Details for: CCDC74A

Gene ID: 90557

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: CCDC74A

Ensembl ID: ENSG00000163040

Description: coiled-coil domain containing 74A

Cell Significance Landscape

Associated with

Significant Cells

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

  • multi-ciliated epithelial cell CL0005012
    CSI 20.39
    rCSI 20.35%
    PRS 97.94
  • ciliated epithelial cell CL0000067
    CSI 14.19
    rCSI 12.47%
    PRS 97.33
  • lung ciliated cell CL1000271
    CSI 10.9
    rCSI 12.6%
    PRS 97.99
  • ciliated cell CL0000064
    CSI 6.9
    rCSI 11.18%
    PRS 97.31
  • deuterosomal cell CL4033044
    CSI 6.3
    rCSI 21.29%
    PRS 96.94
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 5.88
    rCSI 13.41%
    PRS 97.17
  • glioblast CL0000030
    CSI 3.48
    rCSI 5.55%
    PRS 97.58
  • luminal epithelial cell of mammary gland CL0002326
    CSI 3.15
    rCSI 5.72%
    PRS 99.41
  • choroid plexus epithelial cell CL0000706
    CSI 2.94
    rCSI 4.81%
    PRS 97.86

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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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 [CCDC74A](/details-gene/90557), or Coiled-coil domain containing 74A, is a protein-coding gene located on human chromosome 2. Initial characterization of this gene was part of large-scale genome sequencing efforts ([Link](https://doi.org/10.1038/nature03466), [Link](https://doi.org/10.1038/nature03001)). The gene product is a protein containing a coiled-coil domain, a motif typically involved in protein-protein interactions, which is consistent with its annotated molecular function of [protein binding](/details-go/GO:0005515). Expression data indicate that [CCDC74A](/details-gene/90557) is a highly specific and significant marker for ciliated cell lineages. Its exceptionally high expression in [multi-ciliated epithelial cells](/details-cell/CL0005012) and their precursors, [deuterosomal cells](/details-cell/CL4033044), strongly suggests a specialized role in the formation, structure, or function of cilia. ## Cellular Roles and Expression Landscape The expression profile of [CCDC74A](/details-gene/90557) strongly associates it with the biology of ciliated cells. **Overall**, the gene shows its highest significance in cell types responsible for motility and fluid movement, particularly within epithelial linings. The most significant expression is observed in: * [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 20.39) * [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 14.19) * [lung ciliated cell](/details-cell/CL1000271) (CSI: 10.90) * [ciliated columnar cell of tracheobronchial tree](/details-cell/CL0002145) (CSI: 5.88) This pattern highlights [CCDC74A](/details-gene/90557) as a key molecular component of cells essential for mucociliary clearance in the respiratory system. Critically, its high significance in [deuterosomal cells](/details-cell/CL4033044) (CSI: 6.30), which are specialized precursor cells that generate centrioles for the formation of multiple cilia, suggests a potential role in the early stages of ciliogenesis. This is further supported by its expression in other ciliated cell types, such as the [choroid plexus epithelial cell](/details-cell/CL0000706). Interestingly, a notable level of significance is also seen in [glioblast](/details-cell/CL0000030) (CSI: 3.48), a type of brain tumor. While the function in this malignant context is unclear, it may relate to the dysregulation of primary cilia signaling, a known factor in cancer progression. The highly specific expression pattern suggests that [CCDC74A](/details-gene/90557) has a specialized function largely restricted to ciliated lineages. ## Pathways and Molecular Function The primary annotated molecular function for [CCDC74A](/details-gene/90557) is [protein binding](/details-go/GO:0005515). This function is directly supported by its protein structure, which contains a coiled-coil domain. These domains are well-established mediators of protein-protein oligomerization and serve as scaffolds for the assembly of larger protein complexes. Given its cellular expression profile, it is highly probable that the protein-binding capacity of [CCDC74A](/details-gene/90557) is utilized within the complex molecular machinery of cilia. It may function as a structural component of the ciliary axoneme or basal body, or it could be involved in the transport of proteins during ciliogenesis. Its strong association with [deuterosomal cells](/details-cell/CL4033044) suggests it might interact with key proteins involved in the amplification of centrioles, a fundamental step in the development of multi-ciliated cells. ## Research Directions The specific and high-level expression of [CCDC74A](/details-gene/90557) in ciliated cell lineages, particularly during their development, provides a foundation for several testable hypotheses. 1. **Hypothesis 1:** [CCDC74A](/details-gene/90557) is essential for deuterosome-mediated centriole amplification during the differentiation of multi-ciliated epithelial cells. Its depletion would be expected to impair the formation of deuterosomes and result in a pauciciliated or non-ciliated phenotype. 2. **Hypothesis 2:** Within mature cilia, the CCDC74A protein acts as a linker or scaffold protein, and its absence would lead to structural defects or impaired ciliary beating, potentially contributing to ciliopathy-like phenotypes. 3. **Hypothesis 3:** The observed expression in [glioblast](/details-cell/CL0000030) suggests an aberrant reactivation or function of [CCDC74A](/details-gene/90557). This could potentially interfere with primary cilium signaling, which is often involved in regulating cell cycle and proliferation pathways like Sonic Hedgehog (SHH), thereby contributing to tumorigenesis. A key experiment to test Hypothesis 1 would involve using an *in vitro* air-liquid interface (ALI) culture model of primary human bronchial epithelial cells, which differentiates to form a ciliated epithelium. By using CRISPR-Cas9 to knock out [CCDC74A](/details-gene/90557) in these progenitor cells, researchers could assess the impact on ciliogenesis. Endpoints would include quantifying the number of ciliated cells via immunofluorescence for acetylated tubulin, examining deuterosome and basal body formation by electron microscopy, and analyzing the expression of other key ciliogenesis transcription factors and structural components via RNA-seq. **Therapeutic Potential:** Given its highly restricted expression pattern, [CCDC74A](/details-gene/90557) presents a challenging but potentially specific therapeutic target. Systemic inhibition would likely cause severe respiratory and reproductive side effects due to its crucial role in healthy ciliated cells. However, if its role in [glioblast](/details-cell/CL0000030) is validated and found to be tumor-promoting, its low expression in non-ciliated tissues of the central nervous system could make it a candidate for targeted therapies, such as antibody-drug conjugates or antisense oligonucleotides, designed to specifically target the tumor while sparing other tissues. Its potential role in human ciliopathies also warrants investigation, though whether it would be a target for activation or inhibition in that context is currently unknown.

Genular Protein ID: 3398793906

Symbol: CC74A_HUMAN

Name: Coiled-coil domain-containing protein 74A

UniProtKB Accession Codes:

Q96AQ1 Q6P4I5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 DMDM 1 DNASU 1 EMBL 3 Ensembl 2 ExpressionAtlas 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 2 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 15815621

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

PubMed ID: 15815621

DOI: 10.1038/nature03466

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

Sequence Information:

  • Length: 378
  • Mass: 41605
  • Checksum: 61D9EAAA5EDC34F9
  • Sequence:
    • MSGAGVAAGT RPPSSPTPGS RRRRQRPSVG VQSLRPQSPQ LRQSDPQKRN LDLEKSLQFL 
QQQHSEMLAK LHEEIEHLKR ENKDLHYKLI MNQTSQKKDG PSGNHLSRAS APLGARWVCI 
NGVWVEPGGP SPARLKEGSS RTHRPGGKRG RLAGGSADTV RSPADSLSMS SFQSVKSISN 
SGKARPQPGS FNKQDSKADV SQKADLEEEP LLHNSKLDKV PGVQGQARKE KAEASNAGAA 
CMGNSQHQGR QMGAGAHPPM ILPLPLRKPT TLRQCEVLIR ELWNTNLLQT QELRHLKSLL 
EGSQRPQAAP EEASFPRDQE ATHFPKVSTK SLSKKCLSPP VAERAILPAL KQTPKNNFAE 
RQKRLQAMQK RRLHRSVL

Genular Protein ID: 10429623

Symbol: F5GZA4_HUMAN

Name: N/A

UniProtKB Accession Codes:

F5GZA4

Database IDs:

ARBA 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 DNASU 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 2 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 2 Proteomes 2 ProteomicsDB 2 RefSeq 1 SAM 1 SMR 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: 272
  • Mass: 29506
  • Checksum: CA3419FEB5E3A053
  • Sequence:
    • MSGAGVAAGT RPPSSPTPGS RRRRQRPSVG VQSLRPQSPQ LRQSDPQKRN LDLEKSLQFL 
QQQHSEMLAK LHEEIEHLKR ENKDLHYKLI MNQTSQKKDG PSGNHLSRAS APLGARWVCI 
NGVWVEPGGP SPARLKEGSS RTHRPGGKRG RLAGGSADTV RSPADSLSMS SFQSVKSISN 
SGKARPQPGS FNKQDSKADV SQKADLEEEP LLHNSKLDKV PGVQGQASCG TSSPSWKGAR 
GPRQPRRKLA FPGTKKPRIS PRSPPRASPR NA