CDC42BPA

protein-coding

CDC42 binding protein kinase alpha, the group of AGC family kinases

Gene summary

The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase contains multiple functional domains. Its kinase domain is highly similar to that of the myotonic dystrophy protein kinase (DMPK). This kinase also contains a Rac interactive binding (CRIB) domain, and has been shown to bind CDC42. It may function as a CDC42 downstream effector mediating CDC42 induced peripheral actin formation, and promoting cytoskeletal reorganization. Multiple alternatively spliced transcript variants have been described. [provided by RefSeq, Sep 2018]

MANE transcript

NM_001394014.1

Inheritance

—

ClinVar variants

U:200B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr1:226,989,865-227,318,492

External References & Databases

Ensembl (ENSG00000143776)

Transcript & Mutation Effects

hg38 • Region Span ~328.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CDC42BPA variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 173

not providedTotal: 14

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001394014.1. 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			7 clinvar	4 clinvar	3 clinvar	14
missense			180 clinvar	5 clinvar	2 clinvar	187
nonsense			1 clinvar			1
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	200	9	5	214

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001394014.1	RefSeq	NP_001380943.1	37	MANE Select
ENST00000366766.8	Ensembl	ENSP00000355728.5	37	MANE Select
NM_001366010.2	RefSeq	NP_001352939.1	35	Standard
NM_001366011.1	RefSeq	NP_001352940.1	36	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

CDC42 signaling events

Biological Process

protein phosphorylation
cell migration
actomyosin structure organization
actin cytoskeleton reorganization
intracellular signal transduction

Molecular Function

magnesium ion binding
protein serine/threonine kinase activity
protein binding
ATP binding
identical protein binding

Cellular Component

cytoplasm
cell-cell junction
lamellipodium
cell leading edge
actomyosin

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366769
Coding exons: 36
Length: 328610
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125748
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.39	684	884	0.774	0.0000456	11307
Missense (PolyPhen)		162	283.05	0.57234		3558
Synonymous	0.646	295	309	0.953	0.0000158	3137
Loss of Function	7.28	18	94.2	0.191	0.00000511	1192

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00034	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000057	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.000070	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

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 (PubMed:15723050, PubMed:9418861, PubMed:9092543). Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2 (PubMed:21457715). 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, LIMK1 and LIMK2 (PubMed:11340065, PubMed:11399775). May play a role in TFRC-mediated iron uptake (PubMed:20188707). 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:Q3UU96, ECO:0000269|PubMed:11340065, ECO:0000269|PubMed:11399775, ECO:0000269|PubMed:15723050, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:20188707, ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:9092543, ECO:0000269|PubMed:9418861}.;

Recessive Scores

pRec: 0.161

Intolerance Scores

LoFtool: 0.607
RVIS EVS: -1.54
RVIS percentile EVS: 3.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.655

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium