Human Gene Module / Chromosome 4 / CCSER1

CCSER1coiled-coil serine rich protein 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
5 / 0
Aliases
CCSER1, FAM190A
Associated Syndromes
-
Chromosome Band
4q22.1
Associated Disorders
-
Relevance to Autism

A de novo nonsense variant in the CCSER1 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014), while a paternally-transmitted nonsense variant in this gene was observed in all four affected siblings from an ASD multiplex family from the iHART cohort (Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified CCSER1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Molecular Function

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CCSER1 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Recent Recommendation Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
3 Support - Woodbury-Smith M et al. (2022) Yes -
4 Support - Zhou X et al. (2022) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1786C>T p.Arg596Ter stop_gained De novo - - 25363760 De Rubeis S , et al. (2014)
c.1482T>A p.Gly494%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.2362C>G p.Leu788Val missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1566T>G p.Asp522Glu missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.13G>T p.Gly5Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo nonsense variant in the CCSER1 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014), while a paternally-transmitted nonsense variant in this gene was observed in all four affected siblings from an ASD multiplex family from the iHART cohort (Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified CCSER1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Score Delta: Score remained at 2

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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

A de novo nonsense variant in the CCSER1 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014), while a paternally-transmitted nonsense variant in this gene was observed in all four affected siblings from an ASD multiplex family from the iHART cohort (Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified CCSER1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo nonsense variant in the CCSER1 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014), while a paternally-transmitted nonsense variant in this gene was observed in all four affected siblings from an ASD multiplex family from the iHART cohort (Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified CCSER1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Reports Added
[New Scoring Scheme]
7/1/2019
icon
4

Increased from to 4

Description

A de novo nonsense variant in the CCSER1 gene was identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014), while a paternally-transmitted nonsense variant in this gene was observed in all four affected siblings from an ASD multiplex family from the iHART cohort (Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified CCSER1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Krishnan Probability Score

Score 0.48969024174128

Ranking 6396/25841 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 0.21135084744115

Ranking 6994/18225 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 0.66008425497633

Ranking 941/18665 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
Submit New Gene

Report an Error