WAC
Chr 10ADWW domain containing adaptor with coiled-coil
Also known as: BM-016, DESSH, PRO1741, Wwp4
The WAC protein contains a WW domain that mediates protein-protein interactions by binding proline-rich peptide motifs and localizes to nuclear speckles. Loss-of-function mutations cause Desanto-Shinawi syndrome, an autosomal dominant neurodevelopmental disorder. The gene is highly intolerant to loss-of-function variants, indicating haploinsufficiency as the likely pathogenic mechanism.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
WAC · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
RECRUITINGFurther Delineation of the De Santo Shinawi Syndrome Phenotype Using a Series of Individuals Carrying a Pathogenic Variant of the WAC Gene
RECRUITINGExternal Resources
Links to major genomics databases and tools