KIAA0319

Official Full Name

KIAA0319

Organism

Homo sapiens

GeneID

9856

Background

This gene encodes a transmembrane protein that contains a large extracellular domain with multiple polycystic kidney disease (PKD) domains. The encoded protein may play a role in the development of the cerebral cortex by regulating neuronal migration and cell adhesion. Single nucleotide polymorphisms in this gene are associated with dyslexia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

Synonyms

DYX2; NMIG; DYLX2;

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Detailed Information

The protein encoded by KIAA0319 belongs to the class of transmembrane glycoproteins. KIAA0319 is located on the susceptibility locus DYX2 of 6p21-p22. Studies have confirmed that the short arm of chromosome 6 is associated with dyslexia. It is a typical membrane protein-encoding gene that is expressed primarily in the central nervous system, such as the brain. KIAA0319 encodes a complete membrane protein comprising a large extracellular domain and four polycystic kidney disease (PKD) domains, a transmembrane domain and a small intracellular c-terminus. The PKD region plays an important role in the process of cell adhesion.

Evidence from cellular levels suggests that the KIAA0319 protein may be involved in signaling and cell-to-cell interactions. In addition, in animal model studies, knockdown of the embryo Kiaa0319 caused disruption of cortical neuron migration, resulting in the formation of ectopic white matter in some animals, which also revealed a series of behavioral defects, including a rapid, simple space for damage auditory processing. Learning and phoneme processing are similar to dyslexia. KIAA0319 is expressed during mouse and human fetal brain development and is involved in neuronal migration to form the neocortex of the brain. Intrauterine RNAi targeting can inhibit the expression of Kiaa0319 in brain cells. This evidence supports the fact that KIAA0319 may play a role in the development of dyslexia.

In addition, candidate genes for susceptibility to dyslexia such as DCDC2, DYX1C1 and KIAA0319 are co-expressed in cilia. The 77 kb spanning region on chromosome 6p22 (including ACOT13 and TDP2 (formerly known as THEM2 and TTRAP) and the first four exons of KIAA0319 have been associated with dyslexia and reading ability in the general population. More importantly, this chromosomal region is directly related to the language advantage of healthy adults. Within the KIAA0319 / TDP2 / ACOT13 region, single nucleotide polymorphisms were significantly associated with left-sided activation of the posterior superior sulcus (pSTS) during reading and speech hearing tasks. Kiaa0319 gene expression is essential for neocortex development in rats, as suppressed gene expression leads to impaired neuronal migration, reduced midsagittal corpus callosum volume, and impaired processing of complex auditory stimuli. KIAA0319 gene expression could thus represent an important step in the ontogenesis of dyslexia and altered hemispheric asymmetries.

Paracchini et al. studied the functional consequences of these sequence variants in lymphoblastoid cell lines. The risk haplotype consists of rs4504469, rs2038137 and rs2143340, and its expression of KIAA0319 is about 40% lower than that of the non-risk haplotype. Dennis et al. further characterized the 5′ upstream of KIAA0319 and identified a SNP marker rs9461045 that was not only significantly associated with DD (developmental dyslexia) and previously reported to be associated with reading-related traits but it was also found by luciferase-based assays that it could influence gene expression, possibly by alteration of the binding site to transcriptional silencer OCT-1. Therefore, genetic variants influence the functions of KIAA0319 by alteration of gene expression level.

The DNA methylation pattern in the KIAA0319 promoter region may be associated with cognitive control processes that are necessary to perform well under forced attention conditions. KIAA0319 gene expression is not only regulated by DNA variation, but also by DNA methylation.

References:

Schmitz J, et al. KIAA0319, promoter DNA methylation predicts dichotic listening performance in forced-attention conditions. Behavioural Brain Research, 2018, 337:1-7.
Centanni T M, et al. Knockdown of the Dyslexia-Associated Gene Kiaa0319 Impairs Temporal Responses to Speech Stimuli in Rat Primary Auditory Cortex. Cerebral Cortex, 2014, 24(7):1753-1766.
Sun Y, et al. Association study of developmental dyslexia candidate genes DCDC2 and KIAA0319 in Chinese population. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2014, 165(8):627-634.
Shao S, et al. Opposite Associations between Individual KIAA0319 Polymorphisms and Developmental Dyslexia Risk across Populations: A Stratified Meta-Analysis by the Study Population. Scientific Reports, 2016, 6:30454.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry