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Relevance to Autism

Seven loss-of-function variants in the SETD5 gene, five of which were confirmed as de novo in origin, were identified in affected individuals following screening of 996 individuals with ID in Grozeva et al., 2014; two individuals with de novo LoF SETD5 variants were also identified as autistic in the supplementary material (PMID 24680889). A de novo LoF variant and a de novo likely damaging missense variant in the SETD5 gene were identified in two unrelated ASD probands from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2014 (PMID 25363760); de novo missense variants in SETD5 had previously been observed in ASD probands from simplex families (Neale et al., 2012; Iossifov et al., 2012). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report identified SETD5 as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). De novo LoF or damaging missense variants in SETD5 have also been identified in multiple individuals with developmental delay, intellectual disability, and/or epilepsy in the absence of ASD (PMIDs 23020937, 25138099, 27334371, 28191889, 28549204). Fernandes et al., 2018 reviewed a total of 42 individuals with SETD5 mutations from 17 publications and determined that ten of these individuals presented with autistic features (23.8%). Two de novo protein-truncating variants in SETD5 were identified in ASD probands from the Autism Sequencing Consortium in Satterstrom et al., 2020; additional protein-truncating variants in this gene were observed in case samples from the Danish iPSYCH study in this report. Furthermore, 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 SETD5 as a candidate gene with a false discovery rate (FDR) 0.01. 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 Zhou et al., 2022 identified SETD5 as a gene reaching exome-wide significance (P < 2.5E-06).

Molecular Function

This gene is predicted to encode a methyltransferase and resides within the critical interval for the 3p25 microdeletion syndrome.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
De novo loss-of-function mutations in SETD5, encoding a methyltransferase in a 3p25 microdeletion syndrome critical region, cause intellectual disa...
ID
OCD, ASD
Support
Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands.
Congenital heart disease (CHD)
Neurodevelopmental disorders (NDD)
Support
Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.
ID
Support
Phenotypic and genetic analysis of children with unexplained neurodevelopmental delay and neurodevelopmental comorbidities in a Chinese cohort using trio-based whole-exome sequencing
ASD, DD, ID
Support
De novo variants in neurodevelopmental disorders-experiences from a tertiary care center
ID
Support
SETD5 loss-of-function mutation as a likely cause of a familial syndromic intellectual disability with variable phenotypic expression.
ID
Support
Exome sequencing reveals NAA15 and PUF60 as candidate genes associated with intellectual disability.
DD
Dysmorphic features, MCA
Support
De novo gene disruptions in children on the autistic spectrum.
ASD
Support
The utility of exome sequencing in diagnosing pediatric neurodevelopmental disorders in a highly consanguineous population
DD
Support
Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
ASD, DD
Support
Mutations in HECW2 are associated with intellectual disability and epilepsy.
ID, epilepsy/seizures
Support
DD, ID
ADHD, autistic features
Support
Expanding the genetic heterogeneity of intellectual disability.
ID
ADHD
Support
Patterns and rates of exonic de novo mutations in autism spectrum disorders.
ASD
Support
Decoding complex inherited phenotypes in rare disorders: the DECIPHERD initiative for rare undiagnosed diseases in Chile
ID
Support
SETD5 Gene Haploinsufficiency in Three Patients With Suspected KBG Syndrome
Autosomal dominant mental retardation-23 (MRD23),
ASD
Support
Large-scale discovery of novel genetic causes of developmental disorders.
Unknown diagnosis
Support
SETD5 gene variant associated with mild intellectual disability - a case report.
ID
Support
Comparison of first-tier whole-exome sequencing with a multi-step traditional approach for diagnosing paediatric outpatients: An Italian prospective study
Autosomal dominant intellectual developmental diso
Support
Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism
ASD
Support
Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome.
ID
Support
Genomic insights from a deeply phenotyped highly consanguineous neurodevelopmental disorders cohort
ASD, DD
ADHD, epilepsy/seizures
Support
Integrating de novo and inherited variants in 42
ASD
Support
Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.
DD
Support
Clinical Utility of Proband Only Clinical Exome Sequencing in Neurodevelopmental Disorders
ASD, DD, epilepsy/seizures
Support
A novel mutation in a common pathogenic gene (SETD5) associated with intellectual disability: A case report.
Autosomal dominant mental retardation-23 (MRD23)
DD, ID
Support
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.
ASD
Support
Next-generation phenotyping integrated in a national framework for patients with ultrarare disorders improves genetic diagnostics and yields new molecular findings
DD
Support
Clinical Targeted Panel Sequencing Analysis in Clinical Evaluation of Children with Autism Spectrum Disorder in China
ASD
Support
De novo genic mutations among a Chinese autism spectrum disorder cohort.
ASD
Support
ASD
DD, ID
Support
Exome Pool-Seq in neurodevelopmental disorders.
ID
Hypotonia
Support
Deletion of 3p25.3 in a patient with intellectual disability and dysmorphic features with further definition of a critical region.
ID
Support
Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice
ASD
Support
Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder
ASD
Support
Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnose...
Brain abnormalities
Recent Recommendation
Expansion and further delineation of the SETD5 phenotype leading to global developmental delay, variable dysmorphic features, and reduced penetrance.
DD
ADHD, ASD
Recent Recommendation
Low load for disruptive mutations in autism genes and their biased transmission.
ASD
Recent Recommendation
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Recent Recommendation
Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition.
Recent Recommendation
Genetic variations on SETD5 underlying autistic conditions.
ID
Autistic features
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN607R001 
 stop_gained 
 c.1195A>T 
 p.Lys399Ter 
 De novo 
  
 Simplex 
 GEN607R002 
 stop_gained 
 c.1333C>T 
 p.Arg445Ter 
 Unknown 
 Not maternal 
 Multiplex 
 GEN607R003 
 stop_gained 
 c.1866C>G 
 p.Tyr622Ter 
 Unknown 
 Not maternal 
 Simplex 
 GEN607R004 
 frameshift_variant 
 c.2177_2178del 
 p.Thr726AsnfsTer39 
 De novo 
  
 Simplex 
 GEN607R005 
 stop_gained 
 c.3001C>T 
 p.Arg1001Ter 
 De novo 
  
 Simplex 
 GEN607R006 
 frameshift_variant 
 c.3771dup 
 p.Ser1258GlufsTer65 
 De novo 
  
 Simplex 
 GEN607R007 
 frameshift_variant 
 c.3856del 
 p.Ser1286LeufsTer84 
 De novo 
  
 Simplex 
 GEN607R008 
 missense_variant 
 c.1405G>A 
 p.Val469Ile 
 De novo 
  
 Simplex 
 GEN607R009 
 missense_variant 
 c.2005G>A 
 p.Gly669Arg 
 De novo 
  
 Simplex 
 GEN607R010 
 stop_gained 
 c.2302C>T 
 p.Arg768Ter 
 De novo 
  
 Simplex 
 GEN607R011 
 copy_number_loss 
  
  
 De novo 
  
 Unknown 
 GEN607R012 
 splice_site_variant 
 c.547_567+60del 
  
 De novo 
  
 Simplex 
 GEN607R013 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN607R014 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN607R015 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN607R016 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN607R017 
 stop_gained 
 c.922C>T 
 p.Arg308Ter 
 De novo 
  
 Simplex 
 GEN607R018 
 missense_variant 
 c.1405G>A 
 p.Val469Ile 
 De novo 
  
 Simplex 
 GEN607R019 
 missense_variant 
 c.3773G>C 
 p.Ser1258Thr 
 De novo 
  
 Simplex 
 GEN607R020 
 missense_variant 
 c.2348G>A 
 p.Arg783His 
 Familial 
 Paternal 
 Simplex 
 GEN607R021 
 missense_variant 
 c.2348G>A 
 p.Arg783His 
 Familial 
 Maternal 
 Simplex 
 GEN607R022 
 missense_variant 
 c.1712G>C 
 p.Gly571Ala 
 Familial 
 Paternal 
 Simplex 
 GEN607R023 
 missense_variant 
 c.2006G>C 
 p.Gly669Ala 
 Familial 
 Paternal 
 Simplex 
 GEN607R024 
 missense_variant 
 c.2006G>C 
 p.Gly669Ala 
 Familial 
 Maternal 
 Simplex 
 GEN607R025 
 missense_variant 
 c.2006G>C 
 p.Gly669Ala 
 Familial 
 Maternal 
 Multiplex 
 GEN607R026 
 missense_variant 
 c.2653T>C 
 p.Tyr885His 
 Familial 
 Maternal 
 Simplex 
 GEN607R027 
 missense_variant 
 c.3174G>C 
 p.Gln1058His 
 Familial 
 Maternal 
 Simplex 
 GEN607R028 
 missense_variant 
 c.3817A>C 
 p.Ser1273Arg 
 Familial 
 Maternal 
 Simplex 
 GEN607R029 
 missense_variant 
 c.31A>G 
 p.Thr11Ala 
 Familial 
 Paternal 
 Simplex 
 GEN607R030 
 missense_variant 
 c.2468A>G 
 p.Asp823Gly 
 Familial 
 Maternal 
 Simplex 
 GEN607R031 
 missense_variant 
 c.1374A>T 
 p.Ser458= 
 Familial 
 Paternal 
 Simplex 
 GEN607R032 
 missense_variant 
 c.1550C>T 
 p.Ala517Val 
 Familial 
 Maternal 
 Simplex 
 GEN607R033 
 missense_variant 
 c.4081G>T 
 p.Val1361Phe 
 Familial 
 Paternal 
 Simplex 
 GEN607R034 
 missense_variant 
 c.4115C>T 
 p.Thr1372Ile 
 Familial 
 Paternal 
 Multiplex 
 GEN607R035 
 stop_gained 
 c.598G>T 
 p.Glu200Ter 
 Unknown 
  
 Unknown 
 GEN607R036 
 missense_variant 
 c.1022G>A 
 p.Arg341His 
 Unknown 
  
 Unknown 
 GEN607R037 
 missense_variant 
 c.2348G>A 
 p.Arg783His 
 Unknown 
  
 Unknown 
 GEN607R038 
 missense_variant 
 c.3305G>A 
 p.Gly1102Asp 
 Unknown 
  
 Unknown 
 GEN607R039 
 missense_variant 
 c.3527G>A 
 p.Arg1176Gln 
 Unknown 
  
 Unknown 
 GEN607R040 
 missense_variant 
 c.3635C>T 
 p.Pro1212Leu 
 Unknown 
  
 Unknown 
 GEN607R041 
 missense_variant 
 c.952T>C 
 p.Phe318Leu 
 Unknown 
  
 Unknown 
 GEN607R042 
 missense_variant 
 c.2164C>G 
 p.Pro722Ala 
 Unknown 
  
 Unknown 
 GEN607R043 
 missense_variant 
 c.2351G>A 
 p.Trp784Ter 
 Unknown 
  
 Unknown 
 GEN607R044 
 missense_variant 
 c.2942T>G 
 p.Phe981Cys 
 Unknown 
  
 Unknown 
 GEN607R045 
 missense_variant 
 c.3907G>A 
 p.Ala1303Thr 
 Unknown 
  
 Unknown 
 GEN607R046 
 missense_variant 
 c.367C>T 
 p.Arg123Trp 
 Unknown 
  
 Unknown 
 GEN607R047 
 missense_variant 
 c.2307G>T 
 p.Arg769Ser 
 Unknown 
  
 Unknown 
 GEN607R048 
 missense_variant 
 c.2920G>C 
 p.Asp974His 
 Unknown 
  
 Unknown 
 GEN607R049 
 stop_gained 
 c.3154G>T 
 p.Gly1052Ter 
 De novo 
  
 Unknown 
 GEN607R050 
 stop_gained 
 c.2158G>T 
 p.Glu720Ter 
 De novo 
  
 Simplex 
 GEN607R051 
 frameshift_variant 
  
 p.Thr552AsnfsTer5 
 De novo 
  
  
 GEN607R052 
 stop_gained 
 c.2918C>G 
 p.Ser973Ter 
 Familial 
 Paternal 
 Multiplex 
 GEN607R053 
 splice_site_variant 
 c.1524+1G>A 
  
 Familial 
 Paternal 
  
 GEN607R054 
 missense_variant 
 c.1043G>A 
 p.Arg348Gln 
 De novo 
  
  
 GEN607R055 
 frameshift_variant 
 c.3855dup 
 p.Ser1286LeufsTer37 
 De novo 
  
 Simplex 
 GEN607R056 
 frameshift_variant 
 c.71+1947_71+1948insA 
  
 De novo 
  
  
 GEN607R057 
 splice_site_variant 
 c.1783-2A>T 
  
 De novo 
  
  
 GEN607R058 
 stop_gained 
 c.3001C>T 
 p.Arg1001Ter 
 De novo 
  
  
 GEN607R059 
 frameshift_variant 
 c.71+876dup 
  
 De novo 
  
  
 GEN607R060 
 splice_site_variant 
 c.2347-7A>G 
  
 De novo 
  
  
 GEN607R061 
 splice_site_variant 
 c.2347-7A>G 
  
 De novo 
  
  
 GEN607R062 
 frameshift_variant 
 c.71+2260del 
  
 De novo 
  
  
 GEN607R063 
 frameshift_variant 
 c.3246del 
 p.Ala1083LeufsTer61 
 De novo 
  
  
 GEN607R064 
 frameshift_variant 
 c.71+1947_71+1948insA 
  
 Familial 
 Maternal 
 Simplex 
 GEN607R065 
 splice_site_variant 
 c.2347-7A>G 
  
 De novo 
  
  
 GEN607R066 
 stop_gained 
 c.2955T>A 
 p.Tyr985Ter 
 Familial 
 Maternal 
 Multi-generational 
 GEN607R067 
 frameshift_variant 
 c.71+1186_71+1201del 
  
 Unknown 
  
 Not simplex 
 GEN607R068 
 splice_site_variant 
 c.2476+1G>A 
  
  
  
 Simplex 
 GEN607R069 
 stop_gained 
 c.2302C>T 
 p.Arg768Ter 
 De novo 
  
 Simplex 
 GEN607R070 
 stop_gained 
 c.1333C>T 
 p.Arg445Ter 
 De novo 
  
  
 GEN607R071 
 frameshift_variant 
 c.1125dup 
 p.Val376CysfsTer9 
 De novo 
  
  
 GEN607R072 
 frameshift_variant 
 c.2025_2026del 
 p.Gly676ValfsTer2 
 De novo 
  
 Simplex 
 GEN607R073 
 stop_gained 
 c.814C>T 
 p.Gln272Ter 
 De novo 
  
 Simplex 
 GEN607R074 
 frameshift_variant 
 c.3531_3534del 
 p.Gly1179AlafsTer10 
 De novo 
  
 Simplex 
 GEN607R075 
 intron_variant 
 c.71+904A>G 
  
 De novo 
  
 Simplex 
 GEN607R076 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN607R077 
 frameshift_variant 
 c.959del 
 p.Lys320AsnfsTer15 
 De novo 
  
 Simplex 
 GEN607R078 
 frameshift_variant 
 c.1573_1574del 
 p.Leu525ArgfsTer17 
 De novo 
  
 Simplex 
 GEN607R079 
 frameshift_variant 
 c.1967del 
 p.Leu656Ter 
 De novo 
  
  
 GEN607R080 
 stop_gained 
 c.2644C>T 
 p.Arg882Ter 
 De novo 
  
  
 GEN607R081 
 frameshift_variant 
 c.*3dup 
  
 De novo 
  
  
 GEN607R082 
 missense_variant 
 c.3929C>T 
 p.Ser1310Leu 
 Familial 
 Maternal 
  
 GEN607R083 
 missense_variant 
 c.1022G>A 
 p.Arg341His 
 Familial 
 Paternal 
  
 GEN607R084 
 missense_variant 
 c.1022G>A 
 p.Arg341His 
 Familial 
 Paternal 
  
 GEN607R085 
 missense_variant 
 c.3929C>T 
 p.Ser1310Leu 
 Unknown 
  
  
 GEN607R086 
 missense_variant 
 c.2698C>T 
 p.Arg900Cys 
 Unknown 
  
  
 GEN607R087 
 missense_variant 
 c.2698C>T 
 p.Arg900Cys 
 Unknown 
  
  
 GEN607R088 
 missense_variant 
 c.2269C>T 
 p.Arg757Cys 
 Unknown 
  
  
 GEN607R089 
 missense_variant 
 c.625C>T 
 p.Arg209Trp 
 Unknown 
  
  
 GEN607R090 
 missense_variant 
 c.1763G>A 
 p.Arg588Gln 
 Unknown 
  
  
 GEN607R091 
 missense_variant 
 c.2300G>A 
 p.Arg767His 
 Unknown 
  
  
 GEN607R092 
 missense_variant 
 c.3407C>T 
 p.Ser1136Phe 
 Unknown 
  
  
 GEN607R093 
 missense_variant 
 c.1591C>T 
 p.Arg531Trp 
 Unknown 
  
  
 GEN607R094 
 missense_variant 
 c.3107G>A 
 XP_005265353.1:p.Arg1036Gln 
 Unknown 
  
  
 GEN607R095 
 missense_variant 
 c.2933G>A 
 p.Arg978Gln 
 Unknown 
  
  
 GEN607R096 
 missense_variant 
 c.3106C>T 
 XP_005265353.1:p.Arg1036Trp 
 Unknown 
  
  
 GEN607R097 
 missense_variant 
 c.2932C>T 
 p.Arg978Trp 
 Unknown 
  
  
 GEN607R098 
 missense_variant 
 c.2932C>T 
 p.Arg978Trp 
 Unknown 
  
  
 GEN607R099 
 missense_variant 
 c.1663G>A 
 p.Gly555Ser 
 Unknown 
  
  
 GEN607R100 
 stop_gained 
 c.2734C>T 
 p.Arg912Ter 
 Familial 
 Maternal 
  
 GEN607R101 
 frameshift_variant 
 c.4106dup 
 p.Ser1370GlufsTer10 
 Unknown 
  
  
 GEN607R102 
 frameshift_variant 
 c.4106dup 
 p.Ser1370GlufsTer10 
 Unknown 
  
  
 GEN607R103 
 frameshift_variant 
 c.3066_3087dup 
 p.Glu1030ArgfsTer8 
 Unknown 
  
  
 GEN607R104 
 stop_gained 
 c.1576G>T 
 p.Glu526Ter 
 Unknown 
  
  
 GEN607R105 
 frameshift_variant 
 c.1013_1014del 
 p.Val338GlyfsTer7 
 Unknown 
  
  
 GEN607R106 
 frameshift_variant 
 c.2949del 
 p.Met984CysfsTer7 
 Unknown 
  
  
 GEN607R107 
 frameshift_variant 
 c.4032_4033del 
 p.Ala1345Ter 
 Unknown 
  
  
 GEN607R108 
 splice_site_variant 
 c.1782+1G>T 
  
 Unknown 
  
  
 GEN607R109 
 stop_gained 
 c.195T>A 
 p.Ser65%3D 
 Unknown 
  
  
 GEN607R110 
 stop_gained 
 c.2021T>G 
 p.Leu674Ter 
 Unknown 
  
  
 GEN607R111 
 stop_gained 
 c.2205C>G 
 p.Thr735%3D 
 Unknown 
  
  
 GEN607R112 
 stop_gained 
 c.2644C>T 
 p.Arg882Ter 
 Unknown 
  
  
 GEN607R113 
 stop_gained 
 c.3520C>T 
 p.Arg1174Ter 
 Unknown 
  
  
 GEN607R114 
 missense_variant 
 c.848G>A 
 p.Arg283Gln 
 Familial 
 Maternal 
  
 GEN607R115 
 missense_variant 
 c.2237C>T 
 p.Pro746Leu 
 Unknown 
  
  
 GEN607R116 
 missense_variant 
 c.3731G>A 
 p.Cys1244Tyr 
 Unknown 
  
  
 GEN607R117 
 missense_variant 
 c.1591C>T 
 p.Arg531Trp 
 Unknown 
  
  
 GEN607R118 
 missense_variant 
 c.2416C>T 
 p.Gln806Ter 
 Unknown 
  
  
 GEN607R119 
 missense_variant 
 c.2933G>A 
 p.Arg978Gln 
 Unknown 
  
  
 GEN607R120 
 missense_variant 
 c.1030G>A 
 p.Gly344Ser 
 Unknown 
  
  
 GEN607R121 
 missense_variant 
 c.2348G>A 
 p.Arg783His 
 Unknown 
  
  
 GEN607R122 
 frameshift_variant 
 c.2154del 
 p.Val719LeufsTer18 
 De novo 
  
 Unknown 
 GEN607R123 
 stop_gained 
 c.598G>T 
 p.Glu200Ter 
 Unknown 
  
  
 GEN607R124 
 stop_gained 
 c.814C>T 
 p.Gln272Ter 
 Unknown 
  
  
 GEN607R125 
 missense_variant 
 c.2929T>A 
 p.Phe977Ile 
 Familial 
 Paternal 
  
 GEN607R126 
 missense_variant 
 c.894A>G 
 p.Ile298Met 
 De novo 
  
 Simplex 
 GEN607R127 
 missense_variant 
 c.4216T>A 
 p.Ser1406Thr 
 De novo 
  
  
 GEN607R128 
 missense_variant 
 c.554C>T 
 p.Thr185Met 
 De novo 
  
  
 GEN607R129 
 missense_variant 
 c.977T>C 
 p.Leu326Pro 
 De novo 
  
  
 GEN607R130 
 missense_variant 
 c.2509C>T 
 p.Arg837Cys 
 De novo 
  
  
 GEN607R131 
 missense_variant 
 c.3235A>G 
 p.Lys1079Glu 
 De novo 
  
  
 GEN607R132 
 splice_region_variant 
 c.2347-7A>G 
  
 De novo 
  
  
 GEN607R133 
 frameshift_variant 
 c.2438dup 
 p.Asn814GlufsTer2 
 De novo 
  
  
 GEN607R134 
 missense_variant 
 c.3737G>T 
 p.Ser1246Ile 
 Unknown 
  
 Simplex 
 GEN607R135 
 splice_site_variant 
 c.2476+2T>C 
  
 Unknown 
  
 Simplex 
 GEN607R136 
 frameshift_variant 
 c.2177_2178del 
 p.Thr726AsnfsTer39 
 Unknown 
  
 Simplex 
 GEN607R137 
 missense_variant 
 c.1282C>T 
 p.Pro428Ser 
 Unknown 
  
  
 GEN607R138 
 stop_gained 
 c.922C>T 
 p.Arg308Ter 
 De novo 
  
 Simplex 
 GEN607R139a 
 splice_site_variant 
 c.3196-2A>G 
  
 Familial 
 Both parents 
  
 GEN607R140 
 stop_gained 
 c.2983C>T 
 p.Arg995Ter 
 Unknown 
  
  
 GEN607R141 
 copy_number_loss 
  
  
 Unknown 
  
  
 GEN607R142 
 frameshift_variant 
 c.3855dup 
 p.Ser1286LeufsTer37 
 De novo 
  
 Simplex 
 GEN607R143 
 splice_site_variant 
 c.1783-2A>G 
  
 De novo 
  
  
 GEN607R144 
 stop_gained 
 c.2302C>T 
 p.Arg768Ter 
 De novo 
  
  
 GEN607R145 
 stop_gained 
 c.3556C>T 
 p.Arg1186Ter 
 De novo 
  
  
 GEN607R146 
 missense_variant 
 c.2683A>G 
 p.Met895Val 
 Unknown 
  
  
 GEN607R147 
 missense_variant 
 c.59G>A 
 p.Gly20Glu 
 Unknown 
  
  
 GEN607R148 
 missense_variant 
 c.477A>T 
 p.Glu159Asp 
 Unknown 
  
  
 GEN607R149 
 missense_variant 
 c.2561C>T 
 p.Pro854Leu 
 Unknown 
  
  
 GEN607R150 
 missense_variant 
 c.2683A>G 
 p.Met895Val 
 Unknown 
  
  
 GEN607R151 
 missense_variant 
 c.182G>A 
 p.Arg61Gln 
 Unknown 
  
  
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
3
Deletion-Duplication
 20
 
3
Deletion
 1
 
3
Duplication
 3
 
3
Duplication
 1
 
3
Duplication
 1
 
3
Duplication
 1
 
3
Duplication
 2
 
3
Deletion
 3
 
3
Duplication
 1
 

Model Summary

Setd5 happlodeficient mice show abnormal brain to body weight ratios, neural crest abnormalities, increased LTP, delayed USV, reduced cognitive flexibility, deficits in nest building behavior, and abnormalities in the regulation of gene transcription.

References

Type
Title
Author, Year
Additional
Setd5 is essential for mammalian development and the co-transcriptional regulation of histone acetylation
Primary
Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition.
Additional
Setd5 haploinsufficiency alters neuronal network connectivity and leads to autistic-like behaviors in mice.
Model Type: Genetic
Model Genotype: Homozygous
Mutation: An exchange vector for performing recombinase-mediated cassette exchange was made beginning with pRosa26.Ex1 and inserting a GFP (Emerald)-SV40 poly(A) cassette between SmaI sites located in the first exon of Setd5 resulting in disruption of Setd5 at exon 1.
Allele Type: knockout
Strain of Origin:
Genetic Background: CD-1
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: PMID 27864380
Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Cardiovascular development and function: embryonic1
decreased
 Immunostaining
 E 9.5
Size/growth: embryonic1
decreased
 Macroscopic analysis
 E 10.5
Cardiovascular development and function: embryonic1
abnormal
 Macroscopic analysis
 E 9.5
Mortality/lethality: embryonic1
increased
 General observations
 E 10.5
Embryonic morphology1
abnormal
 Macroscopic analysis
 E 8.5-9.5
Targeted expression1
decreased
 Semi-quantitative PCR (qRT-PCR)
 E 9.5
 Not Reported:


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
ARX aristaless related homeobox 11878 O35085 ChIP
Quill ML , et al. 2011
CCDC85B coiled-coil domain containing 85B 11007 Q15834 Y2H
Rual JF , et al. 2005
CEP70 centrosomal protein 70kDa 80321 Q8NHQ1 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
CHD8 chromodomain helicase DNA binding protein 8 57680 Q9HCK8 CHIP-seq
Cotney J , et al. 2015
DPPA2 Developmental pluripotency-associated protein 2 151871 Q7Z7J5 Y2H
Rual JF , et al. 2005
FMR1 fragile X mental retardation 1 14265 P35922 HITS-CLIP
Darnell JC , et al. 2011
KRT40 keratin 40, type I 125115 Q6A162 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
LDOC1 Protein LDOC1 23641 O95751 Y2H
Venkatesan K , et al. 2008
miR126-5p microRNA 126 406913 N/A in situ hybridization; in silico target prediction; qRT-PCR
Poissonnier L , et al. 2014
miR1265p microRNA 126 406913 N/A Luciferase reporter assay; IP/WB; qRT-PCR
Poissonnier L , et al. 2014
MTUS2 microtubule associated tumor suppressor candidate 2 23281 J3KQA9 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
NAGK N-acetylglucosamine kinase 55577 Q9UJ70 IP; LC-MS/MS
Huttlin EL , et al. 2015
PRMT2 protein arginine methyltransferase 2 3275 P55345 IP; LC-MS/MS
Huttlin EL , et al. 2015
PRR20E Proline-rich protein 20E 122183 P86478 IP; LC-MS/MS
Huttlin EL , et al. 2015
SKAP1 Src kinase-associated phosphoprotein 1 8631 Q86WV1-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
TOP3B topoisomerase (DNA) III beta 8940 O95985 MS; HITS-CLIP
Xu D , et al. 2013
TRAF2 TNF receptor-associated factor 2 7186 Q12933 Y2H
Rual JF , et al. 2005

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