/details-gene/220164) promotes Ret-mediated neurite outgrowth, a key process in forming functional neural circuits [[Link](https://doi.org/10.1074/jbc.m403726200)]. The engagement of [DOK6](/details-gene/220164) in these pathways is consistent with its high expression in developing and mature [neurons](/details-cell/CL0000540), where precise signaling is essential for migration, differentiation, and synapse formation. ## Research Directions Given its specific expression and role in neurodevelopment, research on [DOK6](/details-gene/220164) could provide valuable insights into neural circuit formation and pathology. **Testable Hypotheses:** 1. Given its high significance across multiple, functionally distinct classes of cortical interneurons (e.g., [pvalb](/details-cell/CL4023018), [VIP](/details-cell/CL4023016), [sst](/details-cell/CL4023017)), [DOK6](/details-gene/220164) may be essential for establishing the specific laminar positions and synaptic connectivity patterns unique to each interneuron subtype during cortical development. 2. Based on its premier significance in [retinal bipolar neurons](/details-cell/CL0000748), [DOK6](/details-gene/220164) is likely critical for the proper stratification of bipolar cell axon terminals within the inner plexiform layer of the retina, a process dependent on precise axon guidance signaling. **Suggested Experiment:** To test the second hypothesis regarding its role in retinal development, a conditional knockout mouse model could be employed. By crossing a DOK6-floxed mouse with a mouse line expressing Cre recombinase under a bipolar cell-specific promoter (e.g., *Cabp5*-Cre), one could selectively delete [DOK6](/details-gene/220164) in this cell population. Analysis of the resulting retinal tissue using immunofluorescence for bipolar cell markers (e.g., PKCα) and synaptic markers would allow for detailed examination of axonal targeting, dendritic arborization, and synaptic lamination compared to wild-type littermates. **Therapeutic Potential:** As an intracellular docking protein involved in pro-growth signaling, [DOK6](/details-gene/220164) presents an interesting therapeutic target. Its high specificity for the nervous system could minimize off-target effects. Rather than inhibition, therapeutic strategies would likely focus on **activation** or enhancement of its downstream signaling pathways. Such an approach could be explored for promoting nerve regeneration and functional recovery following central nervous system injury (e.g., spinal cord injury) or for mitigating neuronal loss in certain neurodegenerative diseases.

Genular Protein ID: 2552911401

Symbol: DOK6_HUMAN

Name: Docking protein 6

UniProtKB Accession Codes:

Q6PKX4 A6NNG3 Q4V9S3 Q8WUZ8 Q96HI2 Q96LU2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 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 5 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 SIGNOR 1 SMART 3 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 15286081

Title: Dok-6, a novel p62 Dok family member, promotes Ret-mediated neurite outgrowth.

PubMed ID: 15286081

DOI: 10.1074/jbc.m403726200

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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

Sequence Information:

  • Length: 331
  • Mass: 38318
  • Checksum: 0C5EF2BF247091C1
  • Sequence:
    • MASNFNDIVK QGYVKIRSRK LGIFRRCWLV FKKASSKGPR RLEKFPDEKA AYFRNFHKVT 
ELHNIKNITR LPRETKKHAV AIIFHDETSK TFACESELEA EEWCKHLCME CLGTRLNDIS 
LGEPDLLAAG VQREQNERFN VYLMPTPNLD IYGECTMQIT HENIYLWDIH NAKVKLVMWP 
LSSLRRYGRD STWFTFESGR MCDTGEGLFT FQTREGEMIY QKVHSATLAI AEQHERLMLE 
MEQKARLQTS LTEPMTLSKS ISLPRSAYWH HITRQNSVGE IYSLQGHGFG SSKMSRAQTF 
PSYAPEQSEE AQQPLSRSSS YGFSYSSSLI Q