CDC20

Summary

CDC20 (cell division cycle 20, HGNC:1723) is a protein-coding gene on chromosome 1p34.2, encoding Cell division cycle protein 20 homolog (Q12834). Substrate-specific adapter of the anaphase promoting complex/cyclosome (APC/C) complex that confers substrate specificity by binding to substrates and targeting them to the APC/C complex for ubiquitination and degradation. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

CDC20 appears to act as a regulatory protein interacting with several other proteins at multiple points in the cell cycle. It is required for two microtubule-dependent processes, nuclear movement prior to anaphase and chromosome separation.

Source: NCBI Gene 991 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oocyte maturation defect 14 (Strong, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 85 total — 11 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 4
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_001255

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1723
Approved symbol	CDC20
Name	cell division cycle 20
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	p55CDC, CDC20A
Ensembl gene	ENSG00000117399
Ensembl biotype	protein_coding
OMIM	603618
Entrez	991

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000310955, ENST00000372462, ENST00000478882, ENST00000482046, ENST00000856675, ENST00000856676, ENST00000920118, ENST00000920119, ENST00000920120, ENST00000920121, ENST00000920122, ENST00000920123, ENST00000920124, ENST00000920125

RefSeq mRNA: 1 — MANE Select: NM_001255 NM_001255

CCDS: CCDS484

Canonical transcript exons

ENST00000310955 — 11 exons

Exon	Start	End
ENSE00000769655	43361120	43361245
ENSE00000769656	43360733	43360961
ENSE00000769660	43359725	43359821
ENSE00000769661	43359490	43359638
ENSE00001188980	43358981	43359006
ENSE00001189003	43359167	43359396
ENSE00001299211	43359969	43360097
ENSE00001325016	43362951	43363203
ENSE00003489261	43360499	43360593
ENSE00003528848	43362195	43362312
ENSE00003550983	43360193	43360389

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 98.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.0710 / max 394.5165, expressed in 1461 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2510	18.5036	1370
2509	12.1655	1236
2514	0.7957	465
2513	0.5122	322
2512	0.0940	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.72	gold quality
ventricular zone	UBERON:0003053	98.69	gold quality
secondary oocyte	CL:0000655	98.05	gold quality
embryo	UBERON:0000922	95.52	gold quality
ganglionic eminence	UBERON:0004023	95.25	gold quality
left testis	UBERON:0004533	94.68	gold quality
right testis	UBERON:0004534	94.60	gold quality
mucosa of transverse colon	UBERON:0004991	94.52	gold quality
testis	UBERON:0000473	92.79	gold quality
endometrium epithelium	UBERON:0004811	92.56	gold quality
lower esophagus mucosa	UBERON:0035834	91.72	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.69	gold quality
trabecular bone tissue	UBERON:0002483	90.19	gold quality
thymus	UBERON:0002370	89.97	gold quality
stromal cell of endometrium	CL:0002255	88.34	gold quality
adult organism	UBERON:0007023	88.06	gold quality
esophagus mucosa	UBERON:0002469	87.97	gold quality
bone marrow	UBERON:0002371	87.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.66	gold quality
bone element	UBERON:0001474	87.27	gold quality
vermiform appendix	UBERON:0001154	86.42	gold quality
rectum	UBERON:0001052	86.15	gold quality
bone marrow cell	CL:0002092	86.01	gold quality
gingival epithelium	UBERON:0001949	84.32	gold quality
esophagus squamous epithelium	UBERON:0006920	83.38	gold quality
caecum	UBERON:0001153	83.11	gold quality
gingiva	UBERON:0001828	82.67	gold quality
epithelium of esophagus	UBERON:0001976	81.86	gold quality
oral cavity	UBERON:0000167	81.36	gold quality
lymph node	UBERON:0000029	81.02	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-MTAB-10485	yes	1358.41
E-CURD-112	yes	1274.28
E-MTAB-8894	yes	1129.17
E-HCAD-5	yes	910.79
E-CURD-79	yes	806.09
E-MTAB-11121	yes	717.40
E-MTAB-7052	yes	654.34
E-MTAB-6505	yes	644.91
E-HCAD-6	yes	637.48
E-GEOD-114530	yes	634.35
E-GEOD-75140	yes	488.16
E-CURD-84	yes	401.17
E-CURD-114	yes	208.39
E-GEOD-100618	yes	118.33
E-GEOD-110499	yes	69.49

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, MYC, OLIG2, PHF8, TP53, YBX1

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• localization in tail-to-tail array and expression in proliferating cells (PMID:11891222)
• Destruction-box specificities of APC/C(fzy) and APC/C(fzr)& successive activation of APC/C by fzy & fzr establish the temporal substrate degradation pattern, explaining why some endogenous RXXL substrates are degraded by fzy & others by fzr complexes. (PMID:12198152)
• These findings implicate RASSF1A in the regulation of both APC-Cdc20 activity and mitotic progression. (PMID:14743218)
• These results indicate that Bub3 and Cdc20 play additional roles in the integration of cell cycle arrest as transcriptional repressors. (PMID:15388328)
• activation of APC(Cdc20) by Tax provides an explanation for the mitotic abnormalities in HTLV-I-infected cells and is likely to play an important role in the development of adult T cell leukemia (PMID:15623561)
• Up-regulation of cdc20 is associated with gastric cancer (PMID:15701830)
• Functional analysis suggests that an optimum Mad2 binding efficiency of Cdc20 is required during checkpoint arrest and release. (PMID:16497171)
• High level of Cdc20 appears to be more tightly associated with a poor prognosis. (PMID:16572426)
• Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer (PMID:16777988)
• These results suggest that targeting molecules involved in spindle mitotic checkpoint, such as p55CDC/Cdc20, might account for the high cytotoxicity of HDAC inhibitors versus malignant cells. (PMID:16795040)
• There is no interaction between RASSF1A and Cdc20. (PMID:17598981)
• Overexpression of CDC20 is associated with cancer (PMID:17873905)
• SCF(Skp2) and APC(Cdc20) mark MLL for degradation at S phase and late M phase, respectively. (PMID:17908926)
• Data show that Cdc20 and Cks1 direct the spindle checkpoint-independent destruction of cyclin A2. (PMID:18471975)
• Both MCF2 and MCC inhibit APC/C by antagonizing Cdc20, possibly by interaction with the Cdc20-binding site of APC/C. (PMID:18591651)
• Over-expression of mRNA levels of IGFBP-2 and CDC20 is highly related to glioblastomas. (PMID:18953566)
• Ubiquitylation of human Cdc20 is not required to release it from the checkpoint complex, but to degrade it to maintain mitotic arrest. (PMID:18997788)
• The degradation of Cdc20 represents a critical control mechanism to ensure inactivation of APC/C(Cdc20) in response to the spindle assembly checkpoint. (PMID:19098431)
• BubR1 competes with Cdc20 for binding to securin. Interaction of BubR1 and securin is increased by the depletion of Cdc20. Regulation of BubR1 may generate an anaphase-inhibitory signal through the Cdc20-independent interaction of BubR1 with securin. (PMID:19117984)
• Results support a model in which immobilized Mad1/Mad2 at kinetochores provides a template for initial assembly of Mad2 bound to Cdc20 that is then converted to a final mitotic checkpoint inhibitor with Cdc20 bound to BubR1. (PMID:19154722)
• Results show that even an almost complete knockdown of Cdc20 below the detection limit in western blots does neither cause a mitotic block nor significant stabilization of the APC/C(Cdc20) substrates cyclin B and securin. (PMID:19197151)
• regulated but the expression of CDK9, CDC20 and CLK3 was down- regulated in azoospermic testes. (PMID:19426592)
• hMDC1 functionally regulates the normal metaphase-to-anaphase transition by modulating the Cdc20-dependent activation of the APC/C (PMID:19826003)
• Results indicate that Cdc20 also contributes to post-anaphase activation of the APC/C. (PMID:20053638)
• In summary, accelerated ubiquitination and proteolysis of Cdc20 is essential for prometaphase arrest that is mediated via the p38 signaling during SAC activation. (PMID:20054826)
• Data suggest that phosphorylation of Mcl-1 by CDK1-cyclin B1 and its APC/C(Cdc20)-mediated destruction initiates apoptosis if a cell fails to resolve mitosis. (PMID:20526282)
• Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle checkpoint signaling. (PMID:20624902)
• the sequential actions of the APC-c(Cdc20) and APC-c(Cdh1) ubiquitin ligases regulate the clearance of Mps1 levels and are critical for Mps1 functions during the cell cycle in human cells. (PMID:20729194)
• Data show that the N terminus of cyclin A binds directly to Cdc20 and with sufficient affinity that it can outcompete the spindle assembly checkpoint proteins. (PMID:20733051)
• elevated levels of Ubch10 and Cdc20 degrade cyclin B in hpv-16 iinfected cells, required for exit from mitosis, permitting initiation of the next round of DNA synthesis and cell cycle progression. (PMID:20739533)
• These data suggest that APC/C(Cdc20) specifically targets E2F1 for degradation in early mitosis and reveal a novel mechanism for limiting free E2F1 levels in cells, failure of which may compromise cell survival and/or homeostasis. (PMID:20948288)
• Spindle assembly checkpoint protein Cdc20 transcriptionally activates expression of ubiquitin carrier protein UbcH10. (PMID:21454660)
• Anaphase promoting complex subunit 15(APC15) mediates the constant turnover of CDC20 and mitotic checkpoint protein complexes, allowing the spindle checkpoint assembly to respond to the attachment state of kinetochores. (PMID:21926987)
• both p31(comet) and ubiquitination of Cdc20 are critical mechanisms of checkpoint inactivation. They act redundantly to promote Mad2 dissociation from Cdc20. (PMID:21937719)
• These findings expand our knowledge of both Sp100 and Cdc20 as well as their role in ubiquitination. (PMID:22086178)
• p31(comet) negatively regulates the spindle assembly checkpoint by extracting Mad2 from the MCC. (PMID:22100920)
• CDC20-mediated degradation of conductin regulates Wnt/beta-catenin signalling for maximal activity during G1/S. (PMID:22322943)
• APC/C(Cdc20) or APC/C(Cdh1) complexes regulate RAP80 stability during mitosis to the G(1) phase, and these events are critical for a novel function of RAP80 in mitotic progression. (PMID:22426463)
• Aberrant CDC20 expression may play an important role in pancreatic ductal adenocarcinoma tumorigenesis and progression and may thus be useful as a marker of disease progression and prognosis and as a therapeutic target. (PMID:22475564)
• The binding of p31(comet) to Mad2 in the mitotic checkpoint complex may trigger a conformational change in Cdc20 that facilitates its phosphorylation by Cdk, and that the latter process may promote its dissociation from BubR1. (PMID:22566641)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdc20	ENSDARG00000100741
mus_musculus	Cdc20	ENSMUSG00000006398
rattus_norvegicus	Cdc20	ENSRNOG00000028415
drosophila_melanogaster	fzy	FBGN0001086

Paralogs (2): FZR1 (ENSG00000105325), CDC20B (ENSG00000164287)

Protein

Protein identifiers

Cell division cycle protein 20 homolog — Q12834 (reviewed: Q12834)

Alternative names: p55CDC

All UniProt accessions (1): Q12834

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-specific adapter of the anaphase promoting complex/cyclosome (APC/C) complex that confers substrate specificity by binding to substrates and targeting them to the APC/C complex for ubiquitination and degradation. Recognizes and binds the destruction box (D box) on protein substrates. Involved in the metaphase/anaphase transition of cell cycle. Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 induces presynaptic differentiation. The CDC20-APC/C complex promotes proper dilation formation and radial migration by degrading CCDC41.

Subunit / interactions. Component of a complex with CDC20, CDC27, SPATC1 and TUBG1. Interacts with NEUROD2. Interacts with dimeric MAD2L1 in its closed conformation form. Interacts with BUB1B. The phosphorylated form interacts with APC/C. Interacts with NINL. May interact with MAD2L2. Interacts with CDK5RAP2. Interacts with SIRT2. Interacts with isoform 1 of NEK2. Interacts with HSF1 (via phosphorylated form); this interaction occurs in mitosis in a MAD2L1-dependent manner and prevents PLK1-stimulated degradation of HSF1 by blocking the recruitment of the SCF(BTRC) ubiquitin ligase complex. Interacts (via the N-terminal substrate-binding domain) with FBXO5. Interacts with CCNF. Interacts with USP22.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Chromosome. Centromere. Kinetochore. Spindle pole.

Post-translational modifications. Acetylated. Deacetylated at Lys-66 by SIRT2; deacetylation enhances the interaction of CDC20 with CDC27, leading to activation of anaphase promoting complex/cyclosome (APC/C). Phosphorylated during mitosis. Phosphorylated by BUB1 at Ser-41; Ser-72; Ser-92; Ser-153; Thr-157 and Ser-161. Phosphorylated by NEK2. Dephosphorylated by CTDP1. Ubiquitinated and degraded by the proteasome during spindle assembly checkpoint. Deubiquitinated by USP44, leading to stabilize the MAD2L1-CDC20-APC/C ternary complex, thereby preventing premature activation of the APC/C. Ubiquitinated at Lys-490 during prometaphase. Ubiquitination at Lys-485 and Lys-490 has no effect on its ability to bind the APC/C complex. Ubiquitinated by UBR5 when not assembled in a multiprotein complex, leading to its degradation: UBR5 recognizes and binds a degron that is not accessible when CDC20 is part of a complex.

Disease relevance. Oocyte/zygote/embryo maturation arrest 14 (OZEMA14) [MIM:620276] An autosomal recessive female infertility disorder characterized by oocyte maturation arrest, fertilization failure, and/or early embryonic arrest. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the WD repeat CDC20/Fizzy family.

RefSeq proteins (1): NP_001246* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR033010	Cdc20/Fizzy	Family
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR056150	WD40_CDC20-Fz	Domain

Pfam: PF24807

UniProt features (91 total): strand 35, sequence variant 12, modified residue 9, mutagenesis site 9, turn 9, repeat 7, helix 3, cross-link 2, sequence conflict 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
4GGC	X-RAY DIFFRACTION	1.35
9I69	X-RAY DIFFRACTION	1.46
9I68	X-RAY DIFFRACTION	1.5
9I6A	X-RAY DIFFRACTION	1.92
4GGA	X-RAY DIFFRACTION	2.04
4N14	X-RAY DIFFRACTION	2.1
4GGD	X-RAY DIFFRACTION	2.44
6Q6G	ELECTRON MICROSCOPY	3.2
6Q6H	ELECTRON MICROSCOPY	3.2
6TLJ	ELECTRON MICROSCOPY	3.8
5G04	ELECTRON MICROSCOPY	3.9
9N9R	ELECTRON MICROSCOPY	3.9
9N9S	ELECTRON MICROSCOPY	3.9
5LCW	ELECTRON MICROSCOPY	4.2
6F0X	ELECTRON MICROSCOPY	4.6
5KHU	ELECTRON MICROSCOPY	4.8
5KHR	ELECTRON MICROSCOPY	6.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12834-F1	84.39	0.61

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 (11): 41, 66, 70, 72, 92, 106, 153, 157, 161, 485, 490

Mutagenesis-validated functional residues (9):

Position	Phenotype
41	loss of bub1-mediated phosphorylation and inhibition and partially defective spindle-assembly checkpoint; when associate
72	loss of bub1-mediated phosphorylation and inhibition and partially defective spindle-assembly checkpoint; when associate
92	loss of bub1-mediated phosphorylation and inhibition and partially defective spindle-assembly checkpoint; when associate
132	loss of interaction with mad2l1.
153	loss of bub1-mediated phosphorylation and inhibition and partially defective spindle-assembly checkpoint; when associate
157	loss of bub1-mediated phosphorylation and inhibition and partially defective spindle-assembly checkpoint; when associate
161	loss of bub1-mediated phosphorylation and inhibition and partially defective spindle-assembly checkpoint; when associate
485	does not affect its ability to bind the apc/c complex; when associated with r-490.
490	does not affect its ability to bind the apc/c complex; when associated with r-485.

Function

Pathways and Gene Ontology

Reactome pathways

42 pathways

ID	Pathway
R-HSA-141405	Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components
R-HSA-141430	Inactivation of APC/C via direct inhibition of the APC/C complex
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-174048	APC/C:Cdc20 mediated degradation of Cyclin B
R-HSA-174113	SCF-beta-TrCP mediated degradation of Emi1
R-HSA-174154	APC/C:Cdc20 mediated degradation of Securin
R-HSA-174178	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-174184	Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-HSA-176407	Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase
R-HSA-176408	Regulation of APC/C activators between G1/S and early anaphase
R-HSA-176409	APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-176417	Phosphorylation of Emi1
R-HSA-179409	APC-Cdc20 mediated degradation of Nek2A
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-5689880	Ub-specific processing proteases
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-168256	Immune System
R-HSA-174143	APC/C-mediated degradation of cell cycle proteins
R-HSA-176814	Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-179419	APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors

MSigDB gene sets: 572 (showing top): GNF2_CKS1B, GOBP_DENDRITE_DEVELOPMENT, GOBP_CHROMOSOME_ORGANIZATION, MYAATNNNNNNNGGC_UNKNOWN, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, ELVIDGE_HYPOXIA_DN, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, MODULE_451, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, KANG_DOXORUBICIN_RESISTANCE_UP, REACTOME_APC_C_CDC20_MEDIATED_DEGRADATION_OF_CYCLIN_B, GNF2_CENPF

GO Biological Process (23): mitotic sister chromatid cohesion (GO:0007064), mitotic spindle assembly checkpoint signaling (GO:0007094), regulation of mitotic cell cycle (GO:0007346), nervous system development (GO:0007399), positive regulation of cell population proliferation (GO:0008284), protein ubiquitination (GO:0016567), cell differentiation (GO:0030154), anaphase-promoting complex-dependent catabolic process (GO:0031145), positive regulation of synaptic plasticity (GO:0031915), regulation of meiotic nuclear division (GO:0040020), metaphase/anaphase transition of cell cycle (GO:0044784), positive regulation of mitotic metaphase/anaphase transition (GO:0045842), regulation of dendrite development (GO:0050773), cell division (GO:0051301), regulation of meiotic cell cycle (GO:0051445), positive regulation of synapse maturation (GO:0090129), mitotic spindle assembly (GO:0090307), positive regulation of ubiquitin protein ligase activity (GO:1904668), positive regulation of anaphase-promoting complex-dependent catabolic process (GO:1905786), metaphase/anaphase transition of meiosis I (GO:1990949), G2/M transition of mitotic cell cycle (GO:0000086), protein deubiquitination (GO:0016579), SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146)

GO Molecular Function (6): anaphase-promoting complex binding (GO:0010997), histone deacetylase binding (GO:0042826), ubiquitin-like ligase-substrate adaptor activity (GO:1990756), ubiquitin ligase activator activity (GO:1990757), protein binding (GO:0005515), ubiquitin-protein transferase activator activity (GO:0097027)

GO Cellular Component (14): kinetochore (GO:0000776), spindle pole (GO:0000922), nucleoplasm (GO:0005654), anaphase-promoting complex (GO:0005680), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), mitotic checkpoint complex (GO:0033597), perinuclear region of cytoplasm (GO:0048471), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Regulation of APC/C activators between G1/S and early anaphase	3
APC/C-mediated degradation of cell cycle proteins	3
APC/C:Cdc20 mediated degradation of mitotic proteins	2
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	2
Mitotic Prometaphase	2
Mitotic Spindle Checkpoint	1
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	1
Amplification of signal from the kinetochores	1
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Deubiquitination	1
M Phase	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular membraneless organelle	4
mitotic cell cycle	2
regulation of cell cycle	2
cytoplasm	2
sister chromatid cohesion	1
negative regulation of mitotic metaphase/anaphase transition	1
spindle assembly checkpoint signaling	1
mitotic spindle checkpoint signaling	1
system development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
protein modification by small protein conjugation	1
cellular developmental process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
regulation of synaptic plasticity	1
regulation of cell cycle process	1
regulation of meiotic cell cycle	1
regulation of nuclear division	1
meiotic nuclear division	1
regulation of sister chromatid segregation	1
cell cycle phase transition	1
metaphase/anaphase transition of mitotic cell cycle	1
regulation of mitotic metaphase/anaphase transition	1
positive regulation of mitotic nuclear division	1
positive regulation of mitotic sister chromatid separation	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of metaphase/anaphase transition of cell cycle	1
regulation of neuron projection development	1
dendrite development	1
regulation of developmental process	1
cellular process	1
meiotic cell cycle	1
regulation of reproductive process	1
positive regulation of developmental process	1
positive regulation of cellular component organization	1
synapse maturation	1
regulation of synapse maturation	1
mitotic sister chromatid segregation	1

Protein interactions and networks

STRING

5186 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC20	BUB1B	O60566	999
CDC20	BUB3	O43684	999
CDC20	BUB1	O43683	993
CDC20	ANAPC11	Q9NYG5	989
CDC20	CDK1	P06493	985
CDC20	MAD2L1	Q13257	981
CDC20	CDC27	P30260	980
CDC20	FBXO5	Q9UKT4	978
CDC20	CCNB1	P14635	970
CDC20	CCNA2	P20248	970
CDC20	PTTG2	Q9NZH5	970
CDC20	PTTG1	O95997	969
CDC20	ANAPC10	Q9UM13	968
CDC20	AURKB	Q96GD4	966
CDC20	CDC23	Q9UJX2	943

IntAct

228 interactions, top by confidence:

A	B	Type	Score
MAD2L1	CDC20	psi-mi:“MI:0915”(physical association)	0.980
CDC20	MAD2L1	psi-mi:“MI:0915”(physical association)	0.980
CDC20	MAD2L1	psi-mi:“MI:0407”(direct interaction)	0.980
BUB1B	CDC20	psi-mi:“MI:0915”(physical association)	0.980
MAD2L1	CDC20	psi-mi:“MI:0407”(direct interaction)	0.980
CDC20	BUB1B	psi-mi:“MI:0914”(association)	0.980
MAD2L1	CDC20	psi-mi:“MI:0914”(association)	0.980
BUB1B	CDC20	psi-mi:“MI:0914”(association)	0.980

BioGRID (941): CDC20 (Affinity Capture-Western), CDC27 (Affinity Capture-Western), FBXO43 (Affinity Capture-Western), CCNB1 (Biochemical Activity), CDC20 (Reconstituted Complex), CDC20 (Reconstituted Complex), CDC20 (Reconstituted Complex), CCNB1 (Biochemical Activity), CDC20 (Reconstituted Complex), CCNB1 (Biochemical Activity), CCNA2 (Biochemical Activity), CCNB1 (Reconstituted Complex), CDC20 (Affinity Capture-MS), PTTG1 (Reconstituted Complex), CCNB1 (Reconstituted Complex)

ESM2 similar proteins: A0A396ISC0, O00423, O13286, O17468, O61585, O94423, P26309, P38328, P43254, P53197, P78972, P93471, Q04199, Q05BC3, Q09373, Q12834, Q16MY0, Q2TAF3, Q32SG6, Q3E906, Q4PSE4, Q4V7Y7, Q4V8C3, Q54MZ3, Q5H7C0, Q5ZIU8, Q62623, Q652L2, Q6DIP5, Q6NVM2, Q6S7B0, Q7K0L4, Q7ZUV2, Q7ZVL2, Q7ZX22, Q86Y33, Q8BG40, Q8CFJ9, Q8L3Z8, Q8LPL5

Diamond homologs: A0A1L8I2C5, A0A396ISC0, D3Z3I0, F4K5R6, O13286, O65418, O94423, P26309, P53197, P78972, Q12834, Q1HPW4, Q3E906, Q4PSE4, Q54KM3, Q54MZ3, Q5H7C0, Q62623, Q86Y33, Q8L3Z8, Q8LPL5, Q8VZS9, Q9FN19, Q9JJ66, Q9M7I2, Q9R1K5, Q9S7H3, Q9S7I8, Q9SZA4, Q9UM11, A3LQ86, O94411, O94620, P25387, Q09786, Q15269, Q5RFQ3, Q8NEZ3, Q93134, Q9P783

SIGNOR signaling

26 interactions.

A	Effect	B	Mechanism
BUB1	“down-regulates activity”	CDC20	phosphorylation
CDK5RAP2	“down-regulates activity”	CDC20	binding
CDC20	“up-regulates activity”	UBE2S	binding
CDC20	“form complex”	MCC	binding
CDC20	“down-regulates quantity by destabilization”	CCNB1	binding
CDC20	“down-regulates quantity by destabilization”	SP100	binding
TRiC	“up-regulates quantity by stabilization”	CDC20	binding
CDC20	“down-regulates quantity by destabilization”	PHF8	binding
CDC20	“up-regulates activity”	APC-c	binding
CDC20	“down-regulates quantity by destabilization”	REV1	binding
CDC20	“down-regulates quantity by destabilization”	FBXO31	binding
NEK2	“up-regulates activity”	CDC20	phosphorylation
CDK1	“down-regulates activity”	CDC20	phosphorylation
CDK2	“down-regulates activity”	CDC20	phosphorylation
BUB1B	“up-regulates activity”	CDC20	phosphorylation
TBK1	“down-regulates activity”	CDC20	phosphorylation
AURKB	“down-regulates activity”	CDC20	phosphorylation
MAD2L2	“down-regulates activity”	CDC20	binding
PLK1	“down-regulates quantity by destabilization”	CDC20	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 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
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	14	118.4×	2e-26
Inactivation of APC/C via direct inhibition of the APC/C complex	14	96.9×	8e-25
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	16	90.2×	3e-27
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	16	87.0×	5e-27
APC-Cdc20 mediated degradation of Nek2A	15	84.6×	3e-25
Aberrant regulation of mitotic exit in cancer due to RB1 defects	12	83.0×	3e-20
APC/C-mediated degradation of cell cycle proteins	18	80.6×	2e-29
Regulation of mitotic cell cycle	18	80.6×	2e-29

GO biological processes:

GO term	Partners	Fold	FDR
protein branched polyubiquitination	13	128.9×	2e-23
regulation of meiotic cell cycle	12	108.1×	1e-20
anaphase-promoting complex-dependent catabolic process	12	99.1×	4e-20
protein K11-linked ubiquitination	12	55.3×	1e-16
mitotic spindle assembly checkpoint signaling	7	46.3×	8e-09
regulation of mitotic cell cycle	14	39.6×	4e-17
protein K48-linked ubiquitination	14	27.8×	5e-15
cell division	28	15.2×	2e-23

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	1
Uncertain significance	57
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1070387	NC_000001.10:g.(?43392692)(43870241_?)del	Pathogenic
2443916	NM_001255.3(CDC20):c.683A>G (p.Tyr228Cys)	Pathogenic
2443917	NM_001255.3(CDC20):c.965G>A (p.Arg322Gln)	Pathogenic
2443918	NM_001255.3(CDC20):c.544C>T (p.Arg182Ter)	Pathogenic
2443919	NM_001255.3(CDC20):c.810_813dup (p.Gly272fs)	Pathogenic
2443920	NM_001255.3(CDC20):c.1176_1179del (p.Ala391_Cys392insTer)	Pathogenic
2443921	NM_001255.3(CDC20):c.631G>A (p.Ala211Thr)	Pathogenic
2443922	NM_001255.3(CDC20):c.784C>T (p.Arg262Ter)	Pathogenic
2443923	NM_001255.3(CDC20):c.964C>T (p.Arg322Ter)	Pathogenic
2443924	NM_001255.3(CDC20):c.330+1G>A	Pathogenic
2443925	NM_001255.3(CDC20):c.1155G>C (p.Trp385Cys)	Pathogenic
3064850	NM_001255.3(CDC20):c.556+1G>T	Likely pathogenic

SpliceAI

1228 predictions. Top by Δscore:

Variant	Effect	Δscore
1:43359315:G:GT	donor_gain	1.0000
1:43359401:G:GG	donor_gain	1.0000
1:43359415:GAAC:G	donor_gain	1.0000
1:43359485:CCCA:C	acceptor_loss	1.0000
1:43359488:A:T	acceptor_loss	1.0000
1:43359489:G:GT	acceptor_loss	1.0000
1:43359489:GGCAA:G	acceptor_gain	1.0000
1:43359635:GAAG:G	donor_gain	1.0000
1:43359636:AAGG:A	donor_loss	1.0000
1:43359639:G:GA	donor_loss	1.0000
1:43359639:G:GG	donor_gain	1.0000
1:43359640:T:G	donor_loss	1.0000
1:43359718:A:AG	acceptor_gain	1.0000
1:43359718:AT:A	acceptor_gain	1.0000
1:43359719:T:G	acceptor_gain	1.0000
1:43359719:T:TA	acceptor_gain	1.0000
1:43359724:G:A	acceptor_loss	1.0000
1:43359818:GAGG:G	donor_gain	1.0000
1:43359819:AGGGT:A	donor_loss	1.0000
1:43359820:GG:G	donor_gain	1.0000
1:43359821:GG:G	donor_gain	1.0000
1:43359821:GGTAA:G	donor_loss	1.0000
1:43359822:G:GG	donor_gain	1.0000
1:43359823:TAAGA:T	donor_loss	1.0000
1:43359968:G:GA	acceptor_loss	1.0000
1:43360093:CTATT:C	donor_gain	1.0000
1:43360094:TATT:T	donor_gain	1.0000
1:43360095:ATT:A	donor_gain	1.0000
1:43360095:ATTGT:A	donor_loss	1.0000
1:43360096:TT:T	donor_gain	1.0000

AlphaMissense

3259 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:43360210:T:A	W192R	1.000
1:43360210:T:C	W192R	1.000
1:43360571:T:A	W276R	1.000
1:43360571:T:C	W276R	1.000
1:43360592:A:C	S283R	1.000
1:43360733:T:A	S283R	1.000
1:43360733:T:G	S283R	1.000
1:43360833:T:A	W317R	1.000
1:43360833:T:C	W317R	1.000
1:43360860:A:C	S326R	1.000
1:43360862:T:A	S326R	1.000
1:43360862:T:G	S326R	1.000
1:43360957:T:A	V358D	1.000
1:43361129:T:A	W363R	1.000
1:43361129:T:C	W363R	1.000
1:43361163:G:A	G374E	1.000
1:43362210:T:A	W407R	1.000
1:43362210:T:C	W407R	1.000
1:43363037:T:A	W470R	1.000
1:43363037:T:C	W470R	1.000
1:43360068:T:C	L176P	0.999
1:43360070:G:C	D177H	0.999
1:43360071:A:G	D177G	0.999
1:43360071:A:T	D177V	0.999
1:43360212:G:C	W192C	0.999
1:43360212:G:T	W192C	0.999
1:43360232:C:A	A199D	0.999
1:43360336:T:A	W234R	0.999
1:43360336:T:C	W234R	0.999
1:43360358:T:C	L241S	0.999

dbSNP variants (sampled 300 via entrez): RS1000360474 (1:43357355 A>C,T), RS1000928572 (1:43363685 G>C), RS1001902533 (1:43358018 C>G), RS1002108476 (1:43363206 T>C), RS1002269644 (1:43357726 T>C), RS1002593157 (1:43358027 G>C,T), RS1002866391 (1:43358964 G>A), RS1004402910 (1:43363564 T>C), RS1005171783 (1:43358439 T>C,G), RS1005367402 (1:43363607 A>T), RS1005392804 (1:43358040 A>C), RS1005655236 (1:43357225 C>T), RS1005843664 (1:43358488 C>CG), RS1005932278 (1:43357059 C>T), RS1006394021 (1:43359315 G>A)

Disease associations

OMIM: gene MIM:603618 | disease phenotypes: MIM:620276

GenCC curated gene-disease

Disease	Classification	Inheritance
oocyte maturation defect 14	Strong	Autosomal recessive

Mondo (1): oocyte maturation defect 14 (MONDO:0859521)

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0008222	Female infertility
HP:0011462	Young adult onset
HP:0034914	Oocyte maturation arrest

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST003501_5	Asparaginase-induced acute pancreatitis in acute lymphoblastic leukemia (onset time)	4.000000e-09
GCST010696_6	Cortical thickness (min-P)	3.000000e-08
GCST010697_32	Cortical surface area (min-P)	4.000000e-08
GCST010698_63	Subcortical volume (min-P)	3.000000e-09
GCST010699_87	Brain morphology (min-P)	9.000000e-14
GCST010700_24	Cortical thickness (MOSTest)	1.000000e-10
GCST010701_5	Cortical surface area (MOSTest)	1.000000e-08
GCST010702_132	Subcortical volume (MOSTest)	8.000000e-15
GCST010703_201	Brain morphology (MOSTest)	1.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:1001507	asparaginase-induced acute pancreatitis
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523283 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.12	Kd	7650	nM	CHEMBL6168002

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	5
Benzo(a)pyrene	decreases expression, decreases methylation	5
sodium arsenite	decreases expression, increases expression	4
Arsenic Trioxide	affects cotreatment, increases reaction, decreases expression, increases expression, affects binding	3
Zinc	affects cotreatment, affects expression, decreases expression, increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
Cyclosporine	decreases expression	3
arsenite	affects binding, increases reaction, decreases expression	2
cobaltous chloride	decreases expression	2
Zoledronic Acid	decreases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Dibutyl Phthalate	decreases expression, increases expression, decreases reaction	2
Doxorubicin	decreases expression	2
Drugs, Chinese Herbal	decreases expression, affects cotreatment, increases expression	2
Estradiol	decreases expression, increases expression	2
Quercetin	decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tetradecanoylphorbol Acetate	increases expression, affects cotreatment, affects expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
Paclitaxel	affects binding, affects cotreatment, increases reaction, decreases expression	2
Cadmium Chloride	increases reaction, decreases expression, increases degradation, increases ubiquitination, affects binding (+1 more)	2
Genistein	affects expression, increases expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance, decreases abundance, increases expression	2
aristolochic acid I	increases expression	1
afuresertib	decreases expression	1
FR900359	decreases phosphorylation	1
echimidine	affects expression, increases metabolic processing	1
dicrotophos	increases expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4406128	Binding	Binding affinity to CDC20 (unknown origin) by SPR analysis	Discovery of a Dual Tubulin Polymerization and Cell Division Cycle 20 Homologue Inhibitor via Structural Modification on Apcin. — J Med Chem

Clinical trials (associated diseases)

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