Human Gene Module / Chromosome 1 / CTPS1

CTPS1CTP synthase 1

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
2 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
1p34.2
Associated Disorders
-
Relevance to Autism

To evaluate the effects of ASD-associated de novo variants in a family relative context, Kim et al., 2025 defined within-family standardized deviations (WFSD) by subtracting phenotype scores of unaffected family members and standardizing the result in 21,735 families from three ASD cohorts (the Korean Autism cohort, the Simons Simplex Collection, and SPARK); their analysis found that more genes enriched in de novo damaging protein-truncating variants (LOEUF < 0.37) and missense variants (MPC > 2) were identified using WFSD compared to raw phenotype scores, with 38 genes uniquely identified in the WFSD group, including the CTPS1 gene. A de novo loss-of-function variant in the CTPS1 gene was reported in a MSSNG proband in Zhou et al., 2022, while a de novo missense variant with a MPC > 2 was identified in a Korean ASD proband in Kim et al., 2024.

Molecular Function

This gene encodes an enzyme responsible for the catalytic conversion of UTP (uridine triphosphate) to CTP (cytidine triphospate). This reaction is an important step in the biosynthesis of phospholipids and nucleic acids. Activity of this proten is important in the immune system, and loss of function of this gene has been associated with immunodeficiency.

External Links
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Reports related to CTPS1 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Zhou X et al. (2022) Yes -
2 Support - Soo-Whee Kim et al. (2024) Yes -
3 Primary - Soo-Whee Kim et al. (2025) Yes -
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.221A>G p.Tyr74Cys missense_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.55del p.Ile19LeufsTer16 frameshift_variant De novo - Simplex 35982159 Zhou X et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

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.

10/1/2025
3

Initial score established: 3

Krishnan Probability Score

Score 0.041872062782983

Ranking 25776/25841 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 0.93219240396569

Ranking 2905/18225 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 0.94336420398434

Ranking 15659/18665 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 0.35266521898939

Ranking 1984/20870 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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