Human Gene Module / Chromosome 16 / GSE1

GSE1Gse1coiled-coil protein

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 8
Rare Variants / Common Variants
51 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
16q24.1
Associated Disorders
-
Relevance to Autism

TADA analysis of >15,000 Latin American individuals from the GALA Consortium (including 4,717 participants with an ASD diagnosis) in Natividad Avila et al., 2026 identified GSE1 as one of 35 genes reaching genome-wide significance (FDR < 0.05); among the Admixed American (AMR) individuals wtih ASD described in this report were three SPARK probands with de novo loss-of-function variants (one of whom was previously reported in Fu et al., 2022) and a Simons Simplex Collection proband with a de novo synonymous variant originally described in Iossifov et al., 2014. Additional de novo missense variants in this gene were reported in non-AMR ASD probands from the Simons Simplex Collection, the SPARK cohort, and the Sanger_UK10K cohort, as well as in an ASD proband from the MSSNG cohort (De Rubeis et al., 2014; Iossifov et al., 2014; Yuen et al., 2017; Zhou et al., 2022). Inherited loss-of-function and damaging missense (Mis3) variants in GSE1 have also been reported in ASD probands from the Autism Sequencing Consortium and the mAGRE cohort (De Rubeis et al., 2014; Cirnigliaro et al., 2023).

Molecular Function

This gene encodes a proline-rich protein with coiled coil domains that may be a subunit of a BRAF35-HDAC (BHC) histone deacetylase complex. This gene may function as an oncogene in breast cancer and enhanced expression of the encoded protein has been observed in breast cancer patients. GSE1 has been shown to link the HDAC1/CoREST co-repressor complex to DNA damage (Vcelkova et al., 2023).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to GSE1 (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
4 Support - Zhou X et al. (2022) Yes -
5 Support - Fu JM et al. (2022) Yes -
6 Support - Cirnigliaro M et al. (2023) Yes -
7 Support - Vcelkova, Terezia et al. (2023) No -
8 Primary - Natividad Avila, Marina et al. (2026) Yes -
Rare Variants   (51)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
- p.Ser32Leu missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
- p.Arg137Met missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
- p.Arg535Gln missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
- p.Arg712Lys missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
- p.Arg732Gln missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
- p.His504Leu missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
- p.Phe176Leu missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
- p.Pro428Ser missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
- p.Pro550Leu missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
- p.Pro678Leu missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
- p.Pro810Ser missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
- p.Arg1053Trp missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
- p.Lys1109Asn missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
- p.Pro1017Arg missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
- - splice_site_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
c.283T>C p.Ser95Pro missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.990-3C>T p.? splice_region_variant De novo - Unknown 35982159 Zhou X et al. (2022)
- p.Leu16Phe missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
c.1806C>G p.Pro602= synonymous_variant De novo - Unknown 35982160 Fu JM et al. (2022)
- p.Arg399Gly missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
- p.Arg609Trp missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
- p.Arg712Lys missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
- p.Arg712Lys missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
- p.Arg715Trp missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
- p.Arg776Lys missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
- p.Asp165Tyr missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
- p.Phe176Leu missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
- p.Pro104Ser missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
- p.Pro505Leu missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
- p.Pro723Leu missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
- p.Pro810Ser missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
- p.Ser606Leu missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
- p.Ser724Leu missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
c.1385A>G p.His462Arg missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1932C>T p.Ala644= synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
- p.Arg1017His missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
- p.Lys1056Glu missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
- p.Ser1065Tyr missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
- p.phe1018Val missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
c.3389T>C p.Phe1130Ser missense_variant De novo - Unknown 35982159 Zhou X et al. (2022)
c.1102G>A p.Glu368Lys missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1508G>A p.Arg503Gln missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.2580C>T p.Phe860= synonymous_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.3296G>A p.Arg1099Gln missense_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
16:g.85656366G>GGCGGGAGAGGGAGCGCGA - inframe_insertion De novo - - 35982160 Fu JM et al. (2022)
c.1056_1057insC p.Ala353ArgfsTer2 frameshift_variant De novo - Simplex 35982160 Fu JM et al. (2022)
c.366del p.Val123TrpfsTer2 frameshift_variant De novo - Simplex 41912808 Natividad Avila, Marina et al. (2026)
c.366del p.Val123TrpfsTer2 frameshift_variant De novo - Multiplex 41912808 Natividad Avila, Marina et al. (2026)
c.1053_1054del p.Glu352GlyfsTer2 frameshift_variant Familial Maternal Simplex 37506195 Cirnigliaro M et al. (2023)
c.1053_1054del p.Glu352GlyfsTer2 frameshift_variant Familial Paternal Simplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

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.

4/1/2026
2

Initial score established: 2

Krishnan Probability Score

Score 0.57144381430958

Ranking 784/25841 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
Iossifov Probability Score

Score 0.984

Ranking 37/239 scored genes


[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washington’s Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx
Original Source
Sanders TADA Score

Score 0.67422811855073

Ranking 1010/18665 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
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