DNAAF4

DNAAF4
Identifiers
Aliases	DNAAF4, CILD25, DYX1, DYXC1, EKN1, RD, DYX1C1, dyslexia susceptibility 1 candidate 1, dynein axonemal assembly factor 4
External IDs	OMIM: 608706; MGI: 1914935; GeneCards: DNAAF4
Gene location (Human) Chr. Chromosome 15 (human) Band 15q21.3 Start 55,410,525 bp End 55,508,234 bp
Gene location (Mouse) Chr. Chromosome 9 (mouse) Band 9|9 D Start 72,866,067 bp End 72,880,346 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in bronchial epithelial cell secondary oocyte mucosa of paranasal sinus testicle olfactory zone of nasal mucosa right uterine tube gonad right lobe of thyroid gland epithelium of nasopharynx left lobe of thyroid gland Top expressed in spermatocyte seminiferous tubule saccule morula otic vesicle embryo spermatid embryo blastocyst vestibular sensory epithelium More reference expression data BioGPS n/a
Gene ontology Molecular function estrogen receptor binding protein binding Cellular component nucleus plasma membrane cytoplasm centrosome cytosol non-motile cilium extracellular region Biological process nervous system development outer dynein arm assembly regulation of intracellular estrogen receptor signaling pathway regulation of proteasomal protein catabolic process determination of left/right symmetry inner dynein arm assembly neuron migration cilium movement epithelial cilium movement involved in extracellular fluid movement development of the heart Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 161582 67685 Ensembl ENSG00000256061 ENSMUSG00000092192 UniProt Q8WXU2 Q8R368 RefSeq (mRNA) NM_130810 NM_001033559 NM_001033560 NM_001163725 NM_026314 RefSeq (protein) NP_001028731 NP_001028732 NP_570722 NP_001157197 NP_080590 Location (UCSC) Chr 15: 55.41 – 55.51 Mb Chr 9: 72.87 – 72.88 Mb PubMed search
Wikidata
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Dynein axonemal assembly factor 4 is a protein that in humans is encoded by the DNAAF4 gene (often also called DYX1C1). This protein contains 420 amino acids with 3 tetratricopeptide repeat (TPR) domains, thought to mediate protein–protein interactions. It is a protein-coding gene strongly associated with susceptibility to developmental dyslexia, a learning disorder that affects reading ability in otherwise typically developing individuals.

Gene

Although the gene does not show strong homology to many well-characterized proteins, it is highly conserved across species, with significant similarity between humans, mice, and nonhuman primates, indicating an important biological function.

Structure

The DYX1C1 protein consists of approximately 420 amino acids and is characterized by the presence of three tetratricopeptide repeat (TPR) domains, which are structural motifs known to facilitate protein–protein interactions. These domains suggest that DYX1C1 functions as part of larger molecular complexes, potentially playing a role in regulating cellular processes critical for brain development.

Function

The DYX1C1 gene play a crucial role in the function of motile cilia that are on the surface of cells in eukaryotes that beat in sense of rhythmic waves to move fluids, mucus, or cells across tissue surfaces. Research shows that when this gene is disrupted (function has been changed) the leading to defects in the inner and out dynein arms this is required for ciliary motion resulting in conditions like primary ciliary dyskinesia (PCD).Evidence from mice, zebrafish, and humans demonstrates that DYX1C1 acts in the cytoplasm as a dynein axonemal assembly factor, interacting with chaperone proteins and other assembly factors to ensure cilia are built correctly. Without this function, cilia may still form structurally but are immotile, leading to symptoms such as chronic respiratory disease, laterality defects, and infertility. The genes DYX1C1 is a candidate genes linked to dyslexia, and their primary shared function is in neuronal migration during brain development. This means they help guide neurons to their correct positions in the developing neocortex, which is essential for proper brain organisation and function. Specifically, DYX1C1 is required for neurons to transition out of an early “multipolar” stage and move to their final locations; its C-terminal region is critical for this role. In addition to its role in the brain, DYX1C1 also has a separate function in cilia biology, where it helps assemble dynein arms needed for ciliary movement.

A key finding is that DYX1C1 is not only linked to neuronal migration and dyslexia risk, but also plays an important role in the formation and function of motile cilia, which are structures responsible for moving fluids in the brain, airways, and developing embryo. The study shows that DYX1C1 interacts with other cilia-related proteins (such as CPAP and DCDC2) and is involved in cytoplasmic processes that help assemble dynein motor arms required for ciliary movement. When this gene is disrupted, it leads to defects in ciliary motility, causing developmental issues such as abnormal left-right body patterning, hydrocephalus, and impaired fluid flow. Overall, the function of DYX1C1 is best described as a regulator of cilia assembly and activity, linking cellular structural machinery to both neurological development and broader developmental biology.

Clinical significance

A mutation in the DYX1C1 gene has been associated with deficits in reading ability (dyslexia).

Testing

Testing DYX1C1 not only if the protein is functional in case so testing the most effective approaches for testing the role of DYX1C1 because it combines a family-based genetic design with precise cognitive measurements and robust statistical analysis. By using nuclear families with a diagnosed dyslexic proband, the researchers reduce population stratification bias and ensure that genetic transmission patterns are accurately captured. The use of direct DNA sequencing for key DYX1C1 markers (−3GA and 1249GT) strengthens the reliability of variant detection.

References

Further reading