Human Gene Module / Chromosome 11 / ELP4

ELP4Elongator acetyltransferase complex subunit 4

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 7
Rare Variants / Common Variants
11 / 0
Aliases
ELP4, AN,  C11orf19,  PAX6NEB,  PAXNEB,  dJ68P15A.1,  hELP4
Associated Syndromes
-
Chromosome Band
11p13
Associated Disorders
-
Relevance to Autism

A case-control analysis of the frequency of ELP4 CNVs from 2,845 ASD cases compared with 6,469 control individuals identified a significant excess of CNVs in cases vs. controls (P=2.7 x 10-3) (Addis et al., 2015).

Molecular Function

The protein encoded by the ELP4 gene acts as subunit of the RNA polymerase II elongator complex, which is a histone acetyltransferase component of the RNA polymerase II (Pol II) holoenzyme and is involved in transcriptional elongation. Elongator may play a role in chromatin remodeling and is involved in acetylation of histones H3 and probably H4. This gene has also been associated with Rolandic epilepsy.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ELP4 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Pax6 3' deletion results in aniridia, autism and mental retardation Davis LK , et al. (2008) Yes Aniridia
2 Positive Association Centrotemporal sharp wave EEG trait in rolandic epilepsy maps to Elongator Protein Complex 4 (ELP4) Strug LJ , et al. (2009) No -
3 Primary Microdeletions of ELP4 Are Associated with Language Impairment, Autism Spectrum Disorder, and Mental Retardation Addis L , et al. (2015) Yes -
4 Support Genome-wide characteristics of de novo mutations in autism Yuen RK et al. (2016) Yes -
5 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior Doan RN , et al. (2016) Yes -
6 Support Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes Guo H , et al. (2018) Yes -
7 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
Rare Variants   (11)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Unknown - Unknown 26010655 Addis L , et al. (2015)
- - copy_number_loss De novo - Unknown 26010655 Addis L , et al. (2015)
- - copy_number_loss Unknown - Unknown 26010655 Addis L , et al. (2015)
- - copy_number_loss Unknown - Multiplex 26010655 Addis L , et al. (2015)
c.1146+14712T>C - intron_variant - - Unknown 27667684 Doan RN , et al. (2016)
- - copy_number_loss Familial Maternal Unknown 26010655 Addis L , et al. (2015)
- - copy_number_loss Familial Paternal Unknown 26010655 Addis L , et al. (2015)
c.931-7123T>C - intron_variant De novo - Simplex 27525107 Yuen RK et al. (2016)
- - copy_number_loss Familial Maternal Simplex 18322702 Davis LK , et al. (2008)
c.284del p.Ser95TyrfsTer64 frameshift_variant Familial Paternal Simplex 30504930 Guo H , et al. (2018)
c.884_885del p.Thr295IlefsTer17 frameshift_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A case-control analysis of the frequency of ELP4 CNVs from 2,845 ASD cases compared with 6,469 control individuals in PMID 26010655 identified a significant excess of CNVs involving this gene in cases vs. controls (P=2.7 x 10-3); however, the extent of segregation of ELP4 CNVs with ASD and their functional effect remains unclear. This gene has also been associated with rolandic epilepsy (PMID 19172991).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

A case-control analysis of the frequency of ELP4 CNVs from 2,845 ASD cases compared with 6,469 control individuals in PMID 26010655 identified a significant excess of CNVs involving this gene in cases vs. controls (P=2.7 x 10-3); however, the extent of segregation of ELP4 CNVs with ASD and their functional effect remains unclear. This gene has also been associated with rolandic epilepsy (PMID 19172991).

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

Decreased from 3 to 3

Description

A case-control analysis of the frequency of ELP4 CNVs from 2,845 ASD cases compared with 6,469 control individuals in PMID 26010655 identified a significant excess of CNVs involving this gene in cases vs. controls (P=2.7 x 10-3); however, the extent of segregation of ELP4 CNVs with ASD and their functional effect remains unclear. This gene has also been associated with rolandic epilepsy (PMID 19172991).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
10/1/2018
3
icon
3

Decreased from 3 to 3

Description

A case-control analysis of the frequency of ELP4 CNVs from 2,845 ASD cases compared with 6,469 control individuals in PMID 26010655 identified a significant excess of CNVs involving this gene in cases vs. controls (P=2.7 x 10-3); however, the extent of segregation of ELP4 CNVs with ASD and their functional effect remains unclear. This gene has also been associated with rolandic epilepsy (PMID 19172991).

Reports Added
[Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes.2018]
10/1/2016
3
icon
3

Decreased from 3 to 3

Description

A case-control analysis of the frequency of ELP4 CNVs from 2,845 ASD cases compared with 6,469 control individuals in PMID 26010655 identified a significant excess of CNVs involving this gene in cases vs. controls (P=2.7 x 10-3); however, the extent of segregation of ELP4 CNVs with ASD and their functional effect remains unclear. This gene has also been associated with rolandic epilepsy (PMID 19172991).

Reports Added
[Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016]
7/1/2016
3
icon
3

Decreased from 3 to 3

Description

A case-control analysis of the frequency of ELP4 CNVs from 2,845 ASD cases compared with 6,469 control individuals in PMID 26010655 identified a significant excess of CNVs involving this gene in cases vs. controls (P=2.7 x 10-3); however, the extent of segregation of ELP4 CNVs with ASD and their functional effect remains unclear. This gene has also been associated with rolandic epilepsy (PMID 19172991).

Reports Added
[Genome-wide characteristics of de novo mutations in autism2016]
4/1/2015
icon
3

Increased from to 3

Description

A case-control analysis of the frequency of ELP4 CNVs from 2,845 ASD cases compared with 6,469 control individuals in PMID 26010655 identified a significant excess of CNVs involving this gene in cases vs. controls (P=2.7 x 10-3); however, the extent of segregation of ELP4 CNVs with ASD and their functional effect remains unclear. This gene has also been associated with rolandic epilepsy (PMID 19172991).

Krishnan Probability Score

Score 0.36587314212749

Ranking 24017/25841 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 0.012558281209711

Ranking 9834/18225 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 0.9408971035231

Ranking 14734/18665 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 -0.15047616397739

Ranking 14135/20870 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
Submit New Gene

Report an Error