Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

ASXL3

HGNC:29357 (protein-coding gene)

ASXL transcriptional regulator 3

Unique Cases:
51
Disorders:
ID, ASD, EP, SCZ, CP
Last Updated:
January 24, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
ASXL3 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
Putative Polycomb group (PcG) protein. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development. PcG proteins are not required to initiate repression, but to maintain it during later stages of development. They probably act via methylation of histones, rendering chromatin heritably changed in its expressibility (By similarity). {ECO:0000250}. (Source: Uniprot)
Previous symbols
KIAA1713
Alias symbols
No alias sybmols
Chromosomal Location
18q12.1
Genomic Coordinates
GRCh37:chr18:31158541-31331159
GRCh38:chr18:33578219-33751195
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

13.78

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.2

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

No Classification

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Definitive2 Strong2 Supportive1

Publications:

Husson T et. al., Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use., Transl Psychiatry, 2020
Wang T et. al., Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders., Nat Commun, 2020
Kuechler A et. al., Bainbridge-Ropers syndrome caused by loss-of-function variants in ASXL3: a recognizable condition., Eur J Hum Genet, 2017
Balasubramanian M et. al., Delineating the phenotypic spectrum of Bainbridge-Ropers syndrome: 12 new patients with de novo, heterozygous, loss-of-function mutations in ASXL3 and review of published literature., J Med Genet, 2017
Bainbridge MN et. al., De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome., Genome Med, 2013
Dillon OJ et. al., Exome sequencing has higher diagnostic yield compared to simulated disease-specific panels in children with suspected monogenic disorders., Eur J Hum Genet, 2018
Srivastava S et. al., Clinical whole exome sequencing in child neurology practice., Ann Neurol, 2014
Zhu X et. al., Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios., Genet Med, 2015
Coe BP et. al., Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity., Nat Genet, 2019
Dinwiddie DL et. al., De novo frameshift mutation in ASXL3 in a patient with global developmental delay, microcephaly, and craniofacial anomalies., BMC Med Genomics, 2013
Guo H et. al., Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model., Mol Autism, 2018
Wayhelova M et. al., Novel de novo frameshift variant in the ASXL3 gene in a child with microcephaly and global developmental delay., Mol Med Rep, 2019
Verhoeven W et. al., Phenotypic characterization of an older adult male with late-onset epilepsy and a novel mutation in ASXL3 shows overlap with the associated Bainbridge-Ropers syndrome., Neuropsychiatr Dis Treat, 2018
Chinen Y et. al., Mild prominence of the Sylvian fissure in a Bainbridge-Ropers syndrome patient with a novel frameshift variant in ASXL3., Clin Case Rep, 2018
Kurul SH et. al., High diagnostic rate of trio exome sequencing in consanguineous families with neurogenetic diseases., Brain, 2021
Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021
Wang Q et. al., De novo nonsense variant in ASXL3 in a Chinese girl causing Bainbridge-Ropers syndrome: A case report and review of literature., Mol Genet Genomic Med, 2022
Brea-Fernández AJ et. al., Trio-based exome sequencing reveals a high rate of the de novo variants in intellectual disability., Eur J Hum Genet, 2022
Miyake N et. al., Molecular diagnosis of 405 individuals with autism spectrum disorder., Eur J Hum Genet, 2023

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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Autism & Developmental Medicine Institute