CBY1

Summary

CBY1 (chibby 1, beta catenin antagonist, HGNC:1307) is a protein-coding gene on chromosome 22q13.1, encoding Protein chibby homolog 1 (Q9Y3M2). Inhibits the Wnt/Wingless pathway by binding to CTNNB1/beta-catenin and inhibiting beta-catenin-mediated transcriptional activation through competition with TCF/LEF transcription factors.

Beta-catenin is a transcriptional activator and oncoprotein involved in the development of several cancers. The protein encoded by this gene interacts directly with the C-terminal region of beta-catenin, inhibiting oncogenic beta-catenin-mediated transcriptional activation by competing with transcription factors for binding to beta-catenin. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 25776 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 16 total — 2 pathogenic
• Phenotypes (HPO): 37
• MANE Select transcript: NM_015373

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1307
Approved symbol	CBY1
Name	chibby 1, beta catenin antagonist
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	PIGEA14, PIGEA-14, Chibby, Cby, Chibby1
Ensembl gene	ENSG00000100211
Ensembl biotype	protein_coding
OMIM	607757
Entrez	25776

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 37 protein_coding, 6 retained_intron

ENST00000216029, ENST00000396811, ENST00000411557, ENST00000416285, ENST00000467118, ENST00000475924, ENST00000485501, ENST00000489847, ENST00000492537, ENST00000492576, ENST00000867938, ENST00000867939, ENST00000867940, ENST00000867941, ENST00000867942, ENST00000867943, ENST00000867944, ENST00000867945, ENST00000867946, ENST00000867947, ENST00000867948, ENST00000867949, ENST00000867950, ENST00000867951, ENST00000867952, ENST00000867953, ENST00000867954, ENST00000867955, ENST00000930716, ENST00000930717, ENST00000930719, ENST00000930720, ENST00000930722, ENST00000930723, ENST00000930724, ENST00000930725, ENST00000953583, ENST00000953584, ENST00000953585, ENST00000953586, ENST00000953587, ENST00000953588, ENST00000953589

RefSeq mRNA: 2 — MANE Select: NM_015373 NM_001002880, NM_015373

CCDS: CCDS13974

Canonical transcript exons

ENST00000216029 — 5 exons

Exon	Start	End
ENSE00001109354	38656638	38656750
ENSE00001840725	38673159	38673850
ENSE00003468095	38668017	38668132
ENSE00003787248	38671070	38671188
ENSE00003790753	38670884	38670989

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 96.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3861 / max 132.9588, expressed in 1738 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192261	13.3861	1738

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	96.73	gold quality
secondary oocyte	CL:0000655	95.89	gold quality
right uterine tube	UBERON:0001302	95.59	gold quality
tendon of biceps brachii	UBERON:0008188	94.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.66	gold quality
lower esophagus	UBERON:0013473	94.64	gold quality
epithelium of bronchus	UBERON:0002031	94.44	gold quality
bronchial epithelial cell	CL:0002328	94.42	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.35	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.29	gold quality
apex of heart	UBERON:0002098	94.19	gold quality
bronchus	UBERON:0002185	94.16	gold quality
ventricular zone	UBERON:0003053	93.97	gold quality
right atrium auricular region	UBERON:0006631	93.79	gold quality
right coronary artery	UBERON:0001625	93.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.47	gold quality
right adrenal gland cortex	UBERON:0035827	93.40	gold quality
right adrenal gland	UBERON:0001233	93.31	gold quality
left adrenal gland cortex	UBERON:0035825	93.23	gold quality
cardiac atrium	UBERON:0002081	93.21	gold quality
left adrenal gland	UBERON:0001234	93.16	gold quality
popliteal artery	UBERON:0002250	93.13	gold quality
tibial artery	UBERON:0007610	93.12	gold quality
heart left ventricle	UBERON:0002084	93.01	gold quality
left coronary artery	UBERON:0001626	93.00	gold quality
adrenal cortex	UBERON:0001235	92.94	gold quality
adenohypophysis	UBERON:0002196	92.94	gold quality
endocervix	UBERON:0000458	92.89	gold quality
left ovary	UBERON:0002119	92.82	gold quality
cardiac ventricle	UBERON:0002082	92.79	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.93
E-ENAD-20	no	73.02

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A

miRNA regulators (miRDB)

31 targeting CBY1, 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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-562	97.66	65.63	698
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-5189-3P	97.52	66.33	487
HSA-MIR-4314	97.50	67.30	1369

Literature-anchored findings (GeneRIF, showing 27)

• Chibby inhibits beta-catenin-mediated transcriptional activation by competing with Lef-1 to bind to beta-catenin (PMID:12712206)
• PIGEA-14 plays an important role in regulating the intracellular location of polycystin-2 (PMID:15194699)
• As no somatic mutation was detected in C22orf2 in 36 colorectal tumour DNA, our results do not support the implication of Chibby as a tumour suppressor in colorectal carcinogenesis. (PMID:15245581)
• Chibby is not likely to promote colorectal carcinoma tumor development or progression. (PMID:16570344)
• CBY promotes adipocyte differentiation through inhibition of beta catenin signaling. (PMID:17403895)
• intrinsically disordered TC-1 interacts with Cby via its transient helical structure (PMID:17905836)
• 14-3-3epsilon and 14-3-3zeta are identified as Cby-binding partners. (PMID:18573912)
• genes including CHIBBY involved in pediatric ependymomas. (PMID:18663750)
• Alanine substitutions of two or more of four critical leucine residues within the C-terminal heptad repeats eliminate the Cby-Cby interaction. (PMID:19435523)
• These findings unravel the molecular basis through which a combinatorial action of Cby and 14-3-3 proteins controls the dynamic nuclear-cytoplasmic trafficking of beta-catenin. (PMID:19940019)
• Chibby and clusterin were co-immunoprecipitated with NBPF1. (PMID:20096688)
• The N-terminal portion of the CBY1 is unstructured in solution, but the C-terminal half forms a coiled-coil structure. (PMID:21182262)
• Cby plays an important role in organization of both primary and motile cilia in collaboration with Cnx. (PMID:22911743)
• Results from the association analysis suggest that common variation in CBY is not a cause for obesity in the Belgian population. (PMID:23645032)
• Stable expression of CBY1 drives beta catenin cytoplasmatic translocation and impairs beta catenin signaling in BCR-ABL + cells. (PMID:23707389)
• C-terminal polycystin-2 influences the interaction with PIGEA14 (PMID:23838289)
• the impact of BCR-ABL1 on Chibby1, a beta catenin antagonist involved in cell differentiation and transformation (PMID:24339928)
• Study showed that expression of Cby protein was strongly downregulated in laryngeal squamous cell carcinoma (LSCC) tumor tissues in comparison to normal laryngeal mucosa samples. (PMID:25175341)
• Results show the hypermethylation of CBY1 and BCL2-like11 promoters proceeding from DNMT1 is a crucial component of their reduced expression, but it is not directly involved in chronic myeloid leukemia resistance to imatinib. (PMID:25389112)
• CBY1 downregulation in CML comes from reduced protein stability when bound to 14-3-3sigma adapter protein. Dissociation raises CBY1 protein levels by enhancing its stability. The ubiquitin proteasome system reduces 14-3-3sigma-bound CBY1 stability by SUMOylation. (PMID:26147002)
• Cby’s C-terminal domain alone binds to TC-1 with significantly greater affinity compared to full-length Cby, implying that target binding of the coiled-coil domain is affected by the flanking disordered regions. (PMID:27082063)
• FAM92 proteins interact with Cby1 to promote ciliogenesis via regulation of membrane-remodeling processes. (PMID:27528616)
• chronic Cby1 knockdown in colon cancer cells may counteract tumor progression by promoting the mesenchymal-to-epithelial transition process. (PMID:28107095)
• Our study reveals an association between Chibby expression and cancer aerobic glycolysis, which highlights the importance of Wnt/beta-catenin pathway in regulation of energy metabolism of NPC. These results indicate that Chibby and PDK1 are the potential target for NPC treatment. (PMID:29764469)
• Chibby expression was decreased in gastric cancer samples and altered beta-catenin localization in cultured gastric cancer cells. (PMID:30063079)
• Loss of CBY1 results in a ciliopathy characterized by features of Joubert syndrome. (PMID:33131181)
• A novel Lnc408 maintains breast cancer stem cell stemness by recruiting SP3 to suppress CBY1 transcription and increasing nuclear beta-catenin levels. (PMID:33934099)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cby1	ENSDARG00000077409
mus_musculus	Cby1	ENSMUSG00000022428
rattus_norvegicus		ENSRNOG00000090732

Paralogs (3): CCDC70 (ENSG00000123171), CBY2 (ENSG00000174015), CBY3 (ENSG00000204659)

Protein

Protein identifiers

Protein chibby homolog 1 — Q9Y3M2 (reviewed: Q9Y3M2)

Alternative names: ARPP-binding protein, Cytosolic leucine-rich protein, PIGEA-14, PKD2 interactor, Golgi and endoplasmic reticulum-associated 1

All UniProt accessions (3): Q9Y3M2, B0QY53, B0QY54

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits the Wnt/Wingless pathway by binding to CTNNB1/beta-catenin and inhibiting beta-catenin-mediated transcriptional activation through competition with TCF/LEF transcription factors. Has also been shown to play a role in regulating the intracellular trafficking of polycystin-2/PKD2 and possibly of other intracellular proteins. Promotes adipocyte and cardiomyocyte differentiation.

Subunit / interactions. Homodimer. Homodimerization is essential for nuclear localization and interaction with KPNA4 but is dispensable for interaction with CTNNB1. Interacts with polycystin-2/PKD2 and GM130. Interacts with the C-terminal region of CTNNB1. Interacts (C-terminus) with TCIM (C-terminus), TCIM competes with CTNNB1 for the interaction with CBY1. Interacts with FAM92A; this interaction facilitates targeting of FAM92A to cilium basal body. Interacts with CIBAR2. Interacts with KPNA4.

Subcellular location. Nucleus speckle. Cytoplasm. Cytoskeleton. Cilium basal body. Microtubule organizing center. Centrosome. Centriole. Golgi apparatus. trans-Golgi network. Cell projection. Cilium. Flagellum. Nucleus.

Tissue specificity. Widely expressed. Expressed at higher levels in heart, skeletal muscle, kidney and placenta. Also found in brain, lung, liver and testis. Significantly down-regulated in thyroid and metastatic uterine tumors.

Miscellaneous. ‘Chibby’ is Japanese for ‘small’; the gene was so named for the RNAi phenotype seen in flies.

Similarity. Belongs to the chibby family.

RefSeq proteins (2): NP_001002880, NP_056188* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028118	Chibby_fam	Family

Pfam: PF14645

UniProt features (13 total): mutagenesis site 4, region of interest 3, modified residue 2, chain 1, sequence conflict 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4WRQ	X-RAY DIFFRACTION	2.41

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3M2-F1	86.54	0.43

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 (2): 9, 20

Mutagenesis-validated functional residues (4):

Position	Phenotype
91	no effect homodimerization, nuclear localization and interaction with ctnnb1 but a slight reduction in interaction with
98	no effect on its homodimerization. loss of homodimerization; when associated with a-77 or a-84 or a-91 or a-77; a-84 and
77	no effect on homodimerization, nuclear localization and interaction with ctnnb1 but a slight reduction in interaction wi
84	reduced homodimerization. loss of homodimerization; when associated with a-77 or a-91 or a-98 or a-77; a-91 and a-98.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex
R-HSA-162582	Signal Transduction
R-HSA-195721	Signaling by WNT
R-HSA-201681	TCF dependent signaling in response to WNT

MSigDB gene sets: 260 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_PROTEIN_HOMOTETRAMERIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, MODULE_503, GOCC_MICROTUBULE_ORGANIZING_CENTER, BROWNE_HCMV_INFECTION_48HR_DN, GOCC_TRANS_GOLGI_NETWORK

GO Biological Process (12): intracellular protein localization (GO:0008104), negative regulation of Wnt signaling pathway (GO:0030178), floor plate development (GO:0033504), fat cell differentiation (GO:0045444), negative regulation of DNA-templated transcription (GO:0045892), protein homotetramerization (GO:0051289), cardiac muscle cell differentiation (GO:0055007), canonical Wnt signaling pathway (GO:0060070), cilium assembly (GO:0060271), negative regulation of canonical Wnt signaling pathway (GO:0090090), cell projection organization (GO:0030030), cell differentiation (GO:0030154)

GO Molecular Function (4): beta-catenin binding (GO:0008013), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (16): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), trans-Golgi network (GO:0005802), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), nuclear speck (GO:0016607), ciliary basal body (GO:0036064), sperm flagellum (GO:0036126), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
TCF dependent signaling in response to WNT	1
Signal Transduction	1
Signaling by WNT	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membraneless organelle	3
microtubule organizing center	3
Wnt signaling pathway	2
protein binding	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
cytoplasm	2
cilium	2
macromolecule localization	1
negative regulation of signal transduction	1
regulation of Wnt signaling pathway	1
neural tube development	1
anatomical structure development	1
cell differentiation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
protein homooligomerization	1
protein tetramerization	1
cardiocyte differentiation	1
cardiac muscle tissue development	1
striated muscle cell differentiation	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
cellular component organization	1
cellular developmental process	1
identical protein binding	1
protein dimerization activity	1
binding	1
Golgi apparatus subcompartment	1

Protein interactions and networks

STRING

726 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CBY1	CTNNB1	P35222	810
CBY1	LEF1	Q9UJU2	773
CBY1	CIBAR1	A1XBS5	772
CBY1	PKD2	Q13563	761
CBY1	ODF2	Q5BJF6	678
CBY1	TCIM	Q9NR00	669
CBY1	CEP164	Q9UPV0	592
CBY1	CBY2	Q8NA61	518
CBY1	CEP290	O15078	516
CBY1	CIBAR2	Q6ZTR7	512
CBY1	TXNDC9	O14530	490
CBY1	GOLGA2	Q08379	482
CBY1	TSHZ3	Q63HK5	467
CBY1	TSHZ2	Q9NRE2	452
CBY1	CEP83	Q9Y592	452

IntAct

215 interactions, top by confidence:

A	B	Type	Score
CFAP53	CBY1	psi-mi:“MI:0915”(physical association)	0.680
CBY1	CFAP53	psi-mi:“MI:0915”(physical association)	0.680
CBY1	CIBAR1	psi-mi:“MI:0915”(physical association)	0.670
CIBAR1	CBY1	psi-mi:“MI:0915”(physical association)	0.670
DZIP1L	CBY1	psi-mi:“MI:0915”(physical association)	0.670
RALBP1	CBY1	psi-mi:“MI:0915”(physical association)	0.670
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
TTC23L	CBY1	psi-mi:“MI:0915”(physical association)	0.560
CBY1	TTC23L	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	CBY1	psi-mi:“MI:0915”(physical association)	0.560
CIBAR1	CBY1	psi-mi:“MI:0915”(physical association)	0.560
LNX1	CBY1	psi-mi:“MI:0915”(physical association)	0.560
GORASP2	CBY1	psi-mi:“MI:0915”(physical association)	0.560
FAM161B	CBY1	psi-mi:“MI:0915”(physical association)	0.560
TSG101	CBY1	psi-mi:“MI:0915”(physical association)	0.560
ENKD1	CBY1	psi-mi:“MI:0915”(physical association)	0.560
TNFAIP8L3	CBY1	psi-mi:“MI:0915”(physical association)	0.560
ABITRAM	POTEF	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
CBY1	CFAP410	psi-mi:“MI:0914”(association)	0.510
YWHAE	DCAF7	psi-mi:“MI:0914”(association)	0.510
CBY1	CTNNB1	psi-mi:“MI:0407”(direct interaction)	0.440
CBY1	CDK6	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
CBY1	yscO	psi-mi:“MI:0915”(physical association)	0.370
CBY1		psi-mi:“MI:0915”(physical association)	0.370
OLFM2	ZSWIM8	psi-mi:“MI:0914”(association)	0.350

BioGRID (197): FAM92A1 (Two-hybrid), TTC23L (Two-hybrid), CFAP53 (Two-hybrid), CBY1 (Affinity Capture-Western), CBY1 (Two-hybrid), CBY1 (Affinity Capture-MS), CBY1 (Affinity Capture-MS), CBY1 (Affinity Capture-MS), CBY1 (Affinity Capture-MS), CBY1 (Affinity Capture-MS), CBY1 (Affinity Capture-MS), MAP7 (Affinity Capture-MS), CBY1 (Affinity Capture-MS), CBY1 (Affinity Capture-MS), MARK2 (Affinity Capture-MS)

ESM2 similar proteins: A0MZ67, A1L260, A2AMM0, A2VDA9, A4IGC3, A5PJI6, A9C3W3, B1PRL5, B9EKI3, O35711, O35867, O54724, O76878, O94876, O95810, P34609, P55326, P70302, P83093, P84903, P85125, Q0IIE0, Q13586, Q29EP6, Q32PN7, Q58CP9, Q5BKX8, Q5FWS6, Q63918, Q66H98, Q674X7, Q69ZS8, Q69ZZ6, Q6NZI2, Q6P0R8, Q6P402, Q7T019, Q8CJ96, Q8K2Q9, Q8MJK1

Diamond homologs: A6NI87, A6QQS3, Q6AXV6, Q8K4I6, Q8MJK1, Q9CVN6, Q9D1C2, Q9Y3M2, Q32MG2, Q8NA61, Q95JK3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CBY1	down-regulates	CTNNB1	binding
AKT1	“up-regulates activity”	CBY1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 174 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	9	55.5×	5e-12
Activation of BAD and translocation to mitochondria	7	48.9×	9e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	37.0×	4e-07
Activation of BH3-only proteins	7	31.9×	1e-07
Constitutive Signaling by AKT1 E17K in Cancer	6	23.3×	6e-06
RHO GTPases activate PKNs	7	20.4×	2e-06
Intrinsic Pathway for Apoptosis	7	18.8×	3e-06
Oncogenic MAPK signaling	5	11.4×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	13.9×	2e-03
regulation of small GTPase mediated signal transduction	8	7.3×	3e-03
microtubule cytoskeleton organization	9	6.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	6
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
694056	NM_015373.4(CBY1):c.189_190del (p.Gly64_Val65insTer)	Pathogenic
694265	NM_015373.4(CBY1):c.64_65dup (p.Asn23fs)	Pathogenic

SpliceAI

1062 predictions. Top by Δscore:

Variant	Effect	Δscore
22:38668133:G:GG	donor_gain	1.0000
22:38670882:A:AG	acceptor_gain	1.0000
22:38670882:AGTT:A	acceptor_gain	1.0000
22:38670882:AGTTG:A	acceptor_gain	1.0000
22:38670883:G:GA	acceptor_gain	1.0000
22:38670883:GTT:G	acceptor_gain	1.0000
22:38670883:GTTG:G	acceptor_gain	1.0000
22:38670883:GTTGG:G	acceptor_gain	1.0000
22:38671066:CCA:C	acceptor_loss	1.0000
22:38671067:CA:C	acceptor_loss	1.0000
22:38671068:A:AG	acceptor_gain	1.0000
22:38671069:G:GC	acceptor_gain	1.0000
22:38671069:GA:G	acceptor_gain	1.0000
22:38671069:GAGA:G	acceptor_gain	1.0000
22:38671069:GAGAC:G	acceptor_gain	1.0000
22:38671141:G:GT	donor_gain	1.0000
22:38656811:C:G	donor_gain	0.9900
22:38656819:G:GT	donor_gain	0.9900
22:38657144:G:GG	donor_gain	0.9900
22:38668102:G:GT	donor_gain	0.9900
22:38668129:TTCT:T	donor_gain	0.9900
22:38670986:GCAG:G	donor_gain	0.9900
22:38670988:AGGT:A	donor_loss	0.9900
22:38670989:GGTGA:G	donor_loss	0.9900
22:38670990:G:GA	donor_loss	0.9900
22:38670991:T:G	donor_loss	0.9900
22:38671165:A:T	donor_gain	0.9900
22:38671186:ATGGT:A	donor_loss	0.9900
22:38671187:TGGTG:T	donor_loss	0.9900
22:38671189:GTG:G	donor_loss	0.9900

AlphaMissense

813 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:38670965:T:C	F54L	0.999
22:38670967:T:A	F54L	0.999
22:38670967:T:G	F54L	0.999
22:38670980:T:A	W59R	0.999
22:38670980:T:C	W59R	0.999
22:38670982:G:C	W59C	0.999
22:38670982:G:T	W59C	0.999
22:38671154:T:C	L90P	0.999
22:38670966:T:C	F54S	0.998
22:38670981:G:C	W59S	0.997
22:38671163:T:C	L93P	0.997
22:38668076:T:C	F8L	0.996
22:38668078:C:A	F8L	0.996
22:38668078:C:G	F8L	0.996
22:38671115:T:C	L77P	0.996
22:38671178:T:C	L98S	0.996
22:38671188:G:A	M101I	0.996
22:38671188:G:C	M101I	0.996
22:38671188:G:T	M101I	0.996
22:38673174:G:C	A107P	0.996
22:38670960:T:C	L52P	0.995
22:38670975:G:T	G57V	0.995
22:38671136:T:C	L84S	0.995
22:38671167:A:C	K94N	0.995
22:38671167:A:T	K94N	0.995
22:38671124:G:C	R80P	0.994
22:38673160:T:C	L102P	0.994
22:38673175:C:A	A107D	0.994
22:38670966:T:G	F54C	0.993
22:38671185:C:A	D100E	0.992

dbSNP variants (sampled 300 via entrez): RS1000209873 (22:38659775 T>A,G), RS1000413159 (22:38666594 C>T), RS1000516635 (22:38659680 G>A,C), RS1000558023 (22:38655636 C>T), RS1000683999 (22:38660910 A>G), RS1000891298 (22:38671570 T>C), RS1001326506 (22:38670394 C>A,T), RS1001451473 (22:38669435 C>T), RS1001587482 (22:38659837 G>A,C), RS1001763402 (22:38660314 C>A,T), RS1001789901 (22:38670638 A>G), RS1001840506 (22:38670389 C>T), RS1001886426 (22:38655996 A>T), RS1002008116 (22:38662970 A>G), RS1002197610 (22:38660623 T>C)

Disease associations

OMIM: gene MIM:607757 | disease phenotypes: MIM:213300

GenCC curated gene-disease

Disease	Classification	Inheritance
ciliopathy	Moderate	Autosomal recessive
Joubert syndrome	Supportive	Autosomal recessive

Mondo (3): prostate cancer (MONDO:0008315), Joubert syndrome (MONDO:0018772), ciliopathy (MONDO:0005308)

Orphanet (2): Familial prostate cancer (Orphanet:1331), Isolated Joubert syndrome (Orphanet:475)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000202	Orofacial cleft
HP:0000238	Hydrocephalus
HP:0000276	Long face
HP:0000369	Low-set ears
HP:0000426	Prominent nasal bridge
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000612	Iris coloboma
HP:0000639	Nystagmus
HP:0000657	Oculomotor apraxia
HP:0000864	Abnormality of the hypothalamus-pituitary axis
HP:0001161	Hand polydactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001288	Gait disturbance
HP:0001320	Cerebellar vermis hypoplasia
HP:0001337	Tremor
HP:0001696	Situs inversus totalis
HP:0001829	Foot polydactyly
HP:0002084	Encephalocele
HP:0002104	Apnea
HP:0002126	Polymicrogyria
HP:0002251	Aganglionic megacolon
HP:0002269	Abnormality of neuronal migration
HP:0002553	Highly arched eyebrow
HP:0002650	Scoliosis

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003818_40	Resting heart rate	5.000000e-16
GCST007561_72	Sleep duration	4.000000e-08

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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
FR900359	affects phosphorylation	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Phenobarbital	affects expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Vitamin E	increases expression	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

304 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