Summary Statistics:
Gene Score: 4S
Relevance to Autism
A de novo nonsense variant in the PPM1D gene was identifed in an ASD proband from the Simons Simplex Collection in Sanders et al., 2012. Detailed phenotypic characterization of this proband, along with 13 other individuals with truncating variants in the last 2 exons of the PPM1D gene, in Jansen et al., 2017 identified an intellectual disability syndrome; behavioral problems were observed in 11/14 individuals, with ASD reported in 4/14 individuals in this report.
Molecular Function
The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. The expression of this gene is induced in a p53-dependent manner in response to various environmental stresses. While being induced by tumor suppressor protein TP53/p53, this phosphatase negatively regulates the activity of p38 MAP kinase, MAPK/p38, through which it reduces the phosphorylation of p53, and in turn suppresses p53-mediated transcription and apoptosis. This phosphatase thus mediates a feedback regulation of p38-p53 signaling that contributes to growth inhibition and the suppression of stress induced apoptosis.
References
Primary
De novo mutations revealed by whole-exome sequencing are strongly associated with autism.
ASD
Support
Novel truncating PPM1D mutation in a patient with intellectual disability.
Intellectual developmental disorder with gastroint
Support
A Statistical Framework for Mapping Risk Genes from De Novo Mutations in Whole-Genome-Sequencing Studies.
ASD
Support
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Support
Identification of ultra-rare genetic variants in pediatric acute onset neuropsychiatric syndrome (PANS) by exome and whole genome sequencing
Pediatric Acute-Onset Neuropsychiatric Syndrome (P
DD
Support
Short stature leads to a diagnosis of Jansen-de Vries syndrome in two unrelated Taiwanese girls: A case report and literature review
Jansen-de Vries syndrome, DD
ID
Support
Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder
ASD
Support
Two unrelated girls with intellectual disability associated with a truncating mutation in the PPM1D penultimate exon.
Intellectual developmental disorder with gastroint
DD
Recent Recommendation
Jansen-de Vries syndrome, DD, ID
ADHD, autistic features
Recent Recommendation
De Novo Truncating Mutations in the Last and Penultimate Exons of PPM1D Cause an Intellectual Disability Syndrome.
ID
ASD
GEN901R001
stop_gained
c.1281G>A
p.Trp427Ter
De novo
Simplex
GEN901R002
stop_gained
c.1221T>A
p.Cys407Ter
De novo
Simplex
GEN901R003
frameshift_variant
c.988del
p.Gln330ArgfsTer9
De novo
Simplex
GEN901R004
splice_site_variant
c.1033dup
p.Ser345PhefsTer23
De novo
GEN901R005
stop_gained
c.1210C>T
p.Gln404Ter
De novo
GEN901R006
frameshift_variant
c.1041_1042dup
p.Lys348ThrfsTer5
De novo
GEN901R007
stop_gained
c.1339G>T
p.Glu447Ter
De novo
Simplex
GEN901R008
frameshift_variant
c.960_963del
p.Pro321HisfsTer17
De novo
Simplex
GEN901R009
frameshift_variant
c.1022dup
p.His342AlafsTer26
De novo
Simplex
GEN901R010
frameshift_variant
c.1045dup
p.Met349AsnfsTer19
De novo
GEN901R011
frameshift_variant
c.1045dup
p.Met349AsnfsTer19
De novo
Simplex
GEN901R012
stop_gained
c.1281G>A
p.Trp427Ter
De novo
Simplex
GEN901R013
stop_gained
c.1654C>T
p.Arg552Ter
Unknown
GEN901R014
frameshift_variant
c.1176_1183del
p.Leu393AspfsTer2
De novo
Simplex
GEN901R015
stop_gained
c.1057C>T
p.Arg353Ter
Familial
Maternal
GEN901R016
stop_gained
c.1057C>T
p.Arg353Ter
Familial
Paternal
GEN901R017
missense_variant
c.1091G>A
p.Arg364Gln
Familial
Paternal
GEN901R018
missense_variant
c.1525G>C
p.Asp509His
Familial
Maternal
GEN901R019
frameshift_variant
c.1565_1566dup
p.Ala523LysfsTer17
Unknown
GEN901R020
missense_variant
c.1525G>C
p.Asp509His
Unknown
GEN901R021
frameshift_variant
c.1260+137del
De novo
Simplex
GEN901R022
loss_of_function_variant
De novo
GEN901R023
regulatory_region_variant
De novo
GEN901R024
frameshift_variant
c.1022_1023insACCA
p.His342ProfsTer27
De novo
Simplex
GEN901R025
frameshift_variant
c.1028_1029insCAAG
p.Gln344LysfsTer25
De novo
Simplex
GEN901R026
frameshift_variant
c.1565_1566dup
p.Ala523LysfsTer17
Unknown
GEN901R027
frameshift_variant
c.1277dup
p.Trp427MetfsTer7
De novo
GEN901R028
frameshift_variant
c.1270dup
p.Glu424GlyfsTer10
De novo
GEN901R029
missense_variant
c.131C>G
p.Ser44Trp
Familial
Multiplex
GEN901R030
stop_gained
c.1547C>G
p.Ser516Ter
De novo
GEN901R031
stop_gained
c.1654C>T
p.Arg552Ter
De novo
GEN901R032
stop_gained
c.1210C>T
p.Gln404Ter
De novo
GEN901R033
stop_gained
c.1281G>A
p.Trp427Ter
De novo
GEN901R034
frameshift_variant
c.1269_1270del
p.Glu424GlyfsTer9
De novo
GEN901R035
frameshift_variant
c.1278dup
p.Trp427MetfsTer7
De novo
GEN901R036
frameshift_variant
c.1204_1208del
p.Asn402SerfsTer30
De novo
GEN901R037
stop_gained
c.1270G>T
p.Glu424Ter
De novo
GEN901R038
stop_gained
c.1280G>A
p.Trp427Ter
De novo
GEN901R039
stop_gained
c.1280G>A
p.Trp427Ter
De novo
GEN901R040
stop_gained
c.1262C>A
p.Ser421Ter
Familial
Maternal
GEN901R041
frameshift_variant
c.1269_1270del
p.Glu424GlyfsTer9
De novo
GEN901R042
stop_gained
c.1280G>A
p.Trp427Ter
De novo
GEN901R043
stop_gained
c.1210C>T
p.Gln404Ter
De novo
GEN901R044
frameshift_variant
c.1444del
p.Leu482Ter
De novo
GEN901R045
frameshift_variant
c.1535del
p.Asn512IlefsTer2
De novo
GEN901R046
stop_gained
c.1262C>A
p.Ser421Ter
De novo
GEN901R047
stop_gained
c.1573G>T
p.Glu525Ter
De novo
GEN901R048
stop_gained
c.1210C>T
p.Gln404Ter
De novo
GEN901R049
stop_gained
c.1573G>T
p.Glu525Ter
Familial
Maternal
GEN901R050
frameshift_variant
c.1212del
p.Glu405LysfsTer4
Unknown
GEN901R051
stop_gained
c.1349T>G
p.Leu450Ter
De novo
GEN901R052
stop_gained
c.1270G>T
p.Glu424Ter
De novo
GEN901R053
frameshift_variant
c.1200del
p.Tyr401IlefsTer8
De novo
GEN901R054
frameshift_variant
c.1272_1273dup
p.Asp425GlyfsTer7
De novo
GEN901R055
stop_gained
c.1547C>G
p.Ser516Ter
De novo
GEN901R056
frameshift_variant
c.1225_1226del
p.Met409AspfsTer24
De novo
GEN901R057
frameshift_variant
c.1188_1191del
p.Asp397AlafsTer11
Familial
Paternal
GEN901R058
frameshift_variant
c.1387_1388insTA
p.Gly463ValfsTer3
De novo
GEN901R059
frameshift_variant
c.1606del
p.Arg536GlyfsTer3
Familial
Maternal
GEN901R060
frameshift_variant
c.1259dup
p.Ser421ValfsTer13
De novo
GEN901R061
stop_gained
c.1210C>T
p.Gln404Ter
De novo
GEN901R062
stop_gained
c.1281G>A
p.Trp427Ter
De novo
GEN901R063
stop_gained
c.1451T>G
p.Leu484Ter
De novo
GEN901R064
stop_gained
c.1280G>A
p.Trp427Ter
De novo
No Common Variants Available
No Interactions Available
