Human Gene Module / Chromosome 18 / SETBP1

SETBP1SET binding protein 1

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
12 / 34
Rare Variants / Common Variants
107 / 0
Aliases
SETBP1, SEB
Associated Syndromes
Schinzel-Giedion syndrome
Chromosome Band
18q12.3
Associated Disorders
ADHD, ID, EP, EPS, ASD
Relevance to Autism

A de novo LoF variant (frameshift) was identified in a simplex ASD case from the Simons Simplex Collection (O'Roak et al., 2012). More recently, eight loss-of-function variants, three of which were de novo in origin, were identified in patients from DD/ID cohorts; social difficulties and/or other behavioral difficulties were observed in four of these patients (Coe et al., 2014).

Molecular Function

The protein encoded by this gene has been shown to bind the SET nuclear oncogene, which is involved in DNA replication. Mutations in this gene are associated with Schinzel-Giedion midface retraction syndrome (SGMFS) [MIM:269150], a disorder characterized by severe mental retardation, distinctive facial features, and multiple congenital malformations including skeletal abnormalities, genitourinary and renal malformations, cardiac defects, as well as a higher-than-normal prevalence of tumors, notably neuroepithelial neoplasia.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SETBP1 (34 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations O'Roak BJ , et al. (2012) Yes -
2 Support Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study Rauch A , et al. (2012) No ASD
3 Recent Recommendation Refining analyses of copy number variation identifies specific genes associated with developmental delay Coe BP , et al. (2014) No -
4 Support De novo mutations in moderate or severe intellectual disability Hamdan FF , et al. (2014) No Microcephaly
5 Recent Recommendation Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
6 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
7 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No Speech delay
8 Support High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing Martnez F , et al. (2016) No ID
9 Support De novo genic mutations among a Chinese autism spectrum disorder cohort Wang T , et al. (2016) Yes -
10 Support Clinical exome sequencing: results from 2819 samples reflecting 1000 families Trujillano D , et al. (2016) No -
11 Support SETBP1 induces transcription of a network of development genes by acting as an epigenetic hub Piazza R , et al. (2018) No -
12 Support Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model Guo H , et al. (2018) Yes -
13 Support Characterization of intellectual disability and autism comorbidity through gene panel sequencing Aspromonte MC , et al. (2019) Yes -
14 Support - Hildebrand MS et al. (2020) No DD, ID, epilepsy/seizures
15 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes ID
16 Support - Leonardi E et al. (2020) No Epilepsy/seizures, stereotypy
17 Support - Taşkıran EZ et al. (2021) No ADHD, autistic features
18 Support - Jansen NA et al. (2021) No ASD, ADHD, epilepsy/seizures
19 Support - Zou D et al. (2021) No -
20 Support - Pode-Shakked B et al. (2021) No -
21 Support - Xiang J et al. (2021) No -
22 Support - Brea-Fernández AJ et al. (2022) No -
23 Support - Chuan Z et al. (2022) No ID
24 Support - Hu C et al. (2022) Yes -
25 Support - Chen Y et al. (2021) No -
26 Support - Zhou X et al. (2022) Yes -
27 Support - Cardo LF et al. (2023) No -
28 Recent Recommendation - Timberlake AT et al. (2023) No -
29 Support - Sheth F et al. (2023) Yes DD, ID
30 Support - Le Wang et al. (2023) No -
31 Support - Lucie Sedlackova et al. (2024) Yes -
32 Support - Tamam Khalaf et al. (2024) No -
33 Support - Ruohao Wu et al. (2024) Yes -
34 Support - Haley O Oyler et al. (2024) No ASD or autistic features, ADHD, epilepsy/seizures
Rare Variants   (107)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 25217958 Coe BP , et al. (2014)
- - copy_number_loss De novo - - 33867525 Jansen NA et al. (2021)
- - copy_number_loss Unknown - - 38923504 Haley O Oyler et al. (2024)
c.556C>T p.Gln186Ter stop_gained Unknown - - 34145886 Zou D et al. (2021)
c.1596G>A p.Trp532Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.2348T>G p.Leu783Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.551G>T p.Arg184Met missense_variant Unknown - - 35741772 Hu C et al. (2022)
c.821G>A p.Trp274Ter stop_gained De novo - - 33867525 Jansen NA et al. (2021)
c.1630C>T p.Arg544Ter stop_gained De novo - - 33867525 Jansen NA et al. (2021)
c.1633G>T p.Glu545Ter stop_gained De novo - - 33867525 Jansen NA et al. (2021)
c.1777C>T p.Gln593Ter stop_gained De novo - - 33867525 Jansen NA et al. (2021)
c.1873C>T p.Arg625Ter stop_gained De novo - - 33867525 Jansen NA et al. (2021)
c.1876C>T p.Arg626Ter stop_gained De novo - - 33867525 Jansen NA et al. (2021)
c.2982C>G p.Tyr994Ter stop_gained Unknown - - 33867525 Jansen NA et al. (2021)
c.335G>A p.Arg112Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.587G>A p.Gly196Asp missense_variant De novo - - 33004838 Wang T et al. (2020)
c.3120C>A p.Tyr1040Ter stop_gained De novo - - 33867525 Jansen NA et al. (2021)
c.2824C>T p.Arg942Trp missense_variant De novo - - 33004838 Wang T et al. (2020)
c.265C>T p.Gln89Ter stop_gained Unknown - - 38923504 Haley O Oyler et al. (2024)
c.3055C>T p.Arg1019Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.3712G>A p.Asp1238Asn missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.3961C>T p.Arg1321Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.3962G>T p.Arg1321Leu missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.4204C>T p.Arg1402Trp missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.4235G>A p.Arg1412Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.4615C>T p.Pro1539Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1247A>G p.His416Arg missense_variant Unknown - - 35571021 Chuan Z et al. (2022)
c.2572G>A p.Glu858Lys missense_variant Unknown - - 35571021 Chuan Z et al. (2022)
c.532C>T p.Gln178Ter stop_gained De novo - - 38923504 Haley O Oyler et al. (2024)
c.821G>A p.Trp274Ter stop_gained De novo - - 38923504 Haley O Oyler et al. (2024)
c.1408del p.Met470Ter stop_gained De novo - - 38923504 Haley O Oyler et al. (2024)
c.1588C>T p.Arg530Ter stop_gained De novo - - 38923504 Haley O Oyler et al. (2024)
c.1873C>T p.Arg625Ter stop_gained De novo - - 38923504 Haley O Oyler et al. (2024)
c.1876C>T p.Arg626Ter stop_gained Unknown - - 38923504 Haley O Oyler et al. (2024)
c.1596G>A p.Trp532Ter stop_gained De novo - Unknown 25217958 Coe BP , et al. (2014)
c.1873C>T p.Arg625Ter stop_gained Unknown - Unknown 25217958 Coe BP , et al. (2014)
c.1876C>T p.Arg626Ter stop_gained Unknown - Unknown 25217958 Coe BP , et al. (2014)
c.3032C>G p.Ser1011Ter stop_gained De novo - Unknown 25217958 Coe BP , et al. (2014)
c.1774A>T p.Lys592Ter stop_gained De novo - Simplex 23020937 Rauch A , et al. (2012)
c.2612T>C p.Ile871Thr missense_variant De novo - - 27620904 Martnez F , et al. (2016)
c.1765C>T p.Arg589Ter stop_gained De novo - Simplex 33391157 Leonardi E et al. (2020)
c.2426A>G p.Gln809Arg missense_variant Familial Paternal - 35741772 Hu C et al. (2022)
c.2631C>A p.Ser877Arg missense_variant De novo - Simplex 35873028 Chen Y et al. (2021)
c.2572G>A p.Glu858Lys missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.3022C>G p.Arg1008Gly missense_variant Unknown - - 38438125 Tamam Khalaf et al. (2024)
c.2561C>T p.Ser854Phe missense_variant De novo - - 38923504 Haley O Oyler et al. (2024)
c.2572G>A p.Glu858Lys missense_variant De novo - - 38923504 Haley O Oyler et al. (2024)
c.2621A>G p.Asp874Gly missense_variant De novo - - 38923504 Haley O Oyler et al. (2024)
c.427del p.Arg143ValfsTer64 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1493G>A p.Arg498Gln missense_variant Unknown - Simplex 37543562 Sheth F et al. (2023)
c.2960G>A p.Arg987Gln missense_variant Familial Paternal - 33004838 Wang T et al. (2020)
c.3946del p.Ala1316ProfsTer4 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.2213del p.Pro738HisfsTer46 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.2665C>T p.Arg889Ter stop_gained De novo - Simplex 32345733 Hildebrand MS et al. (2020)
c.1630C>T p.Arg544Ter stop_gained De novo - - 35322241 Brea-Fernández AJ et al. (2022)
c.2800A>T p.Lys934Ter stop_gained De novo - - 35322241 Brea-Fernández AJ et al. (2022)
c.1202G>A p.Arg401Gln missense_variant Familial Paternal - 27824329 Wang T , et al. (2016)
c.2311dup p.Ser771PhefsTer26 frameshift_variant Unknown - - 34858471 Xiang J et al. (2021)
c.1777C>T p.Gln593Ter stop_gained De novo - Simplex 34580403 Pode-Shakked B et al. (2021)
c.2601C>G p.Ser867Arg missense_variant De novo - - 38008000 Lucie Sedlackova et al. (2024)
c.2717C>G p.Pro906Arg missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.944_945dup p.Asp316TrpfsTer28 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1568del p.His523LeufsTer32 frameshift_variant De novo - - 33867525 Jansen NA et al. (2021)
c.1676del p.Pro559ArgfsTer21 frameshift_variant De novo - - 33867525 Jansen NA et al. (2021)
c.2156del p.Gly719GlufsTer65 frameshift_variant De novo - - 33867525 Jansen NA et al. (2021)
c.3765dup p.Val1256CysfsTer28 frameshift_variant De novo - - 33867525 Jansen NA et al. (2021)
c.2572G>A p.Glu858Lys missense_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.1198G>A p.Val400Ile missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1553T>C p.Leu518Pro missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1877G>A p.Arg626Gln missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.39dup p.Gly14ArgfsTer49 frameshift_variant Unknown - Unknown 25217958 Coe BP , et al. (2014)
c.3299A>G p.His1100Arg missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.3566G>A p.Arg1189Gln missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.3689C>T p.Thr1230Ile missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.2602G>A p.Asp868Asn missense_variant De novo - Simplex 27848944 Trujillano D , et al. (2016)
c.407_408del p.Ser136TrpfsTer12 frameshift_variant De novo - - 33867525 Jansen NA et al. (2021)
c.726_732del p.Arg243LeufsTer98 frameshift_variant De novo - - 33867525 Jansen NA et al. (2021)
c.1619del p.Ser540ThrfsTer15 frameshift_variant De novo - - 38923504 Haley O Oyler et al. (2024)
c.1763del p.Gly588AspfsTer42 frameshift_variant Unknown - - 38923504 Haley O Oyler et al. (2024)
c.4027G>A p.Asp1343Asn missense_variant Familial Maternal Simplex 30564305 Guo H , et al. (2018)
c.427del p.Arg143ValfsTer152 frameshift_variant Unknown - Unknown 25217958 Coe BP , et al. (2014)
c.1231del p.Leu411TrpfsTer33 frameshift_variant Unknown - Unknown 25217958 Coe BP , et al. (2014)
c.2464del p.Ile822TyrfsTer13 frameshift_variant De novo - Unknown 25217958 Coe BP , et al. (2014)
c.1568del p.His523LeufsTer32 frameshift_variant Familial Maternal - 33004838 Wang T et al. (2020)
c.3799_3800insC p.Gly1267AlafsTer17 frameshift_variant De novo - - 33867525 Jansen NA et al. (2021)
c.2716_2717insGG p.Pro906ArgfsTer56 frameshift_variant De novo - - 33867525 Jansen NA et al. (2021)
c.453_454insTGGG p.Lys152TrpfsTer18 frameshift_variant De novo - - 33867525 Jansen NA et al. (2021)
c.755_756delinsT p.Pro252LeufsTer91 frameshift_variant De novo - - 33867525 Jansen NA et al. (2021)
c.2572G>A p.Glu858Lys missense_variant Familial Maternal Simplex 33391157 Leonardi E et al. (2020)
c.2718dup p.Ser907ValfsTer44 frameshift_variant De novo - Simplex 22495309 O'Roak BJ , et al. (2012)
c.1821del p.Ser608AlafsTer22 frameshift_variant De novo - Simplex 25356899 Hamdan FF , et al. (2014)
c.2076_2092delinsC p.Lys693ProfsTer86 frameshift_variant De novo - - 33867525 Jansen NA et al. (2021)
c.2269_2281del p.Asp757CysfsTer23 frameshift_variant De novo - - 38923504 Haley O Oyler et al. (2024)
c.3347A>G p.His1116Arg missense_variant De novo - Multiplex 33739554 Taşkıran EZ et al. (2021)
c.1877G>A p.Arg626Gln missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2218G>A p.Glu740Lys missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2267C>T p.Pro756Leu missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2199_2203del p.Glu734AlafsTer19 frameshift_variant De novo - - 31209962 Aspromonte MC , et al. (2019)
c.1724_1727del p.Asp575ValfsTer4 frameshift_variant De novo - Simplex 38764027 Ruohao Wu et al. (2024)
c.3017A>G p.Tyr1006Cys missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.3029C>T p.Thr1010Ile missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.3460C>T p.His1154Tyr missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.3962G>A p.Arg1321His missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2199_2203del p.Glu734AlafsTer19 frameshift_variant De novo - Simplex 33391157 Leonardi E et al. (2020)
c.2044_2046delinsAT p.Leu682IlefsTer9 frameshift_variant Unknown - Multiplex 33867525 Jansen NA et al. (2021)
c.2561C>G p.Ser854Cys missense_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.944_945dup p.Asp316TrpfsTer28 frameshift_variant Familial Maternal Multi-generational 37798664 Le Wang et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

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.

4/1/2021
1
icon
1

Score remained at 1

Description

A de novo LoF variant in the SETBP1 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22495309). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[Diagnostic yield of whole-exome sequencing in non-syndromic intellectual disability2021] [Clinical delineation of SETBP1 haploinsufficiency disorder2021]
1/1/2021
1
icon
1

Score remained at 1

Description

A de novo LoF variant in the SETBP1 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22495309). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[Identification of SETBP1 Mutations by Gene Panel Sequencing in Individuals With Intellectual Disability or With "Developmental and Epileptic Encephalopathy"2020]
10/1/2020
1
icon
1

Score remained at 1

Description

A de novo LoF variant in the SETBP1 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22495309). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
10/1/2019
3
icon
1

Decreased from 3 to 1

New Scoring Scheme
Description

A de novo LoF variant in the SETBP1 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22495309). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

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

Decreased from 3 to 3

Description

A de novo LoF variant in the SETBP1 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22495309). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[Characterization of intellectual disability and autism comorbidity through gene panel sequencing.2019]
1/1/2019
3
icon
3

Decreased from 3 to 3

Description

A de novo LoF variant in the SETBP1 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22495309). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.2018]
7/1/2018
3
icon
3

Decreased from 3 to 3

Description

A de novo LoF variant in the SETBP1 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22495309). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[SETBP1 induces transcription of a network of development genes by acting as an epigenetic hub.2018]
4/1/2017
3
icon
3

Decreased from 3 to 3

Description

A de novo LoF variant in the SETBP1 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22495309). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Refining analyses of copy number variation identifies specific genes associated with developmental delay.2014] [Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.2012] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [The contribution of de novo coding mutations to autism spectrum disorder2014] [High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing.2016] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [De novo mutations in moderate or severe intellectual disability.2014]
10/1/2016
3
icon
3

Decreased from 3 to 3

Description

A de novo LoF variant in the SETBP1 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22495309). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing.2016] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016]
1/1/2016
3
icon
3

Decreased from 3 to 3

Description

A de novo LoF variant in the SETBP1 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22495309). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Refining analyses of copy number variation identifies specific genes associated with developmental delay.2014] [Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.2012] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [The contribution of de novo coding mutations to autism spectrum disorder2014]
10/1/2014
icon
3

Increased from to 3

Description

A de novo LoF variant in the SETBP1 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22495309). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Krishnan Probability Score

Score 0.49774287812693

Ranking 2338/25841 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 0.99900292938104

Ranking 1066/18225 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
Original Source
Sanders TADA Score

Score 0.89128171866151

Ranking 5613/18665 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 24

Ranking 84/461 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
LRRC37A11P leucine rich repeat containing 37, member A11, pseudogene Human Protein Binding 342666
NAP1L2 Nucleosome assembly protein 1-like 2 Mouse Protein Binding 17954 P51860
PLEKHF2 pleckstrin homology domain containing, family F (with FYVE domain) member 2 Human Protein Binding 79666 Q9H8W4
SPANXC SPANX family, member C Human Protein Binding 64663 Q8TAD1
SPANXD SPANX family, member D Human Protein Binding 64648 Q9BXN6
XAGE1D Human Protein Binding 9503
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