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Intellectual disability

Gene: CDC42BPB

Amber List (moderate evidence)
CDC42BPB (CDC42 binding protein kinase beta)
EnsemblGeneIds (GRCh38): ENSG00000198752
EnsemblGeneIds (GRCh37): ENSG00000198752
OMIM: 614062, Gene2Phenotype
CDC42BPB is in 3 panels

3 reviews

Ida Ertmanska (Genomics England Curator)

I don't know

Comment on phenotypes: OMIM phenotype accessed 24th Feb 2026.
Created: 24 Feb 2026, 10:44 a.m. | Last Modified: 24 Feb 2026, 10:44 a.m.
Panel Version: 9.279
Further reports (few clinical details):
PMID: 35586607 French et al., 2022
Trio WGS cohort. Case 190 (suppl data): heterozygous for c.2605dup, p.Gln869ProfsTer85, de novo; phenotype described as 'CDC42BPB-related disease'.

PMID: 31785789 Turner et al., 2019
Cohort of 8000+ parent-child trios with NDDs. Cases from suppl data table S2, all variants are de novo:
NDAR_INVAZ651VGG_wes1 - patient with autism, het for CDC42BPB:c.4951G>A, p.Val1651Met - 18 alleles reported in gnomAD v4.1.0
13934.p1 - patient with autism, het for CDC42BPB:c.4805A>G, p.Gln1602Arg - not in gnomAD v4.1.0
13606.p1 - patient with autism, het for CDC42BPB:c.2290C>T, p.Arg764* - 2 alleles in gnomAD v4.1.0
14338.p1 - patient with autism, het for CDC42BPB:c.1891_1893dup, p.Ala631dup - not in gnomAD v4.1.0
DDD4K.04028 - patient with a developmental disorder, het for CDC42BPB:c.3349G>A, p.Ala1117Thr - 32 alleles in gnomAD v4.1.0
DDD4K.02790 - patient with a developmental disorder, het for CDC42BPB:c.1067dup, p.Tyr357Leufs*4 - not in gnomAD v4.1.0
Created: 24 Feb 2026, 10:42 a.m. | Last Modified: 24 Feb 2026, 10:46 a.m.
Panel Version: 9.279

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Chilton-Okur-Chung neurodevelopmental syndrome, OMIM:619841

Publications

Created: 24 Feb 2026, 10:42 a.m.
Last Modified: 24 Feb 2026, 10:46 a.m.
Panel version: 9.278

Sarah Leigh (Genomics England Curator)

Comment on list classification: Not associated with phenotype in OMIM and as possible Gen2Phen gene. At least 12 variants reported in 14 unrelated cases of CDC42BPB-related Neurodevelopmental Disorder. Intellectual disability was apparent in 7/12 cases and at least 5 of these cases were de novo. However, only two of these cases did not have additional genetic changes reported.
Created: 9 Jun 2020, 2:25 p.m. | Last Modified: 9 Jun 2020, 2:57 p.m.
Panel Version: 3.88
Comment on phenotypes: CDC42BPB-related Neurodevelopmental Disorder is assigned by Gen2Phen.
Created: 8 Jun 2020, 5:20 p.m. | Last Modified: 8 Jun 2020, 5:20 p.m.
Panel Version: 3.87
Created: 8 Jun 2020, 5:20 p.m.
Last Modified: 9 Jun 2020, 2:57 p.m.
Panel version: 3.87

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Chilton et al (2020 - PMID: 32031333) report on 14 individuals with missense and loss-of-function CDC42BPB variants.

Features included hypotonia (8/11), DD (12/13 - the 14th was a fetus), ID (7/13), ASD (8/12), clinical seizures (in 3 - a 4th had abnormal EEG without seizures), behavioral abnormalities. Variable non-specific dysmorphic features were reported in some (sparse hair being the most frequent - 4/8). Additional features were observed in few (=<4) incl. cryptorchidism, ophthalmological issues, constipation, kidney abnormalities, micropenis, etc.

All individuals had non-diagnostic prior genetic testing (incl. CMA, FMR1, MECP2, Angelman/Prader-Willi methylation studies, autism gene panel - suggesting relevance to the current panel) or metabolic testing.

Variants were identified following clinical exome sequencing with Sanger confirmation. Most occurred as de novo events (11/14) while inheritance was not available for few (3/14). Missense variants did not display (particular) clustering.

Almost all variants were absent from gnomAD and were predicted to be deleterious in silico (among others almost all had CADD scores >25).

As the authors comment, CDC42BPB encodes myotonic dystrophy-related Cdc42-binding kinase β (MRCKβ) a serine/threonine protein kinase playing a role in regulation of cytoskeletal reorganization and cell migration in nonmuscle cells (through phosporylation of MLC2).

Previous studies have demonstrated that it is ubiquitously expressed with prenatal brain expression.

The gene appears to be intolerant to pLoF (pLI of 1) as well as to missense variants (Z-score of 3.66).

CDC42BPB is a downstream effector of CDC42. Mutations of the latter cause Takenouchi-Kosaki syndrome with DD/ID and some further overlapping features (with CDC42BPB-associated phenotypes).

Homozygous Cdc42bpb KO in mouse appears to be nonviable (MGI:2136459). Loss of gek in the eyes of Drosophila results in disrupted growth cone targeting to the lamina (gek is the fly CDC42BPB ortholog).

Please consider inclusion with amber / green rating in the ID panel (>=4 relevant individuals / variants) and other panels (e.g. for epilepsy, ASD).
Sources: Literature
Created: 6 May 2020, 3:20 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality

Publications

Created: 6 May 2020, 3:20 p.m.

Panel version: 3.35

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
Phenotypes
  • Chilton-Okur-Chung neurodevelopmental syndrome, OMIM:619841
  • Chilton-Okur-Chung neurodevelopmental syndrome, MONDO:0859239
OMIM
614062
Clinvar variants
Variants in CDC42BPB
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

24 Feb 2026, Gel status: 2

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: CDC42BPB were changed from CDC42BPB-related Neurodevelopmental Disorder; Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality to Chilton-Okur-Chung neurodevelopmental syndrome, OMIM:619841; Chilton-Okur-Chung neurodevelopmental syndrome, MONDO:0859239

9 Jun 2020, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: cdc42bpb has been classified as Amber List (Moderate Evidence).

9 Jun 2020, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: cdc42bpb has been classified as Green List (High Evidence).

8 Jun 2020, Gel status: 0

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: CDC42BPB were changed from Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality to CDC42BPB-related Neurodevelopmental Disorder; Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality

6 May 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: CDC42BPB was added gene: CDC42BPB was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: CDC42BPB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CDC42BPB were set to 32031333 Phenotypes for gene: CDC42BPB were set to Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality Penetrance for gene: CDC42BPB were set to unknown Review for gene: CDC42BPB was set to GREEN