Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

WAC

HGNC:17327 (protein-coding gene)

WW domain containing adaptor with coiled-coil

Unique Cases:
24
Disorders:
ID, ASD, EP, ADHD, CP
Last Updated:
November 4, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
WAC is a High Confidence candidate gene classified as Tier 1. Tier 1 genes have three or more de novo pathogenic loss-of-function variants.
Gene Function
Acts as a linker between gene transcription and histone H2B monoubiquitination at 'Lys-120' (H2BK120ub1) (PubMed:21329877). Interacts with the RNA polymerase II transcriptional machinery via its WW domain and with RNF20-RNF40 via its coiled coil region, thereby linking and regulating H2BK120ub1 and gene transcription (PubMed:21329877). Regulates the cell-cycle checkpoint activation in response to DNA damage (PubMed:21329877). Positive regulator of amino acid starvation-induced autophagy (PubMed:... (Source: Uniprot)
Previous symbols
No previous symbols
Alias symbols
Wwp4, FLJ31290, PRO1741, BM-016, MGC10753
Chromosomal Location
10p12.1
Genomic Coordinates
GRCh37:chr10:28821517-28912041
GRCh38:chr10:28532772-28623112
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

9.64

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.08

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

Definitive

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Strong2 Definitive3 Supportive1

Publications:

Leonardi E et. al., A Novel WAC Loss of Function Mutation in an Individual Presenting with Encephalopathy Related to Status Epilepticus during Sleep (ESES)., Genes (Basel), 2020
Uehara T et. al., Three patients with DeSanto-Shinawi syndrome: Further phenotypic delineation., Am J Med Genet A, 2018
DeSanto C et. al., WAC loss-of-function mutations cause a recognisable syndrome characterised by dysmorphic features, developmental delay and hypotonia and recapitulate 10p11.23 microdeletion syndrome., J Med Genet, 2015
Lugtenberg D et. al., De novo loss-of-function mutations in WAC cause a recognizable intellectual disability syndrome and learning deficits in Drosophila., Eur J Hum Genet, 2016
Helbig KL et. al., Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy., Genet Med, 2016
Iossifov I et. al., The contribution of de novo coding mutations to autism spectrum disorder., Nature, 2014
Coe BP et. al., Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity., Nat Genet, 2019
Guo H et. al., Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model., Mol Autism, 2018
de Ligt J et. al., Diagnostic exome sequencing in persons with severe intellectual disability., N Engl J Med, 2012
Grozeva D et. al., Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability., Hum Mutat, 2015
Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021
et. al., , ,

NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.
Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.
DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.
SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.
ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.
GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.
gnomAD
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