PRC1

Summary

PRC1 (protein regulator of cytokinesis 1, HGNC:9341) is a protein-coding gene on chromosome 15q26.1, encoding Protein regulator of cytokinesis 1 (O43663). Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. It is a common-essential gene (DepMap: required in 98.9% of cancer cell lines).

This gene encodes a protein that is involved in cytokinesis. The protein is present at high levels during the S and G2/M phases of mitosis but its levels drop dramatically when the cell exits mitosis and enters the G1 phase. It is located in the nucleus during interphase, becomes associated with mitotic spindles in a highly dynamic manner during mitosis, and localizes to the cell mid-body during cytokinesis. This protein has been shown to be a substrate of several cyclin-dependent kinases (CDKs). It is necessary for polarizing parallel microtubules and concentrating the factors responsible for contractile ring assembly. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 9055 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 115 total
• Phenotypes (HPO): 1
• Cancer dependency (DepMap): dependent in 98.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_003981

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9341
Approved symbol	PRC1
Name	protein regulator of cytokinesis 1
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	ASE1, MAP65
Ensembl gene	ENSG00000198901
Ensembl biotype	protein_coding
OMIM	603484
Entrez	9055

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 13 protein_coding, 8 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000361188, ENST00000394249, ENST00000417173, ENST00000442656, ENST00000553494, ENST00000555455, ENST00000555745, ENST00000555791, ENST00000556129, ENST00000556972, ENST00000556982, ENST00000557763, ENST00000557905, ENST00000559326, ENST00000559811, ENST00000559828, ENST00000560423, ENST00000560605, ENST00000560914, ENST00000879803, ENST00000879804, ENST00000929684, ENST00000929685

RefSeq mRNA: 3 — MANE Select: NM_003981 NM_001267580, NM_003981, NM_199413

CCDS: CCDS32334, CCDS45352, CCDS45353

Canonical transcript exons

ENST00000394249 — 15 exons

Exon	Start	End
ENSE00001295125	90980884	90981033
ENSE00001300205	90970404	90970514
ENSE00001305114	90974136	90974246
ENSE00001312146	90981499	90981669
ENSE00001318740	90969447	90969623
ENSE00002500402	90966040	90967202
ENSE00002513130	90994407	90994535
ENSE00003467397	90984018	90984140
ENSE00003493139	90974585	90974731
ENSE00003524968	90979158	90979294
ENSE00003547682	90976676	90976771
ENSE00003550019	90981748	90981981
ENSE00003561114	90980242	90980389
ENSE00003680400	90984693	90984825
ENSE00003694508	90969079	90969120

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.3131 / max 1263.1084, expressed in 1705 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151591	28.6659	1625
151592	3.8020	1205
151590	1.4188	674
151593	0.4967	262
151589	0.4006	217
151594	0.2822	110
151588	0.2468	130

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.27	gold quality
ganglionic eminence	UBERON:0004023	97.99	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.44	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.02	gold quality
left testis	UBERON:0004533	93.99	gold quality
testis	UBERON:0000473	93.93	gold quality
right testis	UBERON:0004534	93.90	gold quality
bone marrow	UBERON:0002371	93.86	gold quality
stromal cell of endometrium	CL:0002255	92.94	gold quality
mucosa of transverse colon	UBERON:0004991	92.22	gold quality
lower esophagus mucosa	UBERON:0035834	91.98	gold quality
bone marrow cell	CL:0002092	91.14	gold quality
esophagus mucosa	UBERON:0002469	90.19	gold quality
placenta	UBERON:0001987	90.16	gold quality
cerebellar hemisphere	UBERON:0002245	87.77	gold quality
cerebellum	UBERON:0002037	87.70	gold quality
cerebellar cortex	UBERON:0002129	87.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.49	gold quality
rectum	UBERON:0001052	87.33	gold quality
adrenal tissue	UBERON:0018303	86.64	gold quality
colonic epithelium	UBERON:0000397	86.52	gold quality
calcaneal tendon	UBERON:0003701	86.45	gold quality
endometrium	UBERON:0001295	86.13	gold quality
skin of leg	UBERON:0001511	85.81	gold quality
zone of skin	UBERON:0000014	85.75	gold quality
skin of abdomen	UBERON:0001416	85.45	gold quality
tonsil	UBERON:0002372	84.89	gold quality
lymph node	UBERON:0000029	84.46	gold quality
duodenum	UBERON:0002114	84.42	gold quality
vermiform appendix	UBERON:0001154	84.33	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	503.63
E-MTAB-10290	yes	496.65
E-MTAB-10662	yes	444.38
E-HCAD-13	yes	222.79
E-MTAB-8495	yes	178.63
E-HCAD-10	yes	34.93
E-HCAD-5	yes	20.72
E-GEOD-125970	yes	17.05
E-MTAB-6678	yes	8.30
E-ANND-3	yes	7.77
E-GEOD-99795	no	326.87
E-MTAB-6524	no	113.36

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DNAJC2, DNMT1, DNMT3B, E2F4, PAX1, TP53

miRNA regulators (miRDB)

56 targeting PRC1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-4310	99.59	68.84	2527

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• PRC1 is a microtubule-associated protein required to maintain the spindle midzone, and that distinct functions are associated with modular elements of the primary sequence. (PMID:12082078)
• contributes to the correct formation of the spindle during the metaphase (PMID:14744859)
• kinesin family member 4 and its binding partner PRC1 play essential roles in the organization of central spindles and midzone formation (PMID:15297875)
• transcription is controlled by p53 via regulating cytokinesis (PMID:15531928)
• PRC1 is a microtubule bundling protein that is critical to the formation of the central spindle, which is required for abscission but not for furrowing in mammalian cells (PMID:15616196)
• role of PRC1 in midzone formation, indicate that cell cycle-dependent translocation of PRC1 by Kif4 is essential for midzone formation and cytokinesis. (PMID:15625105)
• PRC1 complexes isolated from human cells contain multiple kinesins KIF4A, Kif20A, KIF23 and KIF14. (PMID:16431929)
• PRC1 is an essential factor in controlling the spatiotemporal formation of the midzone in human cells. (PMID:16603632)
• suggest the involvement of a PRC1- kinesin family member 2C/mitotic centromere-associated kinesin complex in breast tumorigenesis, and this complex should be a promising target for the development of novel treatments for breast cancer (PMID:17233835)
• PRC1 is a docking partner for the Polo kinase Plk1 in anaphase cells. During metaphase this is inhibited by Cdk1-cyclin B phosphorylation at T470 and T481. (PMID:17351640)
• These results provide a potential mechanistic basis for the defective cytokinesis phenotype exhibited by HSF2-/- cells, as well as suggest a potential role for PRC1 in HSF2-mediated gene bookmarking. (PMID:18570919)
• Microtubule-associated protein (MAP) Prc1 facilitate Plk1 phosphorylation of HsCyk-4. (PMID:19468300)
• Data propose that PRC1 forms a link between stabilization of CLASP1 association with central spindle microtubules and anti-parallel microtubule elongation. (PMID:19561070)
• The radiosensitizing effect of paclitaxel on KB cells may be due to the down-regulated expression of PRC1 and cyclin B2. (PMID:19664331)
• PRC1’s microtubule binding is mediated by a structured domain with a spectrin-fold and an unstructured Lys/Arg-rich domain. (PMID:20691902)
• Cells depleted of PRC1 failed to form a polarized microtubule array or ectopic furrows following mitotic exit, and recruitment of Aurora B kinase, male germ cell Rac GTPase-activating protein, and RhoA to the cortex was impaired. (PMID:22323288)
• Two distinct mechanisms are involved in CBX2-mediated gene silencing. The short CBX2-2 isoform would repress the transcription in a PRC1-independent fashion, whereas gene repression by the long CBX2-1 isoform is mediated by the PRC1 protein complex. (PMID:22419124)
• findings suggest that PRC1 is regulated by Plk1, rather than Cdk1 as previously proposed, because its activity must be spatiotemporally regulated both preanaphase and postanaphase, and Cdk1 activity is too binary for this purpose (PMID:22621898)
• Different PRC1 paralog family members have nonredundant and locus-specific gene regulatory activities that are essential for human hematopoiesis. (PMID:23349393)
• Studies reveal how interactions between the conserved nonmotor MAP, PRC1, and the motor protein, kinesin-4, generate filament length-dependent tags at microtubule plus ends. PRC1 tags ends of microtubules in dividing cells and the size of these tags increases linearly with filament length. (PMID:23870126)
• PP2A-B55 dephosphorylates PRC1 at the metaphase to anaphase transition. This activity is regulated by the Greatwall (MASTL) kinase and its substrate ENSA, explaining the timing of PRC1 activation in anaphase. (PMID:24120663)
• The presence of CBX4 or CBX8-GFP in the same focus had a minor impact on BMI1 and RING1 recovery kinetics. (PMID:24460908)
• Study finds that frictional forces increase nonlinearly with microtubule-associated proteins (MAP) velocity across microtubules and depend on filament polarity, with NuMA’s friction being lower when moving toward minus ends, EB1’s lower toward plus ends, and PRC1’s exhibiting no directional preference. (PMID:24725408)
• These findings suggest that the aberrant expression of PRC1 may predict biochemical recurrence in men with prostate cancer highlighting its potential as a prognostic marker of this malignancy. (PMID:26898432)
• PRC1 is a novel Wnt target that functions in a positive feedback loop that reinforces Wnt signalling to promote early Hepatocellular Carcinoma recurrence. (PMID:26941395)
• Near-atomic cryo-electron microscopy structure of PRC1 bound to the microtubule has been described. (PMID:27493215)
• PRC1 rs10520699 and rs11852999 polymorphisms were associated with PRC1 transcript levels, but not with patients survival. (PMID:27505863)
• These findings suggest that the identified APLP2, RRM2, and PRC1 signature could be useful for distinguishing between benign (follicular adenoma) and malignant (follicular carcionma and follicular variant of papillary carcinoma) tumors of the thyroid follicular epithelium. (PMID:27796194)
• study reveals that UbE2E1 is an in vivo E2 for the PRC1 ligase complex and thus plays an important role in the regulation of H2A Lys-119 monoubiquitination (PMID:28073915)
• We finally confirmed that PRC1 is a novel downstream target of piperlongumine in gastric cancer. Our findings supported the oncogenic role of PRC1 in gastric carcinogenesis. PRC1 might serve as a prognostic biomarker and potential therapeutic target for gastric carcinoma. (PMID:28190297)
• PRC1 was identified as a type 2 diabetes susceptibility gene. PRC1 plays a role in insulin secretion in vitro. (PMID:28580277)
• PRC1 mRNA and protein expressions were upregulated in lung adenocarcinoma tissues. PRC1 expression was significantly correlated with the Wnt/beta-catenin signaling pathway. (PMID:28646916)
• We discuss targeting PRC1 within the complementary approaches of either normalizing chromosomal instability in aneuploid cancers or creating chromosomal chaos in genomically stable cancers to induce apoptosis. (PMID:29413422)
• reducing PRC1 blocks mitotic exit of hepatocellular carcinoma (HCC) cells at telophase in a spindle assembly checkpoint independent manner, and acts synergistically with microtubule-associated agents (MTAs) to suppress p53-wt or p53-null HCC cells in a p53- or p14ARF-dependent manner; while overexpressing PRC1 increases the resistance of HCC to taxol. (PMID:29748662)
• PRC1 is a key factor in regulating proliferation and the cell cycle, pointing to the potential benefits of PRC1-targeted therapies for oral squamous cell carcinoma. (PMID:29752448)
• findings pave the way to identify sequence-specific DNA-binding proteins implicated in the targeting of mammalian polycomb repressive complex 1 complexes and provide novel link between polycomb repression and cancer (PMID:30068546)
• RNA interference-mediated knockdown of the Drosophila ortholog or PRC1 in insulin-producing cells, a model for mammalian beta cells, conferred increased insulin output. (PMID:30242153)
• Here, the authors show that the collective activity of PRC1 and Kif4A results in relative microtubule sliding and concurrent end-tag formation on antiparallel microtubules. (PMID:30353849)
• BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation. (PMID:30664650)
• BAP1 and PRC1 repressed SLC7A11 expression, and regulated H2Aub ubiquitination, which is important for SLC7A11 repression. (PMID:30907299)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	prc1b	ENSDARG00000005993
danio_rerio	prc1a	ENSDARG00000100918
mus_musculus	Prc1	ENSMUSG00000038943
rattus_norvegicus	Prc1	ENSRNOG00000013057

Protein

Protein identifiers

Protein regulator of cytokinesis 1 — O43663 (reviewed: O43663)

All UniProt accessions (7): O43663, G3V3N7, H0YL53, H0YLA0, H0YM42, H0YNE4, H3BSJ8

UniProt curated annotations — full annotation on UniProt →

Function. Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. Essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. Required for KIF14 localization to the central spindle and midbody. Required to recruit PLK1 to the spindle. Stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle. Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression.

Subunit / interactions. Homodimer. Interacts with the C-terminal Rho-GAP domain and the basic region of RACGAP1. The interaction with RACGAP1 inhibits its GAP activity towards CDC42 in vitro, which may be required for maintaining normal spindle morphology. Interacts (via N-terminus) with the C-terminus of CENPE (via C-terminus); the interaction occurs during late mitosis. Interacts (via N-terminus) with KIF4A (via C-terminus); the interaction is required for the progression of mitosis. Interacts (via N-terminus) with KIF23 (via C-terminus); the interaction occurs during late mitosis. Interacts with KIF14 and KIF20A. Interacts with PLK1. Interacts with KIF20B. Interacts with CCDC66.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Spindle pole. Midbody. Chromosome.

Tissue specificity. Overexpressed in bladder cancer cells.

Post-translational modifications. Phosphorylation by CDK1 in early mitosis holds PRC1 in an inactive monomeric state, during the metaphase to anaphase transition, PRC1 is dephosphorylated, promoting interaction with KIF4A, which then translocates PRC1 along mitotic spindles to the plus ends of antiparallel interdigitating microtubules. Dephosphorylation also promotes MT-bundling activity by allowing dimerization. Phosphorylation by CDK1 prevents PLK1-binding: upon degradation of CDK1 at anaphase and dephosphorylation, it is then phosphorylated by PLK1, leading to cytokinesis.

Domain organisation. Microtubule binding occurs via a basic patch in the central spectrin-like domain and also requires the unstructured C-terminal domain.

Similarity. Belongs to the MAP65/ASE1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
O43663-1	1	yes
O43663-2	2
O43663-3	3
O43663-4	4

RefSeq proteins (3): NP_001254509, NP_003972, NP_955445 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007145	MAP65_Ase1_PRC1	Family

Pfam: PF03999

UniProt features (49 total): helix 14, modified residue 8, region of interest 7, splice variant 4, mutagenesis site 4, coiled-coil region 3, compositionally biased region 2, site 2, sequence variant 2, chain 1, sequence conflict 1, strand 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3NRX	X-RAY DIFFRACTION	1.75
3NRY	X-RAY DIFFRACTION	2
4L6Y	X-RAY DIFFRACTION	3.3
5KMG	ELECTRON MICROSCOPY	3.5
4L3I	X-RAY DIFFRACTION	3.6
7VBG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43663-F1	80.32	0.61

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 377 (tubulin binding); 387 (tubulin binding)

Post-translational modifications (8): 470, 481, 513, 571, 578, 616, 541, 571

Mutagenesis-validated functional residues (4):

Position	Phenotype
470	no effect. abolishes cdk1-mediated phosphorylation, leading to prematurely recruit plk1 to the spindle during prometapha
481	no effect. reduces in vitro cyclin e-cdk2 phosphorylation and causes extensive bundling of microtubules to the mitotic s
577–578	weakly reduces binding to the polo box domains of plk1.
615–616	impairs binding to the polo box domains of plk1, preventing phosphorylation by plk1 and recruitment of plk1 to the spind

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5625900	RHO GTPases activate CIT

MSigDB gene sets: 417 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_CHROMOSOME_ORGANIZATION, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, SHEPARD_BMYB_MORPHOLINO_UP, HORIUCHI_WTAP_TARGETS_DN, KANG_DOXORUBICIN_RESISTANCE_UP, GNF2_CENPF, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, XU_GH1_AUTOCRINE_TARGETS_UP, GNF2_H2AFX, IVANOVA_HEMATOPOIESIS_MATURE_CELL, KONG_E2F3_TARGETS, WIELAND_UP_BY_HBV_INFECTION, MONTERO_THYROID_CANCER_POOR_SURVIVAL_UP

GO Biological Process (6): mitotic spindle elongation (GO:0000022), microtubule cytoskeleton organization (GO:0000226), positive regulation of cell population proliferation (GO:0008284), regulation of cytokinesis (GO:0032465), mitotic spindle midzone assembly (GO:0051256), cell division (GO:0051301)

GO Molecular Function (5): microtubule binding (GO:0008017), kinesin binding (GO:0019894), protein kinase binding (GO:0019901), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (16): spindle pole (GO:0000922), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytoplasm (GO:0005737), spindle (GO:0005819), cytosol (GO:0005829), spindle microtubule (GO:0005876), plasma membrane (GO:0005886), microtubule cytoskeleton (GO:0015630), midbody (GO:0030496), intercellular bridge (GO:0045171), contractile ring (GO:0070938), mitotic spindle midzone (GO:1990023), cytoskeleton (GO:0005856), microtubule (GO:0005874)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase Effectors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
intracellular membraneless organelle	3
mitotic cell cycle process	2
spindle	2
microtubule cytoskeleton	2
mitotic sister chromatid segregation	1
mitotic cell cycle	1
mitotic spindle organization	1
spindle elongation	1
cytoskeleton organization	1
microtubule-based process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cytokinesis	1
regulation of cell cycle process	1
regulation of cell division	1
mitotic spindle elongation	1
spindle midzone assembly	1
mitotic spindle assembly	1
mitotic nuclear division	1
cellular process	1
tubulin binding	1
cytoskeletal protein binding	1
kinase binding	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
microtubule	1
membrane	1
cell periphery	1
cytoskeleton	1
spindle midzone	1
mitotic spindle	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

3446 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRC1	KIF23	Q02241	918
PRC1	KIF4A	O95239	908
PRC1	CENPE	Q02224	859
PRC1	PLK1	P53350	708
PRC1	KIF14	Q15058	674
PRC1	KIF2C	Q99661	647
PRC1	RACGAP1	Q9H0H5	601
PRC1	KIF11	P52732	560
PRC1	CCNB2	O95067	555
PRC1	NUSAP1	Q9BXS6	539
PRC1	ASPM	Q8IZT6	532
PRC1	AURKB	Q96GD4	523
PRC1	INCENP	Q9NQS7	521
PRC1	KIF20A	O95235	508
PRC1	AURKA	O14965	499

IntAct

58 interactions, top by confidence:

A	B	Type	Score
PRC1	TRIM37	psi-mi:“MI:0915”(physical association)	0.630
TRIM37	PRC1	psi-mi:“MI:0915”(physical association)	0.630
PRC1	ACSM1	psi-mi:“MI:0915”(physical association)	0.590
PRC1	CINP	psi-mi:“MI:0915”(physical association)	0.560
PRC1	MAT2A	psi-mi:“MI:0915”(physical association)	0.560
PRC1	PKIA	psi-mi:“MI:0915”(physical association)	0.560
USHBP1	PRC1	psi-mi:“MI:0915”(physical association)	0.550
PRC1	USHBP1	psi-mi:“MI:0915”(physical association)	0.550
LTBR	ZNF724	psi-mi:“MI:0914”(association)	0.530
IFI30	PRC1	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
FOXM1	PES1	psi-mi:“MI:0914”(association)	0.500
Dlg4	PRC1	psi-mi:“MI:0407”(direct interaction)	0.440
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
PLK1	PRC1	psi-mi:“MI:0915”(physical association)	0.400
PRC1	SHANK3	psi-mi:“MI:0915”(physical association)	0.400
PRC1	CHCHD3	psi-mi:“MI:0915”(physical association)	0.400
PRC1	EPB41L2	psi-mi:“MI:0915”(physical association)	0.400
Racgap1		psi-mi:“MI:0915”(physical association)	0.400
PRC1	LDOC1	psi-mi:“MI:0915”(physical association)	0.370
PRC1	KRT20	psi-mi:“MI:0915”(physical association)	0.370
PRC1	CCDC85B	psi-mi:“MI:0915”(physical association)	0.370
EXOSC2	WDR46	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
esxA	PGRMC1	psi-mi:“MI:0914”(association)	0.350
ARHGEF17	PRC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (1058): PRC1 (Affinity Capture-MS), USHBP1 (Two-hybrid), PRC1 (Affinity Capture-MS), KRT20 (Two-hybrid), PRC1 (Two-hybrid), CCDC85B (Two-hybrid), PRC1 (Affinity Capture-Western), PRC1 (Co-fractionation), PRC1 (Proximity Label-MS), PRC1 (Proximity Label-MS), PRC1 (Proximity Label-MS), PRC1 (Affinity Capture-MS), PRC1 (Affinity Capture-Western), PRC1 (Affinity Capture-MS), PRC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IXF6, A0A1W2PR95, A9ZLX4, D2HNY3, D3Z8X7, D3ZND0, E1C760, F4HRV8, H2LP95, O08836, O15068, O43663, O60308, P78318, Q05AA6, Q1LWH4, Q28CB1, Q2IA00, Q3B7T1, Q4KLN4, Q4R6T7, Q5F4B2, Q5PQQ6, Q5QNQ6, Q5R9R1, Q5RHQ8, Q61249, Q63406, Q64096, Q6A028, Q6DDI6, Q6GQV7, Q6INA9, Q7SYB5, Q7Z569, Q80V31, Q80V94, Q8C5W4, Q8C9J3, Q8CDK3

Diamond homologs: O43663, Q99K43

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
PRC1	up-regulates	Spindle_assembly
KIF4A	“up-regulates activity”	PRC1	binding
PRC1	“up-regulates activity”	KIF23	binding
PRC1	“up-regulates activity”	CENPE	binding
PRC1	“up-regulates activity”	KIF14	binding
CyclinY/CDK16	“up-regulates activity”	PRC1	phosphorylation
CDK16	“up-regulates activity”	PRC1	phosphorylation
PLK1	“down-regulates activity”	PRC1	phosphorylation
CyclinE/CDK2	unknown	PRC1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	99
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2498 predictions. Top by Δscore:

Variant	Effect	Δscore
15:90969523:CCA:C	donor_gain	1.0000
15:90969620:CTGG:C	acceptor_gain	1.0000
15:90969621:TGG:T	acceptor_gain	1.0000
15:90969622:GG:G	acceptor_gain	1.0000
15:90969623:GC:G	acceptor_loss	1.0000
15:90969624:C:CC	acceptor_gain	1.0000
15:90969624:CT:C	acceptor_loss	1.0000
15:90969625:T:A	acceptor_loss	1.0000
15:90969627:C:CT	acceptor_gain	1.0000
15:90969628:A:T	acceptor_gain	1.0000
15:90974140:CGTG:C	donor_gain	1.0000
15:90974243:GTTG:G	acceptor_gain	1.0000
15:90974244:TTG:T	acceptor_gain	1.0000
15:90974245:TG:T	acceptor_gain	1.0000
15:90974245:TGCTG:T	acceptor_loss	1.0000
15:90974246:GC:G	acceptor_loss	1.0000
15:90974247:C:CC	acceptor_gain	1.0000
15:90974249:G:C	acceptor_gain	1.0000
15:90974251:G:C	acceptor_gain	1.0000
15:90974251:G:GC	acceptor_gain	1.0000
15:90974259:C:CT	acceptor_gain	1.0000
15:90974581:TTACT:T	donor_loss	1.0000
15:90974582:TACTC:T	donor_loss	1.0000
15:90974583:A:AC	donor_gain	1.0000
15:90974583:ACT:A	donor_gain	1.0000
15:90974584:C:CT	donor_gain	1.0000
15:90974584:CT:C	donor_gain	1.0000
15:90974584:CTC:C	donor_gain	1.0000
15:90974584:CTCT:C	donor_gain	1.0000
15:90974589:T:A	donor_gain	1.0000

AlphaMissense

4073 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:90984720:T:A	R39S	0.999
15:90984720:T:G	R39S	0.999
15:90984721:C:G	R39T	0.999
15:90984759:C:A	W26C	0.999
15:90984759:C:G	W26C	0.999
15:90984761:A:G	W26R	0.999
15:90984761:A:T	W26R	0.999
15:90984772:A:G	L22P	0.999
15:90984124:A:G	M54T	0.998
15:90984136:A:G	L50P	0.998
15:90984091:A:G	L65P	0.997
15:90984103:A:G	L61P	0.997
15:90984749:C:A	G30W	0.997
15:90984133:A:G	L51P	0.996
15:90984730:C:G	R36P	0.996
15:90984745:A:G	I31T	0.996
15:90984748:C:T	G30E	0.996
15:90984760:C:G	W26S	0.996
15:90981938:C:G	R104P	0.995
15:90984123:C:A	M54I	0.995
15:90984123:C:G	M54I	0.995
15:90984123:C:T	M54I	0.995
15:90984721:C:A	R39I	0.995
15:90976704:C:G	R392P	0.994
15:90976722:A:G	L386P	0.994
15:90976725:A:G	L385P	0.994
15:90976737:C:G	R381P	0.994
15:90984722:T:C	R39G	0.994
15:90984749:C:G	G30R	0.994
15:90984749:C:T	G30R	0.994

dbSNP variants (sampled 300 via entrez): RS1000072237 (15:90971697 C>T), RS1000103742 (15:90976951 C>T), RS1000133257 (15:90976668 A>G), RS1000188722 (15:90966708 T>A), RS1000260856 (15:90989416 T>A), RS1000353141 (15:90982558 C>A,T), RS1000465645 (15:90983742 A>G,T), RS1000554239 (15:90994769 G>T), RS1000648745 (15:90986895 A>C,G), RS1000699513 (15:90986581 T>C,G), RS1000701444 (15:90971899 G>A), RS1000749042 (15:90985022 T>C), RS1000818258 (15:90983533 C>G), RS1001136759 (15:90975618 C>T), RS1001153835 (15:90965823 A>T)

Disease associations

OMIM: gene MIM:603484 | disease phenotypes: MIM:114480

GenCC curated gene-disease

Mondo (2): hereditary breast carcinoma (MONDO:0016419), breast carcinoma (MONDO:0004989)

Orphanet (1): Hereditary breast cancer (Orphanet:227535)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0003002	Breast carcinoma

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST000712_17	Type 2 diabetes	2.000000e-10
GCST002352_35	Type 2 diabetes	6.000000e-07
GCST002537_3	Breast cancer	4.000000e-08
GCST003400_7	Type 2 diabetes	4.000000e-06
GCST004599_181	Mean platelet volume	1.000000e-19
GCST004894_125	Type 2 diabetes	2.000000e-09
GCST004894_19	Type 2 diabetes	6.000000e-09
GCST004988_190	Breast cancer	8.000000e-10
GCST005047_108	Type 2 diabetes	8.000000e-08
GCST005047_52	Type 2 diabetes	6.000000e-09
GCST006867_130	Type 2 diabetes	2.000000e-12
GCST007847_84	Type 2 diabetes	2.000000e-10
GCST008512_34	Multisite chronic pain	3.000000e-11
GCST009379_160	Type 2 diabetes	2.000000e-15
GCST010118_52	Type 2 diabetes	1.000000e-22
GCST012332_1	Multisite chronic pain	7.000000e-12
GCST90002395_182	Mean platelet volume	6.000000e-35
GCST90002404_326	Red cell distribution width	6.000000e-14
GCST90002404_327	Red cell distribution width	1.000000e-14
GCST90002404_375	Red cell distribution width	1.000000e-183

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010100	multisite chronic pain
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562840	Breast Cancer, Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	5
bisphenol A	decreases expression, increases expression	3
Doxorubicin	affects response to substance, decreases expression	3
arsenite	affects binding, decreases reaction, decreases expression	2
cobaltous chloride	decreases expression	2
(+)-JQ1 compound	decreases expression	2
Zoledronic Acid	decreases expression	2
Cadmium	decreases expression	2
Cisplatin	decreases expression, increases expression	2
Estradiol	decreases expression, increases expression	2
Methotrexate	affects cotreatment, decreases expression	2
Progesterone	decreases expression, increases expression	2
FR900359	decreases phosphorylation	1
echimidine	decreases expression, increases metabolic processing	1
chloroacetaldehyde	affects expression	1
lasiocarpine	decreases expression, increases metabolic processing	1
propionaldehyde	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
deoxynivalenol	increases expression	1
geraniol	decreases expression	1
trichostatin A	affects expression	1
riddelliine	decreases expression, increases metabolic processing	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
zinc chromate	decreases expression, increases abundance	1
coumarin	decreases phosphorylation	1
leptomycin B	decreases expression	1
diallyl trisulfide	decreases expression	1
bicalutamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00014638	PHASE4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	PHASE4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	PHASE4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	PHASE4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)
NCT00127933	PHASE4	COMPLETED	XeNA Study - A Study of Xeloda (Capecitabine) in Patients With Invasive Breast Cancer
NCT00128297	PHASE4	COMPLETED	Pamidronate Administration in Breast Cancer Patients With Bone Metastases
NCT00129597	PHASE4	UNKNOWN	Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy
NCT00131170	PHASE4	COMPLETED	Paravertebral Block for Breast Surgery
NCT00156039	PHASE4	COMPLETED	Randomized Trial of Follow-up Strategies in Breast Cancer
NCT00160901	PHASE4	COMPLETED	Complementary Therapies for the Reduction of Side Effects During Chemotherapy for Breast Cancer
NCT00171847	PHASE4	TERMINATED	Study of the Efficacy and Safety of Letrozole Combined With Trastuzumab in Patients With Metastatic Breast Cancer
NCT00176046	PHASE4	COMPLETED	Mistletoe Extract in Early or Advanced Breast Cancer, A Feasibility Study
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00234195	PHASE4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
NCT00237133	PHASE4	COMPLETED	Treatment of Locally Advanced Breast Cancer With Letrozole in Postmenopausal Women
NCT00237224	PHASE4	COMPLETED	Open Label Study of Postmenopausal Women With ER and /or PgR Positive Breast Cancer Treated With Letrozole
NCT00241046	PHASE4	TERMINATED	Letrozole in the Treatment of 1st and 2nd Line Hormone Receptor Positive Breast Cancer: Pre-therapeutic Risk Assessment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00323479	PHASE4	COMPLETED	Arthralgia During Anastrozole Therapy for Breast Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00356148	PHASE4	COMPLETED	The Efficacy of Prophylactic Antibiotic Administration During Breast Cancer Surgery in Overweight Patients.
NCT00372476	PHASE4	COMPLETED	Efficacy and Safety of Imatinib and Vinorelbine in Patients With Advanced Breast Cancer
NCT00413491	PHASE4	UNKNOWN	National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations
NCT00484614	PHASE4	UNKNOWN	Study the Role of Positron Emission Mammography in Pre-surgical Planning for Breast Cancer
NCT00485953	PHASE4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00531973	PHASE4	UNKNOWN	A Study of Liposomal Doxorubicin in Women With Breast Cancer Exploiting Tissue Doppler Imaging
NCT00537771	PHASE4	COMPLETED	Liver Safety Under Upfront Arimidex vs Tamoxifen
NCT00544986	PHASE4	COMPLETED	A Prospective,Open-label Study of Anastrozole in Post-menopausal Women With Hormone Sensitive Advanced Breast Cancer
NCT00613275	PHASE4	COMPLETED	Patient Navigation in the Safety Net:CONNECTeDD
NCT00638599	PHASE4	COMPLETED	Comparison of Laryngeal Mask Airway (LMA®) and Tracheal Tube in Modified Radical Mastectomy on Breast Cancer
NCT00647075	PHASE4	UNKNOWN	Yunzhi as Dietary Supplement in Breast Cancer
NCT00688909	PHASE4	COMPLETED	Rheumatological Evaluation of Anastrozole and Letrozole as Adjuvant Treatment in Post-menopausal Women With Breast Cancer
NCT00699101	PHASE4	TERMINATED	Using the Conture® Multi-Lumen Balloon to Deliver Accelerated Partial Breast Brachytherapy
NCT00742222	PHASE4	COMPLETED	Electronic Xoft Intersociety Brachytherapy Trial: Electronic Brachytherapy (EBT) For Treatment of Early Stage Breast Cancer
NCT00754767	PHASE4	TERMINATED	L-Carnitine L-Tartrate in Preventing Peripheral Neuropathy Caused By Chemotherapy in Women With Metastatic Breast Cancer