RCC2

Summary

RCC2 (regulator of chromosome condensation 2, HGNC:30297) is a protein-coding gene on chromosome 1p36.13, encoding Protein RCC2 (Q9P258). Multifunctional protein that may affect its functions by regulating the activity of small GTPases, such as RAC1 and RALA.

The protein encoded by this gene is a guanine exchange factor that is active on RalA, a small GTPase. The encoded protein and RalA are both essential for proper kinetochore-microtubule function in early mitosis. This protein has been shown to be a biomarker for colorectal cancer.

Source: NCBI Gene 55920 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 74 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_018715

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30297
Approved symbol	RCC2
Name	regulator of chromosome condensation 2
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Aliases	TD-60
Ensembl gene	ENSG00000179051
Ensembl biotype	protein_coding
OMIM	609587
Entrez	55920

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 22 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000375433, ENST00000375436, ENST00000474892, ENST00000878232, ENST00000927084, ENST00000927086, ENST00000927087, ENST00000927088, ENST00000927089, ENST00000927090, ENST00000927091, ENST00000927092, ENST00000927093, ENST00000927094, ENST00000927095, ENST00000927097, ENST00000927098, ENST00000927099, ENST00000927100, ENST00000927102, ENST00000927104, ENST00000927106, ENST00000927109

RefSeq mRNA: 2 — MANE Select: NM_018715 NM_001136204, NM_018715

CCDS: CCDS181

Canonical transcript exons

ENST00000375436 — 13 exons

Exon	Start	End
ENSE00001267864	17409974	17410051
ENSE00001267871	17412122	17412194
ENSE00001267874	17413073	17413178
ENSE00001267880	17413537	17413717
ENSE00001267885	17416480	17416646
ENSE00001267891	17420714	17420828
ENSE00001267897	17422203	17422291
ENSE00001267903	17422705	17422836
ENSE00001267910	17425541	17425684
ENSE00001267916	17429106	17429199
ENSE00001364922	17439545	17439677
ENSE00001467085	17406760	17409194
ENSE00001467103	17438230	17438522

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 63.5533 / max 800.2149, expressed in 1828 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10583	22.5112	1799
10587	18.3404	1768
10589	11.7848	1756
10584	7.1782	1696
10590	1.5150	823
10588	1.1076	724
10578	0.5515	264
10582	0.2362	113
10592	0.1805	77
10591	0.1479	46

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	94.63	gold quality
esophagus mucosa	UBERON:0002469	94.31	gold quality
ganglionic eminence	UBERON:0004023	94.31	gold quality
lymph node	UBERON:0000029	94.18	gold quality
monocyte	CL:0000576	93.90	gold quality
skin of abdomen	UBERON:0001416	93.85	gold quality
leukocyte	CL:0000738	93.84	gold quality
stromal cell of endometrium	CL:0002255	93.69	gold quality
zone of skin	UBERON:0000014	93.59	gold quality
ventricular zone	UBERON:0003053	93.52	gold quality
skin of leg	UBERON:0001511	93.37	gold quality
vermiform appendix	UBERON:0001154	92.93	gold quality
granulocyte	CL:0000094	92.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.44	gold quality
mucosa of transverse colon	UBERON:0004991	92.24	gold quality
placenta	UBERON:0001987	92.16	gold quality
rectum	UBERON:0001052	92.15	gold quality
bone marrow	UBERON:0002371	92.09	gold quality
endometrium	UBERON:0001295	91.94	gold quality
saliva-secreting gland	UBERON:0001044	91.52	gold quality
minor salivary gland	UBERON:0001830	91.47	gold quality
tonsil	UBERON:0002372	91.46	gold quality
spleen	UBERON:0002106	91.43	gold quality
bone marrow cell	CL:0002092	91.08	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.79	gold quality
gall bladder	UBERON:0002110	89.78	gold quality
vagina	UBERON:0000996	89.43	gold quality
lung	UBERON:0002048	88.67	gold quality
esophagus	UBERON:0001043	88.59	gold quality
upper lobe of left lung	UBERON:0008952	88.40	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-111727	no	293.71
E-MTAB-7008	no	100.53
E-ANND-3	no	2.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

118 targeting RCC2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
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-548AQ-5P	99.94	71.34	3426
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
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 17)

• Data show that TD-60 is a member of the RCC1 family and that it binds preferentially the nucleotide-free form of the small G protein Rac1. (PMID:12919680)
• Dysregulation of Rac1 and Arf6 function by RCC2 knockdown also abolished persistent migration along fibronectin fibers, indicating a functional role for RCC2 in directional cell movement. (PMID:19738201)
• Studies indicated that DDX21, HNRNPC, and RCC2 were isolated from Ku86 multicomponent complex in response to DNA damage. (PMID:20873769)
• a complex containing cortactin and RCC2/TD60 complex that may play a functional role in cells undergoing mitosis. (PMID:22282019)
• TD-60 is an essential regulator of cell cycle progression during interphase. (PMID:23388455)
• MiR-29c is downregulated in gastric carcinomas and regulates cell proliferation by targeting RCC2. (PMID:23442884)
• Impaired RCC2 affects functional and clinical endpoints of colorectal cancer. High-risk patients with either MSI or MSS tumors can be identified with cost-effective routine RCC2 assays. (PMID:25910952)
• RCC2 exhibits guanine exchange factor activity, in vitro and in cells, for the small GTPase RalA. RCC2 and RalA apparently work together to contribute to the regulation of kinetochore-microtubule interactions in early mitosis. (PMID:26158537)
• RCC2 plays a pivotal role in LUAD metastasis by inducing EMT via activation of MAPK-JNK signaling. (PMID:28606921)
• Study reports that p53 is a transcriptional regulator of RCC2 that acts through its binding to a palindromic motif in the RCC2 promoter. p53 and RCC2 signaling is important for regulation of cell migration and suppression of metastasis. (PMID:28869598)
• RCC2 regulates apoptosis by blocking Rac1 signaling. RCC2 expression in tumor can be a useful marker for predicting chemotherapeutic response. (PMID:29321004)
• results suggest that combined exposure to CSE and PM2.5 induces LCPAT1 expression, which up-regulates autophagy, and promotes lung cancer progression via RCC2. (PMID:29913439)
• RCC2 promotes proliferation and radio-resistance in glioblastoma via activating transcription of DNMT1. (PMID:31277942)
• The mitotic regulator RCC2 promotes glucose metabolism through BACH1-dependent transcriptional upregulation of hexokinase II in glioma. (PMID:36116740)
• LncRNA HOTAIR enhances RCC2 to accelerate cervical cancer progression by sponging miR-331-3p. (PMID:36593385)
• RCC2 promotes prostate cancer cell proliferation and migration through Hh/GLI1 signaling pathway and cancer stem-like cells. (PMID:38008751)
• NudCL2 is required for cytokinesis by stabilizing RCC2 with Hsp90 at the midbody. (PMID:38801297)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rcc2	ENSDARG00000011510
mus_musculus	Rcc2	ENSMUSG00000040945
rattus_norvegicus	Rcc2	ENSRNOG00000006327
drosophila_melanogaster	CG9135	FBGN0031769

Paralogs (9): ALS2 (ENSG00000003393), HERC1 (ENSG00000103657), SERGEF (ENSG00000129158), RCBTB1 (ENSG00000136144), RCBTB2 (ENSG00000136161), RPGR (ENSG00000156313), RCCD1 (ENSG00000166965), RCC1 (ENSG00000180198), RCC1L (ENSG00000274523)

Protein

Protein identifiers

Protein RCC2 — Q9P258 (reviewed: Q9P258)

Alternative names: RCC1-like protein TD-60, Telophase disk protein of 60 kDa

All UniProt accessions (2): Q9P258, A0A024RAC5

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional protein that may affect its functions by regulating the activity of small GTPases, such as RAC1 and RALA. Required for normal progress through the cell cycle, both during interphase and during mitosis. Required for the presence of normal levels of MAD2L1, AURKB and BIRC5 on inner centromeres during mitosis, and for normal attachment of kinetochores to mitotic spindles. Required for normal organization of the microtubule cytoskeleton in interphase cells. Functions as guanine nucleotide exchange factor (GEF) for RALA. Interferes with the activation of RAC1 by guanine nucleotide exchange factors. Prevents accumulation of active, GTP-bound RAC1, and suppresses RAC1-mediated reorganization of the actin cytoskeleton and formation of membrane protrusions. Required for normal cellular responses to contacts with the extracellular matrix of adjacent cells, and for directional cell migration in response to a fibronectin gradient (in vitro).

Subunit / interactions. Interacts with RAC1. Interacts with nucleotide-free and with GDP and GTP-bound forms of RAC1, with a slight preference for GDP-bound RAC1. Binds preferentially to the nucleotide-free form of RAC1. Interacts with CORO1C. Interacts with microtubules.

Subcellular location. Nucleus. Nucleolus. Cytoplasm. Cytoskeleton. Chromosome. Centromere. Spindle. Midbody. Cell membrane.

Induction. Induced by TP53/p53 in response to oxidative stress and DNA damage.

RefSeq proteins (2): NP_001129676, NP_061185* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000408	Reg_chr_condens	Repeat
IPR009091	RCC1/BLIP-II	Homologous_superfamily
IPR028641	RCC2	Family
IPR058923	RCC1-like_dom	Domain

Pfam: PF25390

UniProt features (76 total): strand 35, modified residue 13, helix 9, repeat 7, region of interest 3, compositionally biased region 3, mutagenesis site 2, turn 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5GWN	X-RAY DIFFRACTION	1.31

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P258-F1	88.97	0.82

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 (13): 16, 20, 43, 44, 45, 46, 50, 51, 92, 124, 293, 342, 377

Mutagenesis-validated functional residues (2):

Position	Phenotype
318–325	loss of interaction with rac1.
439	loss of interaction with rac1 and loss of regulation of rac1 activation.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation

MSigDB gene sets: 306 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, RNGTGGGC_UNKNOWN, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, ACTACCT_MIR196A_MIR196B, CCAWYNNGAAR_UNKNOWN, NKX25_02, GOBP_NEGATIVE_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_CHROMOSOME_LOCALIZATION, GOBP_FOCAL_ADHESION_ASSEMBLY, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_RUFFLE_ASSEMBLY, GOBP_REGULATION_OF_FIBROBLAST_MIGRATION

GO Biological Process (13): integrin-mediated signaling pathway (GO:0007229), regulation of fibroblast migration (GO:0010762), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), regulation of cell migration (GO:0030334), negative regulation of GTPase activity (GO:0034260), establishment of protein localization (GO:0045184), focal adhesion assembly (GO:0048041), cell division (GO:0051301), negative regulation of focal adhesion assembly (GO:0051895), positive regulation of attachment of spindle microtubules to kinetochore (GO:0051987), chromosome passenger complex localization to kinetochore (GO:0072356), negative regulation of substrate adhesion-dependent cell spreading (GO:1900025), regulation of ruffle assembly (GO:1900027)

GO Molecular Function (7): RNA binding (GO:0003723), guanyl-nucleotide exchange factor activity (GO:0005085), microtubule binding (GO:0008017), protein kinase binding (GO:0019901), protein domain specific binding (GO:0019904), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (15): nucleolus (GO:0005730), cytosol (GO:0005829), microtubule (GO:0005874), plasma membrane (GO:0005886), midbody (GO:0030496), early endosome membrane (GO:0031901), chromosome, centromeric core domain (GO:0034506), mitotic spindle midzone (GO:1990023), chromosome, centromeric region (GO:0000775), nucleus (GO:0005634), chromosome (GO:0005694), cytoplasm (GO:0005737), spindle (GO:0005819), cytoskeleton (GO:0005856), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Mitotic Prometaphase	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
M Phase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	4
cellular anatomical structure	4
microtubule cytoskeleton	2
chromosomal region	2
cell surface receptor signaling pathway	1
fibroblast migration	1
regulation of cell migration	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G2/M phase transition	1
cell migration	1
regulation of cell motility	1
GTPase activity	1
regulation of GTPase activity	1
negative regulation of biological process	1
negative regulation of hydrolase activity	1
establishment of localization	1
cell-substrate junction assembly	1
cell-matrix adhesion	1
cellular process	1
negative regulation of cell-matrix adhesion	1
focal adhesion assembly	1
regulation of focal adhesion assembly	1
negative regulation of cell-substrate junction organization	1
negative regulation of cell junction assembly	1
attachment of spindle microtubules to kinetochore	1
positive regulation of chromosome segregation	1
regulation of attachment of spindle microtubules to kinetochore	1
protein-containing complex localization	1
protein localization to kinetochore	1
negative regulation of cell-substrate adhesion	1
substrate adhesion-dependent cell spreading	1
regulation of substrate adhesion-dependent cell spreading	1
ruffle assembly	1
regulation of plasma membrane bounded cell projection assembly	1
nucleic acid binding	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1

Protein interactions and networks

STRING

1878 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RCC2	AURKB	Q96GD4	959
RCC2	INCENP	Q9NQS7	943
RCC2	CDCA8	Q53HL2	901
RCC2	HASPIN	Q8TF76	778
RCC2	KIF2C	Q99661	633
RCC2	MAPRE1	Q15691	621
RCC2	PLK1	P53350	591
RCC2	CTTN	Q14247	547
RCC2	HCLS1	P14317	545
RCC2	CORO1C	Q9ULV4	542
RCC2	BUB1	O43683	534
RCC2	CENPA	P49450	491
RCC2	ZDHHC21	Q8IVQ6	491
RCC2	PDS5A	Q29RF7	489
RCC2	AURKA	O14965	478

IntAct

100 interactions, top by confidence:

A	B	Type	Score
FN1	ITGB1	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
VCP	UBXN8	psi-mi:“MI:0914”(association)	0.690
DEF6	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
UNC93B1	GPR89A	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Nedd1		psi-mi:“MI:0914”(association)	0.350
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Racgap1	DDX3X	psi-mi:“MI:0914”(association)	0.350
PHF8	MACROH2A1	psi-mi:“MI:0914”(association)	0.350
Sumo3	GABPB1	psi-mi:“MI:0914”(association)	0.350
INTS14	DKFZP586J0619	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
ORF69	PEPD	psi-mi:“MI:0914”(association)	0.350
VP24	PGRMC1	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
COQ2	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
COQ2	RSL1D1	psi-mi:“MI:0914”(association)	0.350
TNFAIP3	KIF5C	psi-mi:“MI:0914”(association)	0.350

BioGRID (310): RCC2 (Affinity Capture-MS), RCC2 (Affinity Capture-MS), RCC2 (Affinity Capture-MS), MARS (Co-fractionation), RCC2 (Co-fractionation), RCC2 (Co-fractionation), RCC2 (Co-fractionation), RCC2 (Co-fractionation), RCC2 (Co-fractionation), RCC2 (Affinity Capture-MS), RCC2 (Reconstituted Complex), RCC2 (Proximity Label-MS), RCC2 (Affinity Capture-MS), RCC2 (Affinity Capture-MS), RCC2 (Affinity Capture-MS)

ESM2 similar proteins: A0A3L7I2I8, A4IF63, A6QQY2, D2GXS7, D3ZQG6, F7H9X2, G3X9X1, O60733, O95199, P42694, P97570, P97819, Q2T9Z7, Q3UFS0, Q52KW8, Q59H18, Q5GIG6, Q5R8I6, Q5RCZ7, Q5U3Y0, Q5ZLD3, Q6AYI2, Q6DFV5, Q6NXM2, Q6NYE2, Q6P798, Q6PC62, Q6ZPT1, Q7TQP6, Q80TF4, Q8BK67, Q8IY47, Q8K0F1, Q8NDN9, Q8R5L3, Q8VEM9, Q92624, Q96I51, Q96JC1, Q99LJ7

Diamond homologs: A6NED2, D3ZGQ5, F1RD40, O75592, O95199, O95714, P0C5Y8, P18754, P23800, P25171, P25183, P58544, Q15034, Q15751, Q4R828, Q4U2R1, Q52KW8, Q5BIW4, Q5DX34, Q5GLZ8, Q5PQN1, Q5RCZ7, Q6NRS1, Q6NXM2, Q6NYE2, Q6PAV2, Q6ZPR6, Q7TPH6, Q7ZZC8, Q86SG6, Q8BK67, Q8BTU7, Q8IVU3, Q8K1R7, Q8K2J9, Q8NDN9, Q8SSY6, Q8TD19, Q8VE37, Q90XC2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 130 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
Ovarian tumor domain proteases	5	15.8×	4e-03
mRNA Splicing - Minor Pathway	5	12.7×	4e-03
Signaling by ALK fusions and activated point mutants	6	10.2×	4e-03
mRNA Splicing	6	7.5×	5e-03
CHD1 and CHD2 subfamily	6	7.4×	5e-03
RAC2 GTPase cycle	5	7.2×	9e-03
mRNA Polyadenylation	7	7.0×	4e-03
Processing of Capped Intron-Containing Pre-mRNA	7	6.5×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2448 predictions. Top by Δscore:

Variant	Effect	Δscore
1:17412115:AGCTT:A	donor_loss	1.0000
1:17412116:GCTTA:G	donor_loss	1.0000
1:17412117:CTTAC:C	donor_loss	1.0000
1:17412118:TTA:T	donor_loss	1.0000
1:17412120:A:AC	donor_gain	1.0000
1:17412120:ACCA:A	donor_loss	1.0000
1:17412121:C:A	donor_loss	1.0000
1:17412121:C:CC	donor_gain	1.0000
1:17413536:CCCA:C	donor_gain	1.0000
1:17413539:A:AC	donor_gain	1.0000
1:17413540:C:CC	donor_gain	1.0000
1:17413540:CTTCA:C	donor_gain	1.0000
1:17413542:T:TA	donor_gain	1.0000
1:17413595:C:CA	donor_gain	1.0000
1:17413637:AT:A	donor_gain	1.0000
1:17413638:T:TA	donor_gain	1.0000
1:17413713:ACCAG:A	acceptor_gain	1.0000
1:17413714:CCAG:C	acceptor_gain	1.0000
1:17413714:CCAGC:C	acceptor_gain	1.0000
1:17413715:CAG:C	acceptor_gain	1.0000
1:17413715:CAGC:C	acceptor_gain	1.0000
1:17413716:AG:A	acceptor_gain	1.0000
1:17413716:AGC:A	acceptor_loss	1.0000
1:17413717:GC:G	acceptor_loss	1.0000
1:17413718:C:CA	acceptor_loss	1.0000
1:17413718:C:CC	acceptor_gain	1.0000
1:17416476:TCA:T	donor_loss	1.0000
1:17416477:CAC:C	donor_loss	1.0000
1:17416478:A:AC	donor_gain	1.0000
1:17416479:C:CC	donor_gain	1.0000

AlphaMissense

3387 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:17409185:C:G	G492R	1.000
1:17410014:G:T	A475D	1.000
1:17410028:C:A	K470N	1.000
1:17410028:C:G	K470N	1.000
1:17410044:C:T	G465E	1.000
1:17410050:C:T	G463D	1.000
1:17410051:C:G	G463R	1.000
1:17412123:A:G	L462P	1.000
1:17412129:C:A	G460V	1.000
1:17412129:C:T	G460E	1.000
1:17412130:C:A	G460W	1.000
1:17412130:C:G	G460R	1.000
1:17412130:C:T	G460R	1.000
1:17412147:C:A	G454V	1.000
1:17412147:C:T	G454D	1.000
1:17412148:C:G	G454R	1.000
1:17412151:A:G	W453R	1.000
1:17412151:A:T	W453R	1.000
1:17412152:G:C	S452R	1.000
1:17412152:G:T	S452R	1.000
1:17412154:T:G	S452R	1.000
1:17412156:A:T	I451N	1.000
1:17412185:G:C	S441R	1.000
1:17412185:G:T	S441R	1.000
1:17412187:T:G	S441R	1.000
1:17413098:A:G	W430R	1.000
1:17413098:A:T	W430R	1.000
1:17413106:A:G	L427P	1.000
1:17413120:T:A	K422N	1.000
1:17413120:T:G	K422N	1.000

dbSNP variants (sampled 300 via entrez): RS1000120645 (1:17425498 G>A,C), RS1000238836 (1:17410356 A>G), RS1000279124 (1:17436705 A>G), RS1000365810 (1:17416227 G>C), RS1000398257 (1:17439807 T>C), RS1000452262 (1:17439916 G>A,C), RS1000458663 (1:17409991 C>A), RS1000465446 (1:17408148 C>A,T), RS1000534331 (1:17421768 G>A), RS1000552759 (1:17418111 A>G), RS1000561355 (1:17437468 G>A), RS1000631203 (1:17436396 CGA>C), RS1000722851 (1:17426635 C>T), RS1000727564 (1:17408784 AAACTT>A), RS1000790161 (1:17441305 T>C)

Disease associations

OMIM: gene MIM:609587 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000249_1	Basal cell carcinoma	4.000000e-12
GCST002331_3	Basal cell carcinoma	7.000000e-14
GCST002842_1	Basal cell carcinoma	8.000000e-17
GCST003726_7	Basal cell carcinoma	1.000000e-23
GCST005896_24	Non-melanoma skin cancer	1.000000e-24
GCST90013410_1	Basal cell carcinoma	9.000000e-61

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009260	non-melanoma skin carcinoma

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725142 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.61	Kd	2435	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 11 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179164: Binding affinity against RCC2 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	2.4350	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Valproic Acid	affects expression, decreases expression	4
Arsenic	increases expression, affects methylation, affects cotreatment, decreases expression, increases abundance	3
Benzo(a)pyrene	increases expression, affects methylation, decreases methylation	3
Particulate Matter	increases abundance, increases expression, affects cotreatment	3
trichostatin A	affects expression, decreases expression	2
Aflatoxin B1	affects expression, increases expression	2
Cadmium Chloride	increases abundance, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, decreases expression, affects cotreatment	1
decabromobiphenyl ether	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
nutlin 3	increases secretion, affects cotreatment	1
belinostat	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652253	Binding	Binding affinity to human RCC2 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

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TI66	HAP1 RCC2 (-) 1	Cancer cell line	Male
CVCL_TI67	HAP1 RCC2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer