Human Gene Module / Chromosome 2 / CMPK2

CMPK2cytidine/uridine monophosphate kinase 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
4 / 0
Aliases
CMPK2, NDK,  TMPK2,  TYKi,  UMP-CMPK2
Associated Syndromes
-
Chromosome Band
2p25.2
Associated Disorders
-
Relevance to Autism

A de novo nonsense variant in the CMPK2 gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while a de novo frameshift variant in this gene was observed in an ASD proband from a 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 CMPK2 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Molecular Function

This gene encodes one of the enzymes in the nucleotide synthesis salvage pathway that may participate in terminal differentiation of monocytic cells.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CMPK2 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I 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   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1227-2A>C - splice_site_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1306C>T p.Gln436Ter stop_gained De novo - Simplex 25363768 Iossifov I et al. (2014)
c.464del p.Glu155GlyfsTer114 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.466del p.Ala156HisfsTer113 frameshift_variant De novo - 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 CMPK2 gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while a de novo frameshift variant in this gene was observed in an ASD proband from a 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 CMPK2 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 CMPK2 gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while a de novo frameshift variant in this gene was observed in an ASD proband from a 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 CMPK2 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 CMPK2 gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while a de novo frameshift variant in this gene was observed in an ASD proband from a 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 CMPK2 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 CMPK2 gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while a de novo frameshift variant in this gene was observed in an ASD proband from a 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 CMPK2 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Krishnan Probability Score

Score 0.44628807833096

Ranking 14876/25841 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 0.001807965318229

Ranking 11347/18225 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 0.36094852493111

Ranking 234/18665 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 0.087449912194853

Ranking 6384/20870 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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