RSRC1arginine and serine rich coiled-coil 1
Autism Reports / Total Reports
1 / 7Rare Variants / Common Variants
9 / 4Aliases
RSRC1, BM-011, MRT70, SFRS21, SRrp53Associated Syndromes
-Chromosome Band
3q25.32Associated Disorders
ADHD, ASDRelevance to Autism
Homozygous variants in the RSRC1 gene are responsible for a form of autosomal recessive intellectual disability [autosomal recessive intellectual developmental disorder-70 (MRT70); OMIM 618402); behavioral abnormalities including ASD or ADHD are frequently observed in affected individuals (Perez et al., 2018; Scala et al., 2020). Cross-trait meta-analysis of genome-wide studies on schizophrenia, bipolar disorder, autism spectrum disorder, ADHD, and depression identified an intronic variant in the RSRC1 gene (rs1589526) that reached genome-wide association with ASD following MTAG analysis (P-value 1.62E-08) (Wu et al., 2020); SNPs in the RSRC1 gene have previously been shown to reach genome-wide significance for association with depression (Wray et al., 2018; Li et al., 2018; Howard et al., 2019).
Molecular Function
This gene encodes a member of the serine and arginine rich-related protein family. The encoded protein is involved in both constitutive and alternative mRNA splicing.
External Links
SFARI Genomic Platforms
Reports related to RSRC1 (7 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Support | GWAS signals revisited using human knockouts | Maddirevula S et al. (2018) | No | - |
| 2 | Primary | RSRC1 mutation affects intellect and behaviour through aberrant splicing and transcription, downregulating IGFBP3 | Perez Y et al. (2018) | No | ADHD, autistic features |
| 3 | Positive Association | Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression | Wray NR , et al. (2018) | No | - |
| 4 | Positive Association | Common variants on 6q16.2, 12q24.31 and 16p13.3 are associated with major depressive disorder | Li X et al. (2018) | No | - |
| 5 | Positive Association | Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions | Howard DM et al. (2019) | No | - |
| 6 | Recent Recommendation | RSRC1 loss-of-function variants cause mild to moderate autosomal recessive intellectual disability | Scala M et al. (2020) | No | ASD, ADHD |
| 7 | Positive Association | Multi-trait analysis for genome-wide association study of five psychiatric disorders | Wu Y et al. (2020) | Yes | - |
Rare Variants (9)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_loss | Familial | Both parents | Multiplex | 32227164 | Scala M et al. (2020) | |
| - | - | copy_number_loss | Familial | Both parents | Extended multiplex | 32227164 | Scala M et al. (2020) | |
| c.250C>T | p.Arg84Ter | stop_gained | Familial | Both parents | Simplex | 32227164 | Scala M et al. (2020) | |
| c.205C>T | p.Arg69Ter | stop_gained | Familial | Both parents | Multiplex | 29522154 | Perez Y et al. (2018) | |
| c.532-1G>A | - | splice_site_variant | Familial | Both parents | Multiplex | 32227164 | Scala M et al. (2020) | |
| c.268C>T | p.Arg90Ter | stop_gained | Familial | Both parents | Multiplex | 28640246 | Maddirevula S et al. (2018) | |
| c.3G>T | p.Met1? | initiator_codon_variant | Familial | Both parents | Multiplex | 32227164 | Scala M et al. (2020) | |
| c.784C>T | p.Gln262Ter | stop_gained | Familial | Both parents | Extended multiplex | 32227164 | Scala M et al. (2020) | |
| c.320+79201_320+79207dup | - | frameshift_variant | Familial | Both parents | Simplex | 32227164 | Scala M et al. (2020) |
Common Variants (4)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.320+14366C>A | - | intron_variant | - | - | - | 32606422 | Wu Y et al. (2020) | |
| c.357+14352A>G;c.531+14352A>G | - | intron_variant | - | - | - | 29728651 | Li X et al. (2018) | |
| c.409+34483G>A;c.583+34483G>A | - | intron_variant | - | - | - | 29700475 | Wray NR , et al. (2018) | |
| c.321-37866T>C;c.495-37866T>C | - | intron_variant | - | - | - | 30718901 | Howard DM et al. (2019) |
SFARI Gene score
S
Syndromic
Score Delta: Score remained at S
criteria met
See SFARI Gene'scoring criteriaThe 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."
Krishnan Probability Score
Score 0.33994111658024
Ranking 24299/25841 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 3.4102567786081E-5
Ranking 13645/18225 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 0.93656727778281
Ranking 13238/18665 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 -0.16161219231089
Ranking 14473/20870 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.