Details for: DNAAF3

Gene ID: 352909

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: DNAAF3

Ensembl ID: ENSG00000167646

Description: dynein axonemal assembly factor 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • ciliated epithelial cell CL0000067
    CSI 5.34
    rCSI 4.7%
    PRS 97.28
  • multi-ciliated epithelial cell CL0005012
    CSI 4.8
    rCSI 4.79%
    PRS 97.89
  • cardiac muscle cell CL0000746
    CSI 4.61
    rCSI 6.62%
    PRS 97.28
  • deuterosomal cell CL4033044
    CSI 3.1
    rCSI 10.48%
    PRS 96.88
  • megakaryocyte CL0000556
    CSI 3.09
    rCSI 13.39%
    PRS 98.12
  • lung ciliated cell CL1000271
    CSI 2.97
    rCSI 3.44%
    PRS 97.95
  • ciliated cell CL0000064
    CSI 2.94
    rCSI 4.77%
    PRS 97.24
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.91
    rCSI 4.35%
    PRS 97.1
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.36
    rCSI 8.47%
    PRS 97.45

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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  • 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 [DNAAF3](/details-gene/352909) (dynein axonemal assembly factor 3) is a protein-coding gene located on chromosome 19q13.42. It plays a critical role in the assembly of dynein motor complexes, which are essential for the movement of cilia and flagella. Its function is integral to processes such as motile cilium assembly and the establishment of left-right body asymmetry during embryonic development. Expression data indicates that [DNAAF3](/details-gene/352909) is a highly significant gene in ciliated cell types, including those in the respiratory tract, as well as in cardiac muscle cells. Mutations in this gene are known to cause primary ciliary dyskinesia (PCD), a rare genetic disorder characterized by chronic respiratory infections, laterality defects, and infertility [Link](https://doi.org/10.1038/ng.1106). ## Cellular Roles and Expression Landscape The expression profile of [DNAAF3](/details-gene/352909) underscores its specialized function in ciliated and contractile tissues. **Overall**, the gene shows its highest significance in cell types characterized by the presence of motile cilia. This includes [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 5.34), [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 4.80), and more specifically, [lung ciliated cell](/details-cell/CL1000271) (CSI: 2.97) and [ciliated columnar cell of tracheobronchial tree](/details-cell/CL0002145) (CSI: 1.91). Its high significance in [deuterosomal cell](/details-cell/CL4033044) (CSI: 3.10) is also consistent with this role, as deuterosomes are involved in the biogenesis of multiple cilia. Beyond ciliated cells, [DNAAF3](/details-gene/352909) shows high significance in [cardiac muscle cell](/details-cell/CL0000746) (CSI: 4.61), suggesting a potentially important, though less characterized, role in cardiac tissue. The gene is also notably significant in [megakaryocyte](/details-cell/CL0000556)s (CSI: 3.09), hinting at a possible function related to the microtubule-dependent processes involved in platelet formation. Collectively, the data points to [DNAAF3](/details-gene/352909) as a key factor in cellular contexts requiring robust microtubule and dynein-based structures. ## Pathways and Molecular Function The functional annotations for [DNAAF3](/details-gene/352909) align closely with its cellular expression pattern. Its primary annotated biological process is **Axonemal dynein complex assembly** ([GO:0070286](https://www.ebi.ac.uk/QuickGO/term/GO:0070286)), which directly supports its high significance in ciliated cells that rely on dynein motors for motility. This is further specified by its involvement in **Motile cilium assembly** ([GO:0044458](https://www.ebi.ac.uk/QuickGO/term/GO:0044458)). At the molecular level, it is a component of the **Dynein axonemal particle** ([GO:0120293](https://www.ebi.ac.uk/QuickGO/term/GO:0120293)). The physiological consequences of these functions are highlighted by its role in **Determination of left/right symmetry** ([GO:0007368](https://www.ebi.ac.uk/QuickGO/term/GO:0007368)), a process driven by ciliary flow in the embryonic node. Additionally, its annotation for **Heart development** ([GO:0007507](https://www.ebi.ac.uk/QuickGO/term/GO:0007507)) is consistent with its high expression in [cardiac muscle cell](/details-cell/CL0000746)s and the frequent observation of congenital heart defects in patients with primary ciliary dyskinesia. ## Research Directions The established role of [DNAAF3](/details-gene/352909) in primary ciliary dyskinesia provides a strong foundation for further research, particularly concerning its function outside of classic motile cilia. The high significance of [DNAAF3](/details-gene/352909) in cardiac and hematopoietic lineages suggests uncharacterized roles that warrant investigation. Based on the available data, several testable hypotheses can be proposed: 1. The high significance of [DNAAF3](/details-gene/352909) in [cardiac muscle cell](/details-cell/CL0000746)s suggests it is essential for the structure or function of primary (non-motile) cilia in cardiomyocytes, which act as mechanosensors. Dysfunction of [DNAAF3](/details-gene/352909) may impair mechanotransduction in the heart, contributing to the congenital heart defects observed in some ciliopathies. 2. Given its high significance in [megakaryocyte](/details-cell/CL0000556)s and its role in dynein assembly, [DNAAF3](/details-gene/352909) may be required for the extensive microtubule-based cytoskeletal remodeling that drives proplatelet formation and subsequent platelet release. **Experimental Approach:** To test the first hypothesis regarding the role of [DNAAF3](/details-gene/352909) in cardiomyocytes, a targeted knockout could be generated in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) using CRISPR-Cas9. The resulting [DNAAF3](/details-gene/352909)-null hiPSC-CMs could be assessed for defects in primary cilium formation via immunofluorescence microscopy (staining for ciliary markers such as ARL13B and acetylated tubulin). Functional consequences could be evaluated by measuring calcium signaling responses to fluid shear stress, a key mechanosensory function mediated by primary cilia. **Therapeutic Potential:** As [DNAAF3](/details-gene/352909) mutations cause a loss-of-function monogenic disorder (PCD), it is not a target for inhibition. Instead, therapeutic strategies would aim to restore its function. This makes [DNAAF3](/details-gene/352909) a candidate for gene replacement therapy, where a functional copy of the gene could be delivered to affected cells, such as airway epithelial cells, using viral vectors (e.g., AAV). Alternatively, for specific missense mutations, the development of small-molecule pharmacological chaperones that aid in proper protein folding and function could be a viable therapeutic approach.

Genular Protein ID: 3682404837

Symbol: DAAF3_HUMAN

Name: Dynein axonemal assembly factor 3

UniProtKB Accession Codes:

Q8N9W5 A8MUY0 E3W9A1 E9PAX5 Q6P4F6 Q8N9W0 Q96AR2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 4 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 6 ExpressionAtlas 1 GO 5 GeneCards 1 GeneReviews 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 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 4 RNAct 1 RefSeq 4 STRING 1 SignaLink 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

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: 22387996

Title: Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia.

PubMed ID: 22387996

DOI: 10.1038/ng.1106

Sequence Information:

  • Length: 541
  • Mass: 59410
  • Checksum: 58BF0BFAFEC602BC
  • Sequence:
    • MTTPAGSGSG FGSVSWWGLS PALDLQAESP PVDPDSQADT VHSNPELDVL LLGSVDGRHL 
LRTLSRAKFW PRRRFNFFVL ENNLEAVARH MLIFSLALEE PEKMGLQERS ETFLEVWGNA 
LLRPPVAAFV RAQADLLAHL VPEPDRLEEQ LPWLSLRALK FRERDALEAV FRFWAGGEKG 
PQAFPMSRLW DSRLRHYLGS RYDARRGVSD WDLRMKLHDR GAQVIHPQEF RRWRDTGVAF 
ELRDSSAYHV PNRTLASGRL LSYRGERVAA RGYWGDIATG PFVAFGIEAD DESLLRTSNG 
QPVKTAGEIT QHNVTELLRD VAAWGRARAT GGDLEEQQHA EGSPEPGTPA APTPESFTVH 
FLPLNSAQTL HHKSCYNGRF QLLYVACGMV HLLIPELGAC VAPGGNLIVE LARYLVDVRQ 
EQLQGFNTRV RELAQAAGFA PQTGARPSET FARFCKSQES ALGNTVPAVE PGTPPLDILA 
QPLEASNPAL EGLTQPLQGG TPHCEPCQLP SESPGSLSEV LAQPQGALAP PNCESDSKTG 
V