Human Gene Module / Chromosome 9 / ELAVL2

ELAVL2ELAV like neuron-specific RNA binding protein 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 7
Rare Variants / Common Variants
6 / 1
Aliases
ELAVL2, HEL-N1,  HELN1,  HUB
Associated Syndromes
-
Chromosome Band
9p21.3
Associated Disorders
-
Relevance to Autism

A de novo loss-of-function variant in the ELAVL2 gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). RNAi-mediated knockdown on ELAVL2 in primary human neurons and RNA sequencing identified a number of alternatively spliced transcripts downstream of ELAVL2 that overlap with RBFOX1 targets as well as targets of FMR1, as well as alternatively spliced and differentially expressed genes downstream of ELAVL2 that corresponded to a number of known ASD risk genes and genes that encode synaptic proteins (Berto et al., 2016).

Molecular Function

The protein encoded by this gene is a neural-specific RNA-binding protein that is known to bind to several 3' UTRs, including its own and also that of FOS and ID. The encoded protein may recognize a GAAA motif in the RNA.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ELAVL2 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Recent Recommendation ELAVL2-regulated transcriptional and splicing networks in human neurons link neurodevelopment and autism Berto S , et al. (2016) No -
3 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability Lelieveld SH et al. (2016) No -
4 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior Doan RN , et al. (2016) Yes -
5 Positive Association Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017) Yes -
6 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 -
7 Support - Zhou X et al. (2022) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
A>G - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
C>A - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
c.911A>C p.Asn304Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.527G>A p.Arg176Gln missense_variant De novo - - 27479843 Lelieveld SH et al. (2016)
c.998C>A p.Ala333Glu missense_variant De novo - Simplex 31771860 Cappi C , et al. (2019)
c.888_889insACGGATG p.Asp297ThrfsTer5 frameshift_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.229+2217A>T;c.355+2217A>T;c.316+2217A>T;c.325+2217A>T;c.271+2217A>T;c.313+2217A>T;c.280+2217A>T - intron_variant - - - 28540026 Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017)
SFARI Gene score
2

Strong Candidate

A de novo loss-of-function variant in the ELAVL2 gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). RNAi-mediated knockdown on ELAVL2 in primary human neurons and RNA sequencing identified a number of alternatively spliced transcripts downstream of ELAVL2 that overlap with RBFOX1 targets as well as targets of FMR1, as well as alternatively spliced and differentially expressed genes downstream of ELAVL2 that corresponded to a number of known ASD risk genes and genes that encode synaptic proteins (Berto et al., 2016).

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

A de novo loss-of-function variant in the ELAVL2 gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). RNAi-mediated knockdown on ELAVL2 in primary human neurons and RNA sequencing identified a number of alternatively spliced transcripts downstream of ELAVL2 that overlap with RBFOX1 targets as well as targets of FMR1, as well as alternatively spliced and differentially expressed genes downstream of ELAVL2 that corresponded to a number of known ASD risk genes and genes that encode synaptic proteins (Berto et al., 2016).

1/1/2020
3
icon
3

Decreased from 3 to 3

Description

A de novo loss-of-function variant in the ELAVL2 gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). RNAi-mediated knockdown on ELAVL2 in primary human neurons and RNA sequencing identified a number of alternatively spliced transcripts downstream of ELAVL2 that overlap with RBFOX1 targets as well as targets of FMR1, as well as alternatively spliced and differentially expressed genes downstream of ELAVL2 that corresponded to a number of known ASD risk genes and genes that encode synaptic proteins (Berto et al., 2016).

Reports Added
[De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism.2019]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo loss-of-function variant in the ELAVL2 gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). RNAi-mediated knockdown on ELAVL2 in primary human neurons and RNA sequencing identified a number of alternatively spliced transcripts downstream of ELAVL2 that overlap with RBFOX1 targets as well as targets of FMR1, as well as alternatively spliced and differentially expressed genes downstream of ELAVL2 that corresponded to a number of known ASD risk genes and genes that encode synaptic proteins (Berto et al., 2016).

Reports Added
[New Scoring Scheme]
4/1/2017
4
icon
4

Decreased from 4 to 4

Description

A de novo loss-of-function variant in the ELAVL2 gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). RNAi-mediated knockdown on ELAVL2 in primary human neurons and RNA sequencing identified a number of alternatively spliced transcripts downstream of ELAVL2 that overlap with RBFOX1 targets as well as targets of FMR1, as well as alternatively spliced and differentially expressed genes downstream of ELAVL2 that corresponded to a number of known ASD risk genes and genes that encode synaptic proteins (Berto et al., 2016).

Reports Added
[The contribution of de novo coding mutations to autism spectrum disorder2014] [ELAVL2-regulated transcriptional and splicing networks in human neurons link neurodevelopment and autism.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016] [Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with ...2017]
10/1/2016
4
icon
4

Decreased from 4 to 4

Description

A de novo loss-of-function variant in the ELAVL2 gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). RNAi-mediated knockdown on ELAVL2 in primary human neurons and RNA sequencing identified a number of alternatively spliced transcripts downstream of ELAVL2 that overlap with RBFOX1 targets as well as targets of FMR1, as well as alternatively spliced and differentially expressed genes downstream of ELAVL2 that corresponded to a number of known ASD risk genes and genes that encode synaptic proteins (Berto et al., 2016).

Reports Added
[Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016]
7/1/2016
4
icon
4

Decreased from 4 to 4

Description

A de novo loss-of-function variant in the ELAVL2 gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). RNAi-mediated knockdown on ELAVL2 in primary human neurons and RNA sequencing identified a number of alternatively spliced transcripts downstream of ELAVL2 that overlap with RBFOX1 targets as well as targets of FMR1, as well as alternatively spliced and differentially expressed genes downstream of ELAVL2 that corresponded to a number of known ASD risk genes and genes that encode synaptic proteins (Berto et al., 2016).

Reports Added
[Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016]
4/1/2016
icon
4

Increased from to 4

Description

A de novo loss-of-function variant in the ELAVL2 gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). RNAi-mediated knockdown on ELAVL2 in primary human neurons and RNA sequencing identified a number of alternatively spliced transcripts downstream of ELAVL2 that overlap with RBFOX1 targets as well as targets of FMR1, as well as alternatively spliced and differentially expressed genes downstream of ELAVL2 that corresponded to a number of known ASD risk genes and genes that encode synaptic proteins (Berto et al., 2016).

Krishnan Probability Score

Score 0.60362830754826

Ranking 361/25841 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 0.97292770417996

Ranking 2304/18225 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 0.867

Ranking 175/239 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 0.40471059495431

Ranking 285/18665 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 -0.025183703993289

Ranking 9530/20870 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
ALG13 ALG13, UDP-N-acetylglucosaminyltransferase subunit Human Protein Binding 79868 Q9NP73
ALPL alkaline phosphatase, liver/bone/kidney Human Direct Regulation 249 P05186
ANXA11 annexin A11 Human Direct Regulation 311 P50995
APH1A anterior pharynx defective 1 homolog A (C. elegans) Human Direct Regulation 51107 Q96BI3
APOBEC3B DNA dC->dU-editing enzyme APOBEC-3B Human Protein Binding 9582 Q9UH17
APOBEC3D apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3D Human Protein Binding 140564 B2CML4
APOBEC3F DNA dC->dU-editing enzyme APOBEC-3F Human Protein Binding 200316 Q8IUX4
ASIC1 acid sensing ion channel subunit 1 Human Direct Regulation 41 P78348
CCDC12 coiled-coil domain containing 12 Human Protein Binding 151903 J3KR35
CCDC9 Coiled-coil domain-containing protein 9 Human Protein Binding 26093 Q9Y3X0
CCNG1 cyclin G1 Human Direct Regulation 900 P51959
CCNL2 cyclin L2 Human Direct Regulation 81669 Q96S94
CELF5 Human Protein Binding
CWF19L2 Human Protein Binding
DGCR14 DiGeorge syndrome critical region gene 14 Human Protein Binding 8220 Q96DF8
DNAJB2 DnaJ heat shock protein family (Hsp40) member B2 Human Direct Regulation 3300 P25686
ESRP1 Epithelial splicing regulatory protein 1 Human Protein Binding 54845 Q6NXG1-3
EXTL2 exostosin-like glycosyltransferase 2 Human Direct Regulation 2135 Q9UBQ6
GSPT2 G1 to S phase transition 2 Human Protein Binding 23708 Q8IYD1
HIST1H1A Histone H1.1 Human Protein Binding 3024 Q02539
HIST1H1T Histone H1t Human Protein Binding 3010 P22492
HLTF helicase-like transcription factor Human Direct Regulation 6596 Q14527
HYDIN HYDIN, axonemal central pair apparatus protein Human Direct Regulation 54768 Q4G0P3
ICE2 interactor of little elongation complex ELL subunit 2 Human Direct Regulation 79664 Q659A1
IFI6 interferon alpha inducible protein 6 Human Direct Regulation 2537 P09912
MKRN2 makorin ring finger protein 2 Human Protein Binding 23609 B4DPR4
NASP nuclear autoantigenic sperm protein (histone-binding) Human Direct Regulation 4678 P49321
NIN ninein (GSK3B interacting protein) Human Direct Regulation 51199 Q8N4C6
PABPC4L Polyadenylate-binding protein 4-like Human Protein Binding P0CB38
PAIP2B poly(A) binding protein interacting protein 2B Human Protein Binding 400961 Q9ULR5
PI4KA phosphatidylinositol 4-kinase alpha Human Direct Regulation 5297 P42356
POFUT2 protein O-fucosyltransferase 2 Human Direct Regulation 23275 Q9Y2G5
POLR3H polymerase (RNA) III (DNA directed) polypeptide H (22.9kD) Human Protein Binding 171568 Q9Y535
PPIE peptidylprolyl isomerase E (cyclophilin E) Human Protein Binding 10450 Q3S611
PRKRA Interferon-inducible double-stranded RNA-dependent protein kinase activator A Human Protein Binding 8575 O75569-2
PTPRD protein tyrosine phosphatase, receptor type, D Human Direct Regulation 5789 P23468
PUM2 Human Protein Binding
RALY RNA binding protein, autoantigenic (hnRNP-associated with lethal yellow homolog (mouse)) Human Protein Binding 22913 Q9UKM9
RBMXL1 RNA binding motif protein, X-linked-like 1 Human Protein Binding 494115 Q96E39
SH2B1 SH2B adaptor protein 1 Human Direct Regulation 25970 Q9NRF2
SHTN1 shootin 1 Human Direct Regulation 57698 A0MZ66
SREK1 splicing regulatory glutamine/lysine-rich protein 1 Human Direct Regulation 140890 Q8WXA9
SRSF10 serine/arginine-rich splicing factor 10 Human Protein Binding 10772 O75494
SRSF8 Serine/arginine-rich splicing factor 8 Human Protein Binding 10929 Q9BRL6-2
STAU2 staufen, RNA binding protein, homolog 2 (Drosophila) Human Protein Binding 27067 Q9NUL3
TULP4 tubby like protein 4 Human Direct Regulation 56995 Q9NRJ4
WDR13 WD repeat domain 13 Human Direct Regulation 64743 Q9H1Z4
WDR46 WD repeat domain 46 Human Protein Binding 9277 A8K806
YBX2 Y box binding protein 2 Human Protein Binding 51087 Q9Y2T7
ZC3H14 zinc finger CCCH-type containing 14 Human Protein Binding 79882 Q6PJT7
ZNF346 zinc finger protein 346 Human Protein Binding 23567 Q9UL40
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