ANAPC7

Summary

ANAPC7 (anaphase promoting complex subunit 7, HGNC:17380) is a protein-coding gene on chromosome 12q24.11, encoding Anaphase-promoting complex subunit 7 (Q9UJX3). 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.

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 proper protein ubiquitination function of APC/C and for the interaction of APC/C with certain transcription coactivators. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 51434 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Ferguson-Bonni neurodevelopmental syndrome (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 81 total — 1 pathogenic
• Phenotypes (HPO): 17
• Druggable target: yes
• MANE Select transcript: NM_016238

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17380
Approved symbol	ANAPC7
Name	anaphase promoting complex subunit 7
Location	12q24.11
Locus type	gene with protein product
Status	Approved
Aliases	APC7
Ensembl gene	ENSG00000196510
Ensembl biotype	protein_coding
OMIM	606949
Entrez	51434

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 16 protein_coding, 5 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000450008, ENST00000452721, ENST00000455511, ENST00000464697, ENST00000471602, ENST00000481473, ENST00000486321, ENST00000546720, ENST00000547199, ENST00000548234, ENST00000552087, ENST00000552170, ENST00000880052, ENST00000880053, ENST00000880054, ENST00000880055, ENST00000929443, ENST00000929444, ENST00000929445, ENST00000929446, ENST00000929447, ENST00000961551, ENST00000961552, ENST00000961553, ENST00000961554

RefSeq mRNA: 7 — MANE Select: NM_016238 NM_001137664, NM_001385208, NM_001385209, NM_001385210, NM_001385211, NM_001385212, NM_016238

CCDS: CCDS44971, CCDS9145

Canonical transcript exons

ENST00000455511 — 11 exons

Exon	Start	End
ENSE00001425898	110386327	110386469
ENSE00002360528	110372900	110374333
ENSE00003466157	110387739	110387892
ENSE00003501096	110376066	110376216
ENSE00003542305	110396266	110396452
ENSE00003577199	110388512	110388623
ENSE00003587039	110395101	110395220
ENSE00003590539	110382843	110382960
ENSE00003632856	110381752	110381948
ENSE00003667636	110377393	110377617
ENSE00003918680	110403527	110403708

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 97.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.7841 / max 271.3708, expressed in 1815 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133229	29.9066	1814
133228	0.6589	404
133226	0.5266	220
133224	0.4752	169
133227	0.2168	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	97.15	gold quality
esophagus mucosa	UBERON:0002469	96.27	gold quality
lower esophagus mucosa	UBERON:0035834	96.20	gold quality
upper arm skin	UBERON:0004263	96.09	gold quality
right testis	UBERON:0004534	95.57	gold quality
left testis	UBERON:0004533	95.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.44	gold quality
cerebellar hemisphere	UBERON:0002245	95.37	gold quality
cerebellar cortex	UBERON:0002129	95.35	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.29	gold quality
right uterine tube	UBERON:0001302	95.17	gold quality
vagina	UBERON:0000996	95.16	gold quality
ventricular zone	UBERON:0003053	95.06	gold quality
esophagus	UBERON:0001043	94.94	gold quality
cerebellum	UBERON:0002037	94.81	gold quality
ectocervix	UBERON:0012249	94.80	gold quality
cortical plate	UBERON:0005343	94.65	gold quality
right lobe of thyroid gland	UBERON:0001119	94.54	gold quality
minor salivary gland	UBERON:0001830	94.53	gold quality
body of uterus	UBERON:0009853	94.53	gold quality
testis	UBERON:0000473	94.44	gold quality
nasal cavity epithelium	UBERON:0005384	94.39	gold quality
skin of abdomen	UBERON:0001416	94.18	gold quality
mouth mucosa	UBERON:0003729	94.14	gold quality
caudate nucleus	UBERON:0001873	94.13	gold quality
ganglionic eminence	UBERON:0004023	94.13	gold quality
right frontal lobe	UBERON:0002810	93.94	gold quality
left uterine tube	UBERON:0001303	93.90	gold quality
right ovary	UBERON:0002118	93.87	gold quality
putamen	UBERON:0001874	93.84	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)

50 targeting ANAPC7, 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-4455	100.00	65.48	1587
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-1228-3P	99.00	66.53	857
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-6731-3P	98.61	67.86	749
HSA-MIR-1237-3P	98.55	67.65	1423

Literature-anchored findings (GeneRIF, showing 9)

• dysregulation of APC activity, possibly through downregulation of APC7, may be associated with tumorigenesis in breast cancer (PMID:15743504)
• 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)
• Expression of ANAPC7 in fibroadenomas and phylloides tumors of breast is reported. (PMID:18789487)
• The crystal structure of quad mutant of nApc7 (N-terminal fragment, residues 1-147) of human Apc7 at a resolution of 2.5 A, is reported. (PMID:19091741)
• Studies indicate that APC/C(Cdh1) is required to maintain genomic stability. (PMID:19826416)
• 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)
• The results showed that APC2 and APC7 subunits were both over expressed in cancer cell lines (PMID:26046517)
• the contribution of the anaphase-promoting complex/cyclosome subunits APC7 and APC16 to APC/C composition and function in human cells. (PMID:30485802)
• APC7 mediates ubiquitin signaling in constitutive heterochromatin in the developing mammalian brain. (PMID:34942119)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	anapc7	ENSDARG00000063005
mus_musculus	Anapc7	ENSMUSG00000029466
rattus_norvegicus	Anapc7	ENSRNOG00000001283
drosophila_melanogaster	APC7	FBGN0029879

Paralogs (3): CDC27 (ENSG00000004897), CDC23 (ENSG00000094880), CDC16 (ENSG00000130177)

Protein

Protein identifiers

Anaphase-promoting complex subunit 7 — Q9UJX3 (reviewed: Q9UJX3)

Alternative names: Cyclosome subunit 7

All UniProt accessions (3): Q9UJX3, H0YIW2, H0YIX7

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. APC7 is not required for the assembly of the APC/C complex, but has an enzyme-substrate adapter activity mediating the processive ubiquitination of specific substrates. Involved in brain development through the specific ubiquitination and clearance of MKI67 from constitutive heterochromatin after neuronal progenitors exit mitosis.

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.

Subcellular location. Cytoplasm. Cytoskeleton. Nucleus. Spindle.

Disease relevance. Ferguson-Bonni neurodevelopmental syndrome (FERBON) [MIM:619699] An autosomal recessive disorder characterized by global developmental delay, impaired intellectual development, and hypotonia with early motor delay. Additional features may include dysmorphic facies, mild skeletal abnormalities, and hearing loss. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the APC7 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UJX3-1	1	yes
Q9UJX3-2	2

RefSeq proteins (7): NP_001131136, NP_001372137, NP_001372138, NP_001372139, NP_001372140, NP_001372141, NP_057322* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat

Pfam: PF13181, PF13432

UniProt features (57 total): helix 32, repeat 10, strand 4, sequence conflict 3, compositionally biased region 2, mutagenesis site 2, chain 1, region of interest 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
3FFL	X-RAY DIFFRACTION	2.5
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-Q9UJX3-F1	83.33	0.46

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 (1): 229

Mutagenesis-validated functional residues (2):

Position	Phenotype
22	loss of homodimerization; when associated with k-26.
26	loss of homodimerization; when associated with r-22.

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: 268 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, REACTOME_DNA_REPLICATION, HONMA_DOCETAXEL_RESISTANCE, 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, 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 (10): regulation of mitotic cell cycle (GO:0007346), brain development (GO:0007420), 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 (3): protein phosphatase binding (GO:0019903), enzyme-substrate adaptor activity (GO:0140767), protein binding (GO:0005515)

GO Cellular Component (11): heterochromatin (GO:0000792), nucleus (GO:0005634), nucleoplasm (GO:0005654), anaphase-promoting complex (GO:0005680), spindle (GO:0005819), cytosol (GO:0005829), microtubule cytoskeleton (GO:0015630), intercellular bridge (GO:0045171), mitotic spindle (GO:0072686), 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
cellular anatomical structure	4
protein polyubiquitination	3
regulation of cell cycle	2
intracellular membraneless organelle	2
mitotic cell cycle	1
central nervous system development	1
animal organ development	1
head development	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
phosphatase binding	1
protein-macromolecule adaptor activity	1
binding	1
chromatin	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
cytoskeleton	1
spindle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1893 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANAPC7	ANAPC5	Q9UJX4	977
ANAPC7	ANAPC10	Q9UM13	952
ANAPC7	CDC16	Q13042	936
ANAPC7	CDC23	Q9UJX2	933
ANAPC7	ANAPC4	Q9UJX5	898
ANAPC7	ANAPC2	Q9UJX6	784
ANAPC7	ANAPC1	Q9H1A4	747
ANAPC7	ANAPC11	Q9NYG5	731
ANAPC7	ANAPC16	Q96DE5	670
ANAPC7	CUL9	Q8IWT3	587
ANAPC7	CDC20	Q12834	567
ANAPC7	KLHL5	Q96PQ7	539
ANAPC7	CDC27	P30260	512
ANAPC7	FAM216A	Q8WUB2	499
ANAPC7	SCGN	O76038	496

IntAct

110 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
CDC23	CDC27	psi-mi:“MI:0914”(association)	0.860
ANAPC4	CDC27	psi-mi:“MI:0914”(association)	0.860
ANAPC4	BUB1B	psi-mi:“MI:0914”(association)	0.820
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	BUB1B	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
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ANAPC13	CDC27	psi-mi:“MI:0914”(association)	0.640
CDC26	BUB1B	psi-mi:“MI:0914”(association)	0.640
C16orf87	CDC27	psi-mi:“MI:0914”(association)	0.640
PTEN	CDC27	psi-mi:“MI:0914”(association)	0.620

BioGRID (334): ANAPC7 (Reconstituted Complex), ANAPC7 (Affinity Capture-Western), ANAPC7 (Affinity Capture-Western), E2F1 (Affinity Capture-Western), ANAPC7 (Affinity Capture-MS), ANAPC7 (Affinity Capture-Western), ANAPC7 (Affinity Capture-MS), ANAPC7 (Affinity Capture-Western), ANAPC7 (Affinity Capture-MS), ANAPC7 (Protein-peptide), ANAPC7 (Protein-peptide), ANAPC7 (Affinity Capture-Western), ANAPC7 (Affinity Capture-MS), ANAPC7 (Affinity Capture-Western), ANAPC7 (Affinity Capture-MS)

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: Q9UJX3, Q9WVM3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FBXO5	down-regulates	ANAPC7	binding
ANAPC7	“form complex”	APC-c	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 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	138.8×	9e-27
Inactivation of APC/C via direct inhibition of the APC/C complex	14	113.5×	1e-25
APC-Cdc20 mediated degradation of Nek2A	15	99.1×	4e-26
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	15	99.1×	4e-26
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase	12	97.3×	8e-21
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	15	95.6×	8e-26
Phosphorylation of the APC/C	11	93.5×	9e-19
Aberrant regulation of mitotic exit in cancer due to RB1 defects	11	89.2×	1e-18

GO biological processes:

GO term	Partners	Fold	FDR
regulation of meiotic cell cycle	13	122.9×	1e-22
protein branched polyubiquitination	11	114.4×	8e-19
anaphase-promoting complex-dependent catabolic process	13	112.7×	3e-22
protein K11-linked ubiquitination	12	58.1×	2e-16
mitotic spindle assembly checkpoint signaling	7	48.5×	8e-09
regulation of mitotic cell cycle	14	41.6×	4e-17
protein K48-linked ubiquitination	11	22.9×	2e-10
cell division	20	11.4×	7e-14

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	61
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1334173	NM_016238.3(ANAPC7):c.409-2478_818-89del	Pathogenic

SpliceAI

2258 predictions. Top by Δscore:

Variant	Effect	Δscore
12:110374329:CCAAA:C	acceptor_gain	1.0000
12:110374330:CAAA:C	acceptor_gain	1.0000
12:110374330:CAAAC:C	acceptor_gain	1.0000
12:110374331:AAA:A	acceptor_gain	1.0000
12:110374332:AA:A	acceptor_gain	1.0000
12:110374333:ACT:A	acceptor_loss	1.0000
12:110374334:C:CC	acceptor_gain	1.0000
12:110376061:CCTA:C	donor_loss	1.0000
12:110376063:TA:T	donor_loss	1.0000
12:110376065:C:A	donor_loss	1.0000
12:110376079:TA:T	donor_gain	1.0000
12:110376082:A:AC	donor_gain	1.0000
12:110376083:C:CC	donor_gain	1.0000
12:110376096:T:TA	donor_gain	1.0000
12:110376106:CATTG:C	donor_gain	1.0000
12:110376107:A:AC	donor_gain	1.0000
12:110376107:ATTGA:A	donor_gain	1.0000
12:110376213:CTGC:C	acceptor_gain	1.0000
12:110376214:TGC:T	acceptor_gain	1.0000
12:110376217:C:CC	acceptor_gain	1.0000
12:110377389:TTA:T	donor_loss	1.0000
12:110377391:A:AC	donor_gain	1.0000
12:110377391:A:T	donor_loss	1.0000
12:110377392:C:CG	donor_gain	1.0000
12:110377392:CT:C	donor_gain	1.0000
12:110377392:CTAAG:C	donor_gain	1.0000
12:110378666:T:C	acceptor_gain	1.0000
12:110378666:T:TC	acceptor_gain	1.0000
12:110382838:CATA:C	donor_loss	1.0000
12:110382839:ATAC:A	donor_gain	1.0000

AlphaMissense

3939 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:110376129:C:T	G516E	1.000
12:110387812:A:G	W235R	1.000
12:110387812:A:T	W235R	1.000
12:110395110:T:A	R167S	1.000
12:110395110:T:G	R167S	1.000
12:110376073:C:G	A535P	0.999
12:110376094:C:G	A528P	0.999
12:110376120:A:G	L519P	0.999
12:110376130:C:G	G516R	0.999
12:110376130:C:T	G516R	0.999
12:110377405:C:G	A483P	0.999
12:110381812:C:G	A392P	0.999
12:110381847:C:T	G380E	0.999
12:110381848:C:G	G380R	0.999
12:110381848:C:T	G380R	0.999
12:110381853:A:G	L378P	0.999
12:110381893:C:G	A365P	0.999
12:110382843:C:T	G346D	0.999
12:110382844:C:G	G346R	0.999
12:110382856:A:G	W342R	0.999
12:110382856:A:T	W342R	0.999
12:110387800:A:G	W239R	0.999
12:110387800:A:T	W239R	0.999
12:110388547:A:G	L196P	0.999
12:110388607:G:T	A176E	0.999
12:110388608:C:G	A176P	0.999
12:110388610:A:G	L175P	0.999
12:110395111:C:G	R167T	0.999
12:110395135:A:G	L159P	0.999
12:110395176:A:C	C145W	0.999

dbSNP variants (sampled 300 via entrez): RS1000057896 (12:110396289 A>T), RS1000121777 (12:110402661 C>T), RS1000395635 (12:110389998 G>A), RS1000425789 (12:110379741 CACTCCTAG>C), RS1000458883 (12:110373324 C>T), RS1000590710 (12:110401074 A>G,T), RS1000659161 (12:110402370 T>C), RS1000662324 (12:110386064 C>A), RS1000757629 (12:110378631 A>T), RS1000766371 (12:110373526 G>C), RS1000838604 (12:110390414 T>C), RS1000940148 (12:110401354 T>C), RS1001117315 (12:110384295 G>A,C), RS1001335973 (12:110397161 T>C), RS1001356802 (12:110396533 T>C)

Disease associations

OMIM: gene MIM:606949 | disease phenotypes: MIM:619699

GenCC curated gene-disease

Disease	Classification	Inheritance
Ferguson-Bonni neurodevelopmental syndrome	Strong	Autosomal recessive

Mondo (1): Ferguson-Bonni neurodevelopmental syndrome (MONDO:0859220)

Orphanet (0):

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000402	Stenosis of the external auditory canal
HP:0000486	Strabismus
HP:0000767	Pectus excavatum
HP:0000776	Congenital diaphragmatic hernia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001655	Patent foramen ovale
HP:0003593	Infantile onset
HP:0007687	Unilateral ptosis
HP:0008209	Premature ovarian insufficiency
HP:0025516	Coronary-pulmonary artery fistula

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004946_44	Schizophrenia	3.000000e-09
GCST007218_7	QT interval	4.000000e-08
GCST008103_92	Bipolar disorder	1.000000e-06
GCST009204_5	Total intracranial volume	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0004886	intracranial volume measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066347 (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
7.28	Kd	52.48	nM	CHEMBL5653589
7.28	ED50	52.48	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	2147849: Binding affinity to human ANAPC7 incubated for 45 mins by Kinobead based pull down assay	kd	0.0525	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	3
Valproic Acid	affects expression, increases expression	3
Arsenic	affects methylation, decreases expression, increases abundance	2
TAK-243	increases sumoylation	1
bisphenol A	affects cotreatment, increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
M-VAC protocol	decreases response to substance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
eprenetapopt	affects expression, affects reaction	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	increases expression	1
Chelating Agents	affects binding, decreases expression	1
Copper	affects binding, decreases expression	1
Coumestrol	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Ozone	increases abundance, affects expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Tunicamycin	decreases expression	1
Urethane	decreases expression	1
Copper Sulfate	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
CHEMBL5650891	Binding	Binding affinity to human ANAPC7 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

4 cell lines: 2 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_LN92	GM25252	Transformed cell line	Female
CVCL_LN93	GM25253	Transformed cell line	Female
CVCL_SC47	HAP1 ANAPC7 (-) 1	Cancer cell line	Male
CVCL_SC48	HAP1 ANAPC7 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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