ANAPC5

Summary

ANAPC5 (anaphase promoting complex subunit 5, HGNC:15713) is a protein-coding gene on chromosome 12q24.31, encoding Anaphase-promoting complex subunit 5 (Q9UJX4). 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 98.6% of cancer cell lines).

This gene encodes a tetratricopeptide repeat-containing component of the anaphase promoting complex/cyclosome (APC/C), a large E3 ubiquitin ligase that controls cell cycle progression by targeting a number of cell cycle regulators such as B-type cyclins for 26S proteasome-mediated degradation through ubiquitination. The encoded protein is required for the proper ubiquitination function of APC/C and for the interaction of APC/C with transcription coactivators. It also interacts with polyA binding protein and represses internal ribosome entry site-mediated translation. Multiple transcript variants encoding different isoforms have been found for this gene. These differences cause translation initiation at a downstream AUG and result in a shorter protein (isoform b), compared to isoform a.

Source: NCBI Gene 51433 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (No Known Disease Relationship, GenCC)
• Clinical variants (ClinVar): 84 total — 2 pathogenic
• Cancer dependency (DepMap): dependent in 98.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_016237

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15713
Approved symbol	ANAPC5
Name	anaphase promoting complex subunit 5
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	APC5
Ensembl gene	ENSG00000089053
Ensembl biotype	protein_coding
OMIM	606948
Entrez	51433

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 27 protein_coding, 10 retained_intron, 5 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000261819, ENST00000366333, ENST00000422342, ENST00000441917, ENST00000534976, ENST00000535463, ENST00000535472, ENST00000535482, ENST00000535641, ENST00000536416, ENST00000536837, ENST00000538223, ENST00000538334, ENST00000539079, ENST00000539612, ENST00000539871, ENST00000541652, ENST00000541887, ENST00000544314, ENST00000544442, ENST00000545218, ENST00000545801, ENST00000885105, ENST00000885106, ENST00000885107, ENST00000885108, ENST00000885109, ENST00000885110, ENST00000885111, ENST00000885112, ENST00000931275, ENST00000931276, ENST00000931277, ENST00000931278, ENST00000931279, ENST00000931280, ENST00000931281, ENST00000963599, ENST00000963600, ENST00000963601, ENST00000963602, ENST00000963603, ENST00000963604

RefSeq mRNA: 3 — MANE Select: NM_016237 NM_001137559, NM_001330489, NM_016237

CCDS: CCDS45000, CCDS81749, CCDS9220

Canonical transcript exons

ENST00000261819 — 17 exons

Exon	Start	End
ENSE00001191059	121352134	121352411
ENSE00003461088	121337291	121337392
ENSE00003500121	121347802	121347881
ENSE00003512312	121330583	121330672
ENSE00003513953	121318277	121318424
ENSE00003520833	121309701	121309863
ENSE00003534101	121345839	121346031
ENSE00003537337	121342003	121342069
ENSE00003541337	121318501	121318608
ENSE00003556713	121327096	121327231
ENSE00003571085	121331347	121331428
ENSE00003615354	121346896	121347005
ENSE00003629245	121320385	121320459
ENSE00003648677	121328316	121328497
ENSE00003663606	121319697	121319818
ENSE00003785780	121335533	121335723
ENSE00003844764	121308245	121308691

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 98.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.6627 / max 354.5567, expressed in 1822 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133722	46.5380	1821
133721	7.2812	1765
133723	3.8436	1614

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.89	gold quality
body of pancreas	UBERON:0001150	98.81	gold quality
bronchial epithelial cell	CL:0002328	98.33	gold quality
tibia	UBERON:0000979	98.32	gold quality
endocervix	UBERON:0000458	98.29	gold quality
skin of hip	UBERON:0001554	98.23	gold quality
body of uterus	UBERON:0009853	98.21	gold quality
corpus callosum	UBERON:0002336	98.19	gold quality
nerve	UBERON:0001021	98.15	gold quality
tibial nerve	UBERON:0001323	98.15	gold quality
parotid gland	UBERON:0001831	98.13	gold quality
right ovary	UBERON:0002118	98.13	gold quality
granulocyte	CL:0000094	98.09	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.06	gold quality
skin of leg	UBERON:0001511	98.05	gold quality
right lobe of thyroid gland	UBERON:0001119	98.01	gold quality
upper arm skin	UBERON:0004263	98.00	gold quality
cerebellar hemisphere	UBERON:0002245	97.99	gold quality
skin of abdomen	UBERON:0001416	97.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.96	gold quality
stromal cell of endometrium	CL:0002255	97.95	gold quality
epithelium of bronchus	UBERON:0002031	97.95	gold quality
left ovary	UBERON:0002119	97.92	gold quality
pituitary gland	UBERON:0000007	97.91	gold quality
upper leg skin	UBERON:0004262	97.91	gold quality
bronchus	UBERON:0002185	97.90	gold quality
cerebellar cortex	UBERON:0002129	97.89	gold quality
zone of skin	UBERON:0000014	97.86	gold quality
ectocervix	UBERON:0012249	97.86	gold quality
descending thoracic aorta	UBERON:0002345	97.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting ANAPC5, 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-3065-5P	99.97	71.56	3281
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-660-5P	98.16	68.27	680
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-3121-5P	97.30	66.62	1146
HSA-MIR-6082	96.40	70.86	216
HSA-MIR-5591-3P	96.23	67.03	489
HSA-MIR-135A-3P	94.19	66.09	495

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• Results show that Apc5 binds the poly(A) binding protein (PABP), which directly binds the internal ribosome entry site (IRES) element of platelet-derived growth factor 2 mRNA. (PMID:15082755)
• APC5 and APC7 suppress E1A-mediated transformation in a CBP/p300-dependent manner, indicating that these components of the APC/C may be targeted during cellular transformation (PMID:16319895)
• Studies indicate that APC/C(Cdh1) is required to maintain genomic stability. (PMID:19826416)
• Inactivation and disassembly of the anaphase-promoting complex during human cytomegalovirus infection is associated with degradation of the APC5 and APC4 subunits and does not require UL97-mediated phosphorylation of Cdh1. (PMID:20686030)
• coexpression of APC5 and Axin genes significantly downregulated Wnt signaling in human SW480 CRC cells and inhibited cell growth. (PMID:28731177)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	anapc5	ENSDARG00000008461
mus_musculus	Anapc5	ENSMUSG00000029472
rattus_norvegicus	Anapc5	ENSRNOG00000001316
drosophila_melanogaster	ida	FBGN0041147
caenorhabditis_elegans		WBGENE00001583
caenorhabditis_elegans		WBGENE00013443

Protein

Protein identifiers

Anaphase-promoting complex subunit 5 — Q9UJX4 (reviewed: Q9UJX4)

Alternative names: Cyclosome subunit 5

All UniProt accessions (6): Q9UJX4, F5GY68, F5GZ05, F5H0F9, F5H3S5, H0YFB5

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.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Spindle.

Domain organisation. The TPR repeats are six to seven residues longer than a canonical TPR motif.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the APC5 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UJX4-1	1	yes
Q9UJX4-2	2
Q9UJX4-3	3

RefSeq proteins (3): NP_001131031, NP_001317418, NP_057321* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR026000	Apc5_dom	Domain
IPR037679	Apc5	Family
IPR048968	Apc5_N	Domain

Pfam: PF12862, PF21371

UniProt features (70 total): helix 37, repeat 13, splice variant 6, strand 5, turn 4, modified residue 2, chain 1, sequence variant 1, sequence conflict 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-Q9UJX4-F1	81.85	0.40

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 (2): 195, 232

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: 370 (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, WANG_CLIM2_TARGETS_UP, REACTOME_APC_C_CDC20_MEDIATED_DEGRADATION_OF_CYCLIN_B, REACTOME_CONVERSION_FROM_APC_C_CDC20_TO_APC_C_CDH1_IN_LATE_ANAPHASE, MORF_SMC1L1, REACTOME_PHOSPHORYLATION_OF_THE_APC_C, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_NUCLEAR_DIVISION, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, PAL_PRMT5_TARGETS_UP, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_ANAPHASE_PROMOTING_COMPLEX_DEPENDENT_CATABOLIC_PROCESS

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

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

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), anaphase-promoting complex (GO:0005680), spindle (GO:0005819), cytosol (GO:0005829), cytoplasm (GO:0005737), 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
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
protein modification by small protein conjugation	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
microtubule cytoskeleton	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2089 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANAPC5	CDC23	Q9UJX2	999
ANAPC5	CDC16	Q13042	998
ANAPC5	CDC27	P30260	997
ANAPC5	ANAPC11	Q9NYG5	979
ANAPC5	ANAPC7	Q9UJX3	977
ANAPC5	ANAPC10	Q9UM13	977
ANAPC5	ANAPC15	P60006	975
ANAPC5	ANAPC4	Q9UJX5	967
ANAPC5	ANAPC1	Q9H1A4	944
ANAPC5	ANAPC2	Q9UJX6	931
ANAPC5	ANAPC13	Q9BS18	855
ANAPC5	ANAPC16	Q96DE5	850
ANAPC5	CDC26	Q8NHZ8	814
ANAPC5	CDC20	Q12834	801
ANAPC5	FZR1	Q9UM11	717

IntAct

155 interactions, top by confidence:

A	B	Type	Score
CDC20	BUB1B	psi-mi:“MI:0914”(association)	0.980
ANAPC2	CDC27	psi-mi:“MI:0915”(physical association)	0.910
ANAPC4	CDC27	psi-mi:“MI:0914”(association)	0.860
CDC27	CDC16	psi-mi:“MI:0914”(association)	0.860
GRAP2	STAMBP	psi-mi:“MI:0914”(association)	0.810
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
ANAPC16	CDC27	psi-mi:“MI:0914”(association)	0.760
ANAPC16	BUB1B	psi-mi:“MI:0914”(association)	0.730
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
ANAPC2	BUB1B	psi-mi:“MI:0914”(association)	0.730
CDC20	BUB1	psi-mi:“MI:0914”(association)	0.730
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
TTLL1	CDC27	psi-mi:“MI:0914”(association)	0.640
C16orf87	CDC27	psi-mi:“MI:0914”(association)	0.640
ANAPC13	CDC27	psi-mi:“MI:0914”(association)	0.640
CDC26	BUB1B	psi-mi:“MI:0914”(association)	0.640

BioGRID (288): ANAPC5 (Reconstituted Complex), ANAPC5 (Affinity Capture-Western), E2F1 (Affinity Capture-Western), TFDP1 (Affinity Capture-Western), ANAPC5 (Affinity Capture-MS), ANAPC5 (Affinity Capture-Western), ANAPC5 (Affinity Capture-MS), ANAPC1 (Affinity Capture-MS), ANAPC2 (Affinity Capture-MS), ANAPC4 (Affinity Capture-MS), ANAPC5 (Protein-peptide), ANAPC5 (Affinity Capture-Western), ANAPC5 (Affinity Capture-Western), ANAPC5 (Affinity Capture-MS), ANAPC5 (Affinity Capture-MS)

ESM2 similar proteins: A1A5P5, A1L1K3, A7SUU7, B4JHK2, B4NKT1, E9Q6P5, F1QN74, P09913, P50748, Q0P5W1, Q14CX7, Q294E0, Q2KI89, Q32NR4, Q32PH0, Q3U0M1, Q4R6I5, Q4R6M4, Q5R629, Q5RE52, Q5U249, Q5ZKK3, Q60462, Q68F70, Q6AYP3, Q6PA97, Q6QI44, Q80VM3, Q86TV6, Q8BGB2, Q8BH74, Q8BTZ4, Q8BWZ3, Q8C0S4, Q8CIM8, Q8GZN1, Q8IYW2, Q8JGR7, Q8K368, Q8N3P4

Diamond homologs: A1L1K3, Q5RE52, Q5ZKK3, Q8BTZ4, Q9UJX4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ANAPC5	“form complex”	APC-c	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 142 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	85.0×	5e-22
Inactivation of APC/C via direct inhibition of the APC/C complex	13	69.6×	2e-20
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	15	65.4×	1e-22
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	15	63.1×	2e-22
APC-Cdc20 mediated degradation of Nek2A	14	61.0×	6e-21
APC/C-mediated degradation of cell cycle proteins	17	58.9×	1e-24
Regulation of mitotic cell cycle	17	58.9×	1e-24
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase	11	58.9×	4e-16

GO biological processes:

GO term	Partners	Fold	FDR
regulation of meiotic cell cycle	12	80.6×	3e-18
anaphase-promoting complex-dependent catabolic process	12	73.9×	6e-18
protein branched polyubiquitination	10	73.9×	8e-15
protein K11-linked ubiquitination	11	37.8×	1e-12
mitotic spindle assembly checkpoint signaling	6	29.6×	5e-06
regulation of mitotic cell cycle	12	25.3×	8e-12
protein K48-linked ubiquitination	11	16.3×	1e-08
cell division	20	8.1×	7e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	50
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
57609	GRCh38/hg38 12q24.31(chr12:120504068-122459718)x1	Pathogenic
57610	GRCh38/hg38 12q24.31(chr12:121325874-122505529)x1	Pathogenic

SpliceAI

3002 predictions. Top by Δscore:

Variant	Effect	Δscore
12:121308687:CAGAG:C	acceptor_gain	1.0000
12:121308688:AGAG:A	acceptor_gain	1.0000
12:121308689:GAG:G	acceptor_gain	1.0000
12:121308690:AG:A	acceptor_gain	1.0000
12:121308691:GC:G	acceptor_loss	1.0000
12:121308692:C:CA	acceptor_loss	1.0000
12:121308692:C:CC	acceptor_gain	1.0000
12:121308693:T:A	acceptor_loss	1.0000
12:121308696:C:CT	acceptor_gain	1.0000
12:121308697:G:T	acceptor_gain	1.0000
12:121309696:CCTAC:C	donor_loss	1.0000
12:121309697:CTA:C	donor_loss	1.0000
12:121309699:ACC:A	donor_loss	1.0000
12:121309700:C:CT	donor_loss	1.0000
12:121309700:CCTT:C	donor_gain	1.0000
12:121309859:ATGAG:A	acceptor_gain	1.0000
12:121309860:TGAG:T	acceptor_gain	1.0000
12:121309864:C:CC	acceptor_gain	1.0000
12:121309864:CTGA:C	acceptor_loss	1.0000
12:121318272:CTTA:C	donor_loss	1.0000
12:121318273:TTAC:T	donor_loss	1.0000
12:121318274:TACCT:T	donor_loss	1.0000
12:121318275:A:T	donor_loss	1.0000
12:121318276:CCTG:C	donor_gain	1.0000
12:121318420:GGACA:G	acceptor_gain	1.0000
12:121318423:CA:C	acceptor_gain	1.0000
12:121318424:AC:A	acceptor_loss	1.0000
12:121318425:C:CA	acceptor_loss	1.0000
12:121318425:C:CC	acceptor_gain	1.0000
12:121318431:G:GC	acceptor_gain	1.0000

AlphaMissense

4983 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:121331360:A:G	L340P	1.000
12:121331387:G:T	A331D	1.000
12:121331388:C:G	A331P	1.000
12:121331400:C:G	A327P	1.000
12:121335563:A:G	L307P	1.000
12:121335575:G:T	A303D	1.000
12:121335644:C:G	R280P	1.000
12:121335662:A:G	L274P	1.000
12:121346019:C:G	R137P	1.000
12:121346020:G:T	R137S	1.000
12:121346031:C:T	G133D	1.000
12:121346896:C:G	G133R	1.000
12:121346903:A:C	S130R	1.000
12:121346903:A:T	S130R	1.000
12:121346905:T:G	S130R	1.000
12:121331350:A:C	C343W	0.999
12:121331352:A:G	C343R	0.999
12:121331362:A:C	C339W	0.999
12:121331364:A:G	C339R	0.999
12:121331372:T:A	D336V	0.999
12:121331372:T:C	D336G	0.999
12:121331372:T:G	D336A	0.999
12:121331373:C:G	D336H	0.999
12:121331408:A:G	L324P	0.999
12:121331421:C:G	A320P	0.999
12:121335554:A:G	L310P	0.999
12:121335560:G:T	A308D	0.999
12:121335565:A:C	N306K	0.999
12:121335565:A:T	N306K	0.999
12:121335569:A:G	L305P	0.999

dbSNP variants (sampled 300 via entrez): RS1000019377 (12:121317517 G>A), RS1000152768 (12:121333128 C>T), RS1000231546 (12:121314286 C>A), RS1000353813 (12:121308173 T>C,G), RS1000533967 (12:121335350 G>C), RS1000707917 (12:121314593 T>C), RS1000820703 (12:121348101 G>A), RS1000855738 (12:121352389 T>A), RS1000934482 (12:121317215 C>G), RS1001016910 (12:121328208 T>C,G), RS1001149884 (12:121334991 T>A), RS1001207245 (12:121332065 C>T), RS1001319762 (12:121324374 C>T), RS1001400716 (12:121318086 A>G), RS1001422358 (12:121341604 A>T)

Disease associations

OMIM: gene MIM:606948 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	No Known Disease Relationship	Unknown

Mondo (1): schizophrenia (MONDO:0005090)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Bortezomib	decreases expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
Particulate Matter	affects cotreatment, increases abundance, increases expression, decreases expression	2
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
bufotalin	increases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression, decreases expression	1
methylparaben	increases expression	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Glyphosate	decreases expression	1
Caffeine	decreases phosphorylation	1
Chelating Agents	decreases expression, affects binding	1
Copper	decreases expression, affects binding	1
Coumestrol	increases expression	1
Demecolcine	increases expression	1
Formaldehyde	decreases expression	1
Gasoline	increases expression, affects cotreatment, increases abundance	1
Lead	decreases expression	1
Mercuric Chloride	decreases expression	1
Phenobarbital	affects expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Thiram	decreases expression	1
Vincristine	increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety