MCC

Summary

MCC (MCC regulator of Wnt signaling pathway, HGNC:6935) is a protein-coding gene on chromosome 5q22.2, encoding Colorectal mutant cancer protein (P23508). Candidate for the putative colorectal tumor suppressor gene located at 5q21.

This gene is a candidate colorectal tumor suppressor gene that is thought to negatively regulate cell cycle progression. The orthologous gene in the mouse expresses a phosphoprotein associated with the plasma membrane and membrane organelles, and overexpression of the mouse protein inhibits entry into S phase. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4163 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 289 total — 2 pathogenic
• Phenotypes (HPO): 8
• MANE Select transcript: NM_001085377

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6935
Approved symbol	MCC
Name	MCC regulator of Wnt signaling pathway
Location	5q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000171444
Ensembl biotype	protein_coding
OMIM	159350
Entrez	4163

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000302475, ENST00000408903, ENST00000502648, ENST00000505604, ENST00000506605, ENST00000511242, ENST00000511847, ENST00000514701, ENST00000515367, ENST00000624689

RefSeq mRNA: 2 — MANE Select: NM_001085377 NM_001085377, NM_002387

CCDS: CCDS4111, CCDS43351

Canonical transcript exons

ENST00000408903 — 19 exons

Exon	Start	End
ENSE00001261081	113022106	113027482
ENSE00001565862	113384968	113385212
ENSE00001573959	113488245	113488453
ENSE00001589188	113028934	113029056
ENSE00002241324	113043530	113043630
ENSE00002272605	113049093	113049299
ENSE00002277001	113340519	113340730
ENSE00003538361	113151309	113151422
ENSE00003556906	113122684	113122826
ENSE00003570818	113143218	113143360
ENSE00003626540	113063984	113064167
ENSE00003685314	113104192	113104355
ENSE00003755652	113053725	113053959
ENSE00003757438	113101739	113101945
ENSE00003758153	113068080	113068183
ENSE00003758570	113085164	113085310
ENSE00003760122	113082860	113083008
ENSE00003760190	113084101	113084190
ENSE00003760293	113071094	113071234

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 96.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.0264 / max 400.9770, expressed in 1450 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62980	5.9252	1300
62984	1.5038	835
62973	0.4752	118
62976	0.3359	134
62979	0.1881	71
62978	0.1826	70
62974	0.1392	52
62977	0.0710	17
62971	0.0699	23
62972	0.0685	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	96.28	gold quality
gingiva	UBERON:0001828	94.95	gold quality
sural nerve	UBERON:0015488	94.81	gold quality
skin of hip	UBERON:0001554	94.21	gold quality
left ovary	UBERON:0002119	94.16	gold quality
germinal epithelium of ovary	UBERON:0001304	93.98	gold quality
upper leg skin	UBERON:0004262	92.92	gold quality
pigmented layer of retina	UBERON:0001782	92.69	gold quality
retina	UBERON:0000966	92.67	gold quality
endothelial cell	CL:0000115	92.02	gold quality
ovary	UBERON:0000992	91.97	gold quality
seminal vesicle	UBERON:0000998	91.68	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.51	gold quality
right ovary	UBERON:0002118	90.78	gold quality
parietal pleura	UBERON:0002400	90.52	gold quality
esophagus squamous epithelium	UBERON:0006920	89.34	gold quality
pleura	UBERON:0000977	88.37	gold quality
substantia nigra pars compacta	UBERON:0001965	88.27	gold quality
calcaneal tendon	UBERON:0003701	87.71	gold quality
decidua	UBERON:0002450	87.70	gold quality
epithelium of esophagus	UBERON:0001976	87.67	gold quality
squamous epithelium	UBERON:0006914	87.43	gold quality
heart right ventricle	UBERON:0002080	87.37	gold quality
urethra	UBERON:0000057	87.36	gold quality
stromal cell of endometrium	CL:0002255	87.08	gold quality
mammalian vulva	UBERON:0000997	86.43	gold quality
endometrium	UBERON:0001295	86.27	gold quality
endocervix	UBERON:0000458	86.14	gold quality
tibia	UBERON:0000979	85.96	gold quality
urinary bladder	UBERON:0001255	85.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	301.92
E-GEOD-81608	yes	4.65
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

246 targeting MCC, 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-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-373-5P	99.98	75.36	4753

Literature-anchored findings (GeneRIF, showing 16)

• MCC is a nuclear, beta-catenin-interacting protein that can act as a potential tumor suppressor in the serrated colorectal cancer pathway by inhibiting Wnt/beta-catenin signal transduction. (PMID:18591935)
• Results identify MCC as a potential scaffold protein regulating cell movement and able to bind Scrib, beta-catenin and NHERF1/2. (PMID:19555689)
• observed a significant association of the rs11283943 SNP with increased breast cancer risk in an Indian population (PMID:21279955)
• Promoter methylated MCC is associated with inflammatory bowel disease in colorectal cancer. (PMID:22213290)
• MCC regulates lamellipodia formation by binding to Scrib and its downstream partner Myosin-IIB in a multiprotein complex. (PMID:22480440)
• we have shown that promoter methylation of the APC gene does not extend to the neighbouring MCC gene in lung cancer, but LOH is found at both loci. (PMID:22542170)
• targeted by miR-494, which is overexpressed in hepatocellular carcinoma (PMID:23913442)
• cytoplasmic MCC-DBC1 interaction sequesters DBC1 away from the nucleus, thereby removing a brake on DBC1 nuclear targets, such as SIRT1 (PMID:24824780)
• Our results indicate that in sharp contrast to its tumor suppressive role in colorectal cancer, MCC functions as an oncogene in B cells (PMID:25200342)
• Alterations (deletion/methylation/mutation/expression) of MCC and CTNNBIP1 were analyzed in breast cancer patients (N=120) followed by expression/mutation analysis of beta-catenin. The alterations of MCC/CTNNBIP1 showed significant correlation with increased nuclear beta-catenin/p-beta-catenin(Y654) expression. (PMID:27208794)
• MCC might confer alterative genetic susceptibility to colorectal cancer in individuals with schizophrenia promising to shed more light on the relationship between schizophrenia and cancer progression. (PMID:27226254)
• Significantly, miR-4260 was increased in human colorectal cancer tissues with simultaneous downregulation of MCC and SMAD4. (PMID:28638476)
• Study described a novel tumor suppressor function of MCC in the regulation of E-cadherin mediated cell-cell adhesion in colorectal cancer cells. (PMID:29035389)
• Data suggest that millisecond dynamic changes in PDZ1 domain conformation are responsible for higher affinity of scribble PDZ1 for phosphorylated ligands; oligopeptide fragments of RPS6KA2 and MCC were used as ligands in these nuclear magnetic resonance chemical shift experiments. (RPS6KA2 = ribosomal protein S6 kinase 2; MCC = mutated in colorectal cancer protein) (PMID:29144123)
• This study provided new evidence of epistatic association of VAMP5 and MCC with increased risk of Hirschsprung disease (PMID:29695640)
• Two germline mutations can serve as genetic susceptibility screening makers for a lung adenocarcinoma family. (PMID:36781503)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mcc	ENSDARG00000105237
mus_musculus	Mcc	ENSMUSG00000071856
rattus_norvegicus	Mcc	ENSRNOG00000011271
drosophila_melanogaster	CG34404	FBGN0085433

Paralogs (1): USHBP1 (ENSG00000130307)

Protein

Protein identifiers

Colorectal mutant cancer protein — P23508 (reviewed: P23508)

All UniProt accessions (4): A0A096LNU0, A0A096LPB3, D6REY2, P23508

UniProt curated annotations — full annotation on UniProt →

Function. Candidate for the putative colorectal tumor suppressor gene located at 5q21. Suppresses cell proliferation and the Wnt/b-catenin pathway in colorectal cancer cells. Inhibits DNA binding of b-catenin/TCF/LEF transcription factors. Involved in cell migration independently of RAC1, CDC42 and p21-activated kinase (PAK) activation. Represses the beta-catenin pathway (canonical Wnt signaling pathway) in a CCAR2-dependent manner by sequestering CCAR2 to the cytoplasm, thereby impairing its ability to inhibit SIRT1 which is involved in the deacetylation and negative regulation of beta-catenin (CTNB1) transcriptional activity.

Subunit / interactions. Interacts with SCRIB (via phosphorylated PDZ-binding motif), EZR, SNX27, NHERF1 and NHERF2. Interacts with CTNNB1; the interaction is enhanced upon Wnt stimulation. Interacts with MYH10. Interacts with CCAR2.

Subcellular location. Cell membrane. Cell projection. Lamellipodium. Nucleus. Cytoplasm.

Tissue specificity. Expressed in a variety of tissues.

Similarity. Belongs to the MCC family.

Isoforms (2)

UniProt ID	Names	Canonical?
P23508-1	1	yes
P23508-2	2

RefSeq proteins (2): NP_001078846, NP_002378 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019536	USHBP1_PDZ-bd	Domain
IPR040171	USBP1-like	Family

Pfam: PF10506

UniProt features (24 total): sequence variant 8, region of interest 3, compositionally biased region 3, mutagenesis site 2, sequence conflict 2, short sequence motif 2, chain 1, splice variant 1, strand 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6MTU	X-RAY DIFFRACTION	2.14
6MTV	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23508-F1	75.24	0.36

Functional residue map

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

Post-translational modifications (1): 828

Mutagenesis-validated functional residues (2):

Position	Phenotype
828	reduced binding to scrib.
828	higher membrane localization, reduced formation of lamellipodia, accumulation of myh10 at the cell cortex.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 238 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, FREAC2_01, HNF3ALPHA_Q6, RORA1_01, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_REGULATION_OF_EPITHELIAL_CELL_MIGRATION, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, CHANDRAN_METASTASIS_DN, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, CADWELL_ATG16L1_TARGETS_DN, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_MIGRATION

GO Biological Process (6): signal transduction (GO:0007165), negative regulation of epithelial cell migration (GO:0010633), Wnt signaling pathway (GO:0016055), establishment of protein localization (GO:0045184), negative regulation of epithelial cell proliferation (GO:0050680), negative regulation of canonical Wnt signaling pathway (GO:0090090)

GO Molecular Function (3): signaling receptor activity (GO:0038023), calcium ion binding (GO:0005509), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), lamellipodium (GO:0030027), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
epithelial cell migration	1
regulation of epithelial cell migration	1
negative regulation of cell migration	1
negative regulation of multicellular organismal process	1
cell surface receptor signaling pathway	1
establishment of localization	1
negative regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
molecular transducer activity	1
metal ion binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
cell leading edge	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1667 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MCC	MCCC1	Q96RQ3	917
MCC	MCCC2	Q9HCC0	904
MCC	E9PNW1	E9PNW1	694
MCC	PCCA	P05165	594
MCC	TBL1X	O60907	450
MCC	NWD2	Q9ULI1	444
MCC	SCML4	Q8N228	438
MCC	TBL1XR1	Q9BZK7	438
MCC	USHBP1	Q8N6Y0	414
MCC	PXYLP1	Q8TE99	399
MCC	NEK10	Q6ZWH5	395
MCC	TSC22D2	O75157	390
MCC	AP5M1	Q9H0R1	378
MCC	ATAD2B	Q9ULI0	374
MCC	DRICH1	Q6PGQ1	370

IntAct

616 interactions, top by confidence:

A	B	Type	Score
MCC		psi-mi:“MI:0915”(physical association)	0.000
MCC	MYH10	psi-mi:“MI:0915”(physical association)	0.000
MCC	RASAL2	psi-mi:“MI:0915”(physical association)	0.000
MCC	NASP	psi-mi:“MI:0915”(physical association)	0.000
MCC	PFAS	psi-mi:“MI:0915”(physical association)	0.000
MCC	MSH2	psi-mi:“MI:0915”(physical association)	0.000
MCC	RRM1	psi-mi:“MI:0915”(physical association)	0.000
MCC	DDX21	psi-mi:“MI:0915”(physical association)	0.000
MCC	RAB7A	psi-mi:“MI:0915”(physical association)	0.000
MCC	GNB1	psi-mi:“MI:0915”(physical association)	0.000
MCC	PNPT1	psi-mi:“MI:0915”(physical association)	0.000
MCC	MYL12A	psi-mi:“MI:0915”(physical association)	0.000
MCC	PPP2CB	psi-mi:“MI:0915”(physical association)	0.000
MCC	RPS6KA3	psi-mi:“MI:0915”(physical association)	0.000
MCC	PSMA1	psi-mi:“MI:0915”(physical association)	0.000
MCC	SDHB	psi-mi:“MI:0915”(physical association)	0.000
MCC	MCM4	psi-mi:“MI:0915”(physical association)	0.000
MCC	MAPRE1	psi-mi:“MI:0915”(physical association)	0.000
MCC	APEX1	psi-mi:“MI:0915”(physical association)	0.000
MCC	NPM1	psi-mi:“MI:0915”(physical association)	0.000
MCC	FABP5	psi-mi:“MI:0915”(physical association)	0.000
MCC	EIF4G1	psi-mi:“MI:0915”(physical association)	0.000
MCC	CLIC4	psi-mi:“MI:0915”(physical association)	0.000
MCC	BCAS2	psi-mi:“MI:0915”(physical association)	0.000
MCC	EIF3A	psi-mi:“MI:0915”(physical association)	0.000
MCC	AHCY	psi-mi:“MI:0915”(physical association)	0.000
MCC	CRYZ	psi-mi:“MI:0915”(physical association)	0.000
MCC	NUDT21	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (249): MCC (Affinity Capture-MS), MCC (Affinity Capture-MS), MCC (Affinity Capture-MS), MCC (Affinity Capture-MS), MCC (Affinity Capture-MS), MCC (Affinity Capture-MS), MCC (Affinity Capture-MS), MCC (Affinity Capture-MS), MCC (Affinity Capture-MS), MCC (Affinity Capture-MS), MCC (Two-hybrid), CLTC (Affinity Capture-MS), STRN (Affinity Capture-MS), STK24 (Affinity Capture-MS), STRN3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GUX5, A0A1L8GXY6, A2AM05, A6QR54, A9UM82, B3DLE8, O08970, O75334, O75335, P0CAP1, P0DO97, P23508, P27628, P97434, Q08DR9, Q0VF96, Q15007, Q3SWS9, Q3UIJ9, Q4KLT6, Q4V7D3, Q5BIX7, Q5EB94, Q5M775, Q5R923, Q5VZ66, Q6AW69, Q6NRW2, Q6P4K5, Q6PD31, Q6WCQ1, Q7YS99, Q80Y83, Q861Q8, Q8BSS9, Q8BVL9, Q8CDI6, Q8K3K8, Q8R2H7, Q8R5M4

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ATR	“up-regulates activity”	MCC	phosphorylation
PRKDC	“up-regulates activity”	MCC	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 190 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
Orc1 removal from chromatin	14	15.0×	3e-10
Cytosolic tRNA aminoacylation	5	13.2×	5e-04
Ubiquitin-dependent degradation of Cyclin D	8	12.7×	1e-05
SCF(Skp2)-mediated degradation of p27/p21	10	12.4×	1e-06
NIK–>noncanonical NF-kB signaling	9	12.3×	7e-06
AUF1 (hnRNP D0) binds and destabilizes mRNA	8	11.9×	2e-05
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis	8	11.9×	2e-05
GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2	8	11.9×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
regulation of DNA-templated DNA replication initiation	5	28.5×	3e-04
translational initiation	7	13.6×	3e-04
DNA replication	8	7.1×	4e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	14	4.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	241
Likely benign	11
Benign	7

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
14202	NM_001085377.2(MCC):c.2663C>T (p.Ala888Val)	Pathogenic
14203	NM_001085377.2(MCC):c.2087G>A (p.Arg696Gln)	Pathogenic

SpliceAI

5704 predictions. Top by Δscore:

Variant	Effect	Δscore
5:113028928:TTTTA:T	donor_loss	1.0000
5:113028929:TTTAC:T	donor_loss	1.0000
5:113028930:TTACC:T	donor_loss	1.0000
5:113028931:TACC:T	donor_loss	1.0000
5:113028932:ACCT:A	donor_loss	1.0000
5:113029055:CT:C	acceptor_gain	1.0000
5:113029062:T:TC	acceptor_gain	1.0000
5:113049087:CCCTA:C	donor_loss	1.0000
5:113049088:CCTAC:C	donor_loss	1.0000
5:113049089:CTACC:C	donor_loss	1.0000
5:113049090:TACC:T	donor_loss	1.0000
5:113049091:ACCT:A	donor_loss	1.0000
5:113049295:TCCTC:T	acceptor_gain	1.0000
5:113049296:CCTCC:C	acceptor_gain	1.0000
5:113049298:TC:T	acceptor_gain	1.0000
5:113049299:CC:C	acceptor_gain	1.0000
5:113049300:C:CC	acceptor_gain	1.0000
5:113053723:A:AC	donor_gain	1.0000
5:113053724:C:A	donor_loss	1.0000
5:113053724:C:CC	donor_gain	1.0000
5:113053960:C:CC	acceptor_gain	1.0000
5:113063978:CATTA:C	donor_loss	1.0000
5:113063979:ATTAC:A	donor_loss	1.0000
5:113063980:TTACC:T	donor_loss	1.0000
5:113063981:TACCT:T	donor_loss	1.0000
5:113063982:ACC:A	donor_loss	1.0000
5:113064165:CTC:C	acceptor_gain	1.0000
5:113064167:CC:C	acceptor_loss	1.0000
5:113064167:CCTA:C	acceptor_gain	1.0000
5:113064168:CT:C	acceptor_loss	1.0000

AlphaMissense

6743 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:113027477:A:G	L772P	1.000
5:113028941:C:G	A768P	1.000
5:113028949:A:G	L765P	1.000
5:113049178:A:G	L667P	1.000
5:113053733:C:G	A624P	1.000
5:113053738:A:G	L622P	1.000
5:113053744:T:G	Q620P	1.000
5:113053750:A:G	L618P	1.000
5:113053757:C:G	A616P	1.000
5:113053876:A:G	L576P	1.000
5:113053897:A:G	L569P	1.000
5:113071199:A:G	L417P	1.000
5:113071202:A:G	L416P	1.000
5:113071220:A:G	L410P	1.000
5:113082866:A:G	L403P	1.000
5:113082869:C:G	R402P	1.000
5:113082983:A:G	L364P	1.000
5:113143257:A:G	L92P	1.000
5:113143278:A:G	L85P	1.000
5:113027369:A:G	L808P	0.999
5:113027457:C:G	A779P	0.999
5:113027469:C:G	A775P	0.999
5:113029024:A:G	L740P	0.999
5:113049235:A:G	L648P	0.999
5:113049278:C:G	A634P	0.999
5:113049290:C:G	A630P	0.999
5:113053725:C:A	K626N	0.999
5:113053725:C:G	K626N	0.999
5:113053741:T:A	E621V	0.999
5:113053741:T:G	E621A	0.999

dbSNP variants (sampled 300 via entrez): RS1000004380 (5:113310917 C>T), RS1000009302 (5:113217191 A>G,T), RS1000033895 (5:113323220 G>A,C), RS1000036338 (5:113394822 C>A,G), RS1000039762 (5:113248376 G>A), RS1000040293 (5:113360213 G>A), RS1000041399 (5:113073504 A>C), RS1000042289 (5:113386064 A>C), RS1000046542 (5:113031641 C>G), RS1000051007 (5:113123995 T>C), RS1000055458 (5:113470039 T>A), RS1000059703 (5:113231485 C>G), RS1000073024 (5:113437582 A>G), RS1000075358 (5:113477585 A>G), RS1000076345 (5:113376366 G>T)

Disease associations

OMIM: gene MIM:159350 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): colon carcinoma (MONDO:0002032), prostate cancer (MONDO:0008315)

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

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0002891	Uterine leiomyosarcoma
HP:0003003	Colon cancer
HP:0005584	Renal cell carcinoma
HP:0006716	Hereditary nonpolyposis colorectal carcinoma
HP:0006740	Transitional cell carcinoma of the bladder
HP:0006753	Neoplasm of the stomach

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000636_1	Brain cytoarchitecture	2.000000e-06
GCST002588_4	Cerebral amyloid angiopathy	7.000000e-06
GCST008477_23	Emphysema annual change measurement in smokers (adjusted lung density)	9.000000e-06
GCST008830_15	Neurofibrillary tangles	5.000000e-06
GCST008839_413	Height	8.000000e-14
GCST009391_1267	Metabolite levels	6.000000e-06
GCST010105_169	Nicotine dependence symptom count	6.000000e-06
GCST010105_72	Nicotine dependence symptom count	6.000000e-06
GCST010244_114	Triglyceride levels	9.000000e-09
GCST010988_338	Adult body size	3.000000e-09
GCST012490_201	Femur bone mineral density x serum urate levels interaction	1.000000e-09
GCST012490_57	Femur bone mineral density x serum urate levels interaction	3.000000e-11
GCST90020029_1272	Waist circumference adjusted for body mass index	1.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006913	prefrontal cortex cytoarchtiectural measurement
EFO:0007626	emphysema imaging measurement
EFO:0006797	neurofibrillary tangles measurement
EFO:0010545	uridine diphosphate measurement
EFO:0009262	nicotine dependence symptom count
EFO:0004530	triglyceride measurement
EFO:0004531	urate measurement
EFO:0007789	BMI-adjusted waist circumference

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: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects cotreatment	7
methylmercuric chloride	increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
triphenyl phosphate	affects expression, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
lead acetate	affects cotreatment, decreases expression	1
afimoxifene	decreases expression, decreases reaction	1
chromous chloride	affects cotreatment, decreases expression	1
chromic oxide	affects cotreatment, decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	increases methylation	1
cupric chloride	decreases expression	1
nickel sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01169220	PHASE4	COMPLETED	Bowel Preparation for Inpatient Colonoscopy
NCT01170754	PHASE4	COMPLETED	Miralax (PEG 3350) vs. Golytely as Bowel Preparation for Screening Colonoscopy
NCT02052557	PHASE4	COMPLETED	The Effect of Exparel on Post Operative Pain and Narcotic Use After Colon Surgery
NCT02078726	PHASE4	COMPLETED	Glucagon Use in Colonoscopies
NCT02231203	PHASE4	COMPLETED	Effect of Omega-3 Fatty Acids on the Perioperative Immune Response and Erythrocyte Function
NCT02314871	PHASE4	COMPLETED	Effects of Different Types of Perioperative Analgesia on Minimal Residual Disease Development After Colon Cancer Surgery
NCT02746432	PHASE4	UNKNOWN	Insulin Therapy Reduce Post-Operative Inflammatory Response After Curative Colorectal Cancer Resection: Randomization Controlled Trial
NCT02887365	PHASE4	UNKNOWN	A Phase II Study of Tegafur-Uracil as Maintenance Chemotherapy in Patients With Stage II of Colon Cancer
NCT02937506	PHASE4	COMPLETED	Patient Satisfaction With Propofol for Out Patient Colonoscopy
NCT02958566	PHASE4	UNKNOWN	Multimodal Narcotic Limited Perioperative Pain Control With Colorectal Surgery
NCT04269369	PHASE4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT04311099	PHASE4	COMPLETED	Optimal Peripheral Nerve Block After Minimally Invasive Colon Surgery
NCT04709770	PHASE4	UNKNOWN	Low-volume vs High-volume Polyethylene Glycol Based Bowel Preparation for Colonoscopy in People Receiving Hemodialysis
NCT05250648	PHASE4	RECRUITING	Clinical Trial on HIPEC With Mitomycin C in Colon Cancer Peritoneal Metastases (GECOP-MMC)
NCT00002968	PHASE3	COMPLETED	Edrecolomab in Treating Patients With Stage II Colon Cancer
NCT00003835	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Stage III Colon Cancer
NCT00003873	PHASE3	COMPLETED	Fluorouracil With or Without Eniluracil in Treating Patients With Advanced Colorectal Cancer
NCT00004931	PHASE3	COMPLETED	Fluorouracil Plus Leucovorin With or Without Oxaliplatin in Treating Patients With Stage II or Stage III Colon Cancer
NCT00005036	PHASE3	COMPLETED	Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer
NCT00005094	PHASE3	COMPLETED	Celecoxib to Prevent Colorectal Cancer in Patients Who Have Undergone Surgery to Remove Polyps
NCT00025337	PHASE3	COMPLETED	Combination Chemotherapy With or Without Bevacizumab Compared With Bevacizumab Alone in Treating Patients With Advanced or Metastatic Colorectal Cancer That Has Been Previously Treated
NCT00070122	PHASE3	TERMINATED	Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer
NCT00079274	PHASE3	COMPLETED	Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer
NCT00096278	PHASE3	COMPLETED	Fluorouracil, Leucovorin, and Oxaliplatin With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II or Stage III Colon Cancer
NCT00188305	PHASE3	COMPLETED	A Randomized Trial of Cancer Risk and Health Education in Relatives of Colorectal Cancer Patients
NCT00195585	PHASE3	COMPLETED	Study Evaluating Isovorin in Colon Cancer
NCT00217737	PHASE3	ACTIVE_NOT_RECRUITING	Oxaliplatin, Leucovorin, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer
NCT00230646	PHASE3	COMPLETED	Promoting Physical Activity After Colorectal Cancer
NCT00309530	PHASE3	COMPLETED	Randomized Study on Adjuvant Chemotherapy and Adjuvant Chemo-Immunotherapy in Colon Carcinoma Dukes C
NCT00309543	PHASE3	COMPLETED	Randomized Trial on Adjuvant Chemotherapy in Colon Carcinoma Dukes B
NCT00337389	PHASE3	UNKNOWN	Phase III Randomized Study of 5-FU, CoFactor, and Avastin vs. 5-FU, LV and Avastin for First-Line Colorectal Cancer.
NCT00467922	PHASE3	COMPLETED	An Assessment of Goal-Directed Intraoperative Fluid Management in Hand Assisted Laparoscopic Colectomy
NCT00499369	PHASE3	TERMINATED	Irinotecan and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer That Progressed During First-Line Therapy
NCT00509444	PHASE3	COMPLETED	Cancer Prevention and Treatment Among African American Older Adults: Treatment Trial
NCT00646607	PHASE3	COMPLETED	FOLFOX-4 3months Versus 6 Months and Bevacizumab as Adjuvant Therapy for Patients With Stage II/III Colon Cancer
NCT00687830	PHASE3	COMPLETED	Efficacy of Morning-only Bowel Preparation for Afternoon Colonoscopy.
NCT00756548	PHASE3	COMPLETED	BLI850-302: BLI850 vs an Approved Active Control Bowel Preparation in Adult Subjects Undergoing Colonoscopy
NCT00756977	PHASE3	COMPLETED	BLI850 vs an Active Control Bowel Preparation in Adult Subjects Undergoing Colonoscopy
NCT00894725	PHASE3	COMPLETED	Laparoscopic Versus Open Left Colonic Resection
NCT00911170	PHASE3	COMPLETED	PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study