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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CDC42BPB
CDC42 binding protein kinase beta
Chromosome 14 · 14q32.32
NCBI Gene: 9578Ensembl: ENSG00000198752.11HGNC: HGNC:1738UniProt: H0YLY0
98PubMed Papers
21Diseases
0Drugs
30Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedKinase
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
actomyosinactomyosin structure organizationcell migrationprotein kinase activityChilton-Okur-Chung neurodevelopmental syndromeneurodegenerative diseasegenetic disorderNeurodevelopmental disorder
✦AI Summary

CDC42BPB (also known as MRCKβ) is a serine/threonine protein kinase that functions as a critical downstream effector of the small GTPase CDC42, primarily regulating cytoskeleton dynamics and cell migration 1. The kinase phosphorylates key actin regulators including PPP1R12C, MYL9, and PPP1R12A to reorganize the actin cytoskeleton 23. CDC42BPB coordinates with accessory proteins (MYO18A, LURAP1, and FAM89B) to modulate lamellar actomyosin retrograde flow essential for cell protrusion and lamellipodial F-actin dynamics 4. In disease contexts, heterozygous CDC42BPB variants cause Chilton-Okur-Chung neurodevelopmental syndrome; de novo missense, frameshift, and nonsense mutations lead to developmental delay, intellectual disability, autism, hypotonia, and structural brain abnormalities including cerebellar and corpus callosum abnormalities 5. Beyond neurodevelopmental disorders, CDC42BPB shows emerging therapeutic relevance: genome-wide association studies identified CDC42BPB as a potential target for myasthenia gravis 67, and tumor-intrinsic CDC42BPB expression confers resistance to anti-PD-1 immunotherapy in breast cancer, with pharmacological inhibition synergizing with checkpoint blockade 8. CDC42BPB has also been identified in novel oncogenic fusions with ALK in gastrointestinal stromal tumors 9.

Sources cited
1
CDC42BPB functions as a Cdc42 effector regulating epithelial cell polarity and morphogenesis
PMID: 31113848
2
CDC42BPB phosphorylates PPP1R12C and PPP1R12A to regulate actin cytoskeletal reorganization
PMID: 21457715
3
CDC42BPB phosphorylates MYL9/MLC2 for actin cytoskeleton regulation
PMID: 21949762
4
CDC42BPB coordinates with MYO18A and LURAP1 to modulate lamellar actomyosin retrograde flow
PMID: 18854160
5
De novo heterozygous CDC42BPB variants cause neurodevelopmental disorder with developmental delay, intellectual disability, autism, hypotonia, and brain abnormalities
PMID: 32031333
6
CDC42BPB is identified as a potential drug target for myasthenia gravis through Mendelian randomization analysis
PMID: 38659056
7
CDC42BPB is a genetically supported druggable target for myasthenia gravis with colocalization evidence
PMID: 38521921
8
Tumor-intrinsic CDC42BPB confers resistance to anti-PD-1 immunotherapy in breast cancer, and its inhibition synergizes with anti-PD-1 treatment
PMID: 39086134
9
A novel CDC42BPB-ALK fusion was identified in a quadruple wild-type gastrointestinal stromal tumor
PMID: 35319816
Disease Associationsⓘ21
Chilton-Okur-Chung neurodevelopmental syndromeOpen Targets
0.75Strong
neurodegenerative diseaseOpen Targets
0.46Moderate
genetic disorderOpen Targets
0.42Moderate
Neurodevelopmental disorderOpen Targets
0.31Weak
autism spectrum disorderOpen Targets
0.30Weak
Global developmental delayOpen Targets
0.23Weak
Intellectual disabilityOpen Targets
0.23Weak
Atypical behaviorOpen Targets
0.23Weak
Autistic behaviorOpen Targets
0.23Weak
HypotoniaOpen Targets
0.23Weak
SeizureOpen Targets
0.23Weak
brain cancerOpen Targets
0.18Weak
nervous system cancerOpen Targets
0.18Weak
placenta praeviaOpen Targets
0.17Weak
peripheral nervous system diseaseOpen Targets
0.15Weak
Parkinson diseaseOpen Targets
0.13Weak
Mungan syndromeOpen Targets
0.06Suggestive
post-traumatic stress disorderOpen Targets
0.03Suggestive
breast cancerOpen Targets
0.03Suggestive
gastric cancerOpen Targets
0.03Suggestive
Chilton-Okur-Chung neurodevelopmental syndromeUniProt
Pathogenic Variants30
NM_006035.4(CDC42BPB):c.2599C>T (p.Arg867Cys)Pathogenic
CDC42BPB-related neurodevelopmental syndrome|not provided|CDC42BPB-related disorder|Chilton-Okur-Chung neurodevelopmental syndrome
★★☆☆2025→ Residue 867
NM_006035.4(CDC42BPB):c.2758_2759del (p.Glu920fs)Likely pathogenic
Chilton-Okur-Chung neurodevelopmental syndrome|not provided
★★☆☆2025→ Residue 920
NM_006035.4(CDC42BPB):c.2627G>C (p.Arg876Pro)Likely pathogenic
CDC42BPB-related neurodevelopmental syndrome|not provided
★★☆☆2023→ Residue 876
NM_006035.4(CDC42BPB):c.523G>T (p.Asp175Tyr)Likely pathogenic
CDC42BPB-related neurodevelopmental syndrome|Chilton-Okur-Chung neurodevelopmental syndrome|Autism spectrum disorder
★★☆☆2019→ Residue 175
NM_006035.4(CDC42BPB):c.2240G>A (p.Arg747Gln)Pathogenic
not provided
★☆☆☆2025→ Residue 747
NM_006035.4(CDC42BPB):c.530C>T (p.Ala177Val)Likely pathogenic
not provided
★☆☆☆2025→ Residue 177
NM_006035.4(CDC42BPB):c.1258C>T (p.Gln420Ter)Likely pathogenic
not provided
★☆☆☆2025→ Residue 420
NM_006035.4(CDC42BPB):c.3294C>G (p.Tyr1098Ter)Pathogenic
Chilton-Okur-Chung neurodevelopmental syndrome
★☆☆☆2024→ Residue 1098
NM_006035.4(CDC42BPB):c.1456_1459del (p.Glu486fs)Likely pathogenic
not provided
★☆☆☆2024→ Residue 486
NM_006035.4(CDC42BPB):c.2630T>C (p.Leu877Pro)Likely pathogenic
Chilton-Okur-Chung neurodevelopmental syndrome
★☆☆☆2024→ Residue 877
NM_006035.4(CDC42BPB):c.4481G>A (p.Trp1494Ter)Pathogenic
not provided
★☆☆☆2024→ Residue 1494
NM_006035.4(CDC42BPB):c.3713C>T (p.Pro1238Leu)Likely pathogenic
Chilton-Okur-Chung neurodevelopmental syndrome
★☆☆☆2024→ Residue 1238
NM_006035.4(CDC42BPB):c.3811+1G>ALikely pathogenic
not provided
★☆☆☆2023
NM_006035.4(CDC42BPB):c.2716A>C (p.Thr906Pro)Likely pathogenic
Chilton-Okur-Chung neurodevelopmental syndrome
★☆☆☆2023→ Residue 906
NM_006035.4(CDC42BPB):c.2T>C (p.Met1Thr)Likely pathogenic
Chilton-Okur-Chung neurodevelopmental syndrome
★☆☆☆2023→ Residue 1
NM_006035.4(CDC42BPB):c.2726+1G>ALikely pathogenic
Chilton-Okur-Chung neurodevelopmental syndrome
★☆☆☆2023
NM_006035.4(CDC42BPB):c.1411del (p.Leu471fs)Pathogenic
Inborn genetic diseases
★☆☆☆2022→ Residue 471
NM_006035.4(CDC42BPB):c.2346+2T>CLikely pathogenic
not provided
★☆☆☆2022
NM_006035.4(CDC42BPB):c.3615G>A (p.Trp1205Ter)Likely pathogenic
Neurodevelopmental disorder
★☆☆☆2021→ Residue 1205
NM_006035.4(CDC42BPB):c.364C>T (p.Arg122Ter)Pathogenic
not provided
★☆☆☆2020→ Residue 122
View on ClinVar ↗
Related Genes
CDC42Protein interaction92%UBXN2BProtein interaction83%CDC42BPAProtein interaction76%CDC42BPGShared pathway50%FMNL2Shared pathway33%PALLDShared pathway33%
Tissue Expression6 tissues
Heart
100%
Brain
88%
Ovary
75%
Lung
61%
Liver
60%
Bone Marrow
15%
Gene Interaction Network
Click a node to explore
CDC42BPBCDC42UBXN2BCDC42BPACDC42BPGFMNL2PALLD
PROTEIN STRUCTURE
Preparing viewer…
PDB5OTE · 1.68 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.23Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.17 [0.13–0.23]
RankingsWhere CDC42BPB stands among ~20K protein-coding genes
  • #4,868of 20,598
    Most Researched98 · top quartile
  • #1,805of 5,498
    Most Pathogenic Variants30
  • #670of 17,882
    Most Constrained (LOEUF)0.23 · top 5%
Genes detectedCDC42BPB
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
De novo heterozygous missense and loss-of-function variants in CDC42BPB are associated with a neurodevelopmental phenotype.
PMID: 32031333
Am J Med Genet A · 2020
1.00
2
Mendelian randomization and colocalization analysis reveal novel drug targets for myasthenia gravis.
PMID: 38659056
Hum Genomics · 2024
0.90
3
Regulation of Cdc42 and its effectors in epithelial morphogenesis.
PMID: 31113848
J Cell Sci · 2019
0.80
4
Epigenome-wide association studies identify novel DNA methylation sites associated with PTSD: a meta-analysis of 23 military and civilian cohorts.
PMID: 39696436
Genome Med · 2024
0.70
5
DNA methylation as a new tool for the differential diagnosis between T-LBL and lymphocyte-rich thymoma.
PMID: 39329449
J Pathol · 2024
0.60