CDC23

Summary

CDC23 (cell division cycle 23, HGNC:1724) is a protein-coding gene on chromosome 5q31.2, encoding Cell division cycle protein 23 homolog (Q9UJX2). 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 100.0% of cancer cell lines).

The protein encoded by this gene shares strong similarity with Saccharomyces cerevisiae Cdc23, a protein essential for cell cycle progression through the G2/M transition. This protein is a component of anaphase-promoting complex (APC), which is composed of eight protein subunits and highly conserved in eukaryotic cells. APC catalyzes the formation of cyclin B-ubiquitin conjugate that is responsible for the ubiquitin-mediated proteolysis of B-type cyclins. This protein and 3 other members of the APC complex contain the TPR (tetratricopeptide repeat), a protein domain important for protein-protein interaction.

Source: NCBI Gene 8697 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 57 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_004661

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1724
Approved symbol	CDC23
Name	cell division cycle 23
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	APC8, ANAPC8, CUT23
Ensembl gene	ENSG00000094880
Ensembl biotype	protein_coding
OMIM	603462
Entrez	8697

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000394884, ENST00000394886, ENST00000464806, ENST00000471692, ENST00000475021, ENST00000482948, ENST00000483961, ENST00000505120, ENST00000511383, ENST00000892741, ENST00000892742, ENST00000892743, ENST00000892744, ENST00000927074, ENST00000927075, ENST00000962866

RefSeq mRNA: 1 — MANE Select: NM_004661 NM_004661

CCDS: CCDS4200

Canonical transcript exons

ENST00000394886 — 16 exons

Exon	Start	End
ENSE00000764407	138191862	138191937
ENSE00000764409	138192269	138192388
ENSE00000764437	138198605	138198782
ENSE00001129803	138187650	138189148
ENSE00001864115	138213152	138213323
ENSE00003477585	138189633	138189752
ENSE00003486415	138189828	138189906
ENSE00003543478	138192504	138192657
ENSE00003557195	138202113	138202155
ENSE00003583154	138201107	138201239
ENSE00003602062	138212991	138213063
ENSE00003605629	138206547	138206684
ENSE00003613008	138191474	138191535
ENSE00003645295	138201343	138201448
ENSE00003646963	138198199	138198280
ENSE00003685229	138198426	138198523

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 92.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0856 / max 310.2371, expressed in 1776 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63676	13.0856	1776

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	92.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.28	gold quality
ventricular zone	UBERON:0003053	88.78	gold quality
esophagus squamous epithelium	UBERON:0006920	88.69	gold quality
tibia	UBERON:0000979	88.51	gold quality
endothelial cell	CL:0000115	88.25	gold quality
rectum	UBERON:0001052	87.63	gold quality
cerebellar hemisphere	UBERON:0002245	87.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.32	gold quality
cerebellar cortex	UBERON:0002129	87.29	gold quality
epithelium of esophagus	UBERON:0001976	87.21	gold quality
ovary	UBERON:0000992	87.17	gold quality
islet of Langerhans	UBERON:0000006	86.99	gold quality
right ovary	UBERON:0002118	86.93	gold quality
left ovary	UBERON:0002119	86.93	gold quality
calcaneal tendon	UBERON:0003701	86.91	gold quality
body of uterus	UBERON:0009853	86.49	gold quality
endometrium	UBERON:0001295	86.47	gold quality
vagina	UBERON:0000996	86.43	gold quality
palpebral conjunctiva	UBERON:0001812	86.43	gold quality
skin of abdomen	UBERON:0001416	86.37	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.32	gold quality
esophagus mucosa	UBERON:0002469	86.28	gold quality
skin of leg	UBERON:0001511	86.23	gold quality
germinal epithelium of ovary	UBERON:0001304	86.21	gold quality
ectocervix	UBERON:0012249	86.13	gold quality
esophagus	UBERON:0001043	85.99	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.92	gold quality
lower esophagus	UBERON:0013473	85.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.76	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.03
E-MTAB-6379	no	398.35
E-MTAB-7249	no	368.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting CDC23, 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-9-5P	100.00	72.28	2361
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 6)

• We report gene alterations in several components of this complex in human colon cancer cells, including APC6/CDC16 and APC8/CDC23 which are known to be key function elements. (PMID:12629511)
• 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)
• CDC23 is a critical regulator of cell cycle and cell growth, may be involved in thyroid cancer initiation and progression, and may explain the different tumor biology observed by gender. (PMID:21990323)
• Results identified CDC23 as a miR-34c-regulated target that could be responsible for the miR-34c-induced cell cycle arrest. (PMID:25064703)
• LINC00514 promoted CDC23 expression via restraining miR-204-3p activity, leading to papillary thyroid cancer progression. (PMID:30553447)
• Homozygous variants in CDC23 cause female infertility characterized by oocyte maturation defects. (PMID:37768355)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdc23	ENSDARG00000044484
mus_musculus	Cdc23	ENSMUSG00000024370
rattus_norvegicus	Cdc23	ENSRNOG00000024241
drosophila_melanogaster	Cdc23	FBGN0032863
drosophila_melanogaster	CG31687	FBGN0051687
caenorhabditis_elegans		WBGENE00003134

Paralogs (3): CDC27 (ENSG00000004897), CDC16 (ENSG00000130177), ANAPC7 (ENSG00000196510)

Protein

Protein identifiers

Cell division cycle protein 23 homolog — Q9UJX2 (reviewed: Q9UJX2)

Alternative names: Anaphase-promoting complex subunit 8, Cyclosome subunit 8

All UniProt accessions (4): Q9UJX2, D6RBY8, D6RCF8, H0Y936

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. 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 FBXO43; the interaction is direct.

Post-translational modifications. Phosphorylated. Phosphorylation on Thr-562 occurs specifically during mitosis.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the APC8/CDC23 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UJX2-1	1	yes
Q9UJX2-2	2
Q9UJX2-3	3

RefSeq proteins (1): NP_004652* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007192	APC8	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat

Pfam: PF04049, PF13181, PF13414

UniProt features (80 total): helix 33, repeat 13, modified residue 10, turn 6, sequence conflict 4, strand 4, splice variant 3, sequence variant 2, mutagenesis site 2, initiator methionine 1, chain 1, cross-link 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
9GAW	ELECTRON MICROSCOPY	2.9
6Q6G	ELECTRON MICROSCOPY	3.2
6Q6H	ELECTRON MICROSCOPY	3.2
8PKP	ELECTRON MICROSCOPY	3.2
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
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-Q9UJX2-F1	85.74	0.59

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): 2, 273, 467, 562, 565, 578, 582, 588, 593, 596, 147

Mutagenesis-validated functional residues (2):

Position	Phenotype
339	inhibits apc/fzr1 e3 ubiquitin-protein ligase complex activity; when associated with a-374.
374	inhibits apc/fzr1 e3 ubiquitin-protein ligase complex activity; when associated with a-339.

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: 270 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, REACTOME_DNA_REPLICATION, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, BROWNE_HCMV_INFECTION_6HR_DN, 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, GOBP_REGULATION_OF_NUCLEAR_DIVISION, 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, GOBP_CHROMOSOME_LOCALIZATION

GO Biological Process (15): mitotic cell cycle (GO:0000278), ubiquitin-dependent protein catabolic process (GO:0006511), mitotic metaphase chromosome alignment (GO:0007080), metaphase/anaphase transition of mitotic cell cycle (GO:0007091), regulation of exit from mitosis (GO:0007096), regulation of mitotic cell cycle (GO:0007346), protein ubiquitination (GO:0016567), regulation of mitotic metaphase/anaphase transition (GO:0030071), anaphase-promoting complex-dependent catabolic process (GO:0031145), positive regulation of mitotic metaphase/anaphase transition (GO:0045842), 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): ubiquitin-protein transferase activity (GO:0004842), protein binding (GO:0005515)

GO Cellular Component (3): nucleoplasm (GO:0005654), anaphase-promoting complex (GO:0005680), cytosol (GO:0005829)

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
mitotic cell cycle	3
protein polyubiquitination	3
regulation of mitotic cell cycle phase transition	2
regulation of cell cycle	2
metaphase/anaphase transition of mitotic cell cycle	2
cellular anatomical structure	2
cell cycle	1
mitotic nuclear division	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
mitotic sister chromatid segregation	1
metaphase chromosome alignment	1
mitotic cell cycle process	1
mitotic cell cycle phase transition	1
metaphase/anaphase transition of cell cycle	1
exit from mitosis	1
protein modification by small protein conjugation	1
regulation of metaphase/anaphase transition of cell cycle	1
proteasome-mediated ubiquitin-dependent protein catabolic process	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
cellular process	1
meiotic cell cycle	1
regulation of reproductive process	1
ubiquitin-like protein transferase activity	1
binding	1
nuclear lumen	1
nuclear ubiquitin ligase complex	1
cullin-RING ubiquitin ligase complex	1
cytoplasm	1

Protein interactions and networks

STRING

3646 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC23	ANAPC5	Q9UJX4	999
CDC23	CDC16	Q13042	999
CDC23	CDC27	P30260	993
CDC23	ANAPC10	Q9UM13	993
CDC23	ANAPC11	Q9NYG5	979
CDC23	CDC26	Q8NHZ8	973
CDC23	ANAPC4	Q9UJX5	963
CDC23	CDC20	Q12834	943
CDC23	ANAPC7	Q9UJX3	933
CDC23	ANAPC13	Q9BS18	925
CDC23	ANAPC2	Q9UJX6	911
CDC23	ANAPC15	P60006	879
CDC23	ANAPC1	Q9H1A4	857
CDC23	ANAPC16	Q96DE5	805
CDC23	FZR1	Q9UM11	765

IntAct

482 interactions, top by confidence:

A	B	Type	Score
PSMA1	PSMA7	psi-mi:“MI:2364”(proximity)	0.950
ANAPC2	CDC27	psi-mi:“MI:0915”(physical association)	0.910
CDC23	CDC27	psi-mi:“MI:0914”(association)	0.860
ANAPC4	CDC27	psi-mi:“MI:0914”(association)	0.860
GRAP2	STAMBP	psi-mi:“MI:0914”(association)	0.810
CDC23	OPTN	psi-mi:“MI:0915”(physical association)	0.790
OPTN	CDC23	psi-mi:“MI:0915”(physical association)	0.790
GORASP2	CDC23	psi-mi:“MI:0915”(physical association)	0.720
IHO1	CDC23	psi-mi:“MI:0915”(physical association)	0.720
CDC23	KCTD6	psi-mi:“MI:0915”(physical association)	0.720
CDC23	GORASP2	psi-mi:“MI:0915”(physical association)	0.720
CDC23	IHO1	psi-mi:“MI:0915”(physical association)	0.720
KCTD6	CDC23	psi-mi:“MI:0915”(physical association)	0.720
TRIM27	CDC23	psi-mi:“MI:0915”(physical association)	0.670
CDC23	RBPMS	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (467): CDC23 (Reconstituted Complex), CDC23 (Affinity Capture-Western), CDC23 (Two-hybrid), CDC23 (Two-hybrid), CDC23 (Two-hybrid), CDC23 (Two-hybrid), CDC23 (Two-hybrid), CDC23 (Two-hybrid), CDC23 (Two-hybrid), CDC23 (Two-hybrid), OPTN (Two-hybrid), RBPMS (Two-hybrid), RAD54B (Two-hybrid), ANAPC13 (Two-hybrid), GORASP2 (Two-hybrid)

ESM2 similar proteins: A1A4R8, B0BNG0, B3DNN5, E7F590, F8VPK0, O89079, P45432, P49754, P62944, P63009, P63010, Q12996, Q15006, Q28G25, Q2KJ25, Q4QR29, Q5E993, Q5F3K0, Q5KU39, Q5M7J9, Q5R4J9, Q5R882, Q5RBI3, Q5RDW9, Q60445, Q62018, Q6DEU9, Q6DFB8, Q6INS3, Q6N069, Q6PD62, Q6PGP7, Q6TGY8, Q80UM3, Q8AVU9, Q8BGZ4, Q8TAM2, Q8VD72, Q8VY89, Q8VZM1

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

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CDK1	up-regulates	CDC23	phosphorylation
CDC23	“form complex”	APC-c	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 120 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	7	65.3×	3e-10
Inactivation of APC/C via direct inhibition of the APC/C complex	8	61.1×	4e-11
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase	8	61.1×	4e-11
Aberrant regulation of mitotic exit in cancer due to RB1 defects	8	61.1×	4e-11
Phosphorylation of the APC/C	7	56.0×	9e-10
APC-Cdc20 mediated degradation of Nek2A	8	49.8×	2e-10
APC/C:Cdc20 mediated degradation of Cyclin B	7	47.0×	3e-09
Regulation of APC/C activators between G1/S and early anaphase	10	45.4×	5e-12

GO biological processes:

GO term	Partners	Fold	FDR
anaphase-promoting complex-dependent catabolic process	9	65.2×	6e-12
regulation of meiotic cell cycle	8	63.2×	1e-10
protein branched polyubiquitination	7	60.8×	2e-09
protein K11-linked ubiquitination	9	36.4×	7e-10
regulation of mitotic cell cycle	10	24.8×	2e-09
protein K48-linked ubiquitination	7	12.2×	2e-04
cell division	14	6.7×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1619 predictions. Top by Δscore:

Variant	Effect	Δscore
5:138189624:GATAC:G	donor_loss	1.0000
5:138189625:ATACT:A	donor_loss	1.0000
5:138189627:ACTC:A	donor_loss	1.0000
5:138189628:CTC:C	donor_loss	1.0000
5:138189629:T:TG	donor_loss	1.0000
5:138189630:CACAT:C	donor_loss	1.0000
5:138189631:A:AC	donor_gain	1.0000
5:138189631:ACAT:A	donor_gain	1.0000
5:138189632:C:CG	donor_gain	1.0000
5:138189632:CA:C	donor_gain	1.0000
5:138189632:CAT:C	donor_gain	1.0000
5:138189632:CATC:C	donor_gain	1.0000
5:138189632:CATCA:C	donor_gain	1.0000
5:138189749:TTTC:T	acceptor_gain	1.0000
5:138189750:TTC:T	acceptor_gain	1.0000
5:138189750:TTCC:T	acceptor_loss	1.0000
5:138189753:C:CA	acceptor_loss	1.0000
5:138189753:C:CC	acceptor_gain	1.0000
5:138189827:CCCCA:C	donor_gain	1.0000
5:138191470:TCA:T	donor_loss	1.0000
5:138191471:CACTT:C	donor_loss	1.0000
5:138191472:A:AC	donor_gain	1.0000
5:138191472:A:T	donor_loss	1.0000
5:138191473:C:CC	donor_gain	1.0000
5:138191473:CT:C	donor_gain	1.0000
5:138191473:CTTTG:C	donor_gain	1.0000
5:138191531:TAACA:T	acceptor_gain	1.0000
5:138191532:AACA:A	acceptor_gain	1.0000
5:138191533:ACA:A	acceptor_gain	1.0000
5:138191534:CA:C	acceptor_gain	1.0000

AlphaMissense

3896 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:138189136:C:G	G546R	1.000
5:138189659:C:G	A533P	1.000
5:138189670:G:T	A529D	1.000
5:138189709:A:G	L516P	1.000
5:138191477:G:T	A474E	1.000
5:138191480:A:G	L473P	1.000
5:138191522:G:T	A459D	1.000
5:138191523:C:G	A459P	1.000
5:138191869:G:T	A452D	1.000
5:138191870:C:G	A452P	1.000
5:138191905:C:A	G440V	1.000
5:138191905:C:T	G440E	1.000
5:138191906:C:G	G440R	1.000
5:138191906:C:T	G440R	1.000
5:138191911:G:T	A438D	1.000
5:138191924:G:T	R434S	1.000
5:138191929:T:A	D432V	1.000
5:138192281:G:T	A425D	1.000
5:138192282:C:G	A425P	1.000
5:138192320:A:G	L412P	1.000
5:138192330:A:C	Y409D	1.000
5:138192335:T:G	Q407P	1.000
5:138192338:C:A	G406V	1.000
5:138192338:C:T	G406E	1.000
5:138192339:C:A	G406W	1.000
5:138192339:C:G	G406R	1.000
5:138192339:C:T	G406R	1.000
5:138192341:A:G	L405P	1.000
5:138192341:A:T	L405H	1.000
5:138192344:C:T	G404D	1.000

dbSNP variants (sampled 300 via entrez): RS1000001862 (5:138208691 T>C), RS1000035697 (5:138211387 G>C,T), RS1000101623 (5:138201280 T>A), RS1000256745 (5:138192726 G>T), RS1000370993 (5:138202067 G>A), RS1000437408 (5:138209013 G>A), RS1000649594 (5:138214648 C>G), RS1000714204 (5:138208274 G>A), RS1000773848 (5:138207475 C>T), RS1000811377 (5:138197495 A>T), RS1000863364 (5:138194753 C>T), RS1001163577 (5:138208025 G>A), RS1001291310 (5:138201196 T>C,G), RS1001315592 (5:138195013 C>T), RS1001342635 (5:138215203 T>C)

Disease associations

OMIM: gene MIM:603462 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003818_25	Resting heart rate	1.000000e-13
GCST004521_66	Autism spectrum disorder or schizophrenia	1.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067364 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.27	Kd	53.52	nM	CHEMBL3752910
7.27	ED50	53.52	nM	CHEMBL3752910
5.59	Kd	2594	nM	CHEMBL5653589
5.59	ED50	2594	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148033: Binding affinity to human CDC23 incubated for 45 mins by Kinobead based pull down assay	kd	0.0535	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148033: Binding affinity to human CDC23 incubated for 45 mins by Kinobead based pull down assay	kd	2.5942	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	2
Valproic Acid	affects expression	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
lasiocarpine	increases metabolic processing, increases expression	1
triphenyl phosphate	affects expression	1
riddelliine	increases metabolic processing, decreases expression	1
nickel chloride	decreases expression	1
ochratoxin A	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Citrinin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Selenium	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651075	Binding	Binding affinity to human CDC23 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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