Human Gene Module / Chromosome 1 / CACNA1E

CACNA1Ecalcium voltage-gated channel subunit alpha1 E

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
11 / 24
Rare Variants / Common Variants
55 / 0
EAGLE Score
7.5
Moderate Learn More
Aliases
CACNA1E, BII,  CACH6,  CACNL1A6,  Cav2.3
Associated Syndromes
-
Chromosome Band
1q25.3
Associated Disorders
-
Genetic Category
Rare Single Gene Mutation
Relevance to Autism

Two de novo variants (a missense variant and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator) were observed in the CACNA1E gene in ASD probands (O'Roak et al., 2012; Neale et al., 2012). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 1.151E-02 (Takata et al., 2016).

Molecular Function

This gene encodes the alpha-1E subunit of R-type calcium channels, which belong to the 'high-voltage activated' group that may be involved in the modulation of firing patterns of neurons important for information processing.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CACNA1E (24 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Altered cerebellar function in mice lacking CaV2.3 Ca2+ channel Osanai M , et al. (2006) No -
2 Support Cav2.3 channels are critical for oscillatory burst discharges in the reticular thalamus and absence epilepsy Zaman T , et al. (2011) No -
3 Primary Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations O'Roak BJ , et al. (2012) Yes -
4 Support Patterns and rates of exonic de novo mutations in autism spectrum disorders Neale BM , et al. (2012) Yes -
5 Support The CaV2.3 R-type voltage-gated Ca2+ channel in mouse sleep architecture Siwek ME , et al. (2014) No -
6 Recent Recommendation De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia Takata A , et al. (2016) No -
7 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 -
8 Support Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism Chen R , et al. (2017) Yes -
9 Recent Recommendation De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias Helbig KL , et al. (2018) No -
10 Support Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder Munnich A , et al. (2019) Yes -
11 Support De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism Cappi C , et al. (2019) No -
12 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
13 Support A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders Suzuki T et al. (2020) Yes -
14 Support - Mahjani B et al. (2021) Yes -
15 Recent Recommendation - Royer-Bertrand B et al. (2021) No ASD, stereotypy
16 Support - Woodbury-Smith M et al. (2022) Yes -
17 Support - Viggiano M et al. (2022) Yes -
18 Support - Chuan Z et al. (2022) No -
19 Support - Zhou X et al. (2022) Yes -
20 Support - Kipkemoi P et al. (2023) Yes -
21 Support - Balasar et al. (2023) No -
22 Support - Sanchis-Juan A et al. (2023) No -
23 Support - Tamam Khalaf et al. (2024) No ADHD, DD
24 Support - Axel Schmidt et al. (2024) No -
Rare Variants   (55)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.4126C>T p.Gln1376Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.5677C>T p.Gln1893Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.4879C>T p.Gln1627Ter stop_gained Unknown - - 34615535 Mahjani B et al. (2021)
c.2485C>T p.Arg829Ter stop_gained Unknown - - 30343943 Helbig KL , et al. (2018)
c.4165C>T p.Arg1389Ter stop_gained Unknown - - 30343943 Helbig KL , et al. (2018)
c.3549C>A p.Asn1183Lys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.6347G>A p.Arg2116His missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.5197T>G p.Ser1733Ala missense_variant Unknown - - 35571021 Chuan Z et al. (2022)
c.476G>A p.Gly159Asp missense_variant Unknown - - 34615535 Mahjani B et al. (2021)
c.5579-5T>C - splice_region_variant Unknown - - 38438125 Tamam Khalaf et al. (2024)
c.6708C>T p.His2236%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.3731+5A>G - splice_site_variant De novo - Simplex 32530565 Suzuki T et al. (2020)
c.683T>C p.Leu228Pro missense_variant De novo - - 30343943 Helbig KL , et al. (2018)
c.3738C>T p.Asn1246= synonymous_variant De novo - - 22495311 Neale BM , et al. (2012)
c.1042G>C p.Gly348Arg missense_variant De novo - - 30343943 Helbig KL , et al. (2018)
c.1054G>A p.Gly352Arg missense_variant De novo - - 30343943 Helbig KL , et al. (2018)
c.1807A>C p.Ile603Leu missense_variant De novo - - 30343943 Helbig KL , et al. (2018)
c.2069G>A p.Gly690Asp missense_variant De novo - - 30343943 Helbig KL , et al. (2018)
c.2093T>C p.Phe698Ser missense_variant De novo - - 30343943 Helbig KL , et al. (2018)
c.2098G>A p.Ala700Thr missense_variant De novo - - 30343943 Helbig KL , et al. (2018)
c.2101A>G p.Ile701Val missense_variant De novo - - 30343943 Helbig KL , et al. (2018)
c.2104G>A p.Ala702Thr missense_variant De novo - - 30343943 Helbig KL , et al. (2018)
c.2104G>C p.Ala702Pro missense_variant De novo - - 30343943 Helbig KL , et al. (2018)
c.4264A>T p.Ile1422Phe missense_variant De novo - - 30343943 Helbig KL , et al. (2018)
c.4274C>A p.Thr1425Asn missense_variant De novo - - 30343943 Helbig KL , et al. (2018)
c.4288G>A p.Gly1430Arg missense_variant De novo - - 30343943 Helbig KL , et al. (2018)
c.1054G>A p.Gly352Arg missense_variant De novo - - 39039281 Axel Schmidt et al. (2024)
c.6881G>T p.Gly2294Val missense_variant Unknown - - 38438125 Tamam Khalaf et al. (2024)
c.4775C>A p.Thr1592Asn missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1375C>T p.Arg459Trp missense_variant De novo - Simplex 28344757 Chen R , et al. (2017)
c.3422+1G>A p.? splice_site_variant De novo - Simplex 37463579 Kipkemoi P et al. (2023)
c.2104G>A p.Ala702Thr missense_variant Unknown - Simplex 37524782 Balasar et al. (2023)
c.5258G>A p.Arg1753Gln missense_variant De novo - Simplex 31771860 Cappi C , et al. (2019)
c.2485C>T p.Arg829Ter stop_gained Unknown - Simplex 37541188 Sanchis-Juan A et al. (2023)
c.5875C>A p.Gln1959Lys missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.603G>A p.Val201%3D synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.3422+1G>A - splice_site_variant De novo - Simplex 34702355 Royer-Bertrand B et al. (2021)
c.3625G>A p.Gly1209Ser missense_variant De novo - Simplex 22495309 O'Roak BJ , et al. (2012)
c.4688A>G p.Lys1563Arg missense_variant De novo - Simplex 31406558 Munnich A , et al. (2019)
c.1080_1081dup p.Val361GlufsTer9 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.5875C>A p.Gln1959Lys missense_variant Familial Paternal - 35350424 Viggiano M et al. (2022)
c.934A>G p.Thr312Ala missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.1375C>T p.Arg459Trp missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.2555G>C p.Arg852Pro missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.3422C>T p.Pro1141Leu missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.488T>C p.Met163Thr missense_variant De novo - Simplex 34702355 Royer-Bertrand B et al. (2021)
c.5159C>G p.Ala1720Gly missense_variant Unknown Not maternal - 30343943 Helbig KL , et al. (2018)
c.1499A>G p.Gln500Arg missense_variant De novo - Simplex 34702355 Royer-Bertrand B et al. (2021)
c.2060C>T p.Thr687Ile missense_variant De novo - Simplex 34702355 Royer-Bertrand B et al. (2021)
c.2104G>T p.Ala702Ser missense_variant De novo - Simplex 34702355 Royer-Bertrand B et al. (2021)
c.2105C>T p.Ala702Val missense_variant De novo - Simplex 34702355 Royer-Bertrand B et al. (2021)
c.2108T>G p.Val703Gly missense_variant De novo - Simplex 34702355 Royer-Bertrand B et al. (2021)
c.2093T>C p.Phe698Ser missense_variant Unknown - Unknown 27513193 Farwell Hagman KD , et al. (2016)
c.2635C>T p.Arg879Trp missense_variant Unknown - Unknown 27513193 Farwell Hagman KD , et al. (2016)
c.4263_4271delinsG p.Ile1422HisfsTer8 frameshift_variant Familial Paternal - 30343943 Helbig KL , et al. (2018)
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.

4/1/2022
2
icon
1

Decreased from 2 to 1

7/1/2020
2
icon
2

Decreased from 2 to 2

Description

Two de novo variants (a missense variant and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator) were observed in the CACNA1E gene in ASD probands (O'Roak et al., 2012; Neale et al., 2012). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 1.151E-02 (Takata et al., 2016). Mice lacking the Ca(v)2.3 channel exhibited altered cerebellar function (Osanai et al., 2006). Lack of Ca(v)2.3 resulted in a marked decrease in the sensitivity of the animal to -butyrolactone-induced absence epilepsy in brain slices of Ca(v)2.3 knockout mice (Zaman et al., 2011). Ca(v)2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS) (Siwek et al., 2014). Helbig et al., 2018 described a developmental and epileptic encephalopathy with contractures, macrocephaly, and movement disorders associated with de novo missense variants in the CACNA1E gene; functional analysis of four of the missense variants observed in affected individuals (p.Phe698Ser, p.Ile701Val, p.Ala702Thr, and p.Ile603Leu) demonstrated gain-of-function effects.

Reports Added
[A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders2020]
1/1/2020
2
icon
2

Decreased from 2 to 2

Description

Two de novo variants (a missense variant and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator) were observed in the CACNA1E gene in ASD probands (O'Roak et al., 2012; Neale et al., 2012). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 1.151E-02 (Takata et al., 2016). Mice lacking the Ca(v)2.3 channel exhibited altered cerebellar function (Osanai et al., 2006). Lack of Ca(v)2.3 resulted in a marked decrease in the sensitivity of the animal to -butyrolactone-induced absence epilepsy in brain slices of Ca(v)2.3 knockout mice (Zaman et al., 2011). Ca(v)2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS) (Siwek et al., 2014). Helbig et al., 2018 described a developmental and epileptic encephalopathy with contractures, macrocephaly, and movement disorders associated with de novo missense variants in the CACNA1E gene; functional analysis of four of the missense variants observed in affected individuals (p.Phe698Ser, p.Ile701Val, p.Ala702Thr, and p.Ile603Leu) demonstrated gain-of-function effects.

Reports Added
[De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism.2019] [Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020]
10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Two de novo variants (a missense variant and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator) were observed in the CACNA1E gene in ASD probands (O'Roak et al., 2012; Neale et al., 2012). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 1.151E-02 (Takata et al., 2016). Mice lacking the Ca(v)2.3 channel exhibited altered cerebellar function (Osanai et al., 2006). Lack of Ca(v)2.3 resulted in a marked decrease in the sensitivity of the animal to -butyrolactone-induced absence epilepsy in brain slices of Ca(v)2.3 knockout mice (Zaman et al., 2011). Ca(v)2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS) (Siwek et al., 2014). Helbig et al., 2018 described a developmental and epileptic encephalopathy with contractures, macrocephaly, and movement disorders associated with de novo missense variants in the CACNA1E gene; functional analysis of four of the missense variants observed in affected individuals (p.Phe698Ser, p.Ile701Val, p.Ala702Thr, and p.Ile603Leu) demonstrated gain-of-function effects.

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

Decreased from 3 to 3

Description

Two de novo variants (a missense variant and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator) were observed in the CACNA1E gene in ASD probands (O'Roak et al., 2012; Neale et al., 2012). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 1.151E-02 (Takata et al., 2016). Mice lacking the Ca(v)2.3 channel exhibited altered cerebellar function (Osanai et al., 2006). Lack of Ca(v)2.3 resulted in a marked decrease in the sensitivity of the animal to -butyrolactone-induced absence epilepsy in brain slices of Ca(v)2.3 knockout mice (Zaman et al., 2011). Ca(v)2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS) (Siwek et al., 2014). Helbig et al., 2018 described a developmental and epileptic encephalopathy with contractures, macrocephaly, and movement disorders associated with de novo missense variants in the CACNA1E gene; functional analysis of four of the missense variants observed in affected individuals (p.Phe698Ser, p.Ile701Val, p.Ala702Thr, and p.Ile603Leu) demonstrated gain-of-function effects.

Reports Added
[Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder.2019]
10/1/2018
3
icon
3

Decreased from 3 to 3

Description

Two de novo variants (a missense variant and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator) were observed in the CACNA1E gene in ASD probands (O'Roak et al., 2012; Neale et al., 2012). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 1.151E-02 (Takata et al., 2016). Mice lacking the Ca(v)2.3 channel exhibited altered cerebellar function (Osanai et al., 2006). Lack of Ca(v)2.3 resulted in a marked decrease in the sensitivity of the animal to -butyrolactone-induced absence epilepsy in brain slices of Ca(v)2.3 knockout mice (Zaman et al., 2011). Ca(v)2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS) (Siwek et al., 2014). Helbig et al., 2018 described a developmental and epileptic encephalopathy with contractures, macrocephaly, and movement disorders associated with de novo missense variants in the CACNA1E gene; functional analysis of four of the missense variants observed in affected individuals (p.Phe698Ser, p.Ile701Val, p.Ala702Thr, and p.Ile603Leu) demonstrated gain-of-function effects.

Reports Added
[De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias.2018]
4/1/2017
3
icon
3

Decreased from 3 to 3

Description

Two de novo variants (a missense variant and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator) were observed in the CACNA1E gene in ASD probands (O'Roak et al., 2012; Neale et al., 2012). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 1.151E-02 (Takata et al., 2016). Mice lacking the Ca(v)2.3 channel exhibited altered cerebellar function (Osanai et al., 2006). Lack of Ca(v)2.3 resulted in a marked decrease in the sensitivity of the animal to ?-butyrolactone-induced absence epilepsy in brain slices of Ca(v)2.3 knockout mice (Zaman et al., 2011). Ca(v)2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS) (Siwek et al., 2014).

Reports Added
[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Patterns and rates of exonic de novo mutations in autism spectrum disorders.2012] [De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia.2016] [Altered cerebellar function in mice lacking CaV2.3 Ca2 channel.2006] [Cav2.3 channels are critical for oscillatory burst discharges in the reticular thalamus and absence epilepsy.2011] [The CaV2.3 R-type voltage-gated Ca2 channel in mouse sleep architecture.2014] [Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnose...2016] [Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism.2017]
7/1/2016
3
icon
3

Decreased from 3 to 3

Description

Two de novo variants (a missense variant and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator) were observed in the CACNA1E gene in ASD probands (O'Roak et al., 2012; Neale et al., 2012). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 1.151E-02 (Takata et al., 2016). Mice lacking the Ca(v)2.3 channel exhibited altered cerebellar function (Osanai et al., 2006). Lack of Ca(v)2.3 resulted in a marked decrease in the sensitivity of the animal to ?-butyrolactone-induced absence epilepsy in brain slices of Ca(v)2.3 knockout mice (Zaman et al., 2011). Ca(v)2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS) (Siwek et al., 2014).

Reports Added
[Altered cerebellar function in mice lacking CaV2.3 Ca2 channel.2006] [Cav2.3 channels are critical for oscillatory burst discharges in the reticular thalamus and absence epilepsy.2011] [The CaV2.3 R-type voltage-gated Ca2 channel in mouse sleep architecture.2014] [Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnose...2016]
4/1/2016
icon
3

Increased from to 3

Description

Two de novo variants (a missense variant and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator) were observed in the CACNA1E gene in ASD probands (O'Roak et al., 2012; Neale et al., 2012). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 1.151E-02 (Takata et al., 2016). Mice lacking the Ca(v)2.3 channel exhibited altered cerebellar function (Osanai et al., 2006). Lack of Ca(v)2.3 resulted in a marked decrease in the sensitivity of the animal to ?-butyrolactone-induced absence epilepsy in brain slices of Ca(v)2.3 knockout mice (Zaman et al., 2011). Ca(v)2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS) (Siwek et al., 2014).

Krishnan Probability Score

Score 0.597047103121

Ranking 432/25841 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 0.99999999999993

Ranking 25/18225 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
Iossifov Probability Score

Score 0.943

Ranking 94/239 scored genes


[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washington’s Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx
Original Source
Sanders TADA Score

Score 0.94096006178293

Ranking 14757/18665 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
Zhang D Score

Score -0.15782588709529

Ranking 14361/20870 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.
Original Source
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
MET met proto-oncogene Mouse Protein Binding 17295 P16056
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