Human Gene Module / Chromosome 8 / EGR3

EGR3early growth response 3

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
5 / 0
Aliases
EGR3, EGR-3,  PILOT
Associated Syndromes
-
Chromosome Band
8p21.3
Associated Disorders
-
Relevance to Autism

De novo damaging missense variants in the EGR3 gene were identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014) and the SPARK cohort (Feliciano et al., 2019). A meta-analysis of de novo variants in 4773 published ASD trios and 465 SPARK trios using TADA identified EGR3 as a gene with a false discovery rate 0.2.

Molecular Function

This gene encodes a transcriptional regulator that belongs to the EGR family of C2H2-type zinc-finger proteins. It is an immediate-early growth response gene which is induced by mitogenic stimulation. The protein encoded by this gene participates in the transcriptional regulation of genes in controling biological rhythm. It may also play a role in a wide variety of processes including muscle development, lymphocyte development, endothelial cell growth and migration, and neuronal development.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to EGR3 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
3 Support - Zhou X et al. (2022) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.91A>G p.Ser31Gly missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.807G>A p.Pro269%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.758A>G p.Glu253Gly missense_variant De novo - - 31452935 Feliciano P et al. (2019)
c.686A>T p.Glu229Val missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.102C>T p.Asn34%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

De novo damaging missense variants in the EGR3 gene were identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014) and the SPARK cohort (Feliciano et al., 2019). A meta-analysis of de novo variants in 4773 published ASD trios and 465 SPARK trios using TADA identified EGR3 as a gene with a false discovery rate 0.2.

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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

De novo damaging missense variants in the EGR3 gene were identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014) and the SPARK cohort (Feliciano et al., 2019). A meta-analysis of de novo variants in 4773 published ASD trios and 465 SPARK trios using TADA identified EGR3 as a gene with a false discovery rate 0.2.

10/1/2019
icon
3

Increased from to 3

New Scoring Scheme
Description

De novo damaging missense variants in the EGR3 gene were identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014) and the SPARK cohort (Feliciano et al., 2019). A meta-analysis of de novo variants in 4773 published ASD trios and 465 SPARK trios using TADA identified EGR3 as a gene with a false discovery rate 0.2.

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.55232307609135

Ranking 1365/25841 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 0.81109794446274

Ranking 3869/18225 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 0.74240314842931

Ranking 1482/18665 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 0.35028976454619

Ranking 2004/20870 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
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