CDCA2

Summary

CDCA2 (cell division cycle associated 2, HGNC:14623) is a protein-coding gene on chromosome 8p21.2, encoding Cell division cycle-associated protein 2 (Q69YH5). Regulator of chromosome structure during mitosis required for condensin-depleted chromosomes to retain their compact architecture through anaphase.

This gene encodes a targeting subunit of the cell-cycle associated protein, protein phosphatase 1, with a role in targeting this protein to chromatin during anaphase. These two proteins comprise a phosphatase complex that is involved in nuclear envelope reformation and regulation of the DNA damage response. The encoded protein may also play a role in cancer progression. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 157313 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 183 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_152562

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14623
Approved symbol	CDCA2
Name	cell division cycle associated 2
Location	8p21.2
Locus type	gene with protein product
Status	Approved
Aliases	Repo-Man, PPP1R81
Ensembl gene	ENSG00000184661
Ensembl biotype	protein_coding
OMIM	618785
Entrez	157313

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000330560, ENST00000380665, ENST00000518225, ENST00000521098, ENST00000523454, ENST00000936124, ENST00000936125, ENST00000936126

RefSeq mRNA: 3 — MANE Select: NM_152562 NM_001317906, NM_001317907, NM_152562

CCDS: CCDS6049, CCDS83266

Canonical transcript exons

ENST00000330560 — 15 exons

Exon	Start	End
ENSE00001309664	25462054	25462208
ENSE00001316331	25468217	25468413
ENSE00001485790	25506510	25507911
ENSE00001485824	25459233	25459473
ENSE00001769044	25460240	25460300
ENSE00003450634	25466175	25466325
ENSE00003477142	25503373	25503544
ENSE00003494320	25479913	25480124
ENSE00003533390	25483399	25483486
ENSE00003600207	25483966	25484210
ENSE00003636314	25485759	25485837
ENSE00003643260	25469896	25469980
ENSE00003657160	25487246	25487334
ENSE00003662754	25460384	25460554
ENSE00003675321	25488552	25488689

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 91.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.0259 / max 223.1221, expressed in 1409 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88024	9.1910	1290
88023	1.5397	750
88022	1.0560	525
88028	0.0964	28
88027	0.0659	30
88026	0.0500	16
88025	0.0269	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	91.60	gold quality
oocyte	CL:0000023	89.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.53	gold quality
ventricular zone	UBERON:0003053	88.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.97	gold quality
sperm	CL:0000019	86.12	gold quality
left testis	UBERON:0004533	85.58	gold quality
heart right ventricle	UBERON:0002080	85.28	gold quality
right testis	UBERON:0004534	85.28	gold quality
testis	UBERON:0000473	85.20	gold quality
left ventricle myocardium	UBERON:0006566	84.92	gold quality
ganglionic eminence	UBERON:0004023	81.97	gold quality
trabecular bone tissue	UBERON:0002483	79.88	gold quality
bone marrow	UBERON:0002371	79.84	gold quality
myocardium	UBERON:0002349	79.59	gold quality
bone marrow cell	CL:0002092	77.99	gold quality
cardiac ventricle	UBERON:0002082	75.23	gold quality
heart left ventricle	UBERON:0002084	75.21	gold quality
stromal cell of endometrium	CL:0002255	74.62	gold quality
gingival epithelium	UBERON:0001949	74.48	silver quality
jejunal mucosa	UBERON:0000399	72.27	gold quality
cardiac muscle of right atrium	UBERON:0003379	72.27	gold quality
ileal mucosa	UBERON:0000331	71.99	gold quality
vermiform appendix	UBERON:0001154	71.76	gold quality
thymus	UBERON:0002370	71.43	gold quality
adult organism	UBERON:0007023	70.85	gold quality
mucosa of transverse colon	UBERON:0004991	70.43	gold quality
gingiva	UBERON:0001828	70.21	silver quality
rectum	UBERON:0001052	70.19	gold quality
tibialis anterior	UBERON:0001385	70.15	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6911	yes	295.76
E-ANND-3	yes	5.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting CDCA2, 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-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-4471	95.11	66.84	755
HSA-MIR-8059	95.11	66.30	646

Literature-anchored findings (GeneRIF, showing 27)

• Repo-Man forms an essential complex with protein phosphatase 1 (PP1) gamma and is required for the recruitment of PP1 to chromatin (PMID:16492807)
• This study reports essential DNA damage response regulation mediated by Repo-Man-protein phosphatase 1 and further delineate underlying mechanisms. (PMID:20188555)
• Repo-Man promotes H3T11ph dephosphorylation by an indirect mechanism but directly and specifically targets H3T3ph for dephosphorylation by associated PP1gamma. (PMID:21514157)
• This study demonistrated that identify Repo-Man as a key factor that coordinates chromatin remodeling and early events of nuclear envelope reformation during mitotic exit. (PMID:21820363)
• It was shown that Repo-Man and Sds22 contribute to timely Aurora B kinase substrate dephosphorylation on anaphase chromatin. (PMID:22801782)
• Proteomic identification of a large number of novel RepoMan interactors. (PMID:23362328)
• Data indicate that CDCA2 frequently is overexpressed in oral squamous cell carcinoma (OSCC) and might be associated with OSCC progression by preventing cell-cycle arrest and apoptosis. (PMID:23418564)
• Aurora B phosphorylates Repo-Man at S893, preventing its recruitment by histones. (PMID:23746640)
• Here the authors show how Ki-67 and RepoMan form mitotic exit phosphatases by recruiting PP1, how they distinguish between distinct PP1 isoforms and how the assembly of these two holoenzymes are dynamically regulated by Aurora B kinase during mitosis. (PMID:27572260)
• Results report that BubR1 and RepoMan bind directly to PP2A-B56 using an LSPIxE short linear motif (SLiM), where phosphorylation of the Ser residue enhances binding. RepoMan and BubR1 bind B56 using both hydrophobic and electrostatic interactions. (PMID:27998540)
• Repo-Man/PP1 regulates the formation of heterochromatin, dephosphorylates H3S28 and it is necessary and sufficient for heterochromatin protein 1 binding and H3K27me3 recruitment. (PMID:28091603)
• Inhibition of cell division cycle associated 2 (CDCA2) suppressed the proliferation of lung adenocarcinoma (LAC) cells via G1 phase arrest by downregulating cyclin E1(CCNE1), while overexpression of CDCA2 promoted LAC cells proliferation by upregulating CCNE1. (PMID:28423619)
• The p37 controls cortical NuMA levels via the phosphatase PP1 and its regulatory subunit Repo-Man, but it acts independently of Galphai, the kinase Aurora A, and the phosphatase PP2A. (PMID:29222185)
• this study shows that CDCA2 promotes the proliferation of colorectal cancer cells by activating the AKT/CCND1 pathway in vitro and in vivo (PMID:31196027)
• Co-regulation of the antagonistic RepoMan:Aurora-B pair in proliferating cells. (PMID:31967936)
• CDCA2 promotes proliferation and migration of melanoma by upregulating CCAD1. (PMID:32633378)
• Aurora B regulates PP1gamma-Repo-Man interactions to maintain the chromosome condensation state. (PMID:32938714)
• RepoMan stimulates the chromosome-dependent pathway of microtubule assembly. (PMID:33054506)
• CDCA2 promotes tumorigenesis and induces radioresistance in oesophageal squamous cell carcinoma cells. (PMID:34036376)
• CDCA2 protects against oxidative stress by promoting BRCA1-NRF2 signaling in hepatocellular carcinoma. (PMID:34103686)
• Repo-Man/protein phosphatase 1 SUMOylation mediates binding to lamin A and serine 22 dephosphorylation. (PMID:35414260)
• Cell division cycle associated 2 (CDCA2) upregulation promotes the progression of hepatocellular carcinoma in a p53-dependant manner. (PMID:35694386)
• CDCA2 Promotes HCC Cells Development via AKT-mTOR Pathway. (PMID:36588796)
• PPP1R81 correlates with the survival and cell proliferation in lower-grade glioma. (PMID:37083601)
• CDCA2 promotes melanoma progression by inhibiting ubiquitin-mediated degradation of Aurora kinase A. (PMID:37196484)
• A pan-cancer analysis reveals the diagnostic and prognostic role of CDCA2 in low-grade glioma. (PMID:37733705)
• The Role of CDCA2 in tumor genesis, prognosis and future treatments. (PMID:39288736)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-244o22.2	ENSDARG00000068759
mus_musculus	Cdca2	ENSMUSG00000048922
rattus_norvegicus	Cdca2	ENSRNOG00000025302

Paralogs (1): MKI67 (ENSG00000148773)

Protein

Protein identifiers

Cell division cycle-associated protein 2 — Q69YH5 (reviewed: Q69YH5)

Alternative names: Recruits PP1 onto mitotic chromatin at anaphase protein

All UniProt accessions (2): Q69YH5, E9PEI0

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of chromosome structure during mitosis required for condensin-depleted chromosomes to retain their compact architecture through anaphase. Acts by mediating the recruitment of phosphatase PP1-gamma subunit (PPP1CC) to chromatin at anaphase and into the following interphase. At anaphase onset, its association with chromatin targets a pool of PPP1CC to dephosphorylate substrates.

Subunit / interactions. Interacts with PPP1CC.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Phosphorylated by CDK1. May regulate its subcellular location.

Isoforms (2)

UniProt ID	Names	Canonical?
Q69YH5-1	1	yes
Q69YH5-2	2

RefSeq proteins (3): NP_001304835, NP_001304836, NP_689775* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029334	PP1-bd	Domain

Pfam: PF15276

UniProt features (42 total): modified residue 19, compositionally biased region 8, region of interest 5, splice variant 2, sequence variant 2, chain 1, domain 1, cross-link 1, mutagenesis site 1, sequence conflict 1, strand 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5INB	X-RAY DIFFRACTION	1.3
5IOH	X-RAY DIFFRACTION	2.57
5SW9	X-RAY DIFFRACTION	2.85
5D1Z	X-RAY DIFFRACTION	3.17

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q69YH5-F1	46.61	0.01

Antibody-complex structures (SAbDab): 1 — 5D1Z

Functional residue map

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

Post-translational modifications (20): 98, 120, 126, 131, 210, 291, 309, 312, 400, 407, 412, 437, 591, 614, 710, 756, 936, 977, 1000, 762

Mutagenesis-validated functional residues (1):

Position	Phenotype
393–395	abolishes interaction with ppp1cc but not subcellular location.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 205 (showing top): HORIUCHI_WTAP_TARGETS_DN, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GGGTGGRR_PAX4_03, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_ORGANELLE_FISSION, chr8p21, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN, FISCHER_G2_M_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_MITOTIC_NUCLEAR_DIVISION, GOBP_MITOTIC_CELL_CYCLE, DODD_NASOPHARYNGEAL_CARCINOMA_UP, AACTTT_UNKNOWN, WEBER_METHYLATED_IN_COLON_CANCER, FISCHER_DREAM_TARGETS

GO Biological Process (3): chromosome segregation (GO:0007059), regulation of mitotic nuclear division (GO:0007088), cell division (GO:0051301)

GO Molecular Function (1): protein phosphatase regulator activity (GO:0019888)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell cycle process	1
regulation of mitotic cell cycle	1
regulation of cell cycle process	1
regulation of nuclear division	1
mitotic nuclear division	1
cellular process	1
phosphoprotein phosphatase activity	1
phosphatase regulator activity	1
protein phosphatase binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1

Protein interactions and networks

STRING

1258 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDCA2	PPP1CC	P36873	961
CDCA2	CDCA3	Q99618	721
CDCA2	PPP1R10	Q96QC0	709
CDCA2	PPP1R7	Q15435	690
CDCA2	BUB1B	O60566	671
CDCA2	KIF4A	O95239	664
CDCA2	KNL1	Q8NG31	651
CDCA2	NUP153	P49790	638
CDCA2	CDCA8	Q53HL2	634
CDCA2	NUP50	Q9UKX7	632
CDCA2	PPP2R5C	Q13362	608
CDCA2	CDCA7	Q9BWT1	598
CDCA2	CDCA5	Q96FF9	591
CDCA2	HASPIN	Q8TF76	583
CDCA2	NUF2	Q9BZD4	576

IntAct

79 interactions, top by confidence:

A	B	Type	Score
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
NUP50	KPNA4	psi-mi:“MI:0914”(association)	0.830
KPNA2	NUP153	psi-mi:“MI:0914”(association)	0.790
NUP50	KPNA3	psi-mi:“MI:0914”(association)	0.780
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
RAN	NEMP2	psi-mi:“MI:0914”(association)	0.530
B2M	KPNA3	psi-mi:“MI:0914”(association)	0.530
IER2	KPNA3	psi-mi:“MI:0914”(association)	0.530
TCEAL1	CHEK1	psi-mi:“MI:0914”(association)	0.530
PPP2R1A	ENSA	psi-mi:“MI:0914”(association)	0.530
PPP2R5A	CDCA2	psi-mi:“MI:0407”(direct interaction)	0.440
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410

BioGRID (115): CDCA2 (Affinity Capture-MS), CDCA2 (Affinity Capture-MS), CDCA2 (Affinity Capture-MS), CDCA2 (Affinity Capture-MS), CDCA2 (Affinity Capture-MS), CDCA2 (Affinity Capture-MS), CDCA2 (Affinity Capture-MS), CDCA2 (Proximity Label-MS), CDCA2 (Proximity Label-MS), CDCA2 (Proximity Label-MS), CDCA2 (Proximity Label-MS), CDCA2 (Affinity Capture-MS), CDCA2 (Affinity Capture-MS), CDCA2 (Affinity Capture-MS), CDCA2 (Affinity Capture-MS)

ESM2 similar proteins: A0A087WXM9, A0A2K1JJ00, A0JM83, A4IGL8, E1BC15, E9Q5F9, O14513, O35923, O60673, O88491, P46013, P97929, Q14B71, Q28DZ0, Q29RT4, Q3MHH3, Q3TNU4, Q3ZBP0, Q4QY64, Q4V7J0, Q5DTT3, Q5E9A0, Q5F2C3, Q5RD08, Q5VWN6, Q5VYV7, Q61493, Q69YH5, Q6NS59, Q703I1, Q80U59, Q86XD8, Q8IXS0, Q8IYL3, Q8L7I1, Q8N7Z5, Q8NFU7, Q8TEP8, Q92628, Q96BU1

Diamond homologs: E9PVX6, P46013, Q14B71, Q29RT4, Q69YH5

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
AURKB	“down-regulates activity”	CDCA2	phosphorylation
CDCA2	“up-regulates activity”	PPP1CC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
NS1 Mediated Effects on Host Pathways	8	40.8×	7e-09
Nuclear import of Rev protein	6	36.0×	2e-06
Transport of Ribonucleoproteins into the Host Nucleus	5	31.9×	3e-05
RAF activation	5	30.0×	3e-05
Negative regulation of the PI3K/AKT network	5	24.9×	6e-05
Antimicrobial mechanism of IFN-stimulated genes	7	24.6×	2e-06
ISG15 antiviral mechanism	8	21.5×	8e-07
Maturation of DENV proteins	5	18.9×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
NLS-bearing protein import into nucleus	7	74.9×	1e-09
protein import into nucleus	10	19.2×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	137
Likely benign	16
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2425516	NC_000008.10:g.(?24810323)(25892142_?)del	Pathogenic

SpliceAI

2360 predictions. Top by Δscore:

Variant	Effect	Δscore
8:25462029:A:AG	acceptor_gain	1.0000
8:25462037:A:G	acceptor_gain	1.0000
8:25462038:GAGA:G	acceptor_gain	1.0000
8:25462204:CCCAG:C	donor_loss	1.0000
8:25462206:CAGG:C	donor_loss	1.0000
8:25462207:AGG:A	donor_loss	1.0000
8:25462208:GGT:G	donor_loss	1.0000
8:25462209:GT:G	donor_loss	1.0000
8:25462210:T:A	donor_loss	1.0000
8:25466170:CACA:C	acceptor_loss	1.0000
8:25466172:CAG:C	acceptor_loss	1.0000
8:25466173:AGGGC:A	acceptor_loss	1.0000
8:25466174:GGGCA:G	acceptor_gain	1.0000
8:25466321:CTTGA:C	donor_gain	1.0000
8:25466322:TTGA:T	donor_gain	1.0000
8:25466323:TGA:T	donor_gain	1.0000
8:25466324:GA:G	donor_gain	1.0000
8:25466324:GAG:G	donor_gain	1.0000
8:25466326:G:GG	donor_gain	1.0000
8:25468214:T:G	acceptor_gain	1.0000
8:25468215:A:AG	acceptor_gain	1.0000
8:25468216:G:GA	acceptor_gain	1.0000
8:25468216:GCC:G	acceptor_gain	1.0000
8:25468216:GCCA:G	acceptor_gain	1.0000
8:25468339:G:GG	donor_gain	1.0000
8:25468409:CTGAG:C	donor_loss	1.0000
8:25468410:TGAG:T	donor_loss	1.0000
8:25468414:G:T	donor_loss	1.0000
8:25468415:T:A	donor_loss	1.0000
8:25469882:A:AG	acceptor_gain	1.0000

AlphaMissense

6727 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:25484028:T:C	F395L	0.997
8:25484030:T:A	F395L	0.997
8:25484030:T:G	F395L	0.997
8:25503472:A:C	S591R	0.995
8:25503474:T:A	S591R	0.995
8:25503474:T:G	S591R	0.995
8:25484055:T:C	F404L	0.994
8:25484057:T:A	F404L	0.994
8:25484057:T:G	F404L	0.994
8:25462132:T:C	L104P	0.988
8:25462146:G:C	A109P	0.987
8:25484023:T:A	V393D	0.987
8:25484041:T:C	L399S	0.986
8:25503479:T:C	I593T	0.986
8:25462135:T:C	I105T	0.982
8:25466229:T:C	F148L	0.982
8:25466231:C:A	F148L	0.982
8:25466231:C:G	F148L	0.982
8:25462127:C:A	N102K	0.981
8:25462127:C:G	N102K	0.981
8:25484029:T:C	F395S	0.981
8:25484056:T:C	F404S	0.981
8:25462110:G:C	G97R	0.980
8:25484029:T:G	F395C	0.980
8:25460522:T:C	I67T	0.979
8:25484056:T:G	F404C	0.978
8:25462140:T:C	F107L	0.977
8:25462142:C:A	F107L	0.977
8:25462142:C:G	F107L	0.977
8:25484187:T:C	F448L	0.977

dbSNP variants (sampled 300 via entrez): RS1000011764 (8:25499266 A>G), RS1000053201 (8:25501239 T>C), RS1000124921 (8:25501006 A>AT), RS1000349809 (8:25466890 A>G), RS1000372941 (8:25472262 T>A), RS1000511023 (8:25478076 A>G), RS1000517324 (8:25482662 G>A), RS1000541964 (8:25477792 C>T), RS1000612088 (8:25484445 G>A), RS1000705918 (8:25471194 A>G), RS1000757854 (8:25478318 A>G), RS1000786122 (8:25493300 C>A), RS1000849929 (8:25466043 C>G,T), RS1001152089 (8:25501909 T>C), RS1001160527 (8:25467492 T>C)

Disease associations

OMIM: gene MIM:618785 | disease phenotypes: MIM:607684

GenCC curated gene-disease

Mondo (2): myoepithelial tumor (MONDO:0002380), Charcot-Marie-Tooth disease type 2E (MONDO:0011894)

Orphanet (1): Autosomal dominant Charcot-Marie-Tooth disease type 2E (Orphanet:99939)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST006041_43	Major depressive disorder	3.000000e-06
GCST009277_10	Subjective response to placebo treatment in childhood asthma (change in cough/wheeze)	5.000000e-06
GCST010242_159	HDL cholesterol levels	9.000000e-12
GCST010244_336	Triglyceride levels	6.000000e-14
GCST010252_4	Systolic blood pressure x quantitative lifestyle risk score interaction (2df test)	5.000000e-06
GCST010253_2	Systolic blood pressure x quantitative lifestyle risk score interaction (1df test)	8.000000e-07
GCST90000025_326	Appendicular lean mass	3.000000e-12
GCST90016671_6	Visceral adipose tissue volume	3.000000e-11
GCST90020026_611	Hip index	5.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0008344	response to placebo
EFO:0010068	respiratory symptom change measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0006335	systolic blood pressure
EFO:0010724	lifestyle measurement
EFO:0004980	appendicular lean mass
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585
C537994	Charcot-Marie-Tooth disease, Type 2E (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724782 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.70	IC50	200	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178763: Inhibition of CDCA2 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	4
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
bisphenol A	decreases expression, affects cotreatment	2
Valproic Acid	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	increases sumoylation	1
geldanamycin	increases expression	1
sodium arsenate	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
hydroquinone	decreases expression	1
diallyl trisulfide	decreases expression	1
pinosylvin	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
motexafin gadolinium	decreases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	affects expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697493	Binding	Inhibition of CDCA2 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SI10	HAP1 CDCA2 (-) 1	Cancer cell line	Male
CVCL_SI11	HAP1 CDCA2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease