Summary Statistics:
ASD Reports: 43
Recent Reports: 8
Annotated variants: 125
Associated CNVs: 13
Evidence score: 4
Gene Score: 3S
Relevance to Autism
MBD5 was originally identified as a candidate gene in a report describing copy number variation in patients with unexplained mental retardation (Wagenstaller et al., 2007). Since that report, numerous studies have implicated MBD5 haploinsufficiency as being associated with intellectual disability, epilepsy, and autism spectrum disorder (Jaillard et al., 2009; van Bon et al., 2010; Williams et al., 2010; Talkowski et al., 2011). In particular, Talkowski et al. (2011) showed that the MBD5 locus defines the critical region of 2q23.1 microdeletion syndrome and showed significant reduction in MBD5 RNA expression in lymphoblastoid cell lines of individuals with MBD5 deletions. That report also showed association of a missense variant (Gly79Glu) in 6/747 ASD cases compared to 3/3042 controls (P=0.012). More recently, a balanced chromosomal abnormality (BCA) leading to MBD5 disruption was identified in an ASD case (Talkowski et al., 2012). Mullegama et al., 2014 demonstrated that 2q23.1 microduplications affecting the MBD5 gene resulted in a duplication syndrome complementary to the 2q23.1 microdeletion syndrome . De novo likely gene-disruptive/protein-truncating variants in the MBD5 gene have been identified in ASD probands from the Simons Simplex Collection and the Autism Sequencing Consortium (O'Roak et al., 2012; Lim et al., 2017). TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in Satterstrom et al., 2020 identified MBD5 as a candidate gene with a false discovery rate (FDR) 0.01. A de novo loss-of-function variant and several missense variants in the MBD5 gene were reported in ASD proband from the SPARK cohort in Zhou et al., 2022; a two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in this report identified MBD5 as a gene reaching exome-wide significance (P < 2.5E-06).
Molecular Function
This gene encodes a member of the methyl-CpG-binding domain (MBD) family. Mutations in this gene cause mental retardation autosomal dominant type 1. Haploinsufficiency of this gene is associated with a syndrome involving microcephaly, intellectual disabilities, severe speech impairment, and seizures.
References
Primary
Copy-number variations measured by single-nucleotide-polymorphism oligonucleotide arrays in patients with mental retardation.
ID
Support
Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries.
ASD
Support
Genetic landscape of autism spectrum disorder in Vietnamese children
ASD
Support
Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.
Epilepsy
ID, ASD, DD
Support
Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.
ASD
Support
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.
ASD
Support
Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism
ASD
Support
A cryptic microdeletion including MBD5 occurring within the breakpoint of a reciprocal translocation between chromosomes 2 and 5 in a patient with ...
DD
Epilepsy, autistic behaviors
Support
Integrating de novo and inherited variants in 42
ASD
Support
Variable phenotype expression in a family segregating microdeletions of the NRXN1 and MBD5 autism spectrum disorder susceptibility genes.
ASD, ADHD, ID
Macrocephaly
Support
Neurodevelopmental features in 2q23.1 microdeletion syndrome: report of a new patient with intractable seizures and review of literature.
ID
Epilepsy
Support
Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes
ASD
Support
Extended spectrum of MBD5 mutations in neurodevelopmental disorders.
ID
Support
Genetic and Phenotype Analysis of a Chinese Cohort of Infants and Children With Epilepsy
Epilepsy/seizures
Support
Investigation of single-nucleotide variants in MBD5 associated with autism spectrum disorders and schizophrenia phenotypes.
ASD, SCZ
Support
2q23.1 microdeletion of the MBD5 gene in a female with seizures, developmental delay and distinct dysmorphic features.
DD, epilepsy
Support
A novel MBD5 mutation in an intellectually disabled adult female patient with epilepsy: Suggestive of early onset dementia?
ASD, DD, ID, epilepsy/seizures
Support
Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.
ASD
Support
Genome sequencing identifies rare tandem repeat expansions and copy number variants in Lennox-Gastaut syndrome
DD, ID, epilepsy/seizures
Support
Clinical exome sequencing: results from 2819 samples reflecting 1000 families.
ASD, DD
Support
Assessment of 2q23.1 microdeletion syndrome implicates MBD5 as a single causal locus of intellectual disability, epilepsy, and autism spectrum diso...
2q23.1 microdeletion syndrome
DD, epilepsy
Support
Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with develop...
ID, epilepsy/seizures
Microcephaly
Support
The expanding role of MBD genes in autism: identification of a MECP2 duplication and novel alterations in MBD5, MBD6, and SETDB1.
ASD
Support
Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes
MBD5-associated neurodevelopmental disorder (MAND)
Support
The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.
DD, epilepsy/seizures
PDD
Support
The 2q23.1 microdeletion syndrome: clinical and behavioural phenotype.
ID
Support
Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype c...
ASD
Support
Disruption of an EHMT1-associated chromatin-modification module causes intellectual disability.
ID
Support
Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank
ASD
Support
De novo mutations in moderate or severe intellectual disability.
ID, epilepsy/seizures
Absent speech
Support
2q23.1 microdeletion identified by array comparative genomic hybridisation: an emerging phenotype with Angelman-like features?
ID, epilepsy
Autistic behavior
Support
DD, epilepsy/seizures
Stereotypy
Support
Diagnostic exome sequencing identifies a heterozygous MBD5 frameshift mutation in a family with intellectual disability and epilepsy.
Epilepsy/seizures
ASD, ID
Highly Cited
Haploinsufficiency of MBD5 associated with a syndrome involving microcephaly, intellectual disabilities, severe speech impairment, and seizures.
Recent Recommendation
A molecular model for neurodevelopmental disorders.
Recent Recommendation
Phenotypic and molecular convergence of 2q23.1 deletion syndrome with other neurodevelopmental syndromes associated with autism spectrum disorder.
Recent Recommendation
MBD5 haploinsufficiency is associated with sleep disturbance and disrupts circadian pathways common to Smith-Magenis and fragile X syndromes.
2q23.1 microdeletion syndrome
Sleep disturbance
Recent Recommendation
Reciprocal deletion and duplication at 2q23.1 indicates a role for MBD5 in autism spectrum disorder.
ASD
DD, ID
Recent recommendation
Distinct Pathogenic Genes Causing Intellectual Disability and Autism Exhibit a Common Neuronal Network Hyperactivity Phenotype.
Kleefstra syndrome
Recent Recommendation
Disruption of MBD5 contributes to a spectrum of psychopathology and neurodevelopmental abnormalities.
DD, ID
ASD
Recent Recommendation
Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA
ASD
Recent Recommendation
Low load for disruptive mutations in autism genes and their biased transmission.
ASD
GEN345R001
copy_number_loss
Unknown
GEN345R002
missense_variant
c.431C>T
p.Thr144Ile
GEN345R003
missense_variant
c.1382G>A
p.Arg461His
GEN345R004
missense_variant
c.1962C>A
p.Asp654Glu
GEN345R005
missense_variant
c.1963G>A
p.Ala655Thr
Familial
GEN345R006
missense_variant
c.2569G>A
p.Ala857Thr
Familial
GEN345R007
missense_variant
c.3143C>T
p.Thr1048Ile
GEN345R008
synonymous_variant
c.2286C>T
p.His762=
GEN345R009
synonymous_variant
c.3279C>T
p.Val1093=
GEN345R010
copy_number_loss
De novo
GEN345R011
copy_number_loss
De novo
GEN345R012
copy_number_loss
De novo
GEN345R013
copy_number_loss
De novo
GEN345R014
frameshift_variant
c.453_454del
p.Lys151AsnfsTer3
De novo
Simplex
GEN345R015
translocation
De novo
GEN345R016
missense_variant
c.1327G>A
p.Val443Met
Familial
Maternal
Simplex
GEN345R017
missense_variant
c.3740T>C
p.Ile1247Thr
Familial
Paternal
Multiplex
GEN345R018
missense_variant
c.3806A>G
p.Tyr1269Cys
Familial
Paternal
Multiplex
GEN345R019
missense_variant
c.3896G>A
p.Arg1299Gln
Familial
Maternal
Multiplex
GEN345R020
intron_variant
c.114-53T>C
Unknown
Unknown
Unknown
GEN345R021
intron_variant
c.398-22C>A
Unknown
Unknown
Unknown
GEN345R022
synonymous_variant
c.2010C>G
p.Leu670=
Unknown
Unknown
Unknown
GEN345R023
5_prime_UTR_variant
c.-23C>A
Unknown
Unknown
Unknown
GEN345R024
synonymous_variant
c.3930A>G
p.Gln1310=
Unknown
Unknown
Unknown
GEN345R025
splice_site_variant
c.3054+2T>A
Familial
Maternal
Simplex
GEN345R026
copy_number_loss
De novo
Simplex
GEN345R027
copy_number_gain
Familial
Maternal
Simplex
GEN345R028
copy_number_loss
Familial
Paternal
Simplex
GEN345R029
copy_number_loss
De novo
Multiplex (monozygotic twins)
GEN345R030
copy_number_gain
Unknown
GEN345R031
copy_number_loss
De novo
Simplex
GEN345R032
stop_gained
c.440C>G
p.Ser147Ter
De novo
GEN345R033
copy_number_loss
De novo
Simplex
GEN345R034
copy_number_loss
De novo
Unknown
GEN345R035
copy_number_loss
Unknown
Unknown
GEN345R036
copy_number_loss
De novo
Unknown
GEN345R037
copy_number_loss
De novo
Unknown
GEN345R038
copy_number_loss
Unknown
Unknown
GEN345R039
copy_number_loss
Unknown
Unknown
GEN345R040
copy_number_loss
Unknown
Unknown
GEN345R041
copy_number_loss
De novo
Unknown
GEN345R042
copy_number_loss
Unknown
Multiplex
GEN345R043
copy_number_loss
De novo
Unknown
GEN345R044
copy_number_loss
De novo
Unknown
GEN345R045
copy_number_loss
Unknown
Unknown
GEN345R046
copy_number_loss
Unknown
Unknown
GEN345R047
copy_number_loss
Unknown
Unknown
GEN345R048
copy_number_loss
Unknown
Unknown
GEN345R049
copy_number_loss
De novo
Unknown
GEN345R050
complex_structural_alteration
De novo
Unknown
GEN345R051
frameshift_variant
c.150del
p.Thr52HisfsTer31
De novo
Simplex
GEN345R052
copy_number_loss
De novo
GEN345R053
copy_number_gain
Familial
Maternal
Unknown
GEN345R054
copy_number_gain
Familial
Maternal
Unknown
GEN345R055
copy_number_gain
Familial
Maternal
Unknown
GEN345R056
copy_number_gain
Unknown
Unknown
GEN345R057
copy_number_gain
Unknown
Unknown
GEN345R058
copy_number_gain
Unknown
Unknown
GEN345R059
copy_number_gain
Unknown
Unknown
GEN345R060
copy_number_gain
Unknown
Unknown
GEN345R061
copy_number_gain
Unknown
Unknown
GEN345R062
copy_number_gain
Unknown
Unknown
GEN345R063
copy_number_gain
Unknown
Unknown
GEN345R064
copy_number_gain
Unknown
Unknown
GEN345R065
copy_number_gain
Unknown
Unknown
GEN345R066
copy_number_gain
Unknown
Unknown
GEN345R067
copy_number_gain
Unknown
Unknown
GEN345R068
copy_number_gain
Unknown
Unknown
GEN345R069
copy_number_gain
Unknown
Unknown
GEN345R070
copy_number_gain
Unknown
Unknown
GEN345R071
copy_number_gain
Unknown
Unknown
GEN345R072
copy_number_gain
Unknown
Unknown
GEN345R073
copy_number_gain
Unknown
Unknown
GEN345R074
copy_number_gain
Unknown
Unknown
GEN345R075
copy_number_gain
Unknown
Unknown
GEN345R076
copy_number_gain
Unknown
Unknown
GEN345R077
copy_number_gain
Unknown
Unknown
GEN345R078
copy_number_gain
Unknown
Unknown
GEN345R079
copy_number_gain
Unknown
Unknown
GEN345R080
copy_number_gain
Unknown
Unknown
GEN345R081
copy_number_gain
Unknown
Unknown
GEN345R082
copy_number_gain
Unknown
Unknown
GEN345R083
frameshift_variant
p.Thr157GlnfsTer4
De novo
GEN345R084
copy_number_loss
Familial
Paternal
Simplex
GEN345R085
frameshift_variant
c.-25_-12del
De novo
Simplex
GEN345R086
translocation
De novo
GEN345R087
translocation
De novo
GEN345R088
translocation
De novo
GEN345R089
5_prime_UTR_variant
c.-825A>G
Unknown
GEN345R090
5_prime_UTR_variant
c.-443G>A
Familial
Maternal
GEN345R091
5_prime_UTR_variant
c.-286G>A
Unknown
GEN345R092
missense_variant
c.709A>G
p.Ile237Val
Unknown
GEN345R093
missense_variant
c.845G>A
p.Gly282Asp
Familial
Maternal
GEN345R094
missense_variant
c.1862A>T
p.Asn621Ile
Familial
Paternal
GEN345R095
missense_variant
c.1918G>T
p.Gly640Cys
Unknown
Not paternal
GEN345R096
missense_variant
c.2025G>C
p.Met675Ile
Unknown
GEN345R097
missense_variant
c.2173G>T
p.Ala725Ser
Unknown
GEN345R098
missense_variant
c.2550A>G
p.Ile850Met
Unknown
GEN345R099
missense_variant
c.2725C>T
p.His909Tyr
Unknown
GEN345R100
missense_variant
c.2736C>A
p.His912Gln
Unknown
GEN345R101
missense_variant
c.2926T>A
p.Phe976Ile
Unknown
GEN345R102
missense_variant
c.3442A>G
p.Asn1148Asp
Unknown
GEN345R103
missense_variant
c.4045G>A
p.Val1349Met
Unknown
GEN345R104
missense_variant
c.4070G>A
p.Ser1357Asn
Unknown
GEN345R105
frameshift_variant
c.340_347del
p.Lys114GlyfsTer35
De novo
Simplex
GEN345R106
copy_number_loss
Familial
Paternal
Simplex
GEN345R107
stop_gained
c.688C>T
p.Gln230Ter
De novo
Simplex
GEN345R108
frameshift_variant
c.254_255del
p.Arg85AsnfsTer6
Familial
Paternal
Multi-generational
GEN345R109
stop_gained
c.661C>T
p.Leu221=
De novo
GEN345R110
inversion
De novo
GEN345R111
inversion
De novo
GEN345R112
frameshift_variant
c.2173del
p.Ala725ProfsTer20
Unknown
GEN345R113
frameshift_variant
c.2009_2012del
p.Leu670HisfsTer18
De novo
GEN345R114
splice_region_variant
c.4337+8C>A
De novo
Multiplex
GEN345R115
frameshift_variant
c.-299_-298del
De novo
Simplex
GEN345R116
copy_number_loss
Familial
Maternal
GEN345R117
copy_number_loss
Unknown
GEN345R118
stop_gained
c.550C>T
p.Gln184Ter
De novo
GEN345R119
missense_variant
c.1963G>A
p.Ala655Thr
De novo
GEN345R120
missense_variant
c.3632C>T
p.Pro1211Leu
De novo
GEN345R121
stop_gained
c.3685C>T
p.Gln1229Ter
De novo
GEN345R122
missense_variant
c.4972G>A
p.Glu1658Lys
De novo
GEN345R123
stop_gained
c.4170G>A
p.Arg1390%3D
De novo
Simplex
GEN345R124
frameshift_variant
c.2297del
p.Thr766IlefsTer18
Unknown
Simplex
GEN345C001
missense_variant
rs34995577
c.236G>A
p.Gly79Glu
Simons Simplex Collection & Autism Consortium of Boston
Discovery
2
Deletion-Duplication
26
No Animal Model Data Available
Summary Statistics:
Total Interactions: 20
Total Publications: 6
Show all nodes
Hide non-ASD
Interactor Symbol
Interactor Name
Interactor Organism
Entrez ID
Uniprot ID
Interaction Type
Evidence
Reference
APC
adenomatous polyposis coli
324
P25054
Y2H
Bandyopadhyay S , et al. 2010
ASXL2
additional sex combs like 2 (Drosophila)
55252
Q76L83
LC-MS/MS; ChIP
Baymaz HI , et al. 2014
ASXL2
additional sex combs like 2 (Drosophila)
55252
Q76L83
IP; LC-MS/MS
Huttlin EL , et al. 2015
BAP1
BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase)
8314
Q92560
LC-MS/MS; ChIP
Baymaz HI , et al. 2014
BID
BH3 interacting domain death agonist
637
A8ASI8
IP; LC-MS/MS
Huttlin EL , et al. 2015
ETF1
eukaryotic translation termination factor 1
2107
P62495
IP; LC-MS/MS
Huttlin EL , et al. 2015
HDGFRP2
Hepatoma-derived growth factor-related protein 2
84717
Q7Z4V5-2
IP; LC-MS/MS
Huttlin EL , et al. 2015
HMGCS1
3-hydroxy-3-methylglutaryl-CoA synthase 1 (soluble)
3157
Q01581
IP; LC-MS/MS
Huttlin EL , et al. 2015
KDM1B
Lysine-specific histone demethylase 1B
221656
Q8NB78
LC-MS/MS; ChIP
Baymaz HI , et al. 2014
KIAA1549
KIAA1549
57670
Q9HCM3
Y2H
Nakayama M , et al. 2002
LZIC
leucine zipper and CTNNBIP1 domain containing
84328
Q8WZA0
IP; LC-MS/MS
Huttlin EL , et al. 2015
MEF2C
myocyte enhancer factor 2C
4208
Q06413
Y2H
Bandyopadhyay S , et al. 2010
NAA50
N(alpha)-acetyltransferase 50, NatE catalytic subunit
80218
Q9GZZ1
IP; LC-MS/MS
Huttlin EL , et al. 2015
NME2P1
Putative nucleoside diphosphate kinase
O60361
IP; LC-MS/MS
Huttlin EL , et al. 2015
PMVK
Phosphomevalonate kinase
10654
Q15126
IP; LC-MS/MS
Huttlin EL , et al. 2015
SNX3
sorting nexin 3
8724
O60493
IP; LC-MS/MS
Huttlin EL , et al. 2015
UBE2E1
ubiquitin-conjugating enzyme E2E 1
7324
P51965
IP; LC-MS/MS
Huttlin EL , et al. 2015
UBE2T
ubiquitin-conjugating enzyme E2T (putative)
29089
Q9NPD8
IP; LC-MS/MS
Huttlin EL , et al. 2015
FMR1
fragile X mental retardation 1
14265
P35922
HITS-CLIP
Darnell JC , et al. 2011
Sap18
Sin3-associated polypeptide 18
20220
O55128
IP/WB
Anderson DM , et al. 2009