KIAA0319

Chr 6

KIAA0319

ENSG00000137261UniProt: Q5VV43

Involved in neuronal migration during development of the cerebral neocortex. May function in a cell autonomous and a non-cell autonomous manner and play a role in appropriate adhesion between migrating neurons and radial glial fibers. May also regulate growth and differentiation of dendrites

Primary Disease Associations & Inheritance

UniProtDyslexia 2
105
ClinVar variants
6
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— KIAA0319
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 73 VUS of 105 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.99LOEUF
pLI 0.000
Z-score 1.59
OE 0.76 (0.58–0.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.46Z-score
OE missense 0.95 (0.88–1.01)
567 obs / 598.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.76 (0.58–0.99)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.88–1.01)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 37 / 49.0Missense obs/exp: 567 / 598.8Syn Z: 1.46

ClinVar Variant Classifications

105 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS73
Likely Benign15
Benign11
5
Pathogenic
1
Likely Pathogenic
73
VUS
15
Likely Benign
11
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
1
0
1
VUS
0
70
3
0
73
Likely Benign
0
8
3
4
15
Benign
0
7
1
3
11
Total085137105

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KIAA0319 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
KIAA0319 GENE; KIAA0319
MIM #609269 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic variant in KIAA0319, but not in DYX1C1, is associated with risk of dyslexia: an integrated meta-analysis.
Zou L et al.·Am J Med Genet B Neuropsychiatr Genet
2012Meta-analysis
Frontotemporal dementia and language networks: cortical thickness reduction is driven by dyslexia susceptibility genes.
Paternicó D et al.·Sci Rep
2016
Genetic variants of FOXP2 and KIAA0319/TTRAP/THEM2 locus are associated with altered brain activation in distinct language-related regions.
Pinel P et al.·J Neurosci
2012
A common variant associated with dyslexia reduces expression of the KIAA0319 gene.
Dennis MY et al.·PLoS Genet
2009
KIAA0319 Genotype Predicts the Number of Past Concussions in a Division I Football Team: A Pilot Study.
Walter A et al.·J Neurotrauma
2019
Targeted analysis of dyslexia-associated regions on chromosomes 6, 12 and 15 in large multigenerational cohorts.
Chapman NH et al.·PLoS One
2025Cohort
Dyslexia risk gene relates to representation of sound in the auditory brainstem.
Neef NE et al.·Dev Cogn Neurosci
2017
Identification of NCAN as a candidate gene for developmental dyslexia.
Einarsdottir E et al.·Sci Rep
2017
Association of a rare variant with mismatch negativity in a region between KIAA0319 and DCDC2 in dyslexia.
Czamara D et al.·Behav Genet
2011
Specific Learning Disorders: Variation Analysis of 15 Candidate Genes in 9 Multiplex Families.
Calì F et al.·Medicina (Kaunas)
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
KIAA0319 Plays a Critical Role in Cortical Neuronal Maturation and Synaptic Development Through a Dyslexia-Associated Gene Network.
Scandura MJ et al.·Biol Psychiatry
2025
KIAA0319 modulates Alzheimer's disease risk through PMM2 regulation: Evidence from integrated pQTL-mediation and transcriptomic analyses.
Wen P et al.·J Alzheimers Dis Rep
2025🔓 Open Access
Investigation of Association Between Expression of DYX1C1, KIAA0319, and ROBO1 Genes and Specific Learning Disorder in Children and Adolescents.
Bayyurt B et al.·J Mol Neurosci
2024
Cumulative genetic score of KIAA0319 affects reading ability in Chinese children: moderation by parental education and mediation by rapid automatized naming.
Zhao J et al.·Behav Brain Funct
2023🔓 Open Access
Dyslexia associated gene KIAA0319 regulates cell cycle during human neuroepithelial cell development.
Paniagua S et al.·Front Cell Dev Biol
2022🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Subconcussive Head ImpactOmega-3 Fatty Acids

Omega-3 Fatty Acids and Subconcussive Head Impacts

RECRUITING
NCT06736925Phase NAIndiana UniversityStarted 2025-02-28
Omega-3 Fatty Acids (EPA plus DHA)Organic soybean oilSoccer Heading Model
Brain MalformationNeuronal Migration DisorderCognition Disorder

Human Epilepsy Genetics--Neuronal Migration Disorders Study

RECRUITING
NCT00041600Harvard University Faculty of MedicineStarted 1996-04

External Resources

Links to major genomics databases and tools