Human Gene Module / Chromosome 1 / CDC42BPA

CDC42BPACDC42 binding protein kinase alpha

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
6 / 7
Rare Variants / Common Variants
10 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
1q42.13
Associated Disorders
-
Relevance to Autism

A maternally-inherited complex genomic rearrangement involving duplication of seven exons and a nested deletion that partially deleted one exon of the CDC42BPA gene was identified by long-read whole-genome sequencing in Mortazavi et al., 2026 in an individual with a diagnosis of ASD and intellectual disability (REACH000529); this rearrangement was predicted to result in protein truncation. Multiple de novo missense variants and a de novo splice-region variant in CDC42BPA have been previously reported in ASD probands from the Simons Simplex Collection, the SPARK cohort, the Autism Sequencing Consortium, and the MSSNG cohort (De Rubeis et al., 2014; Yuen et al., 2017; Satterstrom et al., 2020; Zhou et al., 2022).

Molecular Function

The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase contains multiple functional domains. Its kinase domain is highly similar to that of the myotonic dystrophy protein kinase (DMPK). This kinase also contains a Rac interactive binding (CRIB) domain, and has been shown to bind CDC42. It may function as a CDC42 downstream effector mediating CDC42 induced peripheral actin formation, and promoting cytoskeletal reorganization. Chen et al., 1999 had previously demonstrated that CDC42BPA was involved in the regulation of neurite outgrowth in PC12 cells promoted by Cdc42 and Rac.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CDC42BPA (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Chen, X Q et al. (1999) No -
2 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , 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 Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
5 Support - Zhou X et al. (2022) Yes -
6 Support - Trost B et al. (2022) Yes -
7 Primary - Mortazavi, Milad et al. (2026) Yes -
Rare Variants   (10)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Familial Maternal Simplex 41806827 Mortazavi, Milad et al. (2026)
- - copy_number_loss Familial Maternal Simplex 41806827 Mortazavi, Milad et al. (2026)
c.1604A>C p.Lys535Thr missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.1295A>G p.Gln432Arg missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.143G>A p.Arg48Lys missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.2001+5del p.? splice_region_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.2982C>T p.Ser994= synonymous_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.1861C>T p.Leu621= synonymous_variant De novo - Multiplex 36368308 Trost B et al. (2022)
c.5246G>C p.Arg1749Pro missense_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.713T>G p.Val238Gly missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
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.

4/1/2026
3

Initial score established: 3

Krishnan Probability Score

Score 0.49682996714209

Ranking 2499/25841 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 0.99992014796463

Ranking 650/18225 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 0.57641909843937

Ranking 636/18665 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 0.38891241343301

Ranking 1575/20870 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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