Details for: DCDC2

Gene ID: 51473

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: DCDC2

Ensembl ID: ENSG00000146038

Description: doublecortin domain containing 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • parietal epithelial cell CL1000452
    CSI 15.6
    rCSI 41.7%
    PRS 94.58
  • lung ciliated cell CL1000271
    CSI 14.53
    rCSI 16.81%
    PRS 93.68
  • ependymal cell CL0000065
    CSI 13.14
    rCSI 26.67%
    PRS 85.85
  • pancreatic ductal cell CL0002079
    CSI 12.78
    rCSI 24.85%
    PRS 96.84
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 12.04
    rCSI 17.06%
    PRS 95.81
  • ciliated cell CL0000064
    CSI 11.53
    rCSI 18.68%
    PRS 92.58
  • kidney connecting tubule epithelial cell CL1000768
    CSI 11.52
    rCSI 29.21%
    PRS 94.12
  • choroid plexus epithelial cell CL0000706
    CSI 10.81
    rCSI 17.7%
    PRS 93.56
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 9.64
    rCSI 25.13%
    PRS 97.76
  • mononuclear phagocyte CL0000113
    CSI 9.56
    rCSI 21.04%
    PRS 97.93
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 9.2
    rCSI 23.79%
    PRS 95.54
  • intrahepatic cholangiocyte CL0002538
    CSI 8.72
    rCSI 20.93%
    PRS 96.3
  • epithelial cell CL0000066
    CSI 8.17
    rCSI 12.56%
    PRS 88.64
  • cholangiocyte CL1000488
    CSI 7.85
    rCSI 47.03%
    PRS 95.17
  • fallopian tube secretory epithelial cell CL4030006
    CSI 7.59
    rCSI 7.3%
    PRS 95.82
  • kidney collecting duct principal cell CL1001431
    CSI 7.26
    rCSI 36.52%
    PRS 93.9
  • renal alpha-intercalated cell CL0005011
    CSI 7.08
    rCSI 9.47%
    PRS 97.79
  • ciliated epithelial cell CL0000067
    CSI 7.01
    rCSI 6.16%
    PRS 91.83
  • renal interstitial pericyte CL1001318
    CSI 6.83
    rCSI 18.82%
    PRS 96.04
  • epithelial cell of proximal tubule CL0002306
    CSI 6.81
    rCSI 16.63%
    PRS 92.75
  • Mueller cell CL0000636
    CSI 5.65
    rCSI 12.88%
    PRS 93.58
  • stem cell CL0000034
    CSI 5.45
    rCSI 5.25%
    PRS 95.34
  • pulmonary alveolar type 1 cell CL0002062
    CSI 5.22
    rCSI 30.11%
    PRS 95.17
  • lung secretory cell CL1000272
    CSI 5.08
    rCSI 12.58%
    PRS 97.76
  • kidney collecting duct intercalated cell CL1001432
    CSI 4.82
    rCSI 34.44%
    PRS 93.75
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 4.61
    rCSI 17.41%
    PRS 90.74
  • glandular epithelial cell CL0000150
    CSI 4.48
    rCSI 11.8%
    PRS 99.02
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 4.19
    rCSI 9.55%
    PRS 92.06
  • multi-ciliated epithelial cell CL0005012
    CSI 4.08
    rCSI 4.07%
    PRS 93.56
  • glioblast CL0000030
    CSI 3.6
    rCSI 5.75%
    PRS 92.58
  • retinal pigment epithelial cell CL0002586
    CSI 3.17
    rCSI 6.3%
    PRS 94.78
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.9
    rCSI 2.25%
    PRS 98.03
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 2.88
    rCSI 7.01%
    PRS 89.15
  • pancreatic acinar cell CL0002064
    CSI 2.73
    rCSI 3.63%
    PRS 97.53
  • hepatocyte CL0000182
    CSI 2.7
    rCSI 4.84%
    PRS 95.22
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 2.65
    rCSI 22.88%
    PRS 93.33
  • kidney connecting tubule principal cell CL4030018
    CSI 2.54
    rCSI 18.45%
    PRS 96.69
  • kidney epithelial cell CL0002518
    CSI 2.42
    rCSI 4.63%
    PRS 99.1
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 2.35
    rCSI 13.84%
    PRS 90.89
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 2.33
    rCSI 24.63%
    PRS 94.27
  • luminal epithelial cell of mammary gland CL0002326
    CSI 2.13
    rCSI 3.88%
    PRS 98.27
  • amacrine cell CL0000561
    CSI 2.13
    rCSI 6.18%
    PRS 92.12
  • renal principal cell CL0005009
    CSI 1.94
    rCSI 5.04%
    PRS 96.26
  • podocyte CL0000653
    CSI 1.83
    rCSI 8.14%
    PRS 96.69
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.72
    rCSI 6.18%
    PRS 89.4
  • direct pathway medium spiny neuron CL4023026
    CSI 0.77
    rCSI 18.45%
    PRS 88.52
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.57
    rCSI 13.8%
    PRS 88.26

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 [DCDC2](/details-gene/51473) (doublecortin domain containing 2) is a protein-coding gene located on chromosome 6p22.3. It encodes a protein containing doublecortin domains, which are known to bind microtubules. Functionally, [DCDC2](/details-gene/51473) is critically involved in the assembly and function of cilia, microtubule organization, and neuronal development. Its expression profile reflects this, with high significance in a wide array of ciliated epithelial cells, including those in the lung, kidney, pancreas, and brain. Clinically, mutations in [DCDC2](/details-gene/51473) are associated with a spectrum of human genetic disorders, including reading disability, a renal-hepatic ciliopathy, neonatal sclerosing cholangitis, and a form of hereditary deafness, underscoring its essential role in ciliary function across multiple organ systems ([Link](https://doi.org/10.1073/pnas.0508591102), [Link](https://doi.org/10.1016/j.ajhg.2014.12.002), [Link](https://doi.org/10.1002/humu.23031), [Link](https://doi.org/10.1093/hmg/ddv009)). ## Cellular Roles and Expression Landscape The expression pattern of [DCDC2](/details-gene/51473) strongly indicates a primary role in specialized epithelial tissues that rely on motile or primary cilia for their function. **Overall**, the gene shows the highest significance in various epithelial cell types. It is a top marker for [parietal epithelial cell](/details-cell/CL1000452) in the kidney, [lung ciliated cell](/details-cell/CL1000271), and [ependymal cell](/details-cell/CL0000065) lining the brain ventricles. Its prominence extends to other secretory and transport-related epithelia, including [pancreatic ductal cell](/details-cell/CL0002079), various kidney tubule cells ([kidney loop of Henle thin descending limb epithelial cell](/details-cell/CL1001111), [kidney connecting tubule epithelial cell](/details-cell/CL1000768)), [choroid plexus epithelial cell](/details-cell/CL0000706), and [cholangiocyte](/details-cell/CL1000488). This consistent high expression across diverse ciliated epithelial populations solidifies its identity as a key regulator of ciliary biology. Interestingly, [DCDC2](/details-gene/51473) also shows significant expression in certain immune cell populations, such as [kidney interstitial alternatively activated macrophage](/details-cell/CL1000695) and the broader [mononuclear phagocyte](/details-cell/CL0000113) category. While the primary cilium is known to exist on macrophages and can modulate inflammatory signaling, the specific role of [DCDC2](/details-gene/51473) in these immune cells is less established and suggests a potential function beyond its classical roles in epithelial tissues. ## Pathways and Molecular Function The functional annotations for [DCDC2](/details-gene/51473) are highly consistent with its expression profile and known disease associations. The gene's products are localized to ciliary and microtubule-associated structures, including the [cilium](/details-cell/GO:0005929), [axoneme](/details-cell/GO:0005930), and [microtubule cytoskeleton](/details-cell/GO:0015630). Its involvement in biological processes is dominated by ciliary functions, such as [cilium assembly](/details-cell/GO:0060271) and its regulation ([regulation of cilium assembly](/details-cell/GO:1902017)). This molecular role directly explains why mutations cause ciliopathies affecting the kidney, liver, and inner ear, as highlighted in several studies ([Link](https://doi.org/10.1016/j.ajhg.2014.12.002), [Link](https://doi.org/10.1093/hmg/ddv009)). Furthermore, [DCDC2](/details-gene/51473) is implicated in crucial signaling pathways, including the [regulation of wnt signaling pathway](/details-cell/GO:0030111) and [positive regulation of smoothened signaling pathway](/details-cell/GO:0045880). The disruption of Wnt signaling has been specifically proposed as the mechanism by which [DCDC2](/details-gene/51473) mutations cause renal-hepatic ciliopathy ([Link](https://doi.org/10.1016/j.ajhg.2014.12.002)). The gene's connection to [neuron migration](/details-cell/GO:0001764) and [dendrite morphogenesis](/details-cell/GO:0048813) provides a molecular basis for its association with reading disability and neuronal development ([Link](https://doi.org/10.1073/pnas.0508591102)). ## Research Directions The established role of [DCDC2](/details-gene/51473) as a key ciliary protein whose mutation leads to severe developmental disorders provides a clear foundation for future investigation. **Proposed Hypotheses:** 1. Given its high expression in [cholangiocytes](/details-cell/CL1000488) and the causal link between its mutation and neonatal sclerosing cholangitis ([Link](https://doi.org/10.1016/j.jhep.2016.07.017)), we hypothesize that **[DCDC2](/details-gene/51473) is essential for the mechanosensory function of the primary cilium in bile duct epithelial cells, and its loss disrupts cilia-mediated signaling pathways (e.g., Wnt or Hippo) that control ductal homeostasis, leading to fibrosis and cholangiopathy.** 2. The significant expression of [DCDC2](/details-gene/51473) in [kidney interstitial alternatively activated macrophage](/details-cell/CL1000695) suggests a previously unappreciated role in immunomodulation. We hypothesize that **in renal macrophages, [DCDC2](/details-gene/51473) contributes to the structure of the primary cilium, which acts as a signaling hub for anti-inflammatory pathways. Loss of [DCDC2](/details-gene/51473) function in these cells may impair their ability to adopt a reparative M2-like phenotype, thus contributing to chronic inflammation and fibrosis in the context of ciliopathies.** **Experimental Approach:** To test the first hypothesis, one could employ a human cholangiocyte organoid model. Using CRISPR-Cas9, patient-specific mutations associated with sclerosing cholangitis would be introduced into the [DCDC2](/details-gene/51473) locus. The resulting organoids would be subjected to fluid-flow shear stress to simulate bile flow. The functional readout would include: (1) high-resolution imaging to assess cilium length and morphology; (2) RNA-sequencing to profile transcriptional changes, with a focus on Wnt/Hippo pathway targets and fibrotic markers (e.g., ACTA2, COL1A1); and (3) functional assays to measure changes in organoid growth, cyst formation, and barrier integrity. **Therapeutic Potential:** As the diseases associated with [DCDC2](/details-gene/51473) are typically recessive, loss-of-function disorders, the gene is not a candidate for therapeutic inhibition. Instead, therapeutic strategies would need to focus on restoring its function. For monogenic diseases like the associated ciliopathies, gene therapy represents a potential long-term avenue. AAV-mediated delivery of a functional copy of the [DCDC2](/details-gene/51473) cDNA to affected tissues, such as the liver or kidney, could theoretically rescue the cellular phenotype. However, significant challenges related to delivery, efficiency, and safety would need to be overcome. Small molecule chaperones that could stabilize misfolded DCDC2 protein resulting from certain missense mutations might offer an alternative, though this would be mutation-specific.

Genular Protein ID: 2605540374

Symbol: DCDC2_HUMAN

Name: Doublecortin domain-containing protein 2

UniProtKB Accession Codes:

Q9UHG0 Q5VTR8 Q5VTR9 Q86W35 Q9UFD1 Q9UHG1 Q9ULR6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CORUM 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 20 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 9 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 3 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 2 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: 10601354

Title: A new antigen recognized by cytolytic T lymphocytes on a human kidney tumor results from reverse strand transcription.

PubMed ID: 10601354

DOI: 10.1084/jem.190.12.1793

PubMed ID: 10574461

Title: Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain.

PubMed ID: 10574461

DOI: 10.1093/dnares/6.5.329

PubMed ID: 12168954

Title: Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.

PubMed ID: 12168954

DOI: 10.1093/dnares/9.3.99

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

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: 16278297

Title: DCDC2 is associated with reading disability and modulates neuronal development in the brain.

PubMed ID: 16278297

DOI: 10.1073/pnas.0508591102

PubMed ID: 25557784

Title: DCDC2 mutations cause a renal-hepatic ciliopathy by disrupting Wnt signaling.

PubMed ID: 25557784

DOI: 10.1016/j.ajhg.2014.12.002

PubMed ID: 25601850

Title: A missense mutation in DCDC2 causes human recessive deafness DFNB66, likely by interfering with sensory hair cell and supporting cell cilia length regulation.

PubMed ID: 25601850

DOI: 10.1093/hmg/ddv009

PubMed ID: 27319779

Title: DCDC2 mutations cause neonatal sclerosing cholangitis.

PubMed ID: 27319779

DOI: 10.1002/humu.23031

PubMed ID: 27469900

Title: Mutations in DCDC2 (doublecortin domain containing protein 2) in neonatal sclerosing cholangitis.

PubMed ID: 27469900

DOI: 10.1016/j.jhep.2016.07.017

Sequence Information:

  • Length: 476
  • Mass: 52834
  • Checksum: 50DD06EA2FB9BD53
  • Sequence:
    • MSGSSARSSH LSQPVVKSVL VYRNGDPFYA GRRVVIHEKK VSSFEVFLKE VTGGVQAPFG 
AVRNIYTPRT GHRIRKLDQI QSGGNYVAGG QEAFKKLNYL DIGEIKKRPM EVVNTEVKPV 
IHSRINVSAR FRKPLQEPCT IFLIANGDLI NPASRLLIPR KTLNQWDHVL QMVTEKITLR 
SGAVHRLYTL EGKLVESGAE LENGQFYVAV GRDKFKKLPY SELLFDKSTM RRPFGQKASS 
LPPIVGSRKS KGSGNDRHSK STVGSSDNSS PQPLKRKGKK EDVNSEKLTK LKQNVKLKNS 
QETIPNSDEG IFKAGAERSE TRGAAEVQED EDTQVEVPVD QRPAEIVDEE EDGEKANKDA 
EQKEDFSGMN GDLEEEGGRE ATDAPEQVEE ILDHSEQQAR PARVNGGTDE ENGEELQQVN 
NELQLVLDKE RKSQGAGSGQ DEADVDPQRP PRPEVKITSP EENENNQQNK DYAAVA