Human Gene Module / Chromosome 3 / ZBTB20

ZBTB20Zinc finger and BTB domain containing 20

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
8 / 32
Rare Variants / Common Variants
67 / 0
Aliases
ZBTB20, RP11-553L6.5,  DPZF,  HOF,  ODA-8S,  ZNF288
Associated Syndromes
3q13.31 microdeletion syndrome, Primrose syndrome, Primrose syndrome, DD, Primrose syndrome, DD, ID
Chromosome Band
3q13.31
Associated Disorders
DD/NDD, ADHD, ID, ASD
Relevance to Autism

Missense variants in the ZBTB20 gene were identified in eight patients with Primrose syndrome (MIM 259050), a condition characterized by increased growth of the brain and body height, intellectual disability, autism, and other behavioral concerns. Four of the Primrose syndrome patients that were identified with ZBTB20 missense variants also presented with autism (Cordeddu et al., 2014). ZBTB20 lies within the minimum region of overlap for 3q13.31 (del3q13.31) microdeletion syndrome (MIM 615433), a multisystem disorder characterized by increased postnatal growth, hypotonia, intellectual disability, disturbed behavior, and unusual facial features, as well as autism in some cases (Molin et al., 2012; Shuvarikov et al., 2013).

Molecular Function

May be a transcription factor that may be involved in hematopoiesis, oncogenesis, and immune responses. ZBTB20 has been shown to act as a cell-fate determinant for CA1 pyramidal neurons in the hippocampus (Xie et al., 2010; Ren et al., 2012).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ZBTB20 (32 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Hippocampus-like corticoneurogenesis induced by two isoforms of the BTB-zinc finger gene Zbtb20 in mice Nielsen JV , et al. (2007) No -
2 Support Zbtb20-induced CA1 pyramidal neuron development and area enlargement in the cerebral midline cortex of mice Nielsen JV , et al. (2009) No -
3 Support Zbtb20 is essential for the specification of CA1 field identity in the developing hippocampus Xie Z , et al. (2010) No -
4 Support A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic facial features Molin AM , et al. (2011) No DD, ASD
5 Support Regulation of hippocampus-dependent memory by the zinc finger protein Zbtb20 in mature CA1 neurons Ren A , et al. (2012) No -
6 Support Recurrent HERV-H-mediated 3q13.2-q13.31 deletions cause a syndrome of hypotonia and motor, language, and cognitive delays Shuvarikov A , et al. (2013) No ID, ASD
7 Primary Mutations in ZBTB20 cause Primrose syndrome Cordeddu V , et al. (2014) No ID, ASD
8 Recent Recommendation Neurodevelopmental disorders associated with dosage imbalance of ZBTB20 correlate with the morbidity spectrum of ZBTB20 candidate target genes Rasmussen MB , et al. (2014) No ASD, ADHD, TS
9 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
10 Support Novel de novo mutations in ZBTB20 in Primrose syndrome with congenital hypothyroidism Mattioli F , et al. (2016) No -
11 Recent Recommendation Zbtb20 modulates the sequential generation of neuronal layers in developing cortex Tonchev AB , et al. (2016) No -
12 Support Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnosed diseases Farwell Hagman KD , et al. (2016) No -
13 Support High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing Martnez F , et al. (2016) No ID, autistic behavior
14 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior Doan RN , et al. (2016) Yes -
15 Support The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies Redin C , et al. (2016) Yes ADHD, TS
16 Support Lessons learned from additional research analyses of unsolved clinical exome cases Eldomery MK , et al. (2017) No -
17 Support Novel de novo ZBTB20 mutations in three cases with Primrose syndrome and constant corpus callosum anomalies Alby C , et al. (2018) No DD, ID, behavioral problems
18 Support Clinical and functional characterization of two novel ZBTB20 mutations causing Primrose syndrome Stellacci E , et al. (2018) No DD, macrocephaly
19 Recent Recommendation Neurodevelopmental disorder-associated ZBTB20 gene variants affect dendritic and synaptic structure Jones KA , et al. (2018) No -
20 Support Refining the Primrose syndrome phenotype: A study of five patients with ZBTB20 de novo variants and a review of the literature Cleaver R , et al. (2019) No -
21 Support Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort Callaghan DB , et al. (2019) Yes -
22 Support Expansion of the Primrose syndrome phenotype through the comparative analysis of two new case reports with ZBTB20 variants Ferreira LD , et al. (2019) No ASD
23 Support Primrose syndrome: a phenotypic comparison of patients with a ZBTB20 missense variant versus a 3q13.31 microdeletion including ZBTB20 Juven A , et al. (2020) No ASD, ADHD
24 Support Primrose syndrome: Characterization of the phenotype in 42 patients Melis D et al. (2020) No ASD, ADHD
25 Support Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability Chevarin M et al. (2020) No Marfanoid habitus
26 Support - Trakadis Y et al. (2021) Yes DD
27 Support - Li D et al. (2022) Yes -
28 Support - Woodbury-Smith M et al. (2022) Yes -
29 Support - Zhou X et al. (2022) Yes -
30 Support - Jiayi Li et al. (2024) No Autistic behavior
31 Support - M Cecilia Poli et al. () No -
32 Support - Ruohao Wu et al. (2024) Yes -
Rare Variants   (67)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - inversion De novo - - 27841880 Redin C , et al. (2016)
- - translocation De novo - - 27841880 Redin C , et al. (2016)
- - translocation De novo - - 25062845 Rasmussen MB , et al. (2014)
- - copy_number_loss De novo - - 25062845 Rasmussen MB , et al. (2014)
- - copy_number_loss De novo - Simplex 32071410 Juven A , et al. (2020)
c.*312del - frameshift_variant De novo - - 32266967 Melis D et al. (2020)
c.278C>A p.Thr93Asn stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.*953_*955del - inframe_deletion De novo - - 32266967 Melis D et al. (2020)
c.-309-27710G>A - intron_variant - - Unknown 27667684 Doan RN , et al. (2016)
c.-349-27829del - intron_variant - - Unknown 27667684 Doan RN , et al. (2016)
c.235C>T p.His79Tyr missense_variant Unknown - - 34968013 Li D et al. (2022)
c.152C>G p.Ser51Ter stop_gained De novo - - 34363551 Trakadis Y et al. (2021)
c.*135del - frameshift_variant De novo - - 29737001 Stellacci E , et al. (2018)
- p.Arg2284Ter stop_gained De novo - - 27513193 Farwell Hagman KD , et al. (2016)
c.1739G>A p.Cys580Tyr missense_variant De novo - - 32266967 Melis D et al. (2020)
c.1760T>C p.Phe587Ser missense_variant De novo - - 32266967 Melis D et al. (2020)
c.1766C>A p.Ala589Asp missense_variant De novo - - 32266967 Melis D et al. (2020)
c.1794C>G p.Phe598Leu missense_variant De novo - - 32266967 Melis D et al. (2020)
c.1813C>T p.Pro605Ser missense_variant Unknown - - 32266967 Melis D et al. (2020)
c.1871A>C p.His624Pro missense_variant Unknown - - 32266967 Melis D et al. (2020)
c.1873A>G p.Met625Val missense_variant De novo - - 32266967 Melis D et al. (2020)
c.1898C>T p.Ala633Val missense_variant De novo - - 32266967 Melis D et al. (2020)
c.*677del - frameshift_variant Unknown Not paternal - 32266967 Melis D et al. (2020)
c.1832G>C p.Cys611Ser missense_variant De novo - - 27620904 Martnez F , et al. (2016)
c.1749C>G p.Cys583Trp missense_variant De novo - - 30637921 Cleaver R , et al. (2019)
c.1850T>C p.Leu617Ser missense_variant De novo - - 30637921 Cleaver R , et al. (2019)
c.1879A>G p.Thr627Ala missense_variant De novo - - 30637921 Cleaver R , et al. (2019)
c.1943C>T p.Ser648Phe missense_variant De novo - - 30637921 Cleaver R , et al. (2019)
c.1967A>G p.His656Arg missense_variant De novo - - 30637921 Cleaver R , et al. (2019)
c.1805G>A p.Gly602Asp missense_variant De novo - - 38177409 M Cecilia Poli et al. ()
c.1768A>C p.Lys590Gln missense_variant De novo - - 25017102 Cordeddu V , et al. (2014)
c.1771C>G p.Gln591Glu missense_variant De novo - - 25017102 Cordeddu V , et al. (2014)
c.1787A>G p.His596Arg missense_variant De novo - - 25017102 Cordeddu V , et al. (2014)
c.1802C>T p.Thr601Ile missense_variant De novo - - 25017102 Cordeddu V , et al. (2014)
c.1805G>C p.Gly602Ala missense_variant De novo - - 25017102 Cordeddu V , et al. (2014)
c.1811A>C p.Lys604Thr missense_variant De novo - - 25017102 Cordeddu V , et al. (2014)
c.1861C>T p.Leu621Phe missense_variant De novo - - 25017102 Cordeddu V , et al. (2014)
c.1876G>A p.Val626Met missense_variant Unknown - - 25017102 Cordeddu V , et al. (2014)
c.1856del p.Asp619ValfsTer8 frameshift_variant Unknown - - 34968013 Li D et al. (2022)
c.1931C>T p.Thr644Ile missense_variant De novo - - 29737001 Stellacci E , et al. (2018)
c.1822T>C p.Cys608Arg missense_variant De novo - - 31321892 Ferreira LD , et al. (2019)
c.1832G>A p.Cys611Tyr missense_variant De novo - Simplex 29681083 Alby C , et al. (2018)
c.1837C>T p.Arg613Cys missense_variant De novo - Simplex 29681083 Alby C , et al. (2018)
c.1906T>C p.Cys636Arg missense_variant De novo - Simplex 29681083 Alby C , et al. (2018)
c.1760T>G p.Phe587Cys missense_variant De novo - Simplex 32071410 Juven A , et al. (2020)
c.1817A>C p.His606Pro missense_variant De novo - Simplex 32071410 Juven A , et al. (2020)
c.1837C>T p.Arg613Cys missense_variant De novo - Simplex 32071410 Juven A , et al. (2020)
c.1862T>C p.Leu621Pro missense_variant De novo - Simplex 32071410 Juven A , et al. (2020)
c.1939A>C p.Ser647Arg missense_variant De novo - Simplex 32071410 Juven A , et al. (2020)
c.1955A>G p.His652Arg missense_variant De novo - Simplex 32071410 Juven A , et al. (2020)
c.1927T>A p.Phe643Ile missense_variant De novo - Simplex 38087819 Jiayi Li et al. (2024)
c.1906T>C p.Cys636Arg missense_variant De novo - Simplex 38764027 Ruohao Wu et al. (2024)
c.-505-1G>A - splice_site_variant Unknown - Multiplex 31038196 Callaghan DB , et al. (2019)
- - copy_number_loss De novo - Multiplex (monozygotic twins) 32071410 Juven A , et al. (2020)
c.1862T>C p.Leu621Pro missense_variant De novo - Simplex 32277047 Chevarin M et al. (2020)
c.626A>G p.Gln209Arg missense_variant Unknown Not maternal - 32266967 Melis D et al. (2020)
c.1847C>T p.Ser616Phe missense_variant De novo - Simplex 27061120 Mattioli F , et al. (2016)
c.2221G>A p.Gly741Arg missense_variant De novo - Simplex 27061120 Mattioli F , et al. (2016)
c.2073C>T p.Pro691%3D synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1786C>T p.His596Tyr missense_variant De novo - Simplex 28327206 Eldomery MK , et al. (2017)
c.8707A>G p.Ser2903Gly missense_variant De novo - - 27513193 Farwell Hagman KD , et al. (2016)
c.1873A>G p.Met625Val missense_variant Unknown Not maternal - 31321892 Ferreira LD , et al. (2019)
c.172_178delinsAA p.Ser58AsnfsTer7 frameshift_variant De novo - Simplex 32071410 Juven A , et al. (2020)
c.-350+33132G>T - intron_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
c.1020C>G p.Tyr340Ter stop_gained De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
c.1723A>T p.Lys575Ter stop_gained De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
c.286G>C p.Glu96Gln missense_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants  

No common variants reported.

SFARI Gene score
1S

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2020
1
icon
1

Score remained at 1

Description

Missense variants in the ZBTB20 gene were recently identified in eight patients diagnosed with Primrose syndrome; seven of these variants were de novo in origin, and six of these variants were experimentally shown to have functional effects (i.e. reduced promoter binding and impaired function in repressing reporter expression) in a dominant-negative manner. These missense variants were not observed in public or in-house databases. Two of the patients diagnosed with Primrose syndrome that carried de novo functional missense variants were reported in the supplementary material as also presenting with autism (PMID 25017102). ZBTB20 also resides within the critical region for 3q13.31 deletion syndrome, a multisystem disorder marked by intellectual disability, disturbed behavior, and other features (PMID 22180640, PMID 23878096).

Reports Added
[Primrose syndrome: Characterization of the phenotype in 42 patients2020] [Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability2020]
1/1/2020
1
icon
1

Score remained at 1

Description

Missense variants in the ZBTB20 gene were recently identified in eight patients diagnosed with Primrose syndrome; seven of these variants were de novo in origin, and six of these variants were experimentally shown to have functional effects (i.e. reduced promoter binding and impaired function in repressing reporter expression) in a dominant-negative manner. These missense variants were not observed in public or in-house databases. Two of the patients diagnosed with Primrose syndrome that carried de novo functional missense variants were reported in the supplementary material as also presenting with autism (PMID 25017102). ZBTB20 also resides within the critical region for 3q13.31 deletion syndrome, a multisystem disorder marked by intellectual disability, disturbed behavior, and other features (PMID 22180640, PMID 23878096).

Reports Added
[Primrose syndrome: a phenotypic comparison of patients with a ZBTB20 missense variant versus a 3q13.31 microdeletion including ZBTB20.2020]
10/1/2019
3S
icon
1

Decreased from 3S to 1

New Scoring Scheme
Description

Missense variants in the ZBTB20 gene were recently identified in eight patients diagnosed with Primrose syndrome; seven of these variants were de novo in origin, and six of these variants were experimentally shown to have functional effects (i.e. reduced promoter binding and impaired function in repressing reporter expression) in a dominant-negative manner. These missense variants were not observed in public or in-house databases. Two of the patients diagnosed with Primrose syndrome that carried de novo functional missense variants were reported in the supplementary material as also presenting with autism (PMID 25017102). ZBTB20 also resides within the critical region for 3q13.31 deletion syndrome, a multisystem disorder marked by intellectual disability, disturbed behavior, and other features (PMID 22180640, PMID 23878096).

Reports Added
[New Scoring Scheme]
7/1/2019
3S
icon
3S

Decreased from 3S to 3S

Description

Missense variants in the ZBTB20 gene were recently identified in eight patients diagnosed with Primrose syndrome; seven of these variants were de novo in origin, and six of these variants were experimentally shown to have functional effects (i.e. reduced promoter binding and impaired function in repressing reporter expression) in a dominant-negative manner. These missense variants were not observed in public or in-house databases. Two of the patients diagnosed with Primrose syndrome that carried de novo functional missense variants were reported in the supplementary material as also presenting with autism (PMID 25017102). ZBTB20 also resides within the critical region for 3q13.31 deletion syndrome, a multisystem disorder marked by intellectual disability, disturbed behavior, and other features (PMID 22180640, PMID 23878096).

Reports Added
[Expansion of the Primrose syndrome phenotype through the comparative analysis of two new case reports with ZBTB20 variants.2019]
4/1/2019
3S
icon
3S

Decreased from 3S to 3S

Description

Missense variants in the ZBTB20 gene were recently identified in eight patients diagnosed with Primrose syndrome; seven of these variants were de novo in origin, and six of these variants were experimentally shown to have functional effects (i.e. reduced promoter binding and impaired function in repressing reporter expression) in a dominant-negative manner. These missense variants were not observed in public or in-house databases. Two of the patients diagnosed with Primrose syndrome that carried de novo functional missense variants were reported in the supplementary material as also presenting with autism (PMID 25017102). ZBTB20 also resides within the critical region for 3q13.31 deletion syndrome, a multisystem disorder marked by intellectual disability, disturbed behavior, and other features (PMID 22180640, PMID 23878096).

Reports Added
[Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort.2019]
1/1/2019
3S
icon
3S

Decreased from 3S to 3S

Description

Missense variants in the ZBTB20 gene were recently identified in eight patients diagnosed with Primrose syndrome; seven of these variants were de novo in origin, and six of these variants were experimentally shown to have functional effects (i.e. reduced promoter binding and impaired function in repressing reporter expression) in a dominant-negative manner. These missense variants were not observed in public or in-house databases. Two of the patients diagnosed with Primrose syndrome that carried de novo functional missense variants were reported in the supplementary material as also presenting with autism (PMID 25017102). ZBTB20 also resides within the critical region for 3q13.31 deletion syndrome, a multisystem disorder marked by intellectual disability, disturbed behavior, and other features (PMID 22180640, PMID 23878096).

Reports Added
[Refining the Primrose syndrome phenotype: A study of five patients with ZBTB20 de novo variants and a review of the literature.2019]
10/1/2018
3S
icon
3S

Decreased from 3S to 3S

Description

Missense variants in the ZBTB20 gene were recently identified in eight patients diagnosed with Primrose syndrome; seven of these variants were de novo in origin, and six of these variants were experimentally shown to have functional effects (i.e. reduced promoter binding and impaired function in repressing reporter expression) in a dominant-negative manner. These missense variants were not observed in public or in-house databases. Two of the patients diagnosed with Primrose syndrome that carried de novo functional missense variants were reported in the supplementary material as also presenting with autism (PMID 25017102). ZBTB20 also resides within the critical region for 3q13.31 deletion syndrome, a multisystem disorder marked by intellectual disability, disturbed behavior, and other features (PMID 22180640, PMID 23878096).

Reports Added
[Neurodevelopmental disorder-associated ZBTB20 gene variants affect dendritic and synaptic structure.2018]
4/1/2017
3S
icon
3S

Decreased from 3S to 3S

Description

Missense variants in the ZBTB20 gene were recently identified in eight patients diagnosed with Primrose syndrome; seven of these variants were de novo in origin, and six of these variants were experimentally shown to have functional effects (i.e. reduced promoter binding and impaired function in repressing reporter expression) in a dominant-negative manner. These missense variants were not observed in public or in-house databases. Two of the patients diagnosed with Primrose syndrome that carried de novo functional missense variants were reported in the supplementary material as also presenting with autism (PMID 25017102). ZBTB20 also resides within the critical region for 3q13.31 deletion syndrome, a multisystem disorder marked by intellectual disability, disturbed behavior, and other features (PMID 22180640, PMID 23878096).

Reports Added
[A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic...2011] [Recurrent HERV-H-mediated 3q13.2-q13.31 deletions cause a syndrome of hypotonia and motor, language, and cognitive delays.2013] [Neurodevelopmental disorders associated with dosage imbalance of ZBTB20 correlate with the morbidity spectrum of ZBTB20 candidate target genes.2014] [Mutations in ZBTB20 cause Primrose syndrome.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Hippocampus-like corticoneurogenesis induced by two isoforms of the BTB-zinc finger gene Zbtb20 in mice.2007] [Zbtb20-induced CA1 pyramidal neuron development and area enlargement in the cerebral midline cortex of mice.2009] [Zbtb20 is essential for the specification of CA1 field identity in the developing hippocampus.2010] [Regulation of hippocampus-dependent memory by the zinc finger protein Zbtb20 in mature CA1 neurons.2012] [Novel de novo mutations in ZBTB20 in Primrose syndrome with congenital hypothyroidism.2016] [Zbtb20 modulates the sequential generation of neuronal layers in developing cortex.2016] [Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnose...2016] [High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing.2016] [Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016] [Lessons learned from additional research analyses of unsolved clinical exome cases.2017]
10/1/2016
3S
icon
3S

Decreased from 3S to 3S

Description

Missense variants in the ZBTB20 gene were recently identified in eight patients diagnosed with Primrose syndrome; seven of these variants were de novo in origin, and six of these variants were experimentally shown to have functional effects (i.e. reduced promoter binding and impaired function in repressing reporter expression) in a dominant-negative manner. These missense variants were not observed in public or in-house databases. Two of the patients diagnosed with Primrose syndrome that carried de novo functional missense variants were reported in the supplementary material as also presenting with autism (PMID 25017102). ZBTB20 also resides within the critical region for 3q13.31 deletion syndrome, a multisystem disorder marked by intellectual disability, disturbed behavior, and other features (PMID 22180640, PMID 23878096).

Reports Added
[High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing.2016] [Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016]
7/1/2016
3S
icon
3S

Decreased from 3S to 3S

Description

Missense variants in the ZBTB20 gene were recently identified in eight patients diagnosed with Primrose syndrome; seven of these variants were de novo in origin, and six of these variants were experimentally shown to have functional effects (i.e. reduced promoter binding and impaired function in repressing reporter expression) in a dominant-negative manner. These missense variants were not observed in public or in-house databases. Two of the patients diagnosed with Primrose syndrome that carried de novo functional missense variants were reported in the supplementary material as also presenting with autism (PMID 25017102). ZBTB20 also resides within the critical region for 3q13.31 deletion syndrome, a multisystem disorder marked by intellectual disability, disturbed behavior, and other features (PMID 22180640, PMID 23878096).

Reports Added
[Zbtb20 modulates the sequential generation of neuronal layers in developing cortex.2016] [Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnose...2016]
4/1/2016
3S
icon
3S

Decreased from 3S to 3S

Description

Missense variants in the ZBTB20 gene were recently identified in eight patients diagnosed with Primrose syndrome; seven of these variants were de novo in origin, and six of these variants were experimentally shown to have functional effects (i.e. reduced promoter binding and impaired function in repressing reporter expression) in a dominant-negative manner. These missense variants were not observed in public or in-house databases. Two of the patients diagnosed with Primrose syndrome that carried de novo functional missense variants were reported in the supplementary material as also presenting with autism (PMID 25017102). ZBTB20 also resides within the critical region for 3q13.31 deletion syndrome, a multisystem disorder marked by intellectual disability, disturbed behavior, and other features (PMID 22180640, PMID 23878096).

Reports Added
[A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic...2011] [Recurrent HERV-H-mediated 3q13.2-q13.31 deletions cause a syndrome of hypotonia and motor, language, and cognitive delays.2013] [Neurodevelopmental disorders associated with dosage imbalance of ZBTB20 correlate with the morbidity spectrum of ZBTB20 candidate target genes.2014] [Mutations in ZBTB20 cause Primrose syndrome.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Hippocampus-like corticoneurogenesis induced by two isoforms of the BTB-zinc finger gene Zbtb20 in mice.2007] [Zbtb20-induced CA1 pyramidal neuron development and area enlargement in the cerebral midline cortex of mice.2009] [Zbtb20 is essential for the specification of CA1 field identity in the developing hippocampus.2010] [Regulation of hippocampus-dependent memory by the zinc finger protein Zbtb20 in mature CA1 neurons.2012] [Novel de novo mutations in ZBTB20 in Primrose syndrome with congenital hypothyroidism.2016]
1/1/2015
3S
icon
3S

Decreased from 3S to 3S

Description

Missense variants in the ZBTB20 gene were recently identified in eight patients diagnosed with Primrose syndrome; seven of these variants were de novo in origin, and six of these variants were experimentally shown to have functional effects (i.e. reduced promoter binding and impaired function in repressing reporter expression) in a dominant-negative manner. These missense variants were not observed in public or in-house databases. Two of the patients diagnosed with Primrose syndrome that carried de novo functional missense variants were reported in the supplementary material as also presenting with autism (PMID 25017102). ZBTB20 also resides within the critical region for 3q13.31 deletion syndrome, a multisystem disorder marked by intellectual disability, disturbed behavior, and other features (PMID 22180640, PMID 23878096).

Reports Added
[Large-scale discovery of novel genetic causes of developmental disorders.2014]
7/1/2014
icon
3S

Increased from to 3S

Description

Missense variants in the ZBTB20 gene were recently identified in eight patients diagnosed with Primrose syndrome; seven of these variants were de novo in origin, and six of these variants were experimentally shown to have functional effects (i.e. reduced promoter binding and impaired function in repressing reporter expression) in a dominant-negative manner. These missense variants were not observed in public or in-house databases. Two of the patients diagnosed with Primrose syndrome that carried de novo functional missense variants were reported in the supplementary material as also presenting with autism (PMID 25017102). ZBTB20 also resides within the critical region for 3q13.31 deletion syndrome, a multisystem disorder marked by intellectual disability, disturbed behavior, and other features (PMID 22180640, PMID 23878096).

Krishnan Probability Score

Score 0.50313475751475

Ranking 1955/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.98255723040765

Ranking 2062/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
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Sanders TADA Score

Score 0.94867928396869

Ranking 17782/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Larsen Cumulative Evidence Score

Score 33

Ranking 67/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score 0.16946517259417

Ranking 4821/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
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