Human Gene Module / Chromosome 18 / ELP2

ELP2elongator acetyltransferase complex subunit 2

SFARI Gene Score
2S
Strong Candidate, Syndromic Criteria 2.1, Syndromic
Autism Reports / Total Reports
1 / 7
Rare Variants / Common Variants
18 / 0
Aliases
ELP2, MRT58,  SHINC-2,  STATIP1,  StIP
Associated Syndromes
-
Chromosome Band
18q12.2
Associated Disorders
DD/NDD, ID, ASD, EPS
Relevance to Autism

Biallelic variants in the ELP2 gene have been shown to be responsible for a form of autosomal-recessive intellectual disability (Najmabadi et al., 2011; Cohen et al., 2015; Turkyilmaz and Sager, 2020; Dogan et al., 2021); affected individuals frequently display behavioral abnormalities such as self-injurious behavior and aggressive behavior, as well as stereotypic movements. Kojic et al. 2021 characterized eight individuals with biallelic variants in ELP2 (6 novel individuals and the two individuals originally identified in Cohen et al., 2015) and reported that autism spectrum disorder was observed in the two individuals from Cohen et al., 2015 and three novel individuals; ELP2 variants identified in patients were subsequently experimentally shown to result in impaired protein stability and reduced Elongator activity. Furthermore, modeling disease-associated ELP2 variants in mice in Kojic et al., 2021 recapitulated phenotypic features observed in patients (including developmental delay, microcephaly, motor deficits, and autistic features).

Molecular Function

The protein encoded by this gene is a core subunit of the elongator complex, a histone acetyltransferase complex that associates with RNA polymerase II. In addition to histone acetylation, the encoded protein effects transcriptional elongation and may help remodel chromatin.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ELP2 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Deep sequencing reveals 50 novel genes for recessive cognitive disorders Najmabadi H , et al. (2011) No ID
2 Primary - Cohen JS et al. (2015) No ASD, DD, ID
3 Support - Strauss KA et al. (2018) No DD
4 Support - Dogan M et al. (2021) No DD, ID, stereotypy
5 Support - Turkyilmaz A et al. (2020) No DD, ID, stereotypy
6 Recent Recommendation - Kojic M et al. (2021) No ASD, DD, ID, epilepsy/seizures
7 Support - Soo-Whee Kim et al. (2024) Yes -
Rare Variants   (18)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- p.Gln553Ter stop_gained Familial - Simplex 33976153 Kojic M et al. (2021)
- p.Arg462Gln missense_variant Familial - Simplex 33976153 Kojic M et al. (2021)
- p.His206Arg missense_variant Familial - Simplex 33976153 Kojic M et al. (2021)
- p.Leu444Ser missense_variant Familial - Simplex 33976153 Kojic M et al. (2021)
- p.Thr405Ile missense_variant Familial - Unknown 33976153 Kojic M et al. (2021)
c.1888C>A p.Leu630Ile missense_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
- p.Arg820SerfsTer3 frameshift_variant Familial - Simplex 33976153 Kojic M et al. (2021)
- p.Asn506LysfsTer8 frameshift_variant Familial - Simplex 33976153 Kojic M et al. (2021)
- p.Leu98PhefsTer10 frameshift_variant Familial - Unknown 33976153 Kojic M et al. (2021)
c.812A>G p.His271Arg missense_variant Familial Maternal Multiplex 25847581 Cohen JS et al. (2015)
c.1579C>T p.Arg527Trp missense_variant Familial Paternal Multiplex 25847581 Cohen JS et al. (2015)
c.1385A>G p.Arg462Gln missense_variant Familial Both parents Simplex 33976153 Kojic M et al. (2021)
c.1580G>A p.Ser527Asn missense_variant Familial Maternal Simplex 33510603 Turkyilmaz A et al. (2020)
c.1385G>A p.Arg462Gln missense_variant Familial Both parents Multiplex 33393008 Dogan M et al. (2021)
c.1385A>G p.Asp462Gly missense_variant Familial Both parents Simplex 28726809 Strauss KA et al. (2018)
c.1383G>A p.Trp461Ter splice_site_variant Familial Paternal Simplex 33510603 Turkyilmaz A et al. (2020)
c.1385G>T p.Arg462Leu missense_variant Familial Both parents Multiplex 21937992 Najmabadi H , et al. (2011)
c.1663A>C p.Thr555Pro missense_variant Familial Both parents Multiplex 21937992 Najmabadi H , et al. (2011)
Common Variants  

No common variants reported.

SFARI Gene score
2S

Strong Candidate, Syndromic

Score Delta: Score remained at 2S

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.

S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2022
icon
2S

Increased from to 2S

Krishnan Probability Score

Score 0.41052528679807

Ranking 22648/25841 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 1.3072018332189E-7

Ranking 15630/18225 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 0.94100380958281

Ranking 14773/18665 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 0.20200011207527

Ranking 4233/20870 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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