Human Gene Module / Chromosome 17 / EIF5A

EIF5Aeukaryotic translation initiation factor 5A

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
10 / 0
Aliases
-
Associated Syndromes
Faundes-Banka syndrome, DD, ID
Chromosome Band
17p13.1
Associated Disorders
-
Relevance to Autism

De novo damaging missense variants in the EIF5A gene have been identified in ASD probands from the Autism Sequencing Consortium and the BARAKA-Qatar Study (Satterstrom et al., 2020; Abdi et al., 2023). One of the seven individuals with Faundes-Banka syndrome described in Faundes et al., 2021 was reported to have autism spectrum disorder and ADHD; the EIF5A missense variant identified in this individual (p.Glu122Lys) was experimentally shown to reduce eIF5A-ribosome interactions in polysome profiling assays.

Molecular Function

The protein encoded by this gene enables U6 snRNA binding activity and protein N-terminus binding activity and is involved in several processes, including cellular response to virus, positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator, and tumor necrosis factor-mediated signaling pathway. De novo heterozygous mutations in this gene are responsible for Faundes-Banka syndrome (OMIM 619376), an autosomal dominant disorder characterized by variable combinations of developmental delay and microcephaly, as well as micrognathia and other dysmorphic features (Faundes et al., 2021).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to EIF5A (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
2 Support - Víctor Faundes et al. (2021) No ASD, ADHD
3 Support - Zhou X et al. (2022) Yes -
4 Primary - Mona Abdi et al. (2023) Yes ADHD, DD
Rare Variants   (10)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.303T>C p.Asp101= synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.415C>T p.Arg139Ter stop_gained De novo - - 33547280 Víctor Faundes et al. (2021)
c.202T>C p.Cys68Arg missense_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.233C>A p.Thr78Asn missense_variant De novo - - 33547280 Víctor Faundes et al. (2021)
c.221C>T p.Pro74Leu missense_variant De novo - Simplex 37805537 Mona Abdi et al. (2023)
c.406G>A p.Gly136Arg missense_variant De novo - - 33547280 Víctor Faundes et al. (2021)
c.415C>G p.Arg139Gly missense_variant De novo - - 33547280 Víctor Faundes et al. (2021)
c.433C>T p.Pro145Ser missense_variant De novo - - 33547280 Víctor Faundes et al. (2021)
c.454G>A p.Glu152Lys missense_variant De novo - - 33547280 Víctor Faundes et al. (2021)
c.324dup p.Met109TyrfsTer10 frameshift_variant De novo - - 33547280 Víctor Faundes et al. (2021)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Score Delta: Score remained at 3

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

1/1/2024
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.44617855879782

Ranking 14953/25841 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 0.89087690369671

Ranking 3302/18225 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 0.7928004083735

Ranking 2089/18665 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 -0.18709972580609

Ranking 15129/20870 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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