CAND1

Summary

CAND1 (cullin associated and neddylation dissociated 1, HGNC:30688) is a protein-coding gene on chromosome 12q14.3-q15, encoding Cullin-associated NEDD8-dissociated protein 1 (Q86VP6). Key assembly factor of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes that promotes the exchange of the substrate-recognition F-box subunit in SCF complexes, thereby playing a key role in the cellular repertoire of SCF complexes. It is a selective cancer dependency (DepMap: 33.0% of cell lines).

This gene encodes an essential regulator of Cullin-RING ubiquitin ligases, which are in involved in ubiquitinylation of proteins degraded by the Ub proteasome system. The encoded protein binds to unneddylated cullin-RING box protein complexes and acts as an inhibitor of cullin neddylation and of Skp1, cullin, and F box ubiquitin ligase complex assembly and activity. In mammalian cell culture, this protein predominantly localizes to the cytoplasm. Knockdown of this gene in preadipocytes results in blocked adipogenesis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55832 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 91 total — 1 pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 33.0% of screened cell lines
• MANE Select transcript: NM_018448

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30688
Approved symbol	CAND1
Name	cullin associated and neddylation dissociated 1
Location	12q14.3-q15
Locus type	gene with protein product
Status	Approved
Aliases	TIP120A, DKFZp434M1414, KIAA0829, TIP120
Ensembl gene	ENSG00000111530
Ensembl biotype	protein_coding
OMIM	607727
Entrez	55832

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000535146, ENST00000539109, ENST00000539434, ENST00000540319, ENST00000540525, ENST00000541058, ENST00000544619, ENST00000545606, ENST00000909423

RefSeq mRNA: 4 — MANE Select: NM_018448 NM_001329674, NM_001329675, NM_001329676, NM_018448

CCDS: CCDS8977

Canonical transcript exons

ENST00000545606 — 15 exons

Exon	Start	End
ENSE00000920685	67297748	67297853
ENSE00000920686	67298950	67299095
ENSE00000920687	67302323	67302615
ENSE00000920688	67304605	67304746
ENSE00000920689	67305104	67306597
ENSE00001100526	67292622	67292776
ENSE00001100530	67295033	67295156
ENSE00001244663	67269358	67269785
ENSE00001801565	67311693	67311800
ENSE00001805471	67310152	67310316
ENSE00002212138	67312606	67319953
ENSE00003468612	67307397	67307492
ENSE00003495560	67297407	67297663
ENSE00003608795	67309901	67310070
ENSE00003677657	67281910	67282053

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 98.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.5414 / max 553.7314, expressed in 1821 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126560	24.8255	1810
126564	15.0466	1773
126562	2.0716	1205
126561	1.8558	1126
126565	0.6962	418
126558	0.4203	209
126563	0.3705	141
126559	0.2549	126

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	98.58	gold quality
ventricular zone	UBERON:0003053	98.54	gold quality
ganglionic eminence	UBERON:0004023	98.21	gold quality
cortical plate	UBERON:0005343	98.21	gold quality
embryo	UBERON:0000922	97.36	gold quality
stromal cell of endometrium	CL:0002255	97.13	gold quality
calcaneal tendon	UBERON:0003701	96.27	gold quality
islet of Langerhans	UBERON:0000006	95.46	gold quality
endothelial cell	CL:0000115	95.35	gold quality
vermiform appendix	UBERON:0001154	94.71	gold quality
left ovary	UBERON:0002119	94.38	gold quality
ovary	UBERON:0000992	94.35	gold quality
right ovary	UBERON:0002118	94.13	gold quality
endometrium	UBERON:0001295	94.08	gold quality
parietal pleura	UBERON:0002400	94.03	gold quality
germinal epithelium of ovary	UBERON:0001304	93.84	gold quality
tonsil	UBERON:0002372	93.84	gold quality
body of pancreas	UBERON:0001150	93.78	gold quality
rectum	UBERON:0001052	93.62	gold quality
skin of abdomen	UBERON:0001416	93.60	gold quality
caecum	UBERON:0001153	93.57	gold quality
prefrontal cortex	UBERON:0000451	93.50	gold quality
tibia	UBERON:0000979	93.45	gold quality
right adrenal gland	UBERON:0001233	93.45	gold quality
pancreas	UBERON:0001264	93.45	gold quality
right adrenal gland cortex	UBERON:0035827	93.38	gold quality
gall bladder	UBERON:0002110	93.31	gold quality
adrenal gland	UBERON:0002369	93.26	gold quality
mucosa of stomach	UBERON:0001199	93.17	gold quality
colonic epithelium	UBERON:0000397	93.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

194 targeting CAND1, 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-1252-5P	100.00	69.80	2774
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-4668-3P	100.00	68.74	2635
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-181A-5P	99.99	72.96	2995

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 33.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 21)

• selectively binds to unneddylated CUL1 and is dissociated by CUL1 neddylation (PMID:12504025)
• binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3 ligase complex (PMID:12504026)
• TIP120A functions as a negative regulator of SCF E3 ubiquitin ligases and may modulate other cullin ligases in a similar fashion. (PMID:12609982)
• CAND1 & COP9 signalosome (CSN), major deneddylase of cullins, bind to unneddylated CUL1 in mutually exclusive way. Suppression of CAND1 expression by siRNA enhanced interaction between CUL1 & CSN, suggesting that CAND1 inhibited binding of CSN to CUL1. (PMID:16036220)
• SCCRO recruits Ubc12 approximately NEDD8 to the CAND1-Cul1-ROC1 complex but that this is not sufficient to dissociate or overcome the inhibitory effects of CAND1 on cullin neddylation (PMID:18826954)
• miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression. (PMID:20820187)
• CAND1 does not function by sequestering cullins in vivo to prevent substrate receptor autoubiquitination and is likely to regulate cullin RING ligase activity via alternative mechanisms (PMID:21249194)
• COMMD1 (copper metabolism MURR1 domain-containing protein 1) regulates Cullin RING ligases by preventing CAND1 (Cullin-associated Nedd8-dissociated protein 1) binding. (PMID:21778237)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• The Epstein-Barr virus protein BPLF1, is targeted to cullin-RING ubiquitin ligases (CRLs) via the interaction of the conserved helix-2 with helix-23 of cullins, at a site involved in electrostatic interaction with CAND1. (PMID:22474075)
• CAND1 promotes PLK4-mediated centriole overduplication and is frequently disrupted in prostate cancer. (PMID:23019411)
• We demonstrate that the accumulation of p27 is associated with an increase of CAND1 and a decrease of Skp2 during adipogenesis of human LiSa-2 preadipocytes. CAND1 knockdown reduces p27 and blocks adipogenesis. (PMID:23328082)
• Study shows that Cand1 can unambiguously stimulate SCF activity in vitro by enabling an F box protein-Skp1 complex to access Cul1 that was previously occupied by a different F box protein-Skp1 complex, and that Cand1 promotes assembly in vivo of new F box proteins with pre-existing Cul1 molecules. (PMID:23453757)
• Data show that the differentiation of LiSa-2 preadipocytes is associated with an increase of cullin-associated and neddylation-dissociated 1 (CAND1), COP9 signalosome (CSN), neddylated cullin 3 (Cul3) and the BTB protein Keap1. (PMID:26219975)
• describe the identification of the structural determinants responsible for the CA IX/CAND1 interaction (PMID:28388044)
• miR-33a and CAND1 played an important role in lung cancer proliferation and cell migration (PMID:28871425)
• CAND1 regulates lunapark for the proper tubular network of the endoplasmic reticulum. (PMID:31511573)
• Cullin-associated and neddylation-dissociated 1 protein (CAND1) governs cardiac hypertrophy and heart failure partially through regulating calcineurin degradation. (PMID:35661710)
• Systemwide disassembly and assembly of SCF ubiquitin ligase complexes. (PMID:37028429)
• Structural and mechanistic insights into the CAND1-mediated SCF substrate receptor exchange. (PMID:37339624)
• ASCC3 promotes the immunosuppression and progression of non-small cell lung cancer by impairing the type I interferon response via CAND1-mediated ubiquitination inhibition of STAT3. (PMID:38148115)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cand1	ENSDARG00000017841
mus_musculus	Cand1	ENSMUSG00000020114
rattus_norvegicus	Cand1	ENSRNOG00000007834
caenorhabditis_elegans		WBGENE00013606

Paralogs (1): CAND2 (ENSG00000144712)

Protein

Protein identifiers

Cullin-associated NEDD8-dissociated protein 1 — Q86VP6 (reviewed: Q86VP6)

Alternative names: Cullin-associated and neddylation-dissociated protein 1, TBP-interacting protein of 120 kDa A, p120 CAND1

All UniProt accessions (4): Q86VP6, A0A0C4DGH5, F5H6I6, H0YH27

UniProt curated annotations — full annotation on UniProt →

Function. Key assembly factor of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes that promotes the exchange of the substrate-recognition F-box subunit in SCF complexes, thereby playing a key role in the cellular repertoire of SCF complexes. Acts as a F-box protein exchange factor. The exchange activity of CAND1 is coupled with cycles of neddylation conjugation: in the deneddylated state, cullin-binding CAND1 binds CUL1-RBX1, increasing dissociation of the SCF complex and promoting exchange of the F-box protein. Probably plays a similar role in other cullin-RING E3 ubiquitin ligase complexes.

Subunit / interactions. Interacts with TBP. Part of a complex that contains CUL1 and RBX1. Interacts with unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5. Does not bind neddylated CUL1. Interaction with cullins is abolished in presence of COMMD1, which antagonizes with CAND1 for interacting with cullins. Interacts with ERCC6. Interacts with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions are bridged by cullins and strongly inhibits the neddylation of cullins.

Subcellular location. Cytoplasm. Nucleus.

Induction. Repressed by miR-148a.

Miscellaneous. A model has been proposed to explain the mechanisms of cullin-RING E3 ubiquitin ligase complexes assembly. According to this hypothesis, cullin-RING E3 ubiquitin ligase complexes exist in a ‘stable’ active state when saturated with substrate, occluding access to deneddylation by the COP9 signalosome (CSN) complex. The neddylation-conjugated cullin-RING E3 ubiquitin ligase complexes mediate ubiquitination of substrates and can recruit downstream factors involved in substrate degradation. Depletion of the substrate promotes the ability of CSN to bind the cullin-RING E3 ubiquitin ligase complex and mediate deneddylation. In this ‘intermediate’ deneddylated state, the complex can bind CAND1 and enter the ’exchange’ state, resulting in high increase in dissociation rate of the substrate-recognition subunit. The resulting CAND1-cullin-RING complex rapidly assembles with another available substrate-recognition subunit to form an unstable ternary intermediate and yield a new cullin-RING E3 ubiquitin ligase complex. Subsequent neddylation of the cullin, which is stabilized by substrate, completes the cycle.

Similarity. Belongs to the CAND family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86VP6-1	1	yes
Q86VP6-2	2
Q86VP6-3	3

RefSeq proteins (4): NP_001316603, NP_001316604, NP_001316605, NP_060918* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR013932	TATA-bd_TIP120	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR039852	CAND1/CAND2	Family

Pfam: PF08623, PF13513, PF25782

UniProt features (148 total): helix 76, repeat 27, strand 19, turn 6, sequence conflict 6, modified residue 5, splice variant 4, sequence variant 2, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
7Z8R	ELECTRON MICROSCOPY	2.7
7Z8V	ELECTRON MICROSCOPY	2.7
8OR3	ELECTRON MICROSCOPY	2.9
7Z8T	ELECTRON MICROSCOPY	3
1U6G	X-RAY DIFFRACTION	3.1
7ZBZ	ELECTRON MICROSCOPY	3.1
8OR0	ELECTRON MICROSCOPY	3.1
8OR2	ELECTRON MICROSCOPY	3.2
8CDK	ELECTRON MICROSCOPY	3.32
8CDJ	ELECTRON MICROSCOPY	3.4
7ZBW	ELECTRON MICROSCOPY	3.5
8H3Q	ELECTRON MICROSCOPY	3.76
4A0C	X-RAY DIFFRACTION	3.8
8OR4	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VP6-F1	86.95	0.53

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 (5): 2, 55, 335, 558, 971

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-8951664	Neddylation
R-HSA-917937	Iron uptake and transport
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-382551	Transport of small molecules
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 274 (showing top): E2F_Q4, REACTOME_INNATE_IMMUNE_SYSTEM, E2F4DP1_01, GCM_GSPT1, MODULE_255, GOCC_SECRETORY_GRANULE, TTTGTAG_MIR520D, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GCM_ZNF198, MODULE_317, TATTATA_MIR374, AP2_Q3, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, ATGTTAA_MIR302C, GOBP_REGULATION_OF_RNA_POLYMERASE_II_TRANSCRIPTION_PREINITIATION_COMPLEX_ASSEMBLY

GO Biological Process (6): SCF complex assembly (GO:0010265), protein ubiquitination (GO:0016567), cell differentiation (GO:0030154), negative regulation of catalytic activity (GO:0043086), positive regulation of RNA polymerase II transcription preinitiation complex assembly (GO:0045899), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (2): TBP-class protein binding (GO:0017025), protein binding (GO:0005515)

GO Cellular Component (12): ubiquitin ligase complex (GO:0000151), extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), membrane (GO:0016020), cullin-RING ubiquitin ligase complex (GO:0031461), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Innate Immune System	1
Post-translational protein modification	1
Transport of small molecules	1
Immune System	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular membrane-bounded organelle	2
cytoplasm	2
protein-containing complex assembly	1
protein modification by small protein conjugation	1
cellular developmental process	1
catalytic activity	1
negative regulation of molecular function	1
regulation of catalytic activity	1
positive regulation of protein-containing complex assembly	1
regulation of RNA polymerase II transcription preinitiation complex assembly	1
RNA polymerase II preinitiation complex assembly	1
positive regulation of transcription initiation by RNA polymerase II	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
general transcription initiation factor binding	1
binding	1
intracellular protein-containing complex	1
transferase complex	1
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1
ubiquitin ligase complex	1
secretory granule	1
cytoplasmic vesicle lumen	1
extracellular vesicle	1
intracellular organelle lumen	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

1906 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAND1	CUL1	Q13616	993
CAND1	RBX1	P62877	958
CAND1	NEDD8	Q15843	935
CAND1	SKP1	P34991	901
CAND1	COPS5	Q92905	814
CAND1	SKP2	Q13309	811
CAND1	PSMD14	O00487	789
CAND1	CUL2	Q13617	781
CAND1	CUL4B	Q13620	770
CAND1	CUL3	Q13618	766
CAND1	CUL4A	Q13619	754
CAND1	UBE2M	P61081	717
CAND1	ELOB	Q15370	715
CAND1	RNF7	Q9UBF6	677
CAND1	TBP	P20226	670

IntAct

186 interactions, top by confidence:

A	B	Type	Score
CUL1	RBX1	psi-mi:“MI:0914”(association)	0.980
CUL1	CAND1	psi-mi:“MI:0915”(physical association)	0.960
CUL1	CAND1	psi-mi:“MI:0407”(direct interaction)	0.960
CAND1	CUL1	psi-mi:“MI:0914”(association)	0.960
CAND1	CUL1	psi-mi:“MI:0915”(physical association)	0.960
CUL1	CAND1	psi-mi:“MI:0914”(association)	0.960
CUL1	SKP1	psi-mi:“MI:0914”(association)	0.960
CUL5	SOCS2	psi-mi:“MI:0914”(association)	0.880
CAND1	CUL4B	psi-mi:“MI:0407”(direct interaction)	0.840
CAND1	CUL4B	psi-mi:“MI:0915”(physical association)	0.840
CUL4B	RBX1	psi-mi:“MI:0914”(association)	0.820
CUL4B	COPS2	psi-mi:“MI:0914”(association)	0.790
CUL3	CAND1	psi-mi:“MI:0915”(physical association)	0.750
FBXL17	BACH1	psi-mi:“MI:0914”(association)	0.730

BioGRID (1281): CAND1 (Reconstituted Complex), CAND1 (Affinity Capture-Western), CAND1 (Affinity Capture-Western), CAND1 (Affinity Capture-MS), CAND1 (Affinity Capture-MS), CAND1 (Affinity Capture-MS), CAND1 (Affinity Capture-MS), CAND1 (Affinity Capture-RNA), CAND1 (Co-fractionation), CAND1 (Co-fractionation), CAND1 (Co-fractionation), CAND1 (Co-fractionation), CAND1 (Co-fractionation), IPO9 (Co-fractionation), TMCO1 (Co-fractionation)

ESM2 similar proteins: A1A5G0, A1A5K2, A2AGT5, A2VE21, A7MBJ5, D4ABY2, G5EEM5, O35643, O81742, P22892, P52303, P53620, P55060, P62944, P63009, P63010, P97536, Q08DS7, Q0WW26, Q10567, Q14008, Q1ZXQ8, Q29AE5, Q32PG1, Q4AEF8, Q4U0G1, Q5N749, Q5R6L5, Q5RHR0, Q66JI9, Q6DDM4, Q6DKD7, Q6GM65, Q6Z382, Q6ZQ38, Q7Z460, Q80TV8, Q86VP6, Q8H852, Q94FN2

Diamond homologs: A7MBJ5, G5ED41, O75155, P97536, Q5BAH2, Q5R6L5, Q6ZQ38, Q6ZQ73, Q86KD1, Q86VP6, Q8L5Y6, Q9R0L4, Q9VKY2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 175 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
DNA Damage Recognition in GG-NER	8	19.5×	2e-06
Formation of TC-NER Pre-Incision Complex	7	12.7×	2e-04
Neddylation	20	8.1×	3e-10

GO biological processes:

GO term	Partners	Fold	FDR
protein neddylation	7	33.0×	1e-06
regulation of protein neddylation	5	31.4×	1e-04
intrinsic apoptotic signaling pathway	7	16.8×	6e-05
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	6	15.1×	6e-04
proteasome-mediated ubiquitin-dependent protein catabolic process	17	6.0×	2e-06
protein ubiquitination	19	5.3×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	73
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1340105	GRCh37/hg19 12q14.3-15(chr12:66045645-68872343)x1	Pathogenic

SpliceAI

2632 predictions. Top by Δscore:

Variant	Effect	Δscore
12:67269778:GACTT:G	donor_gain	1.0000
12:67281904:T:A	acceptor_gain	1.0000
12:67281907:TA:T	acceptor_loss	1.0000
12:67281908:A:AG	acceptor_gain	1.0000
12:67281908:AG:A	acceptor_gain	1.0000
12:67281908:AGGTT:A	acceptor_loss	1.0000
12:67281909:G:A	acceptor_gain	1.0000
12:67281909:G:GT	acceptor_gain	1.0000
12:67281909:GGT:G	acceptor_gain	1.0000
12:67281909:GGTT:G	acceptor_gain	1.0000
12:67281909:GGTTT:G	acceptor_gain	1.0000
12:67281983:A:T	donor_gain	1.0000
12:67282050:AATG:A	donor_gain	1.0000
12:67282051:ATG:A	donor_gain	1.0000
12:67282054:G:GG	donor_gain	1.0000
12:67282054:GT:G	donor_loss	1.0000
12:67282055:T:A	donor_loss	1.0000
12:67292619:CAGT:C	acceptor_loss	1.0000
12:67292620:A:AG	acceptor_gain	1.0000
12:67292621:G:GG	acceptor_gain	1.0000
12:67292621:GT:G	acceptor_gain	1.0000
12:67292621:GTC:G	acceptor_gain	1.0000
12:67292621:GTCT:G	acceptor_gain	1.0000
12:67292621:GTCTT:G	acceptor_gain	1.0000
12:67292774:GTG:G	donor_gain	1.0000
12:67292777:G:GG	donor_gain	1.0000
12:67292777:G:T	donor_loss	1.0000
12:67295023:A:AG	acceptor_gain	1.0000
12:67295027:AT:A	acceptor_gain	1.0000
12:67295028:T:G	acceptor_gain	1.0000

AlphaMissense

8074 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:67269761:T:G	M15R	1.000
12:67269772:G:C	D19H	1.000
12:67269773:A:G	D19G	1.000
12:67269773:A:T	D19V	1.000
12:67269778:G:A	D21N	1.000
12:67269778:G:C	D21H	1.000
12:67269779:A:C	D21A	1.000
12:67269779:A:G	D21G	1.000
12:67269779:A:T	D21V	1.000
12:67269780:C:A	D21E	1.000
12:67269780:C:G	D21E	1.000
12:67269784:A:G	R23G	1.000
12:67269784:A:T	R23W	1.000
12:67269785:G:C	R23T	1.000
12:67269785:G:T	R23M	1.000
12:67281910:G:C	R23S	1.000
12:67281910:G:T	R23S	1.000
12:67281911:T:C	F24L	1.000
12:67281912:T:C	F24S	1.000
12:67281912:T:G	F24C	1.000
12:67281913:T:A	F24L	1.000
12:67281913:T:G	F24L	1.000
12:67281915:T:A	M25K	1.000
12:67281915:T:C	M25T	1.000
12:67281915:T:G	M25R	1.000
12:67281916:G:A	M25I	1.000
12:67281916:G:C	M25I	1.000
12:67281916:G:T	M25I	1.000
12:67281917:G:A	A26T	1.000
12:67281917:G:C	A26P	1.000

dbSNP variants (sampled 300 via entrez): RS1000011277 (12:67287561 C>T), RS1000123397 (12:67312004 C>G), RS1000339564 (12:67304999 A>C,G), RS1000364423 (12:67318701 C>T), RS1000528090 (12:67268622 C>G,T), RS1000533518 (12:67278743 T>A), RS1000538120 (12:67313445 T>C), RS1000586742 (12:67272885 C>T), RS1000611527 (12:67299137 A>G), RS1000619891 (12:67290943 A>G), RS1000707345 (12:67285179 C>G), RS1000756009 (12:67285563 G>A), RS1000767411 (12:67279927 AT>A), RS1000812376 (12:67268649 C>T), RS1000820228 (12:67280299 C>T)

Disease associations

OMIM: gene MIM:607727 | 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

8 associations (top):

Study	Trait	p-value
GCST000461_6	Hippocampal atrophy	5.000000e-06
GCST002611_4	Expressive vocabulary in infants	7.000000e-07
GCST004735_37	Epstein-Barr virus copy number in lymphoblastoid cell lines	5.000000e-07
GCST004791_3	Amyotrophic lateral sclerosis (C9orf72 mutation interaction)	3.000000e-06
GCST006628_43	Systolic blood pressure	5.000000e-10
GCST009391_680	Metabolite levels	7.000000e-06
GCST010242_399	HDL cholesterol levels	7.000000e-10
GCST010244_91	Triglyceride levels	3.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005039	hippocampal atrophy
EFO:0006316	infant expressive language ability
EFO:0006335	systolic blood pressure
EFO:0010506	kynurenic acid measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement

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): CHEMBL6067277 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.96	Kd	110.4	nM	CHEMBL3752910
6.96	ED50	110.4	nM	CHEMBL3752910
5.76	Kd	1737	nM	CHEMBL5653589
5.76	ED50	1737	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147987: Binding affinity to human CAND1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1104	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147987: Binding affinity to human CAND1 incubated for 45 mins by Kinobead based pull down assay	kd	1.7373	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	4
bisphenol A	decreases expression, increases expression	2
sodium arsenite	decreases expression, increases expression	2
Caffeine	decreases phosphorylation, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
lead acetate	affects cotreatment, increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization	1
zinc protoporphyrin	affects cotreatment, increases expression	1
cobaltous chloride	increases expression	1
epigallocatechin gallate	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases mutagenesis	1
Carcinogens	increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651029	Binding	Binding affinity to human CAND1 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

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