CDC42BPB

Chr 14AD

CDC42 binding protein kinase beta

Also known as: CHOCNS, MRCKB

NCBI Gene: 9578 ENSG00000198752 OMIM: 614062

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.121 OMIM phenotype

Clinical Summary— CDC42BPB

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

34 unique Pathogenic / Likely Pathogenic· 306 VUS of 496 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.12LOEUF

pLI 1.000

Z-score 8.63

OE 0.06 (0.03–0.12)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

3.66Z-score

OE missense 0.68 (0.64–0.72)

686 obs / 1013.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.06 (0.03–0.12)

0≤0.351.4

Missense OE?0.68 (0.64–0.72)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 6 / 98.4Missense obs/exp: 686 / 1013.9Syn Z: -0.55

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedCDC42BPB-related neurodevelopmental disorderLOFAD

This gene — mechanism propensity

0.3594th %ile

GOF

0.3986th %ile

LOF

0.72top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 59% of P/LP variants are LoF · LOEUF 0.12

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

496 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic28

VUS306

Likely Benign103

Benign12

Conflicting4

Pathogenic

Likely Pathogenic

306

VUS

103

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	1	0	0	6
Likely Pathogenic	15	13	0	0	28
VUS	9	282	13	2	306
Likely Benign	0	51	9	43	103
Benign	0	2	2	8	12
Conflicting	—				4
Total	29	349	24	53	459

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

51 pathogenic / likely-pathogenic (of 67) ClinVar copy-number / structural variants overlap CDC42BPB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →