CDC16

Summary

CDC16 (cell division cycle 16, HGNC:1720) is a protein-coding gene on chromosome 13q34, encoding Cell division cycle protein 16 homolog (Q13042). 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 functions as a protein ubiquitin ligase and is a component of the multiprotein APC complex. The APC complex is a cyclin degradation system that governs exit from mitosis by targeting cell cycle proteins for degredation by the 26S proteasome. Each component protein of the APC complex is highly conserved among eukaryotic organisms. This protein, and other APC complex proteins, contain a tetratricopeptide repeat (TPR) domain; a protein domain that is often involved in protein-protein interactions and the assembly of multiprotein complexes. Multiple alternatively spliced transcript variants, encoding distinct proteins, have been identified.

Source: NCBI Gene 8881 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 124 total — 4 pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_001078645

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1720
Approved symbol	CDC16
Name	cell division cycle 16
Location	13q34
Locus type	gene with protein product
Status	Approved
Aliases	APC6, ANAPC6, CUT9
Ensembl gene	ENSG00000130177
Ensembl biotype	protein_coding
OMIM	603461
Entrez	8881

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000252457, ENST00000252458, ENST00000356221, ENST00000360383, ENST00000375308, ENST00000375310, ENST00000461716, ENST00000484907, ENST00000494581, ENST00000494766, ENST00000628084, ENST00000650489, ENST00000889274, ENST00000889275, ENST00000889276, ENST00000889277, ENST00000889278, ENST00000960228, ENST00000960229, ENST00000960230

RefSeq mRNA: 7 — MANE Select: NM_001078645 NM_001078645, NM_001318517, NM_001318518, NM_001330101, NM_001330104, NM_001330105, NM_003903

CCDS: CCDS81786, CCDS81787, CCDS9542

Canonical transcript exons

ENST00000356221 — 18 exons

Exon	Start	End
ENSE00000893875	114265150	114265240
ENSE00001131242	114262879	114263014
ENSE00001291492	114244890	114244969
ENSE00001466662	114272184	114272723
ENSE00001615209	114243257	114243348
ENSE00001690393	114243856	114243989
ENSE00001699894	114242121	114242280
ENSE00001884326	114234897	114235132
ENSE00003484719	114246000	114246049
ENSE00003585049	114236799	114236896
ENSE00003616731	114238990	114239028
ENSE00003617777	114236645	114236699
ENSE00003620574	114259335	114259398
ENSE00003621233	114239350	114239490
ENSE00003640155	114250549	114250674
ENSE00003664103	114261887	114261948
ENSE00003672542	114257078	114257230
ENSE00003683553	114246931	114247004

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 98.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.8942 / max 133.0869, expressed in 1812 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136284	13.0198	1798
136283	6.2495	1737
136285	1.1732	744
136286	0.9631	604
136288	0.3089	132
136287	0.1797	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.53	gold quality
bronchial epithelial cell	CL:0002328	98.28	gold quality
epithelium of bronchus	UBERON:0002031	97.78	gold quality
bronchus	UBERON:0002185	97.61	gold quality
body of pancreas	UBERON:0001150	97.08	gold quality
left ovary	UBERON:0002119	96.78	gold quality
body of uterus	UBERON:0009853	96.78	gold quality
endocervix	UBERON:0000458	96.68	gold quality
nerve	UBERON:0001021	96.65	gold quality
tibial nerve	UBERON:0001323	96.65	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.62	gold quality
right ovary	UBERON:0002118	96.59	gold quality
skin of abdomen	UBERON:0001416	96.58	gold quality
germinal epithelium of ovary	UBERON:0001304	96.50	gold quality
cervix squamous epithelium	UBERON:0006922	96.48	gold quality
mucosa of stomach	UBERON:0001199	96.42	gold quality
skin of hip	UBERON:0001554	96.37	gold quality
ectocervix	UBERON:0012249	96.26	gold quality
skin of leg	UBERON:0001511	96.25	gold quality
rectum	UBERON:0001052	96.24	gold quality
lateral globus pallidus	UBERON:0002476	96.15	gold quality
ovary	UBERON:0000992	96.14	gold quality
adenohypophysis	UBERON:0002196	96.13	gold quality
trabecular bone tissue	UBERON:0002483	96.13	gold quality
pancreatic ductal cell	CL:0002079	96.08	gold quality
gingival epithelium	UBERON:0001949	96.03	gold quality
smooth muscle tissue	UBERON:0001135	96.01	gold quality
middle temporal gyrus	UBERON:0002771	96.00	gold quality
endometrium	UBERON:0001295	95.99	gold quality
zone of skin	UBERON:0000014	95.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.36

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TFDP1

miRNA regulators (miRDB)

10 targeting CDC16, 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-589-3P	99.91	69.62	2088
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-299-5P	98.56	71.14	1140
HSA-MIR-4684-3P	98.24	69.91	1075
HSA-MIR-1267	98.24	69.05	837
HSA-MIR-4724-3P	97.57	67.31	785

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 3)

• TFDP1, CUL4A, and CDC16 are probable targets of an amplification mechanism and therefore may be involved, together or separately, in development and/or progression of some hepatocellular carcinomas (PMID:12029633)
• 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)
• DEPDC1B Promotes Melanoma Angiogenesis and Metastasis through Sequestration of Ubiquitin Ligase CDC16 to Stabilize Secreted SCUBE3. (PMID:35088579)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdc16	ENSDARG00000055470
mus_musculus	Cdc16	ENSMUSG00000038416
rattus_norvegicus	Cdc16	ENSRNOG00000017536
drosophila_melanogaster	Cdc16	FBGN0025781
caenorhabditis_elegans		WBGENE00001281

Paralogs (3): CDC27 (ENSG00000004897), CDC23 (ENSG00000094880), ANAPC7 (ENSG00000196510)

Protein

Protein identifiers

Cell division cycle protein 16 homolog — Q13042 (reviewed: Q13042)

Alternative names: Anaphase-promoting complex subunit 6, CDC16 homolog, Cyclosome subunit 6

All UniProt accessions (3): Q13042, A0A3B3ISD2, Q5T8C6

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. V-shaped 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 PPP5C and CDC20. Interacts with CDC26. Interacts with FBXO43.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle.

Post-translational modifications. Phosphorylated. Phosphorylation on Ser-560 occurs specifically during mitosis.

Domain organisation. TPR repeats 1-7 mediate homodimerization, while the C-terminal TPR repeats bind to CDC26, burying its hydrophobic N-terminus.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the APC6/CDC16 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q13042-1	1	yes
Q13042-2	2
Q13042-3	3
Q13042-4	4

RefSeq proteins (7): NP_001072113, NP_001305446, NP_001305447, NP_001317030, NP_001317033, NP_001317034, NP_003894 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat

Pfam: PF12895, PF13424

UniProt features (75 total): helix 32, repeat 14, turn 11, modified residue 6, strand 4, splice variant 3, sequence conflict 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
3HYM	X-RAY DIFFRACTION	2.8
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-Q13042-F1	78.89	0.48

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 (6): 112, 490, 560, 581, 595, 599

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: 233 (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, 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, KAAB_FAILED_HEART_ATRIUM_DN, 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_CELL_CYCLE_PHASE_TRANSITION

GO Biological Process (9): regulation of mitotic cell cycle (GO:0007346), protein ubiquitination (GO:0016567), 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 (1): protein binding (GO:0005515)

GO Cellular Component (9): nucleoplasm (GO:0005654), anaphase-promoting complex (GO:0005680), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), mitotic spindle (GO:0072686), nucleus (GO:0005634), spindle (GO:0005819), cytoskeleton (GO:0005856)

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
protein polyubiquitination	3
cellular anatomical structure	3
regulation of cell cycle	2
intracellular membraneless organelle	2
mitotic cell cycle	1
protein modification by small protein conjugation	1
proteasome-mediated ubiquitin-dependent protein catabolic process	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
cellular process	1
meiotic cell cycle	1
regulation of reproductive process	1
binding	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
cytoplasm	1
spindle	1
intracellular membrane-bounded organelle	1
microtubule cytoskeleton	1

Protein interactions and networks

STRING

2514 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC16	CDC23	Q9UJX2	999
CDC16	ANAPC5	Q9UJX4	998
CDC16	CDC27	P30260	993
CDC16	CDC26	Q8NHZ8	990
CDC16	ANAPC4	Q9UJX5	988
CDC16	USP6	P35125	987
CDC16	ANAPC10	Q9UM13	983
CDC16	ANAPC16	Q96DE5	960
CDC16	ANAPC1	Q9H1A4	937
CDC16	ANAPC7	Q9UJX3	936
CDC16	ANAPC2	Q9UJX6	925
CDC16	ANAPC11	Q9NYG5	920
CDC16	TBC1D7	Q9P0N9	896
CDC16	TBC1D20	Q96BZ9	876
CDC16	CDC20	Q12834	871

IntAct

151 interactions, top by confidence:

A	B	Type	Score
CDC20	BUB1B	psi-mi:“MI:0914”(association)	0.980
LAMTOR5	LAMTOR4	psi-mi:“MI:0914”(association)	0.960
CDC16	CDC26	psi-mi:“MI:0915”(physical association)	0.940
CDC26	CDC16	psi-mi:“MI:0915”(physical association)	0.940
CDC16	CDC26	psi-mi:“MI:0914”(association)	0.940
BUB1B	CDC27	psi-mi:“MI:0914”(association)	0.900
CDC23	CDC27	psi-mi:“MI:0914”(association)	0.860
CDC27	CDC16	psi-mi:“MI:0914”(association)	0.860
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
ANAPC5	CDC27	psi-mi:“MI:0914”(association)	0.810
CDC16	BUB1B	psi-mi:“MI:0914”(association)	0.790
CDC23	BUB1B	psi-mi:“MI:0914”(association)	0.790
CDC16	CDC20	psi-mi:“MI:0915”(physical association)	0.770
ANAPC16	CDC27	psi-mi:“MI:0914”(association)	0.760
ANAPC16	BUB1B	psi-mi:“MI:0914”(association)	0.730
CDC20	BUB1	psi-mi:“MI:0914”(association)	0.730
ANAPC10	CDC16	psi-mi:“MI:0915”(physical association)	0.710
MAD2L1	INSR	psi-mi:“MI:0914”(association)	0.700
ANAPC13	CDC27	psi-mi:“MI:0914”(association)	0.640
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640

BioGRID (520): CDC16 (Reconstituted Complex), CDC16 (Affinity Capture-Western), CDC26 (Two-hybrid), CDC16 (Affinity Capture-RNA), CDC16 (Affinity Capture-RNA), CDC16 (Affinity Capture-MS), CDC16 (Affinity Capture-Western), CDC16 (Affinity Capture-MS), CDC16 (Reconstituted Complex), CDC16 (Affinity Capture-Western), CDC16 (Affinity Capture-MS), CDC16 (Protein-peptide), CDC16 (Affinity Capture-MS), CDC16 (Affinity Capture-MS), CDC16 (Co-purification)

ESM2 similar proteins: A0A2R8QFQ6, A0A2R8RWN9, D3Z7P3, E9PV86, G3MWR8, O54865, O60907, O89050, O94925, P13264, P16068, P20595, P58058, Q02153, Q08211, Q12800, Q13042, Q14722, Q28141, Q28D01, Q3MHJ2, Q3ULA2, Q4R8H1, Q4ZHR9, Q5R874, Q5RB35, Q5SP67, Q5SRY7, Q5ZHN3, Q6DN14, Q7RTP6, Q7T2U9, Q7Z6J6, Q8BTG7, Q8C6G8, Q8CJ19, Q8K4Q0, Q8N122, Q8N2K0, Q8R349

Diamond homologs: B3DNN5, P09798, P41889, Q13042, Q8R349, O94474

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CDK1	up-regulates	CDC16	phosphorylation
CDC16	“form complex”	APC-c	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 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	13	85.9×	5e-22
Inactivation of APC/C via direct inhibition of the APC/C complex	13	70.3×	2e-20
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	15	66.1×	7e-23
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	15	63.7×	1e-22
APC-Cdc20 mediated degradation of Nek2A	14	61.7×	6e-21
APC/C-mediated degradation of cell cycle proteins	17	59.5×	9e-25
Regulation of mitotic cell cycle	17	59.5×	9e-25
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase	11	59.5×	3e-16

GO biological processes:

GO term	Partners	Fold	FDR
regulation of meiotic cell cycle	12	79.9×	3e-18
anaphase-promoting complex-dependent catabolic process	12	73.3×	6e-18
protein branched polyubiquitination	10	73.3×	5e-15
protein K11-linked ubiquitination	11	37.5×	6e-13
regulation of mitotic cell cycle	14	29.3×	5e-15
mitotic spindle assembly checkpoint signaling	6	29.3×	5e-06
protein K48-linked ubiquitination	11	16.1×	1e-08
regulation of circadian rhythm	6	13.5×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	81
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
146256	GRCh38/hg38 13q34(chr13:114147230-114327173)x3	Pathogenic
1878430	Single allele	Pathogenic
3765511	NC_000013.11:g.114236634_114326291del	Pathogenic
984753	GRCh37/hg19 13q34(chr13:114893728-115093115)x1	Pathogenic

SpliceAI

3090 predictions. Top by Δscore:

Variant	Effect	Δscore
13:114235130:CAG:C	donor_loss	1.0000
13:114235132:GGTG:G	donor_loss	1.0000
13:114235133:G:GA	donor_loss	1.0000
13:114235134:T:G	donor_loss	1.0000
13:114236797:A:AG	acceptor_gain	1.0000
13:114236798:G:GG	acceptor_gain	1.0000
13:114236798:GA:G	acceptor_gain	1.0000
13:114236798:GAA:G	acceptor_gain	1.0000
13:114236897:G:GG	donor_gain	1.0000
13:114238988:A:AG	acceptor_gain	1.0000
13:114238989:G:GG	acceptor_gain	1.0000
13:114239345:C:CA	acceptor_gain	1.0000
13:114239345:C:G	acceptor_gain	1.0000
13:114239348:A:AC	acceptor_loss	1.0000
13:114239348:A:AG	acceptor_gain	1.0000
13:114239348:AGTAT:A	acceptor_gain	1.0000
13:114239349:G:GA	acceptor_gain	1.0000
13:114239349:GT:G	acceptor_gain	1.0000
13:114239349:GTAT:G	acceptor_gain	1.0000
13:114239349:GTATG:G	acceptor_gain	1.0000
13:114239486:CTTCA:C	donor_gain	1.0000
13:114239487:TTCA:T	donor_gain	1.0000
13:114239488:TCA:T	donor_gain	1.0000
13:114239489:CAGTA:C	donor_loss	1.0000
13:114239490:AG:A	donor_loss	1.0000
13:114239491:G:GG	donor_gain	1.0000
13:114239491:GTA:G	donor_loss	1.0000
13:114239492:T:G	donor_loss	1.0000
13:114242117:ACAG:A	acceptor_loss	1.0000
13:114242118:CAGA:C	acceptor_loss	1.0000

AlphaMissense

4113 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:114242148:G:A	G137R	1.000
13:114242148:G:C	G137R	1.000
13:114242148:G:T	G137W	1.000
13:114242149:G:A	G137E	1.000
13:114242185:C:A	A149D	1.000
13:114243935:C:A	A238D	1.000
13:114243971:G:A	C250Y	1.000
13:114243972:C:G	C250W	1.000
13:114244946:T:C	L275P	1.000
13:114244955:T:C	L278P	1.000
13:114246003:T:C	L284P	1.000
13:114246005:T:C	F285L	1.000
13:114246007:C:A	F285L	1.000
13:114246007:C:G	F285L	1.000
13:114246017:C:G	H289D	1.000
13:114246024:T:C	L291P	1.000
13:114246937:T:A	W302R	1.000
13:114246937:T:C	W302R	1.000
13:114246943:G:C	A304P	1.000
13:114246944:C:A	A304E	1.000
13:114246949:G:A	G306R	1.000
13:114246949:G:C	G306R	1.000
13:114246950:G:A	G306E	1.000
13:114246989:C:A	A319D	1.000
13:114247001:T:C	L323P	1.000
13:114250553:G:C	A326P	1.000
13:114250554:C:A	A326D	1.000
13:114250598:G:A	G341R	1.000
13:114250598:G:C	G341R	1.000
13:114250599:G:A	G341E	1.000

dbSNP variants (sampled 300 via entrez): RS1000204352 (13:114256817 T>C), RS1000252636 (13:114249199 A>G), RS1000568434 (13:114238476 A>G), RS1000671314 (13:114234101 A>G), RS1000709586 (13:114234135 A>G), RS1000810305 (13:114243394 A>G), RS1000922744 (13:114238655 G>A,C), RS1000996944 (13:114244424 G>T), RS1001093029 (13:114270506 G>C), RS1001096215 (13:114271588 CCTCAGCCTCCTGA>C), RS1001146400 (13:114253336 T>C), RS1001245208 (13:114249382 T>C), RS1001281751 (13:114248228 T>C), RS1001295782 (13:114270912 A>C,T), RS1001524405 (13:114237862 A>G)

Disease associations

OMIM: gene MIM:603461 | disease phenotypes: MIM:616579

GenCC curated gene-disease

Mondo (1): intellectual disability, autosomal dominant 40 (MONDO:0014699)

Orphanet (1): CHAMP1-related intellectual disability-facial dysmorphism-behavioral abnormalities syndrome (Orphanet:692193)

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004639_4	Prudent dietary pattern	2.000000e-06
GCST007096_70	Pulse pressure	1.000000e-07
GCST007099_51	Systolic blood pressure	1.000000e-10
GCST007267_138	Systolic blood pressure	6.000000e-19
GCST009391_1875	Metabolite levels	4.000000e-06
GCST90000025_1058	Appendicular lean mass	3.000000e-14
GCST90002394_476	Monocyte percentage of white cells	3.000000e-10
GCST90020028_1230	Hip circumference adjusted for BMI	3.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0010411	triacylglycerol 50:4 measurement
EFO:0004980	appendicular lean mass
EFO:0007989	monocyte percentage of leukocytes
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066343 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.17	Kd	68.03	nM	CHEMBL5653589
7.12	ED50	76.01	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148032: Binding affinity to human CDC16 incubated for 45 mins by Kinobead based pull down assay	kd	0.0680	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, decreases expression, increases abundance	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Cyclosporine	increases expression	2
FR900359	increases phosphorylation	1
echimidine	increases expression, increases metabolic processing	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
lasiocarpine	decreases expression, increases metabolic processing	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
motexafin gadolinium	decreases expression, affects cotreatment	1
ICG 001	increases expression	1
7-(benzylamino)-1,3,4,8-tetrahydropyrrolo(4,3,2-de)quinolin-8(1H)-one	decreases expression	1
Temozolomide	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1
Chelating Agents	increases expression, affects binding	1
Copper	affects binding, increases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Lead	affects splicing	1
Metformin	decreases expression, affects cotreatment	1
Quercetin	decreases expression	1
Selenium	decreases expression	1
Valproic Acid	affects 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
CHEMBL5651074	Binding	Binding affinity to human CDC16 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

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2TW	Abcam HEK293T CDC16 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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