CDC42BPB

Gene Facts

• HGNC Symbol: CDC42BPB (HGNC:1738)
• HGNC Name: CDC42 binding protein kinase beta
• Gene type: protein-coding gene
• Locus type: gene with protein product
• Previous symbols: No previous names found
• Alias symbols: MRCKB, KIAA1124
• %HI: 65.08
• pLI: 1
• LOEUF: 0.24
• Cytoband: 14q32.32
• Genomic Coordinates:

  GRCh37/hg19:	chr14:103398717-103523886
  GRCh38/hg38:	chr14:102932380-103057549

• MANE Select Transcript: NM_006035.4 ENST00000361246.7
• 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... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

• Dosage ID: ISCA-20979
• ClinGen Curation ID: CCID:006816
• Curation Status: Complete
• Issue Type: Dosage Curation - Gene
• Haploinsufficiency: Little Evidence for Haploinsufficiency (1)
• Triplosensitivity: No Evidence for Triplosensitivity (0)
• Last Evaluated: 10/24/2018

Haploinsufficiency (HI) Score Details

• HI Score: 1
• HI Evidence Strength: Little Evidence for Haploinsufficiency

HI Disease

• Autism Spectrum Disorder

HI Evidence

• PUBMED: 22495309
  O’Roak et al. (2012) describe a male (sample 13606.p1) with sporadic autism spectrum disorder (ASD) who has a nonverbal IQ (NVIQ) of 60 (Table 1). Whole exome sequencing of the affected individual identified a de novo heterozygous nonsense variant in exon 16 of the CDC42BPB gene (Chr14:103434646G>A) (Supplementary Table 3). This variant causes a premature termination at codon 764 of the CDC42BPB protein (p.Arg764*). This variant was not observed in either parent nor in the unaffected female sibling (13606.s1, Supplementary Table 5). Of note, the affected individual also had a de novo heterozygous missense variant in the H2AFV gene (Chr7:44875121G>A, p.Arg81Cys) which was not observed in either parent nor in the unaffected female sibling. However, the nonsense variant in CDC42BPB was identified, per the authors to be a top ASD risk contributing variant based on the deleteriousness of the variant, functional evidence, or previous studies whereas the missense variant in H2AFV was not. In addition, CDC42BPB was mapped to a highly interconnected beta-catenin/chromatin remodeling protein network ranked significantly for autism candidate genes. This variant is absent from gnomAD as of October 2018.
• PUBMED: 28263302
  Yuen et al. (2017) identified a de novo frameshift deletion in the CDC42BPB gene (Chr14:103442072_103442075delCTTT) in an individual with autism spectrum disorder (sample AU079605; Supplementary Table 4). Within this study cohort no other variants in CDC42BPB were observed in any of the other 2,260 autism cases or in any of the 2,573 controls.

• HI Evidence Comments: De Rubeis et al. (2014; PMID: 25363760) identified a de novo missense variant in exon 36 of the CDC42BPB gene (Chr14:103404494C>T) in an individual with autism spectrum disorder (ASD) (Supplementary Table 3). This variant causes an amino acid change from a valine to a methionine at codon 1651 (p.Val1651Met). In gnomAD this variant has an allele frequency of 0.00001446 (4/276640 alleles, rs201627729). Polyphen and SIFT identify this variant as benign and tolerated, respectively. Within this study cohort no other variants in CDC42BPB were observed in any of the other 3,870 autism cases or in any of the 9,937 ancestry-matched or parental controls.

Triplosensitivity (TS) Score Details

• TS Score: 0
• TS Evidence Strength: No Evidence for Triplosensitivity