FRG1FSHD region gene 1
Autism Reports / Total Reports
3 / 3Rare Variants / Common Variants
5 / 0Aliases
FRG1, FRG1A, FSG1Associated Syndromes
-Chromosome Band
4q35.2Associated Disorders
-Relevance to Autism
Two de novo postzygotic nonsense variants in the FRG1 gene were identified in a cohort of 360 Spanish ASD probands in AlonsoGonzalez et al., 2021. Subsequent TADA analysis of post-zygotic mutations in the discovery cohort of Spanish ASD probands, as well as in a combined ASD cohort of 2171 trios, identified FRG1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.
Molecular Function
This gene maps to a location 100 kb centromeric of the repeat units on chromosome 4q35 which are deleted in facioscapulohumeral muscular dystrophy (FSHD). It is evolutionarily conserved and has related sequences on multiple human chromosomes but DNA sequence analysis did not reveal any homology to known genes. In vivo studies demonstrate the encoded protein is localized to the nucleolus.
External Links
SFARI Genomic Platforms
Reports related to FRG1 (3 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Primary | - | Alonso-Gonzalez A et al. (2021) | Yes | - |
| 2 | Support | - | Zhou X et al. (2022) | Yes | - |
| 3 | Support | - | Asmaa Ali Alharbi et al. (2024) | Yes | ADHD, epilepsy/seizures |
Rare Variants (5)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.683G>A | p.Ser228Asn | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.403A>T | p.Arg135Ter | stop_gained | De novo | - | Simplex | 33431980 | Alonso-Gonzalez A et al. (2021) | |
| c.526G>T | p.Glu176Ter | stop_gained | De novo | - | Simplex | 33431980 | Alonso-Gonzalez A et al. (2021) | |
| c.277C>G | p.Pro93Ala | missense_variant | De novo | - | Simplex | 38721139 | Asmaa Ali Alharbi et al. (2024) | |
| c.280C>A | p.Pro94Thr | missense_variant | De novo | - | Simplex | 38721139 | Asmaa Ali Alharbi et al. (2024) |
Common Variants
No common variants reported.
SFARI Gene score
2
Strong Candidate
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe 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
2
Increased from to 2
Krishnan Probability Score
Score 0.48721886429766
Ranking 7023/25841 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.
ExAC Score
Score 3.6739295210831E-6
Ranking 14597/18225 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
Sanders TADA Score
Score 0.90623001499999
Ranking 7055/18665 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).
Zhang D Score
Score -0.002917673357379
Ranking 8791/20870 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.