Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

MBD5

HGNC:20444 (protein-coding gene)

methyl-CpG binding domain protein 5

Unique Cases:
18
Disorders:
ID, ASD, EP, ADHD, SCZ, BD, CP
Last Updated:
November 4, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
MBD5 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
Non-catalytic component of the polycomb repressive deubiquitinase (PR-DUB) complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-120' (H2AK119ub1) (PubMed:24634419). Important for stability of PR-DUB components and stimulating its ubiquitinase activity (PubMed:36180891). As part of the PR-DUB complex, associates with chromatin enriched in histone marks H3K4me1, H3K4me3, and H3K27Ac, but not in H3K27me3 (PubMed:36180891). The PR-DUB complex is an ... (Source: Uniprot)
Previous symbols
No previous symbols
Alias symbols
FLJ11113, KIAA1461
Chromosomal Location
2q23.1
Genomic Coordinates
GRCh37:chr2:148778580-149271046
GRCh38:chr2:148021011-148516971
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

8.24

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.14

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

Strong

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Supportive1 Strong1 Definitive1

Publications:

Zhou WZ et. al., Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype correlations., Hum Mutat, 2019
Tran KT et. al., Genetic landscape of autism spectrum disorder in Vietnamese children., Sci Rep, 2020
Benson KA et. al., A comparison of genomic diagnostics in adults and children with epilepsy and comorbid intellectual disability., Eur J Hum Genet, 2020
O'Roak BJ et. al., Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders., Science, 2012
O'Roak BJ et. al., Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations., Nature, 2012
Girirajan S et. al., Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder., Am J Hum Genet, 2013
Kleefstra T et. al., Disruption of an EHMT1-associated chromatin-modification module causes intellectual disability., Am J Hum Genet, 2012
Coe BP et. al., Refining analyses of copy number variation identifies specific genes associated with developmental delay., Nat Genet, 2014
Hodge JC et. al., Disruption of MBD5 contributes to a spectrum of psychopathology and neurodevelopmental abnormalities., Mol Psychiatry, 2014
Hesse AN et. al., Retrospective genotype-phenotype analysis in a 305 patient cohort referred for testing of a targeted epilepsy panel., Epilepsy Res, 2018
Kushima I et. al., High-resolution copy number variation analysis of schizophrenia in Japan., Mol Psychiatry, 2017
Feliciano P et. al., Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes., NPJ Genom Med, 2019
Carvill GL et. al., Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1., Nat Genet, 2013
Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021

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