Human Gene Module / Chromosome 11 / CTR9

CTR9CTR9homolog, Paf1/RNA polymerase II complex component

SFARI Gene Score
3S
Suggestive Evidence, Syndromic Criteria 3.1, Syndromic
Autism Reports / Total Reports
5 / 9
Rare Variants / Common Variants
26 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
11p15.4
Associated Disorders
-
Relevance to Autism

De novo variants in the CTR9 gene have been identified in ASD probands, including a rare and potentially deleterious de novo missense variant in a proband from the Autism Sequencing Consortium (De Rubeis et al., 2014; Sanders et al., 2015; Yuen et al., 2017; Turner et al., 2017). Additional de novo variants in this gene have been identified in probands with intellectual disability in Lelieveld et al., 2016, probands from the 2017 Deciphering Developmental Disorders study, and an NDD proband in Hamanaka et al., 2022. Moreover, Hamanaka et al., 2022 classified CTR9 as a high-confidence candidate gene for neurodevelopmental disorders following gene-based enrichment of de novo deleterious SNVs and CNVs in 41,165 novel and previously reported cases and subsequent prioritization based on its similarity to known NDD genes using a deep learning model. Meuwissen et al., 2022 described the clinical and molcular profiles of 13 probands harboring likely pathogenic CTR9 missense variants who presented with a neurodevelopmental disorder characterized by variable degrees of intellectual disability, hypotonia, joint hyperlaxity, speech delay, coordination problems, tremor, and autism spectrum disorder.

Molecular Function

The protein encoded by this gene is a component of the PAF1 complex, which associates with RNA polymerase II and functions in transcriptional regulation and elongation. This complex also plays a role in the modification of histones.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CTR9 (9 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 Support Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci Sanders SJ , et al. (2015) Yes -
3 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability Lelieveld SH et al. (2016) No -
4 Support Prevalence and architecture of de novo mutations in developmental disorders et al. (2017) No -
5 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
6 Support Genomic Patterns of De Novo Mutation in Simplex Autism Turner TN et al. (2017) Yes -
7 Support - Hamanaka K et al. (2022) No -
8 Recent Recommendation - Meuwissen M et al. (2022) No ASD, ADHD
9 Support - Zhou X et al. (2022) Yes -
Rare Variants   (26)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.46-2A>C - splice_site_variant De novo - Simplex 28135719 et al. (2017)
c.45+112T>G - intron_variant De novo - Simplex 28965761 Turner TN et al. (2017)
c.-32_-31dup - 5_prime_UTR_variant De novo - - 26402605 Sanders SJ , et al. (2015)
c.2508+170G>A - intron_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.2515C>T p.Arg839Trp missense_variant De novo - Simplex 28135719 et al. (2017)
c.144+848G>A - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.1687-7G>T - splice_region_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2488C>T p.Arg830Trp missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.1557_1558del p.Tyr520Ter frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.2273C>T p.Ala758Val missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.74C>G p.Pro25Arg missense_variant De novo - Simplex 35468861 Hamanaka K et al. (2022)
c.1A>T p.Met1? initiator_codon_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.43G>A p.Glu15Lys missense_variant De novo - Simplex 35499524 Meuwissen M et al. (2022)
c.74C>G p.Pro25Arg missense_variant De novo - Simplex 35499524 Meuwissen M et al. (2022)
c.76G>C p.Glu26Gln missense_variant De novo - Simplex 35499524 Meuwissen M et al. (2022)
c.109G>C p.Glu37Gln missense_variant De novo - Simplex 35499524 Meuwissen M et al. (2022)
c.254G>A p.Cys85Tyr missense_variant De novo - Simplex 35499524 Meuwissen M et al. (2022)
c.50T>C p.Ile17Thr missense_variant Familial Paternal - 35499524 Meuwissen M et al. (2022)
c.1126G>A p.Glu376Lys missense_variant De novo - Simplex 35499524 Meuwissen M et al. (2022)
c.1364A>G p.Asn455Ser missense_variant De novo - Simplex 35499524 Meuwissen M et al. (2022)
c.1405G>A p.Glu469Lys missense_variant De novo - Simplex 35499524 Meuwissen M et al. (2022)
c.2633G>A p.Arg878Gln missense_variant De novo - Simplex 35499524 Meuwissen M et al. (2022)
c.1405G>A p.Glu469Lys missense_variant De novo - Simplex 27479843 Lelieveld SH et al. (2016)
c.2296A>G p.Thr766Ala missense_variant Unknown Not maternal - 35499524 Meuwissen M et al. (2022)
c.86delinsTCAT p.Glu29delinsValIle inframe_insertion De novo - Simplex 27479843 Lelieveld SH et al. (2016)
c.1598-469_1598-468insAGAGACATTTCCTAGTGC - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
3S

Suggestive Evidence, Syndromic

Score Delta: Score remained at 3S

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

S

Syndromic

See all Category S Genes

The 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."

4/1/2022
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.44602850464698

Ranking 15045/25841 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 0.99999944697879

Ranking 272/18225 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 0.81020509464085

Ranking 2398/18665 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 0.33200749735469

Ranking 2262/20870 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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