Human Gene Module / Chromosome 8 / EFR3A

EFR3AEFR3 homolog A (S. cerevisiae)

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
9 / 9
Rare Variants / Common Variants
24 / 0
Aliases
EFR3A, KIAA0143
Associated Syndromes
-
Chromosome Band
8q24.22
Associated Disorders
-
Relevance to Autism

Rare nonsynonymous variants in the EFR3A gene were found to be more common among cases (16/2196; 0.73%) than matched controls (12/3389; 0.35%), and were statistically more common at conserved nucleotides based on an experiment-wide significance threshold (P=0.0077, permutation test); variants likely to be deleterious were also statistically more common in cases than controls (P=0.017, Fisher exact test) (Gupta et al., 2014).

Molecular Function

This gene encodes a membrane protein that is a component of a protein complex required for PtdIns4P synthesis. Studies with orthologous gene in mouse show that it is differentially expressed in the auditory brainstem neurons of mice with hearing deficit, compared to mice with normal hearing ability, suggesting a role for this gene in hearing.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to EFR3A (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support De novo mutations revealed by whole-exome sequencing are strongly associated with autism Sanders SJ , et al. (2012) Yes -
2 Primary Rare deleterious mutations of the gene EFR3A in autism spectrum disorders Gupta AR , et al. (2014) Yes -
3 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) 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 - Woodbury-Smith M et al. (2022) Yes -
7 Support - Zhou X et al. (2022) Yes -
8 Support - Wang J et al. (2023) Yes -
9 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (24)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
delTAAA - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
- - upstream_gene_variant De novo - Simplex 27525107 Yuen RK et al. (2016)
c.2432A>G p.Tyr811Cys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.929T>C p.Val310Ala missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.148A>G p.Lys50Glu missense_variant Unknown - Unknown 24860643 Gupta AR , et al. (2014)
c.961G>T p.Ala321Ser missense_variant Unknown - Unknown 24860643 Gupta AR , et al. (2014)
c.1009G>C p.Val337Leu missense_variant Unknown - Unknown 24860643 Gupta AR , et al. (2014)
c.1511A>G p.Asp504Gly missense_variant Unknown - Unknown 24860643 Gupta AR , et al. (2014)
c.1523T>C p.Leu508Pro missense_variant Unknown - Unknown 24860643 Gupta AR , et al. (2014)
c.1528A>G p.Ile510Val missense_variant Unknown - Unknown 24860643 Gupta AR , et al. (2014)
c.1583A>G p.Gln528Arg missense_variant Unknown - Unknown 24860643 Gupta AR , et al. (2014)
c.1828A>G p.Met610Val missense_variant Unknown - Unknown 24860643 Gupta AR , et al. (2014)
c.44G>A p.Arg15His missense_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.1750A>G p.Ile584Val missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1013T>C p.Phe338Ser missense_variant De novo - Simplex 22495306 Sanders SJ , et al. (2012)
c.208C>T p.Arg70Cys missense_variant Familial Paternal Simplex 24860643 Gupta AR , et al. (2014)
c.353T>C p.Leu118Pro missense_variant Familial Paternal Simplex 24860643 Gupta AR , et al. (2014)
c.367T>C p.Phe123Leu missense_variant Familial Maternal Simplex 24860643 Gupta AR , et al. (2014)
c.728G>C p.Gly243Ala missense_variant Familial Maternal Simplex 24860643 Gupta AR , et al. (2014)
c.1601T>C p.Ile534Thr missense_variant Familial Maternal Simplex 24860643 Gupta AR , et al. (2014)
c.2353A>G p.Thr785Ala missense_variant Familial Maternal Simplex 24860643 Gupta AR , et al. (2014)
c.3del p.Met1? frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1621_1622insATT p.Ala541delinsAspSer inframe_insertion Familial Maternal Simplex 24860643 Gupta AR , et al. (2014)
c.538_539insTCGCATA p.Gly180ValfsTer3 frameshift_variant Familial Maternal Simplex 24860643 Gupta AR , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Rare nonsynonymous variants in the EFR3A gene were found to be more common among ASD cases (16/2196; 0.73%) than matched controls (12/3389; 0.35%), and were statistically more common at conserved nucleotides based on an experiment-wide significance threshold (P=0.0077, permutation test); variants likely to be deleterious were also statistically more common in cases than controls (P=0.017, Fisher exact test) (PMID 24860643). De novo likely damaging missense variants in EFR3A have also been identified in ASD cases (PMIDs 22495306, 25363760).

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

Rare nonsynonymous variants in the EFR3A gene were found to be more common among ASD cases (16/2196; 0.73%) than matched controls (12/3389; 0.35%), and were statistically more common at conserved nucleotides based on an experiment-wide significance threshold (P=0.0077, permutation test); variants likely to be deleterious were also statistically more common in cases than controls (P=0.017, Fisher exact test) (PMID 24860643). De novo likely damaging missense variants in EFR3A have also been identified in ASD cases (PMIDs 22495306, 25363760).

Reports Added
[New Scoring Scheme]
10/1/2016
3
icon
3

Decreased from 3 to 3

Description

Rare nonsynonymous variants in the EFR3A gene were found to be more common among ASD cases (16/2196; 0.73%) than matched controls (12/3389; 0.35%), and were statistically more common at conserved nucleotides based on an experiment-wide significance threshold (P=0.0077, permutation test); variants likely to be deleterious were also statistically more common in cases than controls (P=0.017, Fisher exact test) (PMID 24860643). De novo likely damaging missense variants in EFR3A have also been identified in ASD cases (PMIDs 22495306, 25363760).

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

Rare nonsynonymous variants in the EFR3A gene were found to be more common among ASD cases (16/2196; 0.73%) than matched controls (12/3389; 0.35%), and were statistically more common at conserved nucleotides based on an experiment-wide significance threshold (P=0.0077, permutation test); variants likely to be deleterious were also statistically more common in cases than controls (P=0.017, Fisher exact test) (PMID 24860643). De novo likely damaging missense variants in EFR3A have also been identified in ASD cases (PMIDs 22495306, 25363760).

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

Increased from to 3

Description

Rare nonsynonymous variants in the EFR3A gene were found to be more common among ASD cases (16/2196; 0.73%) than matched controls (12/3389; 0.35%), and were statistically more common at conserved nucleotides based on an experiment-wide significance threshold (P=0.0077, permutation test); variants likely to be deleterious were also statistically more common in cases than controls (P=0.017, Fisher exact test) (PMID 24860643). De novo likely damaging missense variants in EFR3A have also been identified in ASD cases (PMIDs 22495306, 25363760).

Krishnan Probability Score

Score 0.49180173714754

Ranking 5063/25841 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 0.0092661908323062

Ranking 10059/18225 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 0.49810106620997

Ranking 444/18665 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 67

Ranking 20/461 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 0.23402173002057

Ranking 3708/20870 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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