CDC42BPB

Summary

CDC42BPB (CDC42 binding protein kinase beta, HGNC:1738) is a protein-coding gene on chromosome 14q32.32, encoding Serine/threonine-protein kinase MRCK beta (Q9Y5S2). 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.

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.

Source: NCBI Gene 9578 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Chilton-Okur-Chung neurodevelopmental syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 483 total — 6 pathogenic, 23 likely-pathogenic
• Phenotypes (HPO): 106
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency emerging evidence, triplosensitivity no evidence
• MANE Select transcript: NM_006035

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1738
Approved symbol	CDC42BPB
Name	CDC42 binding protein kinase beta
Location	14q32.32
Locus type	gene with protein product
Status	Approved
Aliases	MRCKB, KIAA1124
Ensembl gene	ENSG00000198752
Ensembl biotype	protein_coding
OMIM	614062
Entrez	9578

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000361246, ENST00000558321, ENST00000558867, ENST00000559043, ENST00000559245, ENST00000559790, ENST00000560492, ENST00000561271, ENST00000634889, ENST00000901190, ENST00000901191, ENST00000935623

RefSeq mRNA: 2 — MANE Select: NM_006035 NM_001411054, NM_006035

CCDS: CCDS91935, CCDS9978

Canonical transcript exons

ENST00000361246 — 37 exons

Exon	Start	End
ENSE00000660534	102946468	102946684
ENSE00000660535	102947721	102947802
ENSE00000660536	102949765	102949904
ENSE00000660537	102950466	102950602
ENSE00000660538	102952498	102952603
ENSE00000660539	102954198	102954275
ENSE00000660540	102954602	102954688
ENSE00000660541	102959631	102959710
ENSE00000660542	102963061	102963155
ENSE00000660543	102964502	102964650
ENSE00000660544	102966282	102966387
ENSE00000660545	102967046	102967170
ENSE00000660546	102968253	102968358
ENSE00001152312	103056999	103057549
ENSE00002547906	102943891	102944487
ENSE00002559885	102968472	102968716
ENSE00003545863	102945662	102945724
ENSE00003980670	102940227	102940324
ENSE00003980671	102932380	102933843
ENSE00003980672	102980773	102981021
ENSE00003980673	102983556	102983756
ENSE00003980674	102938306	102938411
ENSE00003980675	102939610	102939727
ENSE00003980676	102939830	102939947
ENSE00003980677	102938104	102938174
ENSE00003980678	102975684	102975803
ENSE00003980679	102986487	102986580
ENSE00003980680	102999565	102999713
ENSE00003980681	103012097	103012188
ENSE00003980682	102974016	102974149
ENSE00003980683	102971919	102972161
ENSE00003980684	102940046	102940130
ENSE00003980685	102970151	102970261
ENSE00003980686	103003928	103004023
ENSE00003980687	102978126	102978205
ENSE00003980688	102975883	102976049
ENSE00003980689	103008472	103008555

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 96.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.0856 / max 181.5161, expressed in 1763 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
145055	17.3596	1743
145053	4.3922	1501
145052	1.6584	959
145056	1.1178	673
145048	0.6030	264
145057	0.4892	216
145058	0.4528	201
145049	0.0126	5

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	96.26	gold quality
mucosa of stomach	UBERON:0001199	96.13	gold quality
body of uterus	UBERON:0009853	95.87	gold quality
right frontal lobe	UBERON:0002810	95.74	gold quality
metanephros cortex	UBERON:0010533	95.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.70	gold quality
adenohypophysis	UBERON:0002196	95.51	gold quality
prefrontal cortex	UBERON:0000451	95.47	gold quality
left ovary	UBERON:0002119	95.47	gold quality
endocervix	UBERON:0000458	95.38	gold quality
ectocervix	UBERON:0012249	95.38	gold quality
right lung	UBERON:0002167	95.33	gold quality
sural nerve	UBERON:0015488	95.33	gold quality
cortical plate	UBERON:0005343	95.27	gold quality
cerebellar hemisphere	UBERON:0002245	95.26	gold quality
cerebellar cortex	UBERON:0002129	95.23	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.16	gold quality
lower esophagus	UBERON:0013473	95.15	gold quality
skin of leg	UBERON:0001511	95.02	gold quality
tibial nerve	UBERON:0001323	95.01	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.96	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.94	gold quality
right ovary	UBERON:0002118	94.93	gold quality
amygdala	UBERON:0001876	94.91	gold quality
pituitary gland	UBERON:0000007	94.86	gold quality
right coronary artery	UBERON:0001625	94.79	gold quality
right lobe of thyroid gland	UBERON:0001119	94.75	gold quality
anterior cingulate cortex	UBERON:0009835	94.71	gold quality
cingulate cortex	UBERON:0003027	94.69	gold quality
left uterine tube	UBERON:0001303	94.66	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

127 targeting CDC42BPB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488

Functional genomics

ClinGen dosage: haploinsufficiency 2 (emerging evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 10)

• analysis of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta (PMID:18263588)
• Q-PCR results demonstrated VH2 genes were overexpressed in ankylosing spondylitis patients. The sequence analysis revealed the majority of them contained CDC42 binding protein kinase Beta (CDC42 BPB) genes. (PMID:20177145)
• Cdc42-dependent formation of the ZO-1/MRCKbeta complex at the leading edge controls cell migration. (PMID:21240187)
• these results provide further validation for MRCK involvement in regulation of cancer cell invasion. (PMID:21949762)
• The predicted expression of the CDC42BPB gene in the brain (basal ganglia) (effect, 0.14; P = 2.7 x 10-03) was associated with Major Depression. (PMID:29998287)
• The CDC42 effector protein MRCKbeta autophosphorylates on Threonine 1108. (PMID:30667325)
• De novo heterozygous missense and loss-of-function variants in CDC42BPB are associated with a neurodevelopmental phenotype. (PMID:32031333)
• Sequence variant in the CDC42BPB gene is potentially associated with Mullerian duct anomalies. (PMID:32043305)
• Helicobacter pylori-induced gastric cancer is orchestrated by MRCKbeta-mediated Siah2 phosphorylation. (PMID:33536006)
• Tumor-intrinsic CDC42BPB confers resistance to anti-PD-1 immune checkpoint blockade in breast cancer. (PMID:39086134)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdc42bpb	ENSDARG00000019383
mus_musculus	Cdc42bpb	ENSMUSG00000021279
rattus_norvegicus	Cdc42bpb	ENSRNOG00000009675
drosophila_melanogaster	gek	FBGN0023081
caenorhabditis_elegans		WBGENE00006437

Paralogs (5): ROCK1 (ENSG00000067900), CIT (ENSG00000122966), ROCK2 (ENSG00000134318), CDC42BPA (ENSG00000143776), CDC42BPG (ENSG00000171219)

Protein

Protein identifiers

Serine/threonine-protein kinase MRCK beta — Q9Y5S2 (reviewed: Q9Y5S2)

Alternative names: CDC42-binding protein kinase beta, DMPK-like beta, Myotonic dystrophy kinase-related CDC42-binding kinase beta

All UniProt accessions (3): Q9Y5S2, A0A0U1RRC3, H0YLY0

UniProt curated annotations — full annotation on UniProt →

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. In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration. Phosphorylates PPP1R12A. 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.

Subunit / interactions. Homodimer and homotetramer via the coiled coil regions. Interacts tightly with GTP-bound but not GDP-bound CDC42. Interacts with TJP1, when in the presence of catalytically active CDC42. Forms a tripartite complex with MYO18A and LURAP1 with the latter acting as an adapter connecting CDC42BPB and MYO18A. LURAP1 binding results in activation of CDC42BPB by abolition of its negative autoregulation. Interacts with STRIP1, STRN3 and SIKE1. Interacts with CPNE4 (via VWFA domain). Interacts with LURAP1. Interacts (via AGC-kinase C-terminal domain) with FAM89B/LRAP25 (via LRR repeat). Forms a tripartite complex with FAM89B/LRAP25 and LIMK1.

Subcellular location. Cytoplasm. Cell membrane. Cell junction. Cell projection. Lamellipodium.

Tissue specificity. Expressed in all tissues examined, with high levels in heart, brain, placenta and lung.

Post-translational modifications. Proteolytically cleaved by caspases upon apoptosis induction.

Disease relevance. Chilton-Okur-Chung neurodevelopmental syndrome (CHOCNS) [MIM:619841] A disorder characterized by developmental delay, intellectual disability, hypotonia, and structural brain abnormalities including cerebellar vermis hypoplasia and agenesis or hypoplasia of the corpus callosum. Most patients have behavioral abnormalities, including autism spectrum disorder, attention deficit and hyperactivity disorder, and aggression. About half of patients have dysmorphic facial features. Rare involvement of other organ systems may be present. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Maintained in an inactive, closed conformation by an interaction between the kinase domain and the negative autoregulatory C-terminal coiled-coil region. Agonist binding to the phorbol ester binding site disrupts this, releasing the kinase domain to allow N-terminus-mediated dimerization and kinase activation by transautophosphorylation. Inhibited by chelerythrine chloride.

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. DMPK subfamily.

RefSeq proteins (2): NP_001397983, NP_006026* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000095	CRIB_dom	Domain
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR001180	CNH_dom	Domain
IPR001849	PH_domain	Domain
IPR002219	PKC_DAG/PE	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR014930	Myotonic_dystrophy_kinase_coil	Domain
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020454	DAG/PE-bd	Domain
IPR031597	KELK	Domain
IPR042718	MRCKB_STKc	Domain
IPR046349	C1-like_sf	Homologous_superfamily
IPR050839	Rho-assoc_Ser/Thr_Kinase	Family
IPR057529	MRCK/ROCK_PH	Domain

Pfam: PF00069, PF00130, PF00780, PF08826, PF15796, PF25346

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (89 total): helix 21, sequence variant 17, strand 16, modified residue 11, domain 5, turn 4, compositionally biased region 3, region of interest 3, coiled-coil region 2, binding site 2, sequence conflict 2, chain 1, active site 1, zinc finger region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5OTE	X-RAY DIFFRACTION	1.68
4UAL	X-RAY DIFFRACTION	1.71
4UAK	X-RAY DIFFRACTION	1.73
5OTF	X-RAY DIFFRACTION	2
3TKU	X-RAY DIFFRACTION	2.15
3QFV	X-RAY DIFFRACTION	2.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5S2-F1	76.28	0.31

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 200 (proton acceptor)

Ligand- & substrate-binding residues (2): 82–90; 105

Post-translational modifications (11): 221, 233, 239, 423, 671, 954, 1680, 1682, 1686, 1690, 1693

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 404 (showing top): GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, TTTGTAG_MIR520D, TCF4_Q5, ONKEN_UVEAL_MELANOMA_UP, GOBP_ACTOMYOSIN_STRUCTURE_ORGANIZATION, GGCNNMSMYNTTG_UNKNOWN, GOCC_CELL_CELL_JUNCTION, CTTTGTA_MIR524, chr14q32, ACACTCC_MIR122A, GOCC_ACTOMYOSIN, GOCC_LAMELLIPODIUM, GOCC_ANCHORING_JUNCTION, ZF5_01, GOMF_MAGNESIUM_ION_BINDING

GO Biological Process (7): protein phosphorylation (GO:0006468), cytoskeleton organization (GO:0007010), establishment or maintenance of cell polarity (GO:0007163), signal transduction (GO:0007165), cell migration (GO:0016477), actin cytoskeleton organization (GO:0030036), actomyosin structure organization (GO:0031032)

GO Molecular Function (11): magnesium ion binding (GO:0000287), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), zinc ion binding (GO:0008270), protein-containing complex binding (GO:0044877), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (12): cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), lamellipodium (GO:0030027), cell leading edge (GO:0031252), actomyosin (GO:0042641), extracellular exosome (GO:0070062), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	3
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cellular process	2
protein kinase activity	2
phosphorylation	1
protein modification process	1
organelle organization	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell motility	1
cytoskeleton organization	1
actin filament-based process	1
actin cytoskeleton organization	1
metal ion binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
anchoring junction	1
cell leading edge	1
plasma membrane bounded cell projection	1
actin cytoskeleton	1
extracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

2554 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC42BPB	CDC42	P21181	660
CDC42BPB	UBXN2B	Q14CS0	641
CDC42BPB	AMN	Q9BXJ7	608
CDC42BPB	TRAF3	Q13114	603
CDC42BPB	CDC42EP4	Q9H3Q1	562
CDC42BPB	TJP1	Q07157	544
CDC42BPB	MYL2	P10916	520
CDC42BPB	MPRIP	Q6WCQ1	515
CDC42BPB	ARHGEF3	Q9NR81	476
CDC42BPB	SRCIN1	Q9C0H9	466
CDC42BPB	PPP1R12C	Q9BZL4	462
CDC42BPB	ARHGEF33	A8MVX0	456
CDC42BPB	CDC42SE1	Q9NRR8	447
CDC42BPB	CDC42SE2	Q9NRR3	439
CDC42BPB	ARHGEF18	Q6ZSZ5	436

IntAct

81 interactions, top by confidence:

A	B	Type	Score
UBXN2B	VCP	psi-mi:“MI:0914”(association)	0.910
PRKCZ	NIPSNAP2	psi-mi:“MI:0914”(association)	0.730
CSNK2B	RPS6KA4	psi-mi:“MI:0914”(association)	0.640
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
CDC42BPB	MYO18A	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
PTGES3	AIP	psi-mi:“MI:0914”(association)	0.530
APBA3	CLSTN1	psi-mi:“MI:0914”(association)	0.530
LURAP1	TRIM24	psi-mi:“MI:0914”(association)	0.530
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
	AP3D1	psi-mi:“MI:0914”(association)	0.460
	MYL12B	psi-mi:“MI:0914”(association)	0.460
CDC42BPB	TJP1	psi-mi:“MI:0403”(colocalization)	0.460
TJP1	CDC42BPB	psi-mi:“MI:0915”(physical association)	0.460
CDC42BPB	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
Prkcz	GOLIM4	psi-mi:“MI:0914”(association)	0.350
MYO18A	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Tecpr2	PUF60	psi-mi:“MI:0914”(association)	0.350
RXRB	CCNK	psi-mi:“MI:0914”(association)	0.350
PPP5C	SNRNP200	psi-mi:“MI:0914”(association)	0.350
BCAR1	PSMD11	psi-mi:“MI:0914”(association)	0.350
BCAR1	PFN1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
LURAP1L	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (149): CDC42BPB (Affinity Capture-MS), CDC42BPB (Affinity Capture-MS), CDC42BPB (Affinity Capture-MS), CDC42BPB (Co-fractionation), CDC42BPB (Affinity Capture-MS), CDC42BPB (Affinity Capture-MS), CDC42BPB (Affinity Capture-MS), CDC42BPB (Affinity Capture-MS), CDC42BPB (Affinity Capture-MS), CDC42BPB (Affinity Capture-MS), CDC42BPB (Affinity Capture-Western), CDC42BPB (Proximity Label-MS), CDC42BPB (Affinity Capture-MS), CDC42BPB (Affinity Capture-MS), CDC42BPB (Affinity Capture-MS)

ESM2 similar proteins: A0JMA8, A1A5P5, A5WW21, E7F187, E7FDW2, O01583, O14827, O35711, O43150, O54874, P28818, P33175, Q08CX1, Q12756, Q12840, Q21653, Q22908, Q2KI89, Q3UP38, Q3UU96, Q5R629, Q5R9K7, Q5RI75, Q5U245, Q5VT25, Q5W7F2, Q619T5, Q6NRC9, Q6QLM7, Q7SIG6, Q7TT49, Q7TT50, Q7Z3E5, Q86W92, Q8C8U0, Q8CIS0, Q8IZ41, Q8LNZ2, Q8ND30, Q8R0Z2

Diamond homologs: A0A7J6K7I9, A0A7J6K7Y0, A0A7J6KD88, A8X775, B1WAR9, C4YRB7, D2HXI8, E1C2I2, E9PSL7, G1X456, G5EGQ3, M3TYT0, O00506, O01583, O01700, O14578, O54874, O61267, O75116, O77819, O80902, O88643, O97627, P05131, P0CY23, P0CY24, P13677, P21146, P25098, P26817, P26818, P32865, P34100, P35465, P38070, P48562, P49025, P49673, P54265, P70335

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDC42BPB	“up-regulates activity”	MSN	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

483 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	23
Uncertain significance	299
Likely benign	101
Benign	12

Top pathogenic / likely-pathogenic (29)

Variant ID	HGVS	Classification
1069195	NM_006035.4(CDC42BPB):c.364C>T (p.Arg122Ter)	Pathogenic
1076774	NM_006035.4(CDC42BPB):c.3985C>T (p.Gln1329Ter)	Pathogenic
2216856	NM_006035.4(CDC42BPB):c.1411del (p.Leu471fs)	Pathogenic
3343097	NM_006035.4(CDC42BPB):c.4481G>A (p.Trp1494Ter)	Pathogenic
3374852	NM_006035.4(CDC42BPB):c.3294C>G (p.Tyr1098Ter)	Pathogenic
4532603	NM_006035.4(CDC42BPB):c.2240G>A (p.Arg747Gln)	Pathogenic
1067660	NM_006035.4(CDC42BPB):c.3067-2A>G	Likely pathogenic
1251945	NM_006035.4(CDC42BPB):c.3615G>A (p.Trp1205Ter)	Likely pathogenic
2122347	NM_006035.4(CDC42BPB):c.2346+2T>C	Likely pathogenic
2627007	NM_006035.4(CDC42BPB):c.2T>C (p.Met1Thr)	Likely pathogenic
2663783	NM_006035.4(CDC42BPB):c.2726+1G>A	Likely pathogenic
2672127	NM_006035.4(CDC42BPB):c.2716A>C (p.Thr906Pro)	Likely pathogenic
3238803	NM_006035.4(CDC42BPB):c.2758_2759del (p.Glu920fs)	Likely pathogenic
3340896	NM_006035.4(CDC42BPB):c.3811+1G>A	Likely pathogenic
3376343	NM_006035.4(CDC42BPB):c.3713C>T (p.Pro1238Leu)	Likely pathogenic
3391659	NM_006035.4(CDC42BPB):c.1456_1459del (p.Glu486fs)	Likely pathogenic
3766608	NM_006035.4(CDC42BPB):c.2630T>C (p.Leu877Pro)	Likely pathogenic
3781031	NM_006035.4(CDC42BPB):c.530C>T (p.Ala177Val)	Likely pathogenic
4075550	NM_006035.4(CDC42BPB):c.1258C>T (p.Gln420Ter)	Likely pathogenic
694462	NM_006035.4(CDC42BPB):c.523G>T (p.Asp175Tyr)	Likely pathogenic
694463	NM_006035.4(CDC42BPB):c.879C>G (p.Ile293Met)	Likely pathogenic
694465	NM_006035.4(CDC42BPB):c.2612T>C (p.Leu871Pro)	Likely pathogenic
694466	NM_006035.4(CDC42BPB):c.2626C>T (p.Arg876Trp)	Likely pathogenic
694467	NM_006035.4(CDC42BPB):c.2627G>C (p.Arg876Pro)	Likely pathogenic
694468	NM_006035.4(CDC42BPB):c.3896G>A (p.Arg1299Gln)	Likely pathogenic
694469	NM_006035.4(CDC42BPB):c.4049G>C (p.Arg1350Pro)	Likely pathogenic
694470	NM_006035.4(CDC42BPB):c.37_50del (p.Leu13fs)	Likely pathogenic
694471	NM_006035.4(CDC42BPB):c.1630dup (p.Glu544fs)	Likely pathogenic
694472	NM_006035.4(CDC42BPB):c.2290C>T (p.Arg764Ter)	Likely pathogenic

SpliceAI

6535 predictions. Top by Δscore:

Variant	Effect	Δscore
14:102933840:CAGG:C	acceptor_gain	1.0000
14:102938300:CTGTA:C	donor_loss	1.0000
14:102938301:TGTA:T	donor_loss	1.0000
14:102938302:GTACC:G	donor_loss	1.0000
14:102938303:TA:T	donor_loss	1.0000
14:102938304:ACC:A	donor_loss	1.0000
14:102938305:C:CA	donor_loss	1.0000
14:102938407:GCACT:G	acceptor_gain	1.0000
14:102938408:CACT:C	acceptor_gain	1.0000
14:102938408:CACTC:C	acceptor_gain	1.0000
14:102938410:CT:C	acceptor_gain	1.0000
14:102938412:C:CC	acceptor_gain	1.0000
14:102939825:CCTAC:C	donor_loss	1.0000
14:102939827:TA:T	donor_loss	1.0000
14:102939829:CCG:C	donor_gain	1.0000
14:102939851:T:TA	donor_gain	1.0000
14:102939943:CGCTC:C	acceptor_gain	1.0000
14:102939945:CTC:C	acceptor_gain	1.0000
14:102939946:TC:T	acceptor_gain	1.0000
14:102939947:CC:C	acceptor_gain	1.0000
14:102939948:C:CC	acceptor_gain	1.0000
14:102939948:CT:C	acceptor_loss	1.0000
14:102939949:T:G	acceptor_loss	1.0000
14:102939951:C:CT	acceptor_gain	1.0000
14:102939957:C:CT	acceptor_gain	1.0000
14:102940041:CTCA:C	donor_loss	1.0000
14:102940042:TCAC:T	donor_loss	1.0000
14:102940044:A:AC	donor_gain	1.0000
14:102940044:AC:A	donor_gain	1.0000
14:102940045:C:CC	donor_gain	1.0000

AlphaMissense

11261 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:102939657:G:C	H1594D	1.000
14:102939664:G:C	H1591Q	1.000
14:102939664:G:T	H1591Q	1.000
14:102939666:G:C	H1591D	1.000
14:102939670:G:C	F1589L	1.000
14:102939670:G:T	F1589L	1.000
14:102939672:A:G	F1589L	1.000
14:102943915:A:G	W1462R	1.000
14:102943915:A:T	W1462R	1.000
14:102946601:C:A	W1205C	1.000
14:102946601:C:G	W1205C	1.000
14:102946603:A:G	W1205R	1.000
14:102946603:A:T	W1205R	1.000
14:102947728:A:T	I1175K	1.000
14:102947752:G:T	A1167D	1.000
14:102947761:A:T	V1164D	1.000
14:102947776:A:T	V1159D	1.000
14:102949872:C:A	W1114C	1.000
14:102949872:C:G	W1114C	1.000
14:102949873:C:G	W1114S	1.000
14:102949874:A:G	W1114R	1.000
14:102949874:A:T	W1114R	1.000
14:102950470:A:T	V1102D	1.000
14:102980803:G:C	F370L	1.000
14:102980803:G:T	F370L	1.000
14:102980805:A:G	F370L	1.000
14:102980954:A:G	L320P	1.000
14:102983590:A:G	L286P	1.000
14:102983590:A:T	L286H	1.000
14:102983594:A:G	S285P	1.000

dbSNP variants (sampled 300 via entrez): RS1000018391 (14:103013735 C>G), RS1000049597 (14:103013901 C>T), RS1000051943 (14:102947543 C>T), RS1000057670 (14:103031003 T>G), RS1000071597 (14:102971626 G>A), RS1000073730 (14:102979522 T>C), RS1000125621 (14:102971831 A>G), RS1000131401 (14:102964807 G>A,C), RS1000160658 (14:103012241 T>C), RS1000212521 (14:103009255 G>C), RS1000246825 (14:102932617 C>G,T), RS1000277047 (14:103011879 G>C), RS1000302318 (14:102997813 A>T), RS1000303895 (14:102940390 G>A), RS1000321775 (14:103047040 C>A,T)

Disease associations

OMIM: gene MIM:614062 | disease phenotypes: MIM:619841

GenCC curated gene-disease

Disease	Classification	Inheritance
Chilton-Okur-Chung neurodevelopmental syndrome	Strong	Autosomal dominant
complex neurodevelopmental disorder	Moderate	Autosomal dominant

Mondo (4): neurodevelopmental disorder (MONDO:0700092), Chilton-Okur-Chung neurodevelopmental syndrome (MONDO:0859239), autism spectrum disorder (MONDO:0005258), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

106 total (30 of 106 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000028	Cryptorchidism
HP:0000041	Chordee
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000154	Wide mouth
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000276	Long face
HP:0000293	Full cheeks
HP:0000294	Low anterior hairline
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000403	Recurrent otitis media
HP:0000407	Sensorineural hearing impairment
HP:0000421	Epistaxis
HP:0000426	Prominent nasal bridge
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000476	Cystic hygroma
HP:0000486	Strabismus

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001031_2	Large B-cell lymphoma	3.000000e-07
GCST005951_8	Body mass index	7.000000e-09
GCST010002_161	Refractive error	1.000000e-20
GCST90002395_213	Mean platelet volume	5.000000e-20
GCST90011900_109	Serum alkaline phosphatase levels	2.000000e-11
GCST90020024_477	A body shape index	3.000000e-08
GCST90020029_280	Waist circumference adjusted for body mass index	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004533	alkaline phosphatase measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5052 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 139,826 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL5416410	DASATINIB	4	655
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2	1,681
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1667969	SAR-407899 FREE BASE	2	157
CHEMBL1944698	ZOTIRACICLIB	2	2,915
CHEMBL3039513	DECERNOTINIB	2	1,418
CHEMBL574737	UCN-01	2	2,217
CHEMBL3545083	RGB-286638	1	551
CHEMBL494089	GSK-690693	1	2,061
CHEMBL571948	Y-39983	1	705

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — GEK subfamily

Binding affinities (BindingDB)

105 measured of 105 human assays (105 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(6S)-8-(3-pyridazin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)- 1,8-diazaspiro[5.5]undecane	KI	0.026 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
3-[4-(1,8- diazaspiro[5.5]undecan- 8-yl)-1H-pyrrolo[2,3- b]pyridin-3- yl]isothiazole	KI	0.049 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
2-[4-(1,8- diazaspiro[5.5]undecan-8- yl)-1H-pyrrolo[2,3- b]pyridin-3-yl]thiazole	KI	0.063 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
8-[3-(2-pyridyl)-1H- pyrrolo[2,3-b]pyridin-4- yl]-1,8- diazaspiro[5.5]undecane	KI	0.073 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
2-[4-(1,8- diazaspiro[5.5]undecan-8- yl)-1H-pyrrolo[2,3- b]pyridin-3-yl]-5-methyl- thiazole	KI	0.092 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
3-pyrimidin-4-yl-4- [[(3R)-3-piperidyl[oxy]- 1H-pyrrolo[2,3- b]pyridine	KI	0.144 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
2-[4-(2,6- diazaspiro[4.5]decan-2- yl)-1H-pyrrolo[2,3- b]pyridin-3-yl]-5-methyl- thiazole	KI	0.154 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
(3S)-3-N’-cyclopropyl-1-(3-pyrimidin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidine-3,3-diamine	KI	0.202 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
2-(3-pyridazin-4-yl-1H- pyrrolo[2,3-b]pyridin-4-yl)- 2,6-diazaspiro[4.5]decane	KI	0.219 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
4-(1,8- diazaspiro[5.5]undecan-8- yl)-1H-pyrrolo[2,3- b]pyridine-3-carbonitrile	KI	0.249 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
(3S)-1-(3-isothiazol-4-yl- 1H-pyrrolo[2,3-b]pyridin- 4-yl)-N-methyl-piperidin- 3-amine	KI	0.273 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
4-fluoro-1-(3-pyrimidin-4- yl-1H-pyrrolo[2,3- b]pyridin-4-yl)piperidin-3- amine	KI	0.323 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
2-[4-(1,8- diazaspiro[5.5]undecan-8- yl)-1H-pyrrolo[2,3- b]pyridin-3-yl]-4-methyl- thiazole	KI	0.36 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
2-[4-(1,7- diazaspiro[4.4]nonan-7- yl)-1H-pyrrolo[2,3- b]pyridin-3-yl]thiazole	KI	0.37 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
(3S)-N-methyl-1-[3-(2- pyridyl)-1H-pyrrolo[2,3- b]pyridin-4-yl]piperidin-3- amine	KI	0.506 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
2-[3-(2-pyridyl)-1H- pyrrolo[2,3-b]pyridin-4- yl]-2,6- diazaspiro[4.5]decane	KI	0.549 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
(3S)-1-[3-(5-fluoro-3- pyridyl)-1H-pyrrolo[2,3- b]pyridin-4-yl]-N-methyl- piperidin-3-amine	KI	0.729 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
8-[3-(2-methylpyrimidin-5- yl)-1H-pyrrolo[2,3- b]pyridin-4-yl]-1,8- diazaspiro[5.5]undecane	KI	0.786 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
(3S)-N-ethyl-1-(3-pyridazin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-amine	KI	0.802 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
2-[4-(1,9- diazaspiro[4.5]decan-9- yl)-1H-pyrrolo[2,3- b]pyridin-3-yl]-5-methyl- thiazole	KI	0.882 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
3-[4-[(6R)-1,8- diazaspiro[5.5]undecan- 8-yl]-1H-pyrrolo[2,3- b]pyridin-3- yl]isothiazole	KI	0.907 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
2-[4-(1,7- diazaspiro[4.4]nonan-7-yl)- 1H-pyrrolo[2,3-b]pyridin-3- yl]-5-methyl-thiazole	KI	0.93 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
4-(1,7- diazaspiro[4.4]nonan-7- yl)-3-pyridazin-4-yl-1H- pyrrolo[2,3-b]pyridine	KI	0.933 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
4-[(5S)-1,7- diazaspiro[4.4]nonan-7- yl]-3-pyrimidin-5-yl-1H- pyrrolo[2,3-b]pyridine	KI	0.947 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
4-[4-(1,8- diazaspiro[5.5]undecan-8- yl)-1H-pyrrolo[2,3- b]pyridin-3-yl]-2-methyl- thiazole	KI	1 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
N-[[(3S)-3-aminopiperidin-3-yl]methyl]-3-pyrimidin-5-yl-1H-pyrrolo[2,3-b]pyridin-4-amine	KI	1.07 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
4-(3- piperidylmethoxy)-3- pyrimidin-5-yl-1H- pyrrolo[2,3-b]pyridine	KI	1.07 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
4-(2,7- diazaspiro[4.4]nonan-2- yl)-3-pyridazin-4-yl-1H- pyrrolo[2,3-b]pyridine	KI	1.12 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
(6R)-8-(3-pyridazin-4-yl- 1H-pyrrolo[2,3-b]pyridin-4- yl)-1,8- diazaspiro[5.5]undecane	KI	1.18 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
(3S)-N-methyl-1-[3-(3- pyridyl)-1H-pyrrolo[2,3- b]pyridin-4-yl]piperidin-3- amine	KI	1.27 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
Staurosporine	KD	1.7 nM
(3S)-1-[3-(3-fluoro-2- pyridyl)-1H-pyrrolo[2,3- b]pyridin-4-yl]-N-methyl- piperidin-3-amine	KI	1.73 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
4-(1,7- diazaspiro[4.4]nonan-7- yl)-1H-pyrrolo[2,3- b]pyridine-3-carbonitrile	KI	1.92 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
2-[[(3S)-1-(3-pyrimidin-5- yl-1H-pyrrolo[2,3- b]pyridin-4-yl)-3- piperidyl]amino]ethanol	KI	2.23 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
7-(3-pyridazin-4-yl-1H- pyrrolo[2,3-b]pyridin-4-yl)- 2,7-diazaspiro[4.5]decane	KI	2.4 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
8-[3-(2-methylpyrimidin-4- yl)-1H-pyrrolo[2,3- b]pyridin-4-yl]-1,8- diazaspiro[5.5]undecane	KI	2.76 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
(3S)-N-cyclopropyl-1-(3- pyridazin-3-yl-1H- pyrrolo[2,3-b]pyridin-4- yl)piperidin-3-amine	KI	2.77 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
4-(1,7- diazaspiro[4.4]nonan-7- yl)-3-(2-pyridyl)-1H- pyrrolo[2,3-b]pyridine	KI	2.83 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
(3aR,7aS)-1-methyl-5-(3-pyrimidin-5-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)-3,3a,4,6,7,7a-hexahydro-2H-imidazo[4,5-c]pyridine	KI	3.12 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
2-[4-[(6R)-1,8- diazaspiro[5.5]undecan-8- yl]-1H-pyrrolo[2,3- b]pyridin-3-yl]thiazole	KI	3.21 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
Phorbol ester (PDBU)	KD	3.4 nM
(3S)-1-(3-pyrimidin-5-yl- 1H-pyrrolo[2,3-b]pyridin- 4-yl)pyrrolidin-3-amine	KI	3.48 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
3-pyrimidin-5-yl-4- [[(3S)-pyrrolidin-3- yl]methoxy]-1H- pyrrolo[2,3-b]pyridine	KI	3.86 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
4-[(2S)-2- (methoxymethyl)pyrrolidin- 1-yl]-1H-pyrrolo[2,3- b]pyridine-3-carbonitrile	KI	3.89 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
4-[[(3R)-3- piperidyl]oxy]-3- pyrimidin-5-yl-1H- pyrrolo[2,3-b]pyridine	KI	4.01 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
2-[4-[(6R)-1,8- diazaspiro[5.5]undecan-8- yl]-1H-pyrrolo[2,3- b]pyridin-3-yl]-5-methyl- thiazole	KI	4.02 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
N-methyl-1-(3-pyrimidin- 5-yl-1H-pyrrolo[2,3- b]pyridin-4-yl)piperidin-3- amine	KI	4.1 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
2-[4-[(5R)-2,6- diazaspiro[4.5]decan-2- yl]-1H-pyrrolo[2,3- b]pyridin-3-yl]thiazole	KI	4.11 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer
N-[(3R)-1-(3-pyridazin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-yl]acetamide	KI	4.43 nM	US-11447505: Pyrrolo[2,3-b]pyridine compounds and their use in the treatment of cancer

ChEMBL bioactivities

263 potent at pChembl≥5 of 265 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.92	Ki	0.012	nM	CHEMBL5811574
10.82	Ki	0.015	nM	CHEMBL6018230
10.64	Ki	0.023	nM	CHEMBL5764454
10.60	Ki	0.025	nM	CHEMBL5834378
10.59	Ki	0.026	nM	CHEMBL5897575
10.55	Ki	0.028	nM	CHEMBL5963387
10.52	Ki	0.03	nM	CHEMBL6014969
10.41	Ki	0.039	nM	CHEMBL5783588
10.41	Ki	0.039	nM	CHEMBL5762036
10.40	Ki	0.04	nM	CHEMBL5946285
10.31	Ki	0.049	nM	CHEMBL5987759
10.27	Ki	0.054	nM	CHEMBL5816740
10.24	Ki	0.057	nM	CHEMBL5861512
10.22	Ki	0.06	nM	CHEMBL5742314
10.20	Ki	0.063	nM	CHEMBL5748733
10.20	Ki	0.063	nM	CHEMBL5958092
10.19	Ki	0.065	nM	CHEMBL5863351
10.19	Ki	0.065	nM	CHEMBL5764454
10.19	Ki	0.065	nM	CHEMBL5927623
10.14	Ki	0.073	nM	CHEMBL5852471
10.09	Ki	0.081	nM	CHEMBL5796818
10.09	Ki	0.082	nM	CHEMBL5956398
10.05	Ki	0.089	nM	CHEMBL5976859
10.05	Ki	0.09	nM	CHEMBL5811574
10.04	Ki	0.092	nM	CHEMBL5826180
10.04	Ki	0.092	nM	CHEMBL5872303
10.00	Ki	0.1	nM	CHEMBL5808035
9.97	Ki	0.106	nM	CHEMBL6027343
9.92	Ki	0.12	nM	CHEMBL6042256
9.84	Ki	0.144	nM	CHEMBL5998801
9.81	Ki	0.154	nM	CHEMBL5899748
9.77	Ki	0.17	nM	CHEMBL5859006
9.75	Ki	0.179	nM	CHEMBL6060859
9.74	Ki	0.181	nM	CHEMBL5775722
9.73	Ki	0.184	nM	CHEMBL5807019
9.70	Ki	0.202	nM	CHEMBL5875691
9.69	Ki	0.203	nM	CHEMBL5952618
9.69	Ki	0.206	nM	CHEMBL5968389
9.66	Ki	0.219	nM	CHEMBL5758283
9.62	Ki	0.238	nM	CHEMBL6031197
9.60	Ki	0.249	nM	CHEMBL5820797
9.56	Ki	0.273	nM	CHEMBL5779411
9.52	Ki	0.303	nM	CHEMBL6021899
9.52	Ki	0.304	nM	CHEMBL5741390
9.49	Ki	0.323	nM	CHEMBL5772506
9.46	Ki	0.351	nM	CHEMBL5889627
9.44	Ki	0.36	nM	CHEMBL6010426
9.43	Ki	0.37	nM	CHEMBL6024389
9.30	Ki	0.506	nM	CHEMBL6040688
9.26	Ki	0.549	nM	CHEMBL5921774

PubChem BioAssay actives

38 with measured affinity, of 885 total; 26 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715260: Inhibition of human MRCKbeta using KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK as substrate by [gamma-33P]-ATP assay	ic50	0.0007	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148037: Binding affinity to human CDC42BPB incubated for 45 mins by Kinobead based pull down assay	kd	0.0087	uM
[(1R,6R,13R,14R,15S)-13-butanoyloxy-1,6-dihydroxy-4,12,12,15-tetramethyl-5,8-dioxo-14-tetracyclo[8.5.0.02,6.011,13]pentadec-3-enyl] 2-(methylamino)benzoate	1799804: Binding Assay from Article 10.1074/jbc.M707463200: “Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta.”	ki	0.0126	uM
6-piperidin-4-yloxy-2H-isoquinolin-1-one	1424934: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0160	uM
[(1R,6R,13R,14R,15S)-13-butanoyloxy-1,6-dihydroxy-4,12,12,15-tetramethyl-5,8-dioxo-14-tetracyclo[8.5.0.02,6.011,13]pentadec-3-enyl] butanoate	1799804: Binding Assay from Article 10.1074/jbc.M707463200: “Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta.”	kd	0.0170	uM
4-[(1R)-1-aminoethyl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzamide	1424934: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0340	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625031: Binding constant for MRCKB kinase domain	kd	0.0950	uM
(2S,3R,4R,6R,18S)-18-hydroxy-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1424934: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1100	uM
(2R)-2-methyl-2-[[2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino]-N-(2,2,2-trifluoroethyl)butanamide	1424934: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1160	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	625031: Binding constant for MRCKB kinase domain	kd	0.3300	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148037: Binding affinity to human CDC42BPB incubated for 45 mins by Kinobead based pull down assay	kd	0.6230	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	435912: Binding constant for MRCKB kinase domain	kd	0.9100	uM
Nilotinib	625031: Binding constant for MRCKB kinase domain	kd	0.9100	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507630: Binding affinity to MRCKB	kd	1.0000	uM
1-[3-[4-[[4-(2-methoxyethyl)piperazin-1-yl]methyl]phenyl]-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]-3-morpholin-4-ylurea	1424934: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.0200	uM
[(4Z)-2-(hydroxymethyl)-4-[5-methyl-3-(2-methylpropyl)hexylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	1799804: Binding Assay from Article 10.1074/jbc.M707463200: “Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta.”	ki	1.0700	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625031: Binding constant for MRCKB kinase domain	kd	1.1000	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	1424934: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.7260	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435912: Binding constant for MRCKB kinase domain	kd	2.1000	uM
Vandetanib	435912: Binding constant for MRCKB kinase domain	kd	2.5000	uM
4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine	435912: Binding constant for MRCKB kinase domain	kd	2.7000	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	435912: Binding constant for MRCKB kinase domain	kd	3.3000	uM
4-[4-(4-fluorophenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]phenol	435912: Binding constant for MRCKB kinase domain	kd	4.2000	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625031: Binding constant for MRCKB kinase domain	kd	4.8000	uM
Axitinib	625031: Binding constant for MRCKB kinase domain	kd	4.8000	uM
[(2S)-3-hydroxy-2-octanoyloxypropyl] octanoate	1799804: Binding Assay from Article 10.1074/jbc.M707463200: “Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta.”	ki	6.9600	uM

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, increases abundance	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression, affects cotreatment	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	increases methylation	1
coumarin	decreases phosphorylation	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation, increases ADP-ribosylation	1
perfluoro-n-nonanoic acid	increases expression	1
perfluorohexanesulfonic acid	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Oxaliplatin	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1

ChEMBL screening assays

192 unique, capped per target: 192 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1047825	Binding	Residual activity of CDC42BPB at 10 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SI07	HAP1 CDC42BPB (-) 1	Cancer cell line	Male
CVCL_SI08	HAP1 CDC42BPB (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

302 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder