CDC42BPB
protein-codingCDC42 binding protein kinase beta, the group of AGC family kinases
Gene summary
This gene encodes a member of the serine/threonine protein kinase family. The encoded protein contains a Cdc42/Rac-binding p21 binding domain resembling that of PAK kinase. The kinase domain of this protein is most closely related to that of myotonic dystrophy kinase-related ROK. Studies of the similar gene in rat suggested that this kinase may act as a downstream effector of Cdc42 in cytoskeletal reorganization. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~125.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0859239
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0100038
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0859239
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CDC42BPB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006035.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 66 | 7 | 78 | ||
| missense | 2 | 17 | 342 | 56 | 2 | 419 |
| nonsense | 3 | 6 | 9 | 18 | ||
| start loss | 1 | 1 | ||||
| frameshift | 9 | 8 | 17 | |||
| splice donor/acceptor (+/-2bp) | 8 | 4 | 12 | |||
| Total | 5 | 41 | 368 | 122 | 9 | 545 |
Highest pathogenic variant AF is 0.0000037233917
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006026.3 | 37 | MANE Select | |
| Ensembl | ENSP00000355237.2 | 37 | MANE Select | |
| RefSeq | NP_001397983.1 | 36 | Standard | |
| Ensembl | ENSP00000489452.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein phosphorylation
- cytoskeleton organization
- establishment or maintenance of cell polarity
- signal transduction
- cell migration
Molecular Function
- magnesium ion binding
- protein kinase activity
- protein serine/threonine kinase activity
- ATP binding
- Rho GTPase binding
Cellular Component
- cytoplasm
- cytoskeleton
- plasma membrane
- cell-cell junction
- lamellipodium
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000361246
- Coding exons
- 37
- Length
- 125084
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125748
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.66 | 686 | 1.01e+3 | 0.677 | 0.0000638 | 11188 |
| Missense (PolyPhen) | 182 | 393.59 | 0.46241 | 4336 | ||
| Synonymous | -0.553 | 433 | 419 | 1.03 | 0.0000295 | 3268 |
| Loss of Function | 8.63 | 6 | 98.4 | 0.0610 | 0.00000557 | 1083 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000053 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2 (PubMed:21457715, PubMed:21949762). In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). Phosphorylates PPP1R12A (PubMed:21457715). In concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium resulting in its activation and subsequent phosphorylation of CFL1 which is important for lamellipodial F- actin regulation (By similarity). {ECO:0000250|UniProtKB:Q7TT50, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:21949762}.;
Recessive Scores
- pRec
- 0.116
Intolerance Scores
- LoFtool
- 0.0187
- RVIS EVS
- -3.29
- RVIS percentile EVS
- 0.42
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.437
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |