ANAPC1

Summary

ANAPC1 (anaphase promoting complex subunit 1, HGNC:19988) is a protein-coding gene on chromosome 2q13, encoding Anaphase-promoting complex subunit 1 (Q9H1A4). Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. It is a common-essential gene (DepMap: required in 99.5% of cancer cell lines).

This gene encodes a subunit of the anaphase-promoting complex. This complex is an E3 ubiquitin ligase that regulates progression through the metaphase to anaphase portion of the cell cycle by ubiquitinating proteins which targets them for degradation.

Source: NCBI Gene 64682 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Rothmund-Thomson syndrome type 1 (Definitive, GenCC)
• GWAS associations: 18
• Clinical variants (ClinVar): 287 total — 6 pathogenic
• Phenotypes (HPO): 75
• Cancer dependency (DepMap): dependent in 99.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_022662

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19988
Approved symbol	ANAPC1
Name	anaphase promoting complex subunit 1
Location	2q13
Locus type	gene with protein product
Status	Approved
Aliases	MCPR, TSG24, APC1
Ensembl gene	ENSG00000153107
Ensembl biotype	protein_coding
OMIM	608473
Entrez	64682

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 13 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000341068, ENST00000427997, ENST00000451367, ENST00000462785, ENST00000464695, ENST00000467878, ENST00000482177, ENST00000485325, ENST00000489177, ENST00000628342, ENST00000643447, ENST00000917117, ENST00000917120, ENST00000917121, ENST00000917122, ENST00000917123, ENST00000917124, ENST00000917125, ENST00000917126, ENST00000917127, ENST00000917128

RefSeq mRNA: 1 — MANE Select: NM_022662 NM_022662

CCDS: CCDS2093

Canonical transcript exons

ENST00000341068 — 48 exons

Exon	Start	End
ENSE00001008859	111843412	111843599
ENSE00001008860	111847725	111847865
ENSE00001146091	111788234	111788320
ENSE00001146277	111838438	111838512
ENSE00001759193	111858306	111858401
ENSE00001821348	111767640	111769406
ENSE00002437929	111856614	111856679
ENSE00002441208	111822422	111822600
ENSE00002448121	111833220	111833311
ENSE00002452201	111821239	111821453
ENSE00002454352	111784323	111784400
ENSE00002457751	111873308	111873408
ENSE00002461807	111856796	111856886
ENSE00002463879	111868023	111868096
ENSE00002468381	111802428	111802506
ENSE00002470313	111783897	111783964
ENSE00002470690	111803448	111803530
ENSE00002476168	111782369	111782507
ENSE00002478425	111864806	111864951
ENSE00002485077	111778675	111778770
ENSE00002485155	111825777	111825855
ENSE00002486877	111862389	111862598
ENSE00002488866	111800797	111800871
ENSE00002492318	111785360	111785477
ENSE00002495364	111824966	111825036
ENSE00002497849	111780299	111780385
ENSE00002506414	111794818	111794894
ENSE00002514026	111834604	111834872
ENSE00002518012	111847138	111847198
ENSE00002521166	111831286	111831434
ENSE00002523199	111850776	111850910
ENSE00002525972	111863675	111863895
ENSE00002530104	111792362	111792555
ENSE00002535919	111825131	111825167
ENSE00003470964	111794078	111794131
ENSE00003482874	111808947	111809181
ENSE00003534106	111880613	111880849
ENSE00003544011	111878810	111878971
ENSE00003553849	111772341	111772475
ENSE00003562871	111803705	111803839
ENSE00003612319	111818840	111818958
ENSE00003612595	111805802	111805893
ENSE00003622388	111776859	111777057
ENSE00003642670	111872630	111872712
ENSE00003647575	111873613	111873664
ENSE00003652428	111794233	111794323
ENSE00003677420	111815370	111815641
ENSE00003845164	111883942	111884193

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 91.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.8773 / max 224.5924, expressed in 1797 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30141	17.6754	1793
30140	2.2019	953

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.76	gold quality
colonic epithelium	UBERON:0000397	90.52	gold quality
pancreatic ductal cell	CL:0002079	90.38	silver quality
calcaneal tendon	UBERON:0003701	90.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.71	gold quality
tibialis anterior	UBERON:0001385	89.53	gold quality
adrenal tissue	UBERON:0018303	88.73	gold quality
lower esophagus mucosa	UBERON:0035834	88.39	gold quality
endothelial cell	CL:0000115	88.03	gold quality
bone marrow cell	CL:0002092	87.37	gold quality
deltoid	UBERON:0001476	87.35	gold quality
ventricular zone	UBERON:0003053	87.29	gold quality
middle temporal gyrus	UBERON:0002771	86.99	gold quality
vastus lateralis	UBERON:0001379	86.45	gold quality
quadriceps femoris	UBERON:0001377	86.06	gold quality
granulocyte	CL:0000094	85.84	gold quality
ileal mucosa	UBERON:0000331	85.56	gold quality
esophagus mucosa	UBERON:0002469	85.45	gold quality
rectum	UBERON:0001052	85.24	gold quality
skin of abdomen	UBERON:0001416	85.22	gold quality
left ovary	UBERON:0002119	85.02	gold quality
right uterine tube	UBERON:0001302	84.92	gold quality
ectocervix	UBERON:0012249	84.91	gold quality
body of uterus	UBERON:0009853	84.80	gold quality
body of pancreas	UBERON:0001150	84.70	gold quality
right ovary	UBERON:0002118	84.65	gold quality
sural nerve	UBERON:0015488	84.57	gold quality
vermiform appendix	UBERON:0001154	84.54	gold quality
skin of leg	UBERON:0001511	84.51	gold quality
muscle of leg	UBERON:0001383	84.50	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.78
E-MTAB-9801	yes	5.70
E-MTAB-7303	no	235.07
E-MTAB-5061	no	3.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting ANAPC1, 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-3064-3P	100.00	70.09	1254
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 22)

• Cdh1 may function as a component in tumor suppression via proteolysis of Skp2 in colorectal tumorigenesis and may serve as a prognostic marker in colon cancer patients. (PMID:18535175)
• ANAPC1 methylation was probably not implicated in gastric carcinogenesis (PMID:18622497)
• Studies indicate that APC/C(Cdh1) is required to maintain genomic stability. (PMID:19826416)
• These results suggest that APC/C(Cdh1) is involved in ubiquitination and down-regulating the stability of TRB3 protein. (PMID:20064487)
• Data demonstrate that PFKFB3 is essential for cell division and that it is regulated by APC/C-Cdh1 and SKP1-CUL1-F (SCF)-beta-TrCP. (PMID:21402913)
• the ability of Emi1 to inhibit APC/C is negatively regulated by CDKs (PMID:21454540)
• Studies indicate that the APC/C is tightly regulated by its co-activators and by the spindle assembly checkpoint. (PMID:21633387)
• Single nucleotide polymorhpisms of ANAPC1 were associated with nicotine dependence. (PMID:22377092)
• analysis of ubiquitylation of p53 by the APC/C inhibitor Trim39 (PMID:23213260)
• EYA1 is efficiently degraded during mitotic exit in a ANAPC1-dependent manner and these two proteins physically interact. (PMID:23263983)
• Data indicate that regulation of Rad17 turnover is through the Cdh1/anaphase-promoting complex pathway in breast cancer cells. (PMID:23637229)
• Human Cytomegalovirus UL21a but not UL97 can disrupt APC/C function, leading to the accumulation of substrates and that UL21a is necessary and sufficient to induce the degradation of APC1, in addition to the previously reported APC4 and APC5. (PMID:25903336)
• findings suggest a tumor suppressor role for APC/C(Cdh1) in melanocytes and that targeting PAX3 may be a strategy for treating melanoma. (PMID:26329581)
• cryo-EM structure of an APC/C-Cdh1 complex with Apc1(WD40) deleted showed that the mutant APC/C is locked into an inactive conformation in which the UbcH10-binding site of the catalytic module is inaccessible. Additionally, an EM density for Apc15 is not visible (PMID:27601667)
• Data show that FZR1 (Fzr), a cofactor of the multi-subunit E3 ligase complex anaphase-promoting complex/cyclosome (APC/C), represents a therapeutic target in myeloma. (PMID:27655696)
• The ABBA-KEN-ABBA amino acid motif cassette holds the Mitotic Checkpoint Complex (MCC) onto the Anaphase-Promoting Complex-Cyclosome (APC/C) by binding the two Cdc20 molecules in the MCC-APC/C complex. (PMID:27939943)
• in the Alzheimer’s disease (AD)mouse model APP/PS1, lower cdh1 levels were observed in pyramidal neurons in CA1 when compared to age-matched wildtype mice. In this review, we provide a complete list of APC/C substrates that are involved in the nervous system and we discuss their functions. We also summarize recent studies that show neurobiological effects in cdh1 knockout mouse models. (PMID:28505105)
• The anaphase promoting complex/cyclosome (APC/C) E3 ligase is not simply an interaction hub, but a dynamic, multifunctional molecular machine whose structure is remodeled by binding partners to achieve temporal ubiquitylation regulating cell division [Review]. (PMID:30482618)
• Sequence variation at ANAPC1 accounts for 24% of the variability in corneal endothelial cell density. (PMID:30894546)
• Fibroblast studies showed that the intronic mutation causes the activation of a 95 bp pseudoexon, leading to mRNAs with premature termination codons and nonsense-mediated decay, decreased ANAPC1 protein levels, and prolongation of interphase (PMID:31303264)
• Dimerization regulates the human APC/C-associated ubiquitin-conjugating enzyme UBE2S. (PMID:33082289)
• Antibody for Serine 65 Phosphorylated Ubiquitin Identifies PLK1-Mediated Phosphorylation of Mitotic Proteins and APC1. (PMID:35956818)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	anapc1	ENSDARG00000075687
mus_musculus	Anapc1	ENSMUSG00000014355
rattus_norvegicus	Anapc1	ENSRNOG00000016965
drosophila_melanogaster	shtd	FBGN0004391
caenorhabditis_elegans		WBGENE00003133

Protein

Protein identifiers

Anaphase-promoting complex subunit 1 — Q9H1A4 (reviewed: Q9H1A4)

Alternative names: Cyclosome subunit 1, Mitotic checkpoint regulator, Testis-specific gene 24 protein

All UniProt accessions (4): Q9H1A4, A0A2R8YF63, F8WAS1, H0Y564

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.

Post-translational modifications. Phosphorylated. Phosphorylation on Ser-355 occurs specifically during mitosis.

Disease relevance. Rothmund-Thomson syndrome 1 (RTS1) [MIM:618625] A form of Rothmund-Thomson syndrome, a disorder characterized by sparse hair, eyebrows and eyelashes, juvenile cataracts, and poikiloderma, a genodermatosis presenting with mottled pigmentation, telangiectasia and epidermal atrophy. Additional features are short stature, dysplastic nails, and skeletal and dental abnormalities. RTS1 is an autosomal recessive form not associated with an increased risk of cancer. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the APC1 family.

RefSeq proteins (1): NP_073153* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR024990	APC1	Family
IPR041221	APC1_C	Domain
IPR046794	Apc1_MidN	Domain
IPR048971	Apc1_3rd	Domain
IPR049255	Apc1_N	Domain

Pfam: PF12859, PF18122, PF20518, PF21282

UniProt features (201 total): helix 77, strand 68, turn 25, modified residue 19, repeat 4, compositionally biased region 3, region of interest 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
5LGG	X-RAY DIFFRACTION	2.15
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-Q9H1A4-F1	77.46	0.33

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 (19): 51, 60, 202, 286, 291, 313, 341, 343, 355, 362, 373, 377, 537, 547, 555, 571, 686, 688, 916

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): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_DNA_REPLICATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1, REACTOME_APC_C_CDC20_MEDIATED_DEGRADATION_OF_CYCLIN_B, REACTOME_CONVERSION_FROM_APC_C_CDC20_TO_APC_C_CDH1_IN_LATE_ANAPHASE, REACTOME_PHOSPHORYLATION_OF_THE_APC_C, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_ANAPHASE_PROMOTING_COMPLEX_DEPENDENT_CATABOLIC_PROCESS, REACTOME_APC_CDC20_MEDIATED_DEGRADATION_OF_NEK2A, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (9): metaphase/anaphase transition of mitotic cell cycle (GO:0007091), regulation of mitotic cell cycle (GO:0007346), anaphase-promoting complex-dependent catabolic process (GO:0031145), 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 (1): molecular adaptor activity (GO:0060090)

GO Cellular Component (4): nucleoplasm (GO:0005654), anaphase-promoting complex (GO:0005680), cytosol (GO:0005829), nucleus (GO:0005634)

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
mitotic cell cycle	2
regulation of cell cycle	2
cellular anatomical structure	2
mitotic cell cycle phase transition	1
metaphase/anaphase transition of cell cycle	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
cellular process	1
meiotic cell cycle	1
regulation of reproductive process	1
protein modification by small protein conjugation	1
molecular_function	1
binding	1
nuclear lumen	1
nuclear ubiquitin ligase complex	1
cullin-RING ubiquitin ligase complex	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2147 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANAPC1	ANAPC5	Q9UJX4	944
ANAPC1	CDC16	Q13042	937
ANAPC1	ANAPC4	Q9UJX5	924
ANAPC1	CDC27	P30260	920
ANAPC1	ANAPC2	Q9UJX6	872
ANAPC1	CDC23	Q9UJX2	857
ANAPC1	ANAPC10	Q9UM13	852
ANAPC1	CDC20	Q12834	843
ANAPC1	PIF1	Q9H611	827
ANAPC1	ANAPC11	Q9NYG5	773
ANAPC1	NEUROD2	Q15784	771
ANAPC1	P84086	P84086	764
ANAPC1	ANAPC7	Q9UJX3	747
ANAPC1	CDK1	P06493	693
ANAPC1	MAD2L1	Q13257	683

IntAct

187 interactions, top by confidence:

A	B	Type	Score
CDC20	BUB1B	psi-mi:“MI:0914”(association)	0.980
CDC16	CDC26	psi-mi:“MI:0914”(association)	0.940
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
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
IFT70B	IFT56	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
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
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 (318): ANAPC1 (Reconstituted Complex), ANAPC1 (Affinity Capture-Western), ANAPC1 (Affinity Capture-RNA), ANAPC1 (Affinity Capture-RNA), ANAPC1 (Affinity Capture-Western), ANAPC1 (Affinity Capture-Western), USP1 (Affinity Capture-Western), ANAPC1 (Reconstituted Complex), ANAPC1 (Affinity Capture-MS), ANAPC1 (Affinity Capture-Western), ANAPC1 (Affinity Capture-MS), ANAPC1 (Affinity Capture-MS), ANAPC1 (Protein-peptide), ANAPC1 (Affinity Capture-MS), ANAPC1 (Affinity Capture-Western)

ESM2 similar proteins: A0A8M3AJY3, A5WUN7, A6QLR3, B5X1P9, E2AB17, F1MJR8, F1QB81, M0R5D6, O00443, O43310, O60291, P03122, P11299, P15304, P42859, P51111, P59438, Q15018, Q1HKZ5, Q1LUT1, Q1LVP6, Q28HX0, Q2PFD7, Q2T9I9, Q3TCJ1, Q3TEL6, Q3UPF5, Q535K8, Q5E9P1, Q5I0F1, Q5RD34, Q5VUB5, Q5XIQ4, Q5ZHS0, Q61194, Q6GR31, Q6INH1, Q6P4W0, Q6PEE2, Q6UWZ7

Diamond homologs: P24686, P53995, Q54NC6, Q9FFF9, Q9H1A4, Q9URV2

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CDK1	up-regulates	ANAPC1	phosphorylation
PLK1	up-regulates	ANAPC1	phosphorylation
ANAPC1	“form complex”	APC-c	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 172 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	75.3×	3e-23
Inactivation of APC/C via direct inhibition of the APC/C complex	14	61.6×	2e-21
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	16	57.4×	1e-23
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	16	55.3×	3e-23
Phosphorylation of the APC/C	12	55.3×	2e-17
APC/C-mediated degradation of cell cycle proteins	19	54.1×	3e-27
Regulation of mitotic cell cycle	19	54.1×	3e-27
APC-Cdc20 mediated degradation of Nek2A	15	53.8×	1e-21

GO biological processes:

GO term	Partners	Fold	FDR
regulation of meiotic cell cycle	13	70.6×	3e-19
protein branched polyubiquitination	11	65.7×	5e-16
anaphase-promoting complex-dependent catabolic process	13	64.7×	8e-19
mitotic spindle assembly checkpoint signaling	9	35.9×	3e-10
protein K11-linked ubiquitination	12	33.4×	2e-13
regulation of mitotic cell cycle	16	27.3×	2e-16
protein K48-linked ubiquitination	14	16.7×	2e-11
cell division	27	8.8×	8e-16

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	0
Uncertain significance	212
Likely benign	19
Benign	12

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
4076073	GRCh37/hg19 2q13(chr2:112474513-112579384)x1	Pathogenic
692105	NM_022662.4(ANAPC1):c.1778dup (p.Asn593fs)	Pathogenic
692106	NM_022662.4(ANAPC1):c.4373+1G>A	Pathogenic
831508	NC_000002.12:g.(?111818840)(112028864_?)del	Pathogenic
831639	NC_000002.12:g.(?111838438)(112028864_?)del	Pathogenic
832131	NC_000002.12:g.(?111850776)(112028864_?)del	Pathogenic

SpliceAI

7546 predictions. Top by Δscore:

Variant	Effect	Δscore
2:111769223:G:C	donor_gain	1.0000
2:111772336:ATTAC:A	donor_loss	1.0000
2:111772337:TTA:T	donor_loss	1.0000
2:111772338:TA:T	donor_loss	1.0000
2:111772339:A:AT	donor_loss	1.0000
2:111772340:C:CG	donor_loss	1.0000
2:111772340:CCTT:C	donor_gain	1.0000
2:111772471:CCCGA:C	acceptor_gain	1.0000
2:111772472:CCGA:C	acceptor_gain	1.0000
2:111772472:CCGAC:C	acceptor_gain	1.0000
2:111772473:CGA:C	acceptor_gain	1.0000
2:111772473:CGAC:C	acceptor_gain	1.0000
2:111776853:TATTA:T	donor_loss	1.0000
2:111776854:ATTAC:A	donor_loss	1.0000
2:111776855:TTAC:T	donor_loss	1.0000
2:111776856:TACCT:T	donor_loss	1.0000
2:111776857:A:AT	donor_loss	1.0000
2:111776858:C:CA	donor_loss	1.0000
2:111778669:CCATA:C	donor_loss	1.0000
2:111778670:CATA:C	donor_loss	1.0000
2:111778671:ATACC:A	donor_loss	1.0000
2:111778672:TACC:T	donor_loss	1.0000
2:111778673:A:AT	donor_loss	1.0000
2:111778674:C:A	donor_loss	1.0000
2:111780382:CTGG:C	acceptor_gain	1.0000
2:111780386:C:CC	acceptor_gain	1.0000
2:111782392:T:TA	donor_gain	1.0000
2:111782503:TGGAC:T	acceptor_gain	1.0000
2:111782504:GGAC:G	acceptor_gain	1.0000
2:111782505:GAC:G	acceptor_gain	1.0000

AlphaMissense

12727 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:111803790:A:G	L1325P	1.000
2:111805819:C:G	G1303R	1.000
2:111805830:C:T	G1299D	1.000
2:111815446:C:T	G1174D	1.000
2:111815498:A:G	W1157R	1.000
2:111815498:A:T	W1157R	1.000
2:111815567:A:G	W1134R	1.000
2:111815567:A:T	W1134R	1.000
2:111822474:C:G	R980P	1.000
2:111822475:G:T	R980S	1.000
2:111782475:A:T	V1699D	0.999
2:111788288:G:T	A1582D	0.999
2:111792386:C:T	G1563E	0.999
2:111792387:C:G	G1563R	0.999
2:111792387:C:T	G1563R	0.999
2:111800820:A:G	W1425R	0.999
2:111800820:A:T	W1425R	0.999
2:111800845:C:A	W1416C	0.999
2:111800845:C:G	W1416C	0.999
2:111800847:A:G	W1416R	0.999
2:111800847:A:T	W1416R	0.999
2:111802489:A:G	L1387P	0.999
2:111803481:G:T	A1370D	0.999
2:111803490:G:T	A1367D	0.999
2:111803493:C:T	G1366D	0.999
2:111803513:A:C	N1359K	0.999
2:111803513:A:T	N1359K	0.999
2:111803709:A:G	I1352T	0.999
2:111803772:C:T	G1331E	0.999
2:111803790:A:T	L1325H	0.999

dbSNP variants (sampled 300 via entrez): RS1000016869 (2:111767127 G>C), RS1000092760 (2:111883376 G>A), RS1000137181 (2:111825559 T>A,C), RS1000195887 (2:111874352 A>G), RS1000237420 (2:111828710 G>A,C), RS1000238025 (2:111870727 G>A,T), RS1000245722 (2:111884994 G>A,T), RS1000255928 (2:111767427 T>C), RS1000431336 (2:111822184 C>T), RS1000583306 (2:111769914 C>T), RS1000586198 (2:111829664 C>T), RS1000653635 (2:111866860 G>A,C), RS1000684757 (2:111866641 T>C), RS1000715276 (2:111866150 G>A), RS1000780718 (2:111822949 A>G)

Disease associations

OMIM: gene MIM:608473 | disease phenotypes: MIM:618625, MIM:268400

GenCC curated gene-disease

Disease	Classification	Inheritance
Rothmund-Thomson syndrome type 1	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Rothmund-Thomson syndrome type 1	Moderate	AR

Mondo (2): Rothmund-Thomson syndrome type 1 (MONDO:0016368), Rothmund-Thomson syndrome type 2 (MONDO:0016369)

Orphanet (2): Rothmund-Thomson syndrome type 1 (Orphanet:221008), Rothmund-Thomson syndrome type 2 (Orphanet:221016)

HPO phenotypes

75 total (30 of 75 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000026	Male hypogonadism
HP:0000028	Cryptorchidism
HP:0000135	Hypogonadism
HP:0000164	Abnormality of the dentition
HP:0000282	Facial edema
HP:0000403	Recurrent otitis media
HP:0000519	Developmental cataract
HP:0000561	Absent eyelashes
HP:0000670	Carious teeth
HP:0000682	Abnormal dental enamel morphology
HP:0000684	Delayed eruption of teeth
HP:0000691	Microdontia
HP:0000698	Conical tooth
HP:0000821	Hypothyroidism
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000953	Hyperpigmentation of the skin
HP:0000957	Cafe-au-lait spot
HP:0000962	Hyperkeratosis
HP:0001009	Telangiectasia
HP:0001010	Hypopigmentation of the skin
HP:0001029	Poikiloderma
HP:0001041	Facial erythema
HP:0001118	Juvenile cataract
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001510	Growth delay
HP:0001518	Small for gestational age
HP:0001816	Thin nail

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST001762_738	Obesity-related traits	8.000000e-06
GCST002084_7	Allergic sensitization	2.000000e-06
GCST005038_45	Allergic disease (asthma, hay fever or eczema)	2.000000e-10
GCST005038_46	Allergic disease (asthma, hay fever or eczema)	2.000000e-08
GCST006394_52	Intraocular pressure	2.000000e-31
GCST006412_1	Intraocular pressure	2.000000e-33
GCST006979_20	Heel bone mineral density	1.000000e-24
GCST007691_27	Femoral neck bone mineral density	2.000000e-09
GCST007798_23	Asthma	4.000000e-07
GCST007800_71	Asthma (childhood onset)	2.000000e-09
GCST008276_1	Corneal resistance factor	8.000000e-12
GCST008277_1	Corneal hysteresis	4.000000e-14
GCST008315_1	Corneal hysteresis	3.000000e-19
GCST008318_2	Corneal resistance factor	1.000000e-11
GCST008339_40	Corneal endothelial cell density	2.000000e-314
GCST010083_68	Hemoglobin levels	2.000000e-09
GCST011390_1	Corneal resistance factor	3.000000e-148
GCST011391_1	Corneal hysteresis	6.000000e-206

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004810	interleukin-6 measurement
EFO:0005298	allergic sensitization measurement
EFO:0004695	intraocular pressure measurement
EFO:0009270	heel bone mineral density
EFO:0007785	femoral neck bone mineral density
EFO:0010067	corneal resistance factor
EFO:0010066	corneal hysteresis
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, affects expression	1
methylmercuric chloride	decreases expression	1
lasiocarpine	decreases expression, increases metabolic processing	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression	1
riddelliine	decreases expression, increases metabolic processing	1
arsenite	affects binding, decreases reaction	1
o,p’-DDT	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
potassium chromate(VI)	increases expression	1
coumarin	affects phosphorylation	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
scriptaid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1

Clinical trials (associated diseases)

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