CDC27

Summary

CDC27 (cell division cycle 27, HGNC:1728) is a protein-coding gene on chromosome 17q21.32, encoding Cell division cycle protein 27 homolog (P30260). Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

The protein encoded by this gene shares strong similarity with Saccharomyces cerevisiae protein Cdc27, and the gene product of Schizosaccharomyces pombe nuc 2. This protein is a component of the anaphase-promoting complex (APC), which is composed of eight protein subunits and is highly conserved in eukaryotic cells. This complex catalyzes the formation of cyclin B-ubiquitin conjugate, which is responsible for the ubiquitin-mediated proteolysis of B-type cyclins. The protein encoded by this gene and three other members of the APC complex contain tetratricopeptide (TPR) repeats, which are important for protein-protein interactions. This protein was shown to interact with mitotic checkpoint proteins including Mad2, p55CDC and BUBR1, and it may thus be involved in controlling the timing of mitosis. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 2, 22 and Y.

Source: NCBI Gene 996 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 49 total — 1 pathogenic
• Phenotypes (HPO): 2
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_001256

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1728
Approved symbol	CDC27
Name	cell division cycle 27
Location	17q21.32
Locus type	gene with protein product
Status	Approved
Aliases	APC3, ANAPC3, NUC2
Ensembl gene	ENSG00000004897
Ensembl biotype	protein_coding
OMIM	116946
Entrez	996

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 10 protein_coding, 9 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000066544, ENST00000525495, ENST00000526866, ENST00000527547, ENST00000528147, ENST00000528748, ENST00000531206, ENST00000532575, ENST00000532893, ENST00000533415, ENST00000570740, ENST00000570818, ENST00000571643, ENST00000573502, ENST00000573550, ENST00000574304, ENST00000575483, ENST00000575830, ENST00000576484, ENST00000908518, ENST00000908519, ENST00000908520, ENST00000917931, ENST00000917932

RefSeq mRNA: 9 — MANE Select: NM_001256 NM_001114091, NM_001256, NM_001293089, NM_001293091, NM_001353035, NM_001353047, NM_001353049, NM_001353050, NM_001353051

CCDS: CCDS11509, CCDS45720, CCDS74090

Canonical transcript exons

ENST00000066544 — 19 exons

Exon	Start	End
ENSE00001799129	47117703	47121017
ENSE00002166699	47189146	47189295
ENSE00003465781	47142229	47142436
ENSE00003467973	47171917	47172064
ENSE00003471942	47181562	47181637
ENSE00003484602	47122444	47122600
ENSE00003497754	47143883	47143982
ENSE00003510743	47141853	47142025
ENSE00003535464	47129393	47129521
ENSE00003579445	47123886	47123960
ENSE00003580215	47151806	47151918
ENSE00003586509	47137152	47137360
ENSE00003590439	47138739	47138891
ENSE00003591889	47132257	47132374
ENSE00003617717	47169917	47170042
ENSE00003633816	47156913	47157124
ENSE00003667486	47154672	47154786
ENSE00003671618	47158206	47158303
ENSE00003689658	47157230	47157384

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 96.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.3850 / max 475.9794, expressed in 1821 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166599	35.1149	1821
166598	0.1371	51
166597	0.0782	19
208224	0.0547	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.91	gold quality
buccal mucosa cell	CL:0002336	96.32	gold quality
oocyte	CL:0000023	96.29	gold quality
tibia	UBERON:0000979	96.11	gold quality
calcaneal tendon	UBERON:0003701	95.98	gold quality
colonic epithelium	UBERON:0000397	95.47	gold quality
tendon	UBERON:0000043	95.45	gold quality
adrenal tissue	UBERON:0018303	95.45	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.40	gold quality
tendon of biceps brachii	UBERON:0008188	95.33	gold quality
medial globus pallidus	UBERON:0002477	95.20	gold quality
stromal cell of endometrium	CL:0002255	94.67	gold quality
germinal epithelium of ovary	UBERON:0001304	94.44	gold quality
globus pallidus	UBERON:0001875	94.14	gold quality
visceral pleura	UBERON:0002401	93.85	gold quality
substantia nigra pars compacta	UBERON:0001965	93.84	gold quality
islet of Langerhans	UBERON:0000006	93.52	gold quality
parietal pleura	UBERON:0002400	93.52	gold quality
ventricular zone	UBERON:0003053	93.52	gold quality
entorhinal cortex	UBERON:0002728	93.43	gold quality
pleura	UBERON:0000977	93.29	gold quality
gingival epithelium	UBERON:0001949	93.21	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.16	gold quality
bone marrow cell	CL:0002092	92.98	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.89	gold quality
esophagus squamous epithelium	UBERON:0006920	92.67	gold quality
cortical plate	UBERON:0005343	92.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.48	gold quality
tonsil	UBERON:0002372	92.46	gold quality
ganglionic eminence	UBERON:0004023	92.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	yes	43.45
E-ANND-3	yes	11.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPD

miRNA regulators (miRDB)

199 targeting CDC27, 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-5011-5P	100.00	83.46	5820
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-373-5P	99.98	75.36	4753
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AB	99.95	71.31	3488

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 23)

• a single endogenous copy of mir-996 can fully rescue viability, olfactory neuron, and circadian rhythm defects of mir-996/mir-279 double deletion animals. (PMID:26042831)
• The efficacy of endogenous mir-279/996 in restricting RTK/Ras signaling is substantial enough that deletion of these miRNAs can rescue a population of R7 photoreceptors in the absence of the Boss ligand or the Sev receptor. (PMID:29540498)
• the spindle checkpoint may regulate CDC27/APC activity at mitosis (PMID:12429948)
• HOXC10 co-immunoprecipitates the APC subunit CDC27, and its in vitro degradation is reduced in APC-depleted extracts or by competition with the APC substrate cyclin A. (PMID:12853486)
• The interaction is direct and is mediated by the tandem BRCA1 C-terminal domains of MDC1 and the C terminus of the Cdc27 (APC3) subunit of the anaphase-promoting complex/cyclosome. (PMID:17827148)
• phosphorylation of Cdc27 by CKII is involved in TGF-beta-induced activation of APC. (PMID:21209074)
• Cdc20 requires APC3 and APC8 to bind and activate the APC/C when the spindle assembly checkpoint is satisfied, but only APC8 when active, and APC10 is crucial for the destruction of cyclin B1 and securin, but not cyclin A (PMID:21336306)
• the biochemical, structural, and cellular determinants of the novel interaction between MCPH1 and Cdc27 and suggest that this interaction may occur within the larger context of MCPH1-APC/C. (PMID:22139841)
• Data indicate that additional density present in the anaphase-promoting complex (APC/C) structure, proximal to Apc3/Cdc27 of the (tetratricopeptide repeat) lobe, is assigned to the TPR subunit Apc7, a subunit specific to vertebrate APC/C. (PMID:23078409)
• Low cdc27 and high securin expression predict short survival for breast cancer patients. (PMID:23755904)
• Down-regulation of CDC27 protein is associated with radiation resistance. (PMID:23923534)
• The structures show how one APC16 binds asymmetrically to the symmetric APC3 dimer and, together with biochemistry and prior data, explain how APC16 recruits APC7 to APC3. (PMID:25490258)
• These findings suggested that polymorphisms in cdc27 may contribute to the susceptibility of BC though functional studies are needed to further elucidate the underling mechanisms of the associations (PMID:25680405)
• miR-27a could modulate proliferation and radiosensitivity of TNBC cells. CDC-27 is a direct target of miR-27a and its downregulation conferred increased radioresistance of the cells. (PMID:25943633)
• Cdc27 is a novel binding partner of Elmo1.Cdc27-Elmo1 has a cellular role independent from the Elmo-Dock1-Rac signal module. (PMID:26882976)
• mir-218-2 promotes glioblastomas growth, invasion and drug resistance by targeting CDC27 expression. (PMID:27974673)
• The levels of CDC20 and CylinB1 increased and the levels of Ku70 and APC3 decreased after irradiation. APC/C(Cdh1) is involved in regulation of radiosensitivity in human NPC CNE-1 cells. (PMID:28004426)
• Data indicate that UBE2S and APC3 co-regulate the expression level of P21 at G2/M check point via the ubiquitin-proteasome system. (PMID:28257844)
• CDC27 facilitated cells invasion and metastasis via Twist pathway, leading to initiation of epithelial-mesenchymal transition and silencing of Twist expression could reverse this process. (PMID:30308498)
• Hsa_circ_0044226 knockdown attenuates progression of pulmonary fibrosis by inhibiting CDC27. (PMID:32710728)
• A Novel Gene CDC27 Causes SLE and Is Associated With the Disease Activity. (PMID:35418986)
• Circ_0000775 promotes the migration, invasion and EMT of hepatic carcinoma cells by recruiting IGF2BP2 to stabilize CDC27. (PMID:35561648)
• Functional and Genetic Analyses Unveil the Implication of CDC27 in Hemifacial Microsomia. (PMID:38731925)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdc27	ENSDARG00000056258
mus_musculus	Cdc27	ENSMUSG00000020687
rattus_norvegicus	Cdc27	ENSRNOG00000005904
drosophila_melanogaster	Cdc27	FBGN0012058
caenorhabditis_elegans	mat-1	WBGENE00003132

Paralogs (3): CDC23 (ENSG00000094880), CDC16 (ENSG00000130177), ANAPC7 (ENSG00000196510)

Protein

Protein identifiers

Cell division cycle protein 27 homolog — P30260 (reviewed: P30260)

Alternative names: Anaphase-promoting complex subunit 3, CDC27 homolog, H-NUC

All UniProt accessions (13): P30260, E9PRZ6, F6QPS0, G5EA36, I3L1K3, I3L225, I3L2Z8, I3L328, I3L394, I3L3G1, I3L3H6, I3L3Y5, K7EMA6

UniProt curated annotations — full annotation on UniProt →

Function. Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of ‘Lys-11’-linked polyubiquitin chains and, to a lower extent, the formation of ‘Lys-48’- and ‘Lys-63’-linked polyubiquitin chains. The APC/C complex catalyzes assembly of branched ‘Lys-11’-/‘Lys-48’-linked branched ubiquitin chains on target proteins.

Subunit / interactions. Homodimer. The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5. Interacts with RB. Interacts with FAM168B/MANI. Interacts with MCPH1.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Spindle.

Post-translational modifications. Phosphorylated. Phosphorylation on Ser-426 and Thr-446 occurs specifically during mitosis.

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. May be due to competing acceptor splice site.

Similarity. Belongs to the APC3/CDC27 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P30260-1	1	yes
P30260-2	2

RefSeq proteins (9): NP_001107563, NP_001247, NP_001280018, NP_001280020, NP_001339964, NP_001339976, NP_001339978, NP_001339979, NP_001339980 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat

Pfam: PF00515, PF12895, PF13181

UniProt features (80 total): helix 32, modified residue 15, repeat 13, compositionally biased region 5, sequence conflict 3, strand 3, region of interest 2, sequence variant 2, turn 2, chain 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
9FGQ	ELECTRON MICROSCOPY	2.5
3T1N	X-RAY DIFFRACTION	2.6
9GAW	ELECTRON MICROSCOPY	2.9
6Q6G	ELECTRON MICROSCOPY	3.2
6Q6H	ELECTRON MICROSCOPY	3.2
8PKP	ELECTRON MICROSCOPY	3.2
4RG9	X-RAY DIFFRACTION	3.25
4RG6	X-RAY DIFFRACTION	3.3
5G05	ELECTRON MICROSCOPY	3.4
8TAU	ELECTRON MICROSCOPY	3.5
4UI9	ELECTRON MICROSCOPY	3.6
6TNT	ELECTRON MICROSCOPY	3.78
6TLJ	ELECTRON MICROSCOPY	3.8
5G04	ELECTRON MICROSCOPY	3.9
6TM5	ELECTRON MICROSCOPY	3.9
9N9R	ELECTRON MICROSCOPY	3.9
9N9S	ELECTRON MICROSCOPY	3.9
8TAR	ELECTRON MICROSCOPY	4
5LCW	ELECTRON MICROSCOPY	4.2
4RG7	X-RAY DIFFRACTION	4.25
5A31	ELECTRON MICROSCOPY	4.3
5KHU	ELECTRON MICROSCOPY	4.8
5KHR	ELECTRON MICROSCOPY	6.1
5L9T	ELECTRON MICROSCOPY	6.4
5L9U	ELECTRON MICROSCOPY	6.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30260-F1	70.02	0.51

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 (15): 205, 209, 244, 291, 313, 339, 366, 379, 386, 426, 430, 435, 438, 446, 821

Mutagenesis-validated functional residues (1):

Position	Phenotype
821	abolishes binding to mcph1.

Function

Pathways and Gene Ontology

Reactome pathways

47 pathways

ID	Pathway
R-HSA-141430	Inactivation of APC/C via direct inhibition of the APC/C complex
R-HSA-174048	APC/C:Cdc20 mediated degradation of Cyclin B
R-HSA-174084	Autodegradation of Cdh1 by Cdh1:APC/C
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-176412	Phosphorylation of the APC/C
R-HSA-179409	APC-Cdc20 mediated degradation of Nek2A
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-68867	Assembly of the pre-replicative complex
R-HSA-69017	CDK-mediated phosphorylation and removal of Cdc6
R-HSA-8853884	Transcriptional Regulation by VENTX
R-HSA-9687136	Aberrant regulation of mitotic exit in cancer due to RB1 defects
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-141405	Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
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-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-2559583	Cellular Senescence

MSigDB gene sets: 294 (showing top): GOBP_CHROMOSOME_ORGANIZATION, REACTOME_DNA_REPLICATION, BORCZUK_MALIGNANT_MESOTHELIOMA_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, REACTOME_APC_C_CDC20_MEDIATED_DEGRADATION_OF_CYCLIN_B, REACTOME_CONVERSION_FROM_APC_C_CDC20_TO_APC_C_CDH1_IN_LATE_ANAPHASE, REACTOME_PHOSPHORYLATION_OF_THE_APC_C, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_ANAPHASE_PROMOTING_COMPLEX_DEPENDENT_CATABOLIC_PROCESS, REACTOME_APC_CDC20_MEDIATED_DEGRADATION_OF_NEK2A, CMYB_01, GOBP_CELL_CYCLE_PHASE_TRANSITION

GO Biological Process (10): metaphase/anaphase transition of mitotic cell cycle (GO:0007091), regulation of mitotic cell cycle (GO:0007346), protein ubiquitination (GO:0016567), anaphase-promoting complex-dependent catabolic process (GO:0031145), neuron projection development (GO:0031175), cell division (GO:0051301), regulation of meiotic cell cycle (GO:0051445), protein K48-linked ubiquitination (GO:0070936), protein K11-linked ubiquitination (GO:0070979), protein branched polyubiquitination (GO:0141198)

GO Molecular Function (2): protein phosphatase binding (GO:0019903), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), anaphase-promoting complex (GO:0005680), cytoplasm (GO:0005737), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), mitotic spindle (GO:0072686), cytoskeleton (GO:0005856), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
APC/C-mediated degradation of cell cycle proteins	4
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
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	2
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	1
Mitotic Anaphase	1
Cellular Senescence	1
DNA Replication Pre-Initiation	1
Switching of origins to a post-replicative state	1
Generic Transcription Pathway	1
Aberrant regulation of mitotic cell cycle due to RB1 defects	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Regulation of APC/C activators between G1/S and early anaphase	1
Mitotic Spindle Checkpoint	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein polyubiquitination	3
mitotic cell cycle	2
regulation of cell cycle	2
intracellular membraneless organelle	2
mitotic cell cycle phase transition	1
metaphase/anaphase transition of cell cycle	1
protein modification by small protein conjugation	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
neuron development	1
plasma membrane bounded cell projection organization	1
cellular process	1
meiotic cell cycle	1
regulation of reproductive process	1
phosphatase binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear ubiquitin ligase complex	1
cullin-RING ubiquitin ligase complex	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
microtubule cytoskeleton	1
cytoplasm	1
spindle	1

Protein interactions and networks

STRING

3940 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC27	ANAPC5	Q9UJX4	997
CDC27	CDC16	Q13042	993
CDC27	CDC23	Q9UJX2	993
CDC27	ANAPC10	Q9UM13	982
CDC27	ANAPC4	Q9UJX5	981
CDC27	CDC20	Q12834	980
CDC27	MPPE1	Q53F39	963
CDC27	ANAPC2	Q9UJX6	955
CDC27	FZR1	Q9UM11	942
CDC27	ANAPC11	Q9NYG5	932
CDC27	ANAPC1	Q9H1A4	920
CDC27	CDC26	Q8NHZ8	873
CDC27	ANAPC16	Q96DE5	871
CDC27	BUB1B	O60566	845
CDC27	ANAPC13	Q9BS18	794

IntAct

269 interactions, top by confidence:

A	B	Type	Score
CDC20	BUB1B	psi-mi:“MI:0914”(association)	0.980
CDC27	CDC20	psi-mi:“MI:0914”(association)	0.950
CDC20	CDC27	psi-mi:“MI:0915”(physical association)	0.950
CDC20	CDC27	psi-mi:“MI:0914”(association)	0.950
CDC27	CDC20	psi-mi:“MI:0915”(physical association)	0.950
CDC27	MAD2L1	psi-mi:“MI:0915”(physical association)	0.920
ANAPC2	CDC27	psi-mi:“MI:0915”(physical association)	0.910
CDC27	FZR1	psi-mi:“MI:0915”(physical association)	0.910
FZR1	CDC27	psi-mi:“MI:0915”(physical association)	0.910
FZR1	CDC27	psi-mi:“MI:0914”(association)	0.910
BUB1B	CDC27	psi-mi:“MI:0914”(association)	0.900
CDC27	BUB1B	psi-mi:“MI:0914”(association)	0.900
CDC27	BUB1B	psi-mi:“MI:0915”(physical association)	0.900
CDC27	ANAPC4	psi-mi:“MI:0914”(association)	0.860
CDC23	CDC27	psi-mi:“MI:0914”(association)	0.860

BioGRID (797): CDC20 (Affinity Capture-Western), CDC27 (Affinity Capture-Western), CDC27 (Affinity Capture-Western), CDC20 (Reconstituted Complex), BUB1B (Reconstituted Complex), CDC27 (Reconstituted Complex), CDC27 (Reconstituted Complex), ANAPC11 (Affinity Capture-MS), CDC26 (Affinity Capture-MS), CDC27 (Affinity Capture-Western), CDC20 (Reconstituted Complex), BUB1B (Reconstituted Complex), MAD2L1 (Reconstituted Complex), COMT (Two-hybrid), E2F1 (Affinity Capture-Western)

ESM2 similar proteins: A0JMA8, A1A5P5, A2A6Q5, A6QNM3, A7Z061, E7F187, E9Q6P5, F7BJB9, O13046, O76094, P09798, P10505, P17885, P30260, P33731, P38042, P41889, Q05B30, Q06AN9, Q07617, Q13099, Q13416, Q32NR4, Q32NU8, Q3UMY5, Q4R6M4, Q4V8A2, Q5R629, Q5RE52, Q5TYV4, Q5U245, Q5ZKQ3, Q61371, Q6NU95, Q6PA97, Q6XV80, Q7Z3E5, Q7ZUV2, Q86TV6, Q8BGB2

Diamond homologs: A2A6Q5, A7Z061, O94556, P10505, P16522, P30260, P38042, Q4V8A2, Q54J83, Q86B11, Q9STS3, Q19294, Q06AN9, Q8LGU6, Q9N593, P17885, A1A4R8, Q8BGZ4, Q9UJX2

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CDK1	up-regulates	CDC27	phosphorylation
CSNK2A1	up-regulates	CDC27	phosphorylation
PRKAA2	unknown	CDC27	phosphorylation
AMPK	unknown	CDC27	phosphorylation
CDC27	“form complex”	APC-c	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 152 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	82.2×	1e-23
Inactivation of APC/C via direct inhibition of the APC/C complex	14	67.3×	6e-22
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase	13	62.5×	8e-20
APC-Cdc20 mediated degradation of Nek2A	15	58.7×	3e-22
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	15	58.7×	3e-22
Aberrant regulation of mitotic exit in cancer due to RB1 defects	12	57.7×	1e-17
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	15	56.6×	6e-22
Phosphorylation of the APC/C	11	55.4×	5e-16

GO biological processes:

GO term	Partners	Fold	FDR
regulation of meiotic cell cycle	14	85.8×	3e-22
anaphase-promoting complex-dependent catabolic process	14	78.6×	9e-22
protein branched polyubiquitination	11	74.2×	1e-16
mitotic spindle assembly checkpoint signaling	10	44.9×	2e-12
protein K11-linked ubiquitination	13	40.8×	7e-16
regulation of mitotic cell cycle	17	32.7×	4e-19
negative regulation of cellular senescence	5	25.9×	1e-04
negative regulation of double-strand break repair via homologous recombination	5	25.0×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	3
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1696853	NM_001256.6(CDC27):c.1777G>A (p.Ala593Thr)	Pathogenic

SpliceAI

3174 predictions. Top by Δscore:

Variant	Effect	Δscore
17:47121014:CCCA:C	acceptor_gain	1.0000
17:47121015:CCA:C	acceptor_gain	1.0000
17:47121015:CCACT:C	acceptor_gain	1.0000
17:47121016:CA:C	acceptor_gain	1.0000
17:47121016:CAC:C	acceptor_gain	1.0000
17:47121018:C:CC	acceptor_gain	1.0000
17:47121019:T:C	acceptor_gain	1.0000
17:47121020:T:C	acceptor_gain	1.0000
17:47121020:T:TC	acceptor_gain	1.0000
17:47122438:A:AC	donor_gain	1.0000
17:47122439:C:CC	donor_gain	1.0000
17:47122439:CTTA:C	donor_gain	1.0000
17:47122440:TTA:T	donor_loss	1.0000
17:47122441:TA:T	donor_loss	1.0000
17:47122442:A:AC	donor_gain	1.0000
17:47122442:AC:A	donor_loss	1.0000
17:47122443:C:CA	donor_gain	1.0000
17:47122443:CT:C	donor_gain	1.0000
17:47122443:CTG:C	donor_gain	1.0000
17:47122443:CTGA:C	donor_gain	1.0000
17:47122443:CTGAT:C	donor_gain	1.0000
17:47123889:T:A	donor_gain	1.0000
17:47123957:CAGA:C	acceptor_gain	1.0000
17:47123959:GA:G	acceptor_gain	1.0000
17:47123961:C:CC	acceptor_gain	1.0000
17:47129387:TCTTA:T	donor_loss	1.0000
17:47129388:CTTAC:C	donor_loss	1.0000
17:47129389:TTAC:T	donor_loss	1.0000
17:47129390:TACCT:T	donor_loss	1.0000
17:47129391:A:AC	donor_gain	1.0000

AlphaMissense

5384 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:47122504:C:G	A778P	1.000
17:47122508:T:A	K776N	1.000
17:47122508:T:G	K776N	1.000
17:47122512:A:G	I775T	1.000
17:47122528:C:G	G770R	1.000
17:47122528:C:T	G770R	1.000
17:47122539:A:G	L766S	1.000
17:47122548:G:T	A763D	1.000
17:47122549:C:G	A763P	1.000
17:47122554:G:A	S761F	1.000
17:47122555:A:G	S761P	1.000
17:47122557:A:G	F760S	1.000
17:47122566:A:G	L757P	1.000
17:47122569:G:T	A756D	1.000
17:47122570:C:G	A756P	1.000
17:47123890:C:A	G744V	1.000
17:47123890:C:T	G744E	1.000
17:47123891:C:G	G744R	1.000
17:47123891:C:T	G744R	1.000
17:47123898:G:C	F741L	1.000
17:47123898:G:T	F741L	1.000
17:47123900:A:G	F741L	1.000
17:47123903:A:C	Y740D	1.000
17:47123905:A:T	V739D	1.000
17:47123915:C:T	E736K	1.000
17:47123931:T:A	K730N	1.000
17:47123931:T:G	K730N	1.000
17:47123935:A:C	L729W	1.000
17:47123935:A:G	L729S	1.000
17:47123944:A:G	L726P	1.000

dbSNP variants (sampled 300 via entrez): RS1000033037 (17:47151612 A>G), RS1000068813 (17:47128659 G>A), RS1000136271 (17:47145054 T>C), RS1000141689 (17:47178783 T>C), RS1000164833 (17:47134163 G>A), RS1000280669 (17:47123423 C>A,G,T), RS1000286305 (17:47171119 A>T), RS1000291170 (17:47151681 T>C), RS1000374942 (17:47131106 A>G), RS1000407324 (17:47131522 G>C), RS1000428563 (17:47178437 A>G), RS1000475432 (17:47145027 T>A,C), RS1000533710 (17:47124265 A>G), RS1000583719 (17:47159415 C>T), RS1000620603 (17:47173001 C>T)

Disease associations

OMIM: gene MIM:116946 | disease phenotypes:

GenCC curated gene-disease

Mondo (3): breast ductal adenocarcinoma (MONDO:0005590), esophageal atresia (MONDO:0001044), pyloric stenosis (MONDO:0001561)

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0002032	Esophageal atresia
HP:0002021	Pyloric stenosis

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005951_16	Body mass index	4.000000e-08
GCST007637_26	Diffusing capacity of carbon monoxide	1.000000e-07
GCST90020028_1383	Hip circumference adjusted for BMI	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D004933	Esophageal Atresia	C06.198.330; C06.405.117.260; C16.131.314.330
D017219	Gastric Outlet Obstruction	C06.405.748.340
D011707	Pyloric Stenosis	C06.405.748.340.690

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, increases expression, decreases expression	4
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	increases phosphorylation, affects binding, increases reaction	2
Acetaminophen	increases expression	2
Valproic Acid	decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
aflatoxin B2	decreases methylation	1
coumarin	affects phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole	affects binding, decreases reaction, increases reaction	1
CGP 52608	affects binding, increases reaction	1
U 0126	affects expression, affects reaction	1
motexafin gadolinium	increases expression, affects cotreatment, affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Arsenic Trioxide	affects cotreatment, increases expression	1
Vorinostat	decreases expression	1
Atrazine	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Caffeine	increases phosphorylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00556283	PHASE4	COMPLETED	RCT: STARR vs Biofeedback
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00226044	PHASE3	COMPLETED	Rectal and Oral Omeprazole Treatment of Reflux Disease in Infants.
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT03127345	PHASE2	WITHDRAWN	Omega 3 Fatty Acid Treatment for Pediatric Musculoskeletal Health
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery
NCT02033772	Not specified	COMPLETED	Prospective Data Collection of Patients < 6 Months of Age Undergoing Thoracoscopic Surgery
NCT02466451	Not specified	COMPLETED	Study in Children With the Diagnosis of Congenital Diaphragmatic Hernia (CDH) and Oesophageal Atresia (EA)
NCT02525705	Not specified	COMPLETED	Dumping Syndrome After Operation of Esophageal Atresia Type III
NCT02883725	Not specified	COMPLETED	National Register of Oesophageal Atresia
NCT03023865	Not specified	UNKNOWN	Individualized Management for Long Gap Esophageal Atresia
NCT03415893	Not specified	COMPLETED	High-resolution Esophageal Manometry
NCT03455881	Not specified	UNKNOWN	Phenotypic and Genetic Assessment of Tracheal and Esophageal Birth Defects in Patients
NCT03615495	Not specified	COMPLETED	Flourish™ Pediatric Esophageal Atresia
NCT03619408	Not specified	UNKNOWN	Management of Esophagitis Following Repair of Esophageal Atresia
NCT03666767	Not specified	COMPLETED	Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries
NCT03730454	Not specified	ACTIVE_NOT_RECRUITING	Transanastomotic Tube for Proximal Esophageal Atresia With Distal Tracheoesophageal Fistula Repair
NCT03767673	Not specified	UNKNOWN	Cardiorespiratory Performance and Pulmonary Microbiome in Patients After Repair of Esophageal Atresia
NCT03999008	Not specified	UNKNOWN	Oral Viscous Budesonide in Anastomotic Stricture After Esophageal Atresia Repair (OVB in EA)
NCT04072419	Not specified	UNKNOWN	Application of Enhanced Recovery After Surgery for Congenital Esophageal Atresia During Perioperative Period
NCT04136795	Not specified	UNKNOWN	Evaluation of the Respiratory Impact After Conventional or Minimally Invasive Esophageal Atresia Surgery
NCT04259528	Not specified	UNKNOWN	Endoscopic Ultrasound Findings in Esophageal Atresia Following Surgical Repair
NCT04522193	Not specified	RECRUITING	Dumping Syndrome and Esophageal Atresia
NCT04901546	Not specified	COMPLETED	Esophageal Atresia: a Natural Experiment of the Effects of Oral Inoculation on the Gut Microbiome
NCT04932746	Not specified	COMPLETED	The Effect of Dexmedetomidine on Oxygen During One Lung Ventilation in Pediatric Surgery.
NCT05129930	Not specified	COMPLETED	Fluid Overload and Pulmonary Function
NCT05527873	Not specified	COMPLETED	Respiratory Complications of Operated Esophageal Atresia in Children
NCT05995171	Not specified	RECRUITING	Long Term Outcome of Easophageal Atresia : Transmics Profiles in Adolescence
NCT06073158	Not specified	COMPLETED	Molecular Signatures of Esophageal Atresia
NCT06208449	Not specified	UNKNOWN	Robotic Versus Thoracoscopy Versus Thoracotomy Repair for Congenital Esophageal Atresia
NCT06335862	Not specified	ENROLLING_BY_INVITATION	Primary Posterior Tracheopexy Prevents Tracheal Collapse
NCT06731855	Not specified	RECRUITING	An Exploratory Physiological Study of Post-operative Recovery in Surgical Neonates and Dimethylarginine:Arginine Levels