Human Gene Module / Chromosome 12 / ARF3

ARF3ADP ribosylation factor 3

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
3 / 5
Rare Variants / Common Variants
11 / 0
EAGLE Score
1.25
Limited Learn More
Aliases
-
Associated Syndromes
-
Chromosome Band
12q13.12
Associated Disorders
-
Genetic Category
Rare Single Gene Mutation, Syndromic
Relevance to Autism

Three rare and potentially damaging de novo missense variants in the ARF3 gene were identified in ASD probands from the SPARK cohort (Feliciano et al., 2019; Zhou et al., 2022). Transmission and de novo association (TADA) analysis of whole-exome and whole-genome sequencing data from the Autism Sequencing Consortium, the Simons Simplex Collection, the MSSNG cohort, and the SPARK cohort in Trost et al., 2022 identified ARF3 as an ASD-associated gene with a false discovery rate (FDR) < 0.1. De novo missense variants in ARF3 have also been shown to cause a neurodevelopmental syndrome characterized by developmental delay/intellectual disability, epilepsy, and brain abnormalities (Sakamoto et al., 2021; Fasano et al., 2022).

Molecular Function

GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in protein trafficking; may modulate vesicle budding and uncoating within the Golgi apparatus.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ARF3 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
2 Support - Sakamoto M et al. (2021) No ID
3 Support - Zhou X et al. (2022) Yes -
4 Recent Recommendation - Trost B et al. (2022) Yes -
5 Support - Fasano G et al. (2022) No Epilepsy/seizures
Rare Variants   (11)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.224G>A p.Arg75Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.394A>G p.Asn132Asp missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.34C>G p.Leu12Val missense_variant De novo - - 36369169 Fasano G et al. (2022)
c.95C>A p.Thr32Asn missense_variant De novo - - 36369169 Fasano G et al. (2022)
c.139C>T p.Pro47Ser missense_variant De novo - - 36369169 Fasano G et al. (2022)
c.200A>T p.Asp67Val missense_variant De novo - - 36369169 Fasano G et al. (2022)
c.277G>A p.Asp93Asn missense_variant De novo - - 36369169 Fasano G et al. (2022)
c.379A>G p.Lys127Glu missense_variant De novo - - 36369169 Fasano G et al. (2022)
c.74T>C p.Leu25Pro missense_variant De novo - - 31452935 Feliciano P et al. (2019)
c.200A>T p.Asp67Val missense_variant De novo - Simplex 34346499 Sakamoto M et al. (2021)
c.296G>T p.Arg99Leu missense_variant De novo - Simplex 34346499 Sakamoto M et al. (2021)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 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.

1/1/2023
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1

Increased from to 1

Krishnan Probability Score

Score 0.57424549025352

Ranking 676/25841 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 0.62273132360694

Ranking 4885/18225 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 0.90505289385323

Ranking 6918/18665 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 0.38426456735319

Ranking 1639/20870 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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