Summary Statistics:
Gene Score: 4S
Relevance to Autism
Three de novo variants in the ZNF462 gene (one frameshift, two missense) have been identified in simplex ASD cases, with no de novo events in this gene observed in 1,786 unaffected siblings from the Simons Simplex Collection (P=4.03 x 10-3) (De Rubeis et al., 2014; Iossifov et al., 2014; Krumm et al., 2015). Weiss et al., 2017 reported eight subjects from six families with predicted loss of function variants in ZNF462 and overlapping phenotypes including developmental delay, ptosis, metopic ridging, craniosynostosis, and dysgenesis of the corpus callosum; two of the subjects identified in this report were additionally diagnosed with ASD, while another subject exhibited autistic features (hand flapping and inability to demonstrate joint attention or reciprocal play).
Molecular Function
The protein encoded by this gene may be involved in transcriptional regulation (by similarity).
References
Primary
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Support
The contribution of de novo coding mutations to autism spectrum disorder
ASD
Support
Combining exome/genome sequencing with data repository analysis reveals novel gene-disease associations for a wide range of genetic disorders
DD
ID, epilepsy/seizures
Support
Phenotype delineation of ZNF462 related syndrome.
DD
ASD
Support
Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort.
ASD
Support
ZNF462 and KLF12 are disrupted by a de novo translocation in a patient with syndromic intellectual disability and autism spectrum disorder.
ASD, ID
Support
Weiss-Kruszka syndrome, ID
Support
Genomic diagnosis for children with intellectual disability and/or developmental delay.
ASD, ID
Support
Excess of rare, inherited truncating mutations in autism.
ASD
Support
Integrating de novo and inherited variants in 42
ASD
Recent Recommendation
Haploinsufficiency of ZNF462 is associated with craniofacial anomalies, corpus callosum dysgenesis, ptosis, and developmental delay.
DD
ASD or autistic features
Recent Recommendation
Low load for disruptive mutations in autism genes and their biased transmission.
ASD
GEN729R001
frameshift_variant
c.3549del
p.His1183GlnfsTer22
De novo
Simplex
GEN729R002
missense_variant
c.5848C>A
p.Pro1950Thr
De novo
Simplex
GEN729R003
missense_variant
c.5426C>T
p.Ala1809Val
De novo
Simplex
GEN729R004
stop_gained
c.3787C>T
p.Arg1263Ter
Familial
Paternal
Multiplex
GEN729R005
frameshift_variant
c.2979_2980delinsA
p.Val994TrpfsTer147
De novo
Simplex
GEN729R006
frameshift_variant
c.3252+1011del
De novo
Simplex
GEN729R007
copy_number_loss
De novo
Simplex
GEN729R008
copy_number_loss
De novo
Simplex
GEN729R009
frameshift_variant
c.3253-1468del
De novo
Simplex
GEN729R010
missense_variant
c.5680T>G
p.Cys1894Gly
De novo
GEN729R011
translocation
De novo
Simplex
GEN729R012
missense_variant
c.3253-1215G>A
Unknown
Simplex
GEN729R013
stop_gained
c.2590C>T
p.Arg864Ter
Familial
Maternal
GEN729R014
frameshift_variant
c.2542del
p.Cys848ValfsTer66
De novo
GEN729R015
frameshift_variant
c.831_834del
p.Arg277SerfsTer26
De novo
GEN729R016
frameshift_variant
c.3436_3437del
p.Arg1146GlufsTer41
De novo
GEN729R017
stop_gained
c.763C>T
p.Arg255Ter
Familial
Paternal
Simplex
GEN729R018
splice_site_variant
c.7057-2A>G
De novo
GEN729R019
frameshift_variant
c.4016dup
p.Ser1340GlufsTer28
De novo
GEN729R020
frameshift_variant
c.882dup
p.Ser295GlnfsTer64
De novo
GEN729R021
stop_gained
c.4165C>T
p.Gln1389Ter
De novo
GEN729R022
frameshift_variant
c.1234_1235insAA
p.Ser412Ter
Unknown
GEN729R023
frameshift_variant
c.3436_3437del
p.Arg1146GlufsTer41
De novo
GEN729R024
frameshift_variant
c.2049dup
p.Pro684SerfsTer14
De novo
GEN729R025
frameshift_variant
c.3854del
p.Pro1285GlnfsTer7
De novo
GEN729R026
stop_gained
c.2695G>T
p.Glu899Ter
Unknown
Not maternal
GEN729R027
stop_gained
c.1855C>T
p.Gln619Ter
De novo
Simplex
GEN729R028
stop_gained
c.1615C>T
p.Gln539Ter
De novo
Simplex
GEN729R029
missense_variant
c.6619A>G
p.Arg2207Gly
De novo
GEN729R030
inframe_deletion
c.2075_2077del
p.Lys692del
De novo
Simplex
GEN729R031
missense_variant
c.6124C>A
p.Arg2042Ser
De novo
Multiplex
GEN729R032
stop_gained
c.466G>T
p.Glu156Ter
De novo
GEN729R033
missense_variant
c.2804C>T
p.Pro935Leu
De novo
GEN729R034
frameshift_variant
c.6174_6175del
p.Cys2059LeufsTer7
De novo
GEN729R035
synonymous_variant
c.7266G>A
p.Ala2422%3D
De novo
GEN729R036
frameshift_variant
c.2253_2254dup
p.Pro752LeufsTer12
De novo
Simplex
No Common Variants Available
No Interactions Available
