CCDC6

Summary

CCDC6 (coiled-coil domain containing 6, HGNC:18782) is a protein-coding gene on chromosome 10q21.2, encoding Coiled-coil domain-containing protein 6 (Q16204). It is a selective cancer dependency (DepMap: 17.0% of cell lines).

This gene encodes a coiled-coil domain-containing protein. The encoded protein is ubiquitously expressed and may function as a tumor suppressor. A chromosomal rearrangement resulting in the expression of a fusion gene containing a portion of this gene and the intracellular kinase-encoding domain of the ret proto-oncogene is the cause of thyroid papillary carcinoma.

Source: NCBI Gene 8030 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 60 total
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 17.0% of screened cell lines
• MANE Select transcript: NM_005436

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18782
Approved symbol	CCDC6
Name	coiled-coil domain containing 6
Location	10q21.2
Locus type	gene with protein product
Status	Approved
Aliases	PTC, TPC, H4, PTC1
Ensembl gene	ENSG00000108091
Ensembl biotype	protein_coding
OMIM	601985
Entrez	8030

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 retained_intron

ENST00000263102, ENST00000491922, ENST00000518638, ENST00000862752, ENST00000936420, ENST00000936421, ENST00000936422

RefSeq mRNA: 1 — MANE Select: NM_005436 NM_005436

CCDS: CCDS7257

Canonical transcript exons

ENST00000263102 — 9 exons

Exon	Start	End
ENSE00000705227	59788747	59793111
ENSE00000705231	59804420	59804520
ENSE00000705233	59806922	59807078
ENSE00000705237	59814652	59814755
ENSE00000705238	59832525	59832653
ENSE00000705239	59852553	59852702
ENSE00001276175	59812635	59812795
ENSE00001950758	59906122	59906556
ENSE00003659895	59794473	59794597

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 99.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.1000 / max 171.5274, expressed in 1816 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109487	15.1212	1788
109485	7.1075	1712
109486	5.7609	1686
109490	0.9759	612
109488	0.5570	301
109489	0.4270	231
109491	0.1504	60

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.63	gold quality
oocyte	CL:0000023	98.73	gold quality
esophagus squamous epithelium	UBERON:0006920	97.99	gold quality
parotid gland	UBERON:0001831	97.75	gold quality
buccal mucosa cell	CL:0002336	97.69	gold quality
upper leg skin	UBERON:0004262	97.48	gold quality
skin of hip	UBERON:0001554	97.11	gold quality
middle temporal gyrus	UBERON:0002771	96.55	gold quality
saphenous vein	UBERON:0007318	95.79	gold quality
parietal pleura	UBERON:0002400	95.46	gold quality
caput epididymis	UBERON:0004358	95.37	gold quality
jejunal mucosa	UBERON:0000399	95.34	gold quality
amniotic fluid	UBERON:0000173	95.31	gold quality
corpus epididymis	UBERON:0004359	95.17	gold quality
visceral pleura	UBERON:0002401	94.91	gold quality
gingiva	UBERON:0001828	94.75	gold quality
epithelium of esophagus	UBERON:0001976	94.71	gold quality
oral cavity	UBERON:0000167	94.68	gold quality
germinal epithelium of ovary	UBERON:0001304	94.51	gold quality
pharyngeal mucosa	UBERON:0000355	94.44	gold quality
penis	UBERON:0000989	94.42	gold quality
gingival epithelium	UBERON:0001949	94.39	gold quality
squamous epithelium	UBERON:0006914	94.36	gold quality
mammalian vulva	UBERON:0000997	94.25	gold quality
pleura	UBERON:0000977	94.23	gold quality
tendon of biceps brachii	UBERON:0008188	93.91	gold quality
tibia	UBERON:0000979	93.75	gold quality
postcentral gyrus	UBERON:0002581	93.71	gold quality
nipple	UBERON:0002030	93.60	gold quality
superficial temporal artery	UBERON:0001614	93.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): POU3F1

miRNA regulators (miRDB)

269 targeting CCDC6, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
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-8485	100.00	77.57	4731
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-1184	99.99	68.19	1458
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-520D-5P	99.98	73.34	4883
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-524-5P	99.98	73.43	4882

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 17.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 25)

• H4(D10S170) is involved in the cellular response to ataxia telangectasia mutated (ATM) kinase; impairment of H4(D10S170) gene function might have a role in thyroid carcinogenesis. (PMID:17420723)
• frequency of the occurrence of BRAF mutation and/or RET/PTC in H4-PTEN positive tumors was extremely high (75%) in papillary thyroid carcinoma (PMID:18226854)
• PTC1 and PTC3 are highly oncogenic proteins when overexpressed, but result in indolent disease compared with RET-related MTCs due to their relatively low expression from the NCOA4 and CCDC6 promoters in vivo. (PMID:19487296)
• repression of CREB1 activity by CCDC6 has a critical function in the development of human thyroid papillary carcinomas carrying RET/PTC1 activation. (PMID:20498639)
• we discovered previously unidentified kinase fusions that may be promising for molecular-targeted therapy, kinesin family member 5B (KIF5B)-ret proto-oncogene (RET) and coiled-coil domain containing 6 (CCDC6)-RET, in 14 adenocarcinomas (PMID:22327623)
• CCDC6 plays a key role in cell cycle control. (PMID:22363533)
• down-regulation of 14-3-3sigma in the absence of CCDC6 demonstrated their direct association and supports the notion that CCDC6 contributes to cancer development, possibly through malignant pathways involving 14-3-3sigma (PMID:22399611)
• Following genotoxic stress, loss or inactivation of CCDC6 in cancers that carry the CCDC6 fusion, accelerates the dephosphorylation of pH2AX S139, resulting in defective G2 arrest and premature mitotic entry. (PMID:22655027)
• It was shown that FBXW7 interacts with and targets CCDC6 for ubiquitin-mediated proteasomal degradation. FBXW7-mediated CCDC6 degradation was impaired in response to DNA damage. (PMID:23108047)
• CCDC6 is associated with cAMP signaling by fine regulating CREB1 transcriptional activity in normal and transformed thyroid cells. (PMID:23145146)
• CCDC6-RET fusion is associated with lung adenocarcinoma. (PMID:23154560)
• Expression of the CCDC6-RET fusion gene in LC-2/ad cells was demonstrated by the mRNA and protein levels, and the genomic break-point was confirmed by genomic DNA sequencing. (PMID:23578175)
• CCDC6 levels provide valuable insight for OS. (PMID:25302833)
• Results show that RNA-binding protein EWS binds and regulates CCDC6 expression at RNA and protein levels. (PMID:25751255)
• we propose that the amount of CCDC6 protein in primary tumors, as reported in lung, may depend on the impairment of the CCDC6 turnover due to altered protein-protein interaction and post-translational modifications (PMID:25885523)
• Our findings nevertheless suggest that CCDC6-RET fusions identified by multiplex testing are potential targets for nintedanib therapy. (PMID:26787234)
• FGFR inhibitors, particularly BGJ398, are therapeutic options for cholangiocarcinoma patients harboring FGFR2-CCDC6 fusions. (PMID:27216979)
• Results demonstrate that CCDC6 is a direct target of miR-146b which downregulates CCDC6 expression in papillary thyroid cancer (PTC). Also, CCDC6 expression correlates with clinicopathological parameters and exerts significant diagnostic and prognostic value in patients with PTC. (PMID:30503553)
• The identification of two clusters of patients based on CCDC6 and USP7 expession can possibly indicate the use of PARP-inhibitor drugs. (PMID:30786932)
• we propose CCDC6 as a biomarker of drugs sensitivity for MPMs. In case of MPMs expressing low levels of CCDC6 the addition of olaparib to cisplatinum and pemetrexed is expected to be highly beneficial. In case of MPMs expressing normal CCDC6 levels the sensitivity to olaparib can be restored by the addition of P5091. (PMID:31447003)
• Suppression of CCDC6 sensitizes tumor to oncolytic virus M1. (PMID:33338804)
• The circ_FAM53B-miR-183-5p-CCDC6 axis modulates the malignant behaviors of papillary thyroid carcinoma cells. (PMID:35598218)
• RET rearrangements are relevant to histopathologic subtypes and clinicopathological features in Thai papillary thyroid carcinoma patients. (PMID:37188126)
• Competitive binding of circCCDC6 to microRNA-128-3p activates TXNIP/NLRP3 pathway and promotes cerebral ischemia-reperfusion defects. (PMID:37934513)
• CCDC6-RET fusion protein regulates Ras/MAPK signaling through the fusion- GRB2-SHC1 signal niche. (PMID:38805286)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc6b	ENSDARG00000017595
danio_rerio	ccdc6a	ENSDARG00000043334
mus_musculus	Ccdc6	ENSMUSG00000048701
rattus_norvegicus	Ccdc6	ENSRNOG00000024019
drosophila_melanogaster	CG6664	FBGN0036685
caenorhabditis_elegans		WBGENE00011645

Protein

Protein identifiers

Coiled-coil domain-containing protein 6 — Q16204 (reviewed: Q16204)

Alternative names: Papillary thyroid carcinoma-encoded protein, Protein H4

All UniProt accessions (1): Q16204

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Ubiquitously expressed.

Disease relevance. A chromosomal aberration involving CCDC6 is found in papillary thyroid carcinomas (PTCs). Inversion inv(10)(q11.2;q21) generates the RET/CCDC6 (PTC1) oncogene.

Domain organisation. The protein has mostly an alpha helical conformation similar to myosin heavy-chain tail that might adopt a coiled-coil conformation.

RefSeq proteins (1): NP_005427* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019152	DUF2046	Family

Pfam: PF09755

UniProt features (38 total): modified residue 14, compositionally biased region 6, repeat 5, region of interest 4, coiled-coil region 2, sequence conflict 2, initiator methionine 1, chain 1, short sequence motif 1, site 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9O04	ELECTRON MICROSCOPY	3.2
9O0L	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16204-F1	76.03	0.50

Functional residue map

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

Catalytic / active sites (1): 101–102 (breakpoint for translocation to form ret-ccdc6 oncogene)

Post-translational modifications (14): 2, 52, 240, 244, 249, 254, 284, 323, 349, 363, 367, 387, 395, 413

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 305 (showing top): CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, CGGAARNGGCNG_UNKNOWN, AACYNNNNTTCCS_UNKNOWN, chr10q21, USF_C, YY1_Q6, EFC_Q6, IRF7_01, KEGG_PATHWAYS_IN_CANCER, TGACATY_UNKNOWN, TSENG_IRS1_TARGETS_DN, IRF_Q6, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS

GO Biological Process (1): cytoskeleton organization (GO:0007010)

GO Molecular Function (4): structural constituent of cytoskeleton (GO:0005200), SH3 domain binding (GO:0017124), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (3): cytosol (GO:0005829), cytoskeleton (GO:0005856), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
organelle organization	1
structural molecule activity	1
cytoskeleton	1
cytoskeleton organization	1
protein domain specific binding	1
protein binding	1
binding	1
cytoplasm	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

234 interactions, top by confidence:

A	B	Type	Score
C1S	C1R	psi-mi:“MI:0914”(association)	0.900
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2R1A	STRN	psi-mi:“MI:2364”(proximity)	0.880
RALBP1	CCDC6	psi-mi:“MI:0915”(physical association)	0.840
TUBGCP5	TUBG1	psi-mi:“MI:0914”(association)	0.840
PPP4R2	TIPRL	psi-mi:“MI:0914”(association)	0.800
PPP2CB	STRN	psi-mi:“MI:0914”(association)	0.790
PPP4C	TCP1	psi-mi:“MI:0914”(association)	0.730
PPP2CB	CEP43	psi-mi:“MI:0914”(association)	0.730
CCDC6	MTUS2	psi-mi:“MI:0915”(physical association)	0.670
CCDC6	CENPQ	psi-mi:“MI:0915”(physical association)	0.670
FBXO42	GSK3A	psi-mi:“MI:0914”(association)	0.660
LPXN	PCNT	psi-mi:“MI:0914”(association)	0.640
RALBP1	JUN	psi-mi:“MI:0914”(association)	0.640
PPP4C	SUPT5H	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
MAFF	NFE2L1	psi-mi:“MI:0914”(association)	0.590
CCDC6	HMG20A	psi-mi:“MI:0915”(physical association)	0.560
CCDC6	ANKRD23	psi-mi:“MI:0915”(physical association)	0.560
CCDC6	ZNF620	psi-mi:“MI:0915”(physical association)	0.560
CCDC6		psi-mi:“MI:0915”(physical association)	0.560
CCDC6	SNAPC1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (397): CCDC6 (Affinity Capture-MS), CCDC6 (Affinity Capture-MS), CCDC6 (Affinity Capture-MS), CCDC6 (Affinity Capture-MS), CCDC6 (Affinity Capture-MS), CCDC6 (Affinity Capture-MS), CCDC6 (Co-fractionation), CCDC6 (Co-fractionation), CCDC6 (Co-fractionation), SEPT2 (Co-fractionation), CCDC6 (Affinity Capture-MS), CCDC6 (Affinity Capture-MS), P4HB (Affinity Capture-MS), PPP2R1A (Affinity Capture-MS), CCDC6 (Affinity Capture-MS)

ESM2 similar proteins: A1YB07, A4IIE8, D3YZP9, E1BEQ5, O42400, O43439, O70239, O70374, O75069, O94876, P49140, Q02225, Q06455, Q0P485, Q0V989, Q13136, Q16204, Q3LGD4, Q4V872, Q4VCS5, Q5R8Q4, Q5RDH2, Q5SP85, Q61909, Q62415, Q69ZZ6, Q6DFC2, Q6DHL7, Q6NUC6, Q7KW14, Q7PQ25, Q80W04, Q86TB9, Q86YS3, Q8BH60, Q8IY63, Q8R310, Q8VHG2, Q91Z80, Q920B0

Diamond homologs: D3YZP9, Q16204

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CDK2	up-regulates	CCDC6	phosphorylation
ATM	up-regulates	CCDC6	phosphorylation
FBXW7	down-regulates	CCDC6	binding
MAPK3	“up-regulates activity”	CCDC6	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 138 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
Activation of BAD and translocation to mitochondria	6	48.1×	4e-07
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	42.4×	5e-07
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	42.4×	5e-07
Activation of BH3-only proteins	6	31.4×	3e-06
RHO GTPases activate PKNs	6	20.0×	2e-05
Intrinsic Pathway for Apoptosis	6	18.5×	3e-05
Apoptosis	8	14.1×	6e-06
Loss of Nlp from mitotic centrosomes	8	13.4×	7e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	15.3×	8e-03
intracellular protein localization	8	7.0×	8e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — BCC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2437 predictions. Top by Δscore:

Variant	Effect	Δscore
10:59794471:A:AC	donor_gain	1.0000
10:59794472:C:CC	donor_gain	1.0000
10:59794595:GACC:G	acceptor_loss	1.0000
10:59794596:ACC:A	acceptor_loss	1.0000
10:59794597:CCTA:C	acceptor_loss	1.0000
10:59794598:CTAA:C	acceptor_loss	1.0000
10:59794599:T:G	acceptor_loss	1.0000
10:59806951:A:AC	donor_gain	1.0000
10:59806952:C:CC	donor_gain	1.0000
10:59806952:CT:C	donor_gain	1.0000
10:59807074:TGAAT:T	acceptor_gain	1.0000
10:59807075:GAAT:G	acceptor_gain	1.0000
10:59807076:AAT:A	acceptor_gain	1.0000
10:59807076:AATC:A	acceptor_loss	1.0000
10:59807077:AT:A	acceptor_gain	1.0000
10:59807079:C:CC	acceptor_gain	1.0000
10:59807079:CTGAA:C	acceptor_loss	1.0000
10:59812630:CGT:C	donor_loss	1.0000
10:59812631:GTACG:G	donor_loss	1.0000
10:59812632:TA:T	donor_loss	1.0000
10:59812633:A:AC	donor_gain	1.0000
10:59812633:A:C	donor_loss	1.0000
10:59812633:ACG:A	donor_gain	1.0000
10:59812634:C:CG	donor_gain	1.0000
10:59812634:CG:C	donor_gain	1.0000
10:59812634:CGC:C	donor_gain	1.0000
10:59812634:CGCT:C	donor_gain	1.0000
10:59812641:A:C	donor_gain	1.0000
10:59812791:GGATT:G	acceptor_gain	1.0000
10:59812796:C:CC	acceptor_gain	1.0000

AlphaMissense

3102 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:59804469:G:C	S352R	1.000
10:59804469:G:T	S352R	1.000
10:59804471:T:G	S352R	1.000
10:59804520:C:A	R335S	1.000
10:59804520:C:G	R335S	1.000
10:59806922:C:A	R335M	1.000
10:59806922:C:G	R335T	1.000
10:59806926:C:T	E334K	1.000
10:59806932:C:G	D332H	1.000
10:59806934:A:G	M331T	1.000
10:59806934:A:T	M331K	1.000
10:59806938:C:T	E330K	1.000
10:59806940:A:G	L329S	1.000
10:59806942:G:C	S328R	1.000
10:59806942:G:T	S328R	1.000
10:59806944:T:G	S328R	1.000
10:59806946:G:A	S327F	1.000
10:59806947:A:G	S327P	1.000
10:59806950:C:T	E326K	1.000
10:59806951:A:C	S325R	1.000
10:59806951:A:T	S325R	1.000
10:59806952:C:A	S325I	1.000
10:59806953:T:G	S325R	1.000
10:59806958:G:A	S323F	1.000
10:59806958:G:T	S323Y	1.000
10:59806959:A:G	S323P	1.000
10:59806961:A:G	L322P	1.000
10:59806961:A:T	L322H	1.000
10:59806967:C:G	R320P	1.000
10:59806973:A:G	L318P	1.000

dbSNP variants (sampled 300 via entrez): RS1000004678 (10:59851545 G>A), RS1000040187 (10:59808909 T>C), RS1000046039 (10:59850038 T>C), RS1000056215 (10:59907010 C>T), RS1000095598 (10:59856165 G>A), RS1000103138 (10:59906794 C>T), RS1000110376 (10:59815637 T>A,C), RS1000149515 (10:59856420 A>G), RS1000151258 (10:59823118 C>A,T), RS1000158037 (10:59899577 C>G), RS1000159480 (10:59864524 G>A), RS1000184524 (10:59816918 T>C), RS1000216558 (10:59821477 A>T), RS1000217658 (10:59905622 G>C), RS1000247691 (10:59821656 G>A)

Disease associations

OMIM: gene MIM:601985 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST004866_1	Alopecia areata	6.000000e-06
GCST006979_586	Heel bone mineral density	2.000000e-12
GCST007095_140	Systolic blood pressure	6.000000e-07
GCST007095_141	Systolic blood pressure	4.000000e-07
GCST007096_107	Pulse pressure	4.000000e-08
GCST007097_143	Pulse pressure	3.000000e-06
GCST007097_144	Pulse pressure	1.000000e-06
GCST007099_92	Systolic blood pressure	2.000000e-07
GCST009391_1648	Metabolite levels	6.000000e-26
GCST009391_1657	Metabolite levels	7.000000e-06
GCST90002393_353	Monocyte count	8.000000e-13
GCST90002394_343	Monocyte percentage of white cells	3.000000e-15

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0010469	carnitine measurement
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3430904 (CHIMERIC PROTEIN), CHEMBL6195575 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 73,696 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1289601	LENVATINIB	4	8,784
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL4582651	PRALSETINIB	4	1,414
CHEMBL2029988	CEP-32496	2	1,136

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

ChEMBL bioactivities

84 potent at pChembl≥5 of 84 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.2	nM	CHEMBL6133093
9.62	IC50	0.24	nM	CHEMBL6083074
9.54	IC50	0.29	nM	CHEMBL6078603
9.52	IC50	0.3	nM	CHEMBL6133093
9.48	IC50	0.33	nM	CEP-32496
9.40	IC50	0.4	nM	CHEMBL5171764
9.20	IC50	0.63	nM	CHEMBL6143118
9.17	IC50	0.67	nM	CHEMBL4473213
9.01	IC50	0.97	nM	CHEMBL6091882
8.82	IC50	1.5	nM	CHEMBL6120359
8.80	IC50	1.6	nM	CHEMBL5430810
8.66	IC50	2.2	nM	CHEMBL6114884
8.66	IC50	2.2	nM	CHEMBL6132683
8.65	IC50	2.22	nM	STAUROSPORINE
8.64	IC50	2.3	nM	CHEMBL6078603
8.62	IC50	2.4	nM	CHEMBL6102816
8.52	IC50	3	nM	CHEMBL5572034
8.51	IC50	3.1	nM	CHEMBL6083074
8.48	IC50	3.3	nM	CHEMBL6146359
8.47	IC50	3.4	nM	CHEMBL6141799
8.47	IC50	3.4	nM	CHEMBL6132683
8.46	IC50	3.5	nM	CHEMBL6091882
8.43	IC50	3.7	nM	CHEMBL6132745
8.40	IC50	4	nM	CHEMBL6141799
8.38	IC50	4.2	nM	PRALSETINIB
8.38	IC50	4.2	nM	CHEMBL6078524
8.37	IC50	4.3	nM	CHEMBL6078524
8.32	IC50	4.8	nM	CHEMBL6078080
8.31	IC50	4.9	nM	CHEMBL6143118
8.28	IC50	5.3	nM	CHEMBL4644274
8.27	IC50	5.43	nM	CHEMBL4790634
8.27	IC50	5.4	nM	CHEMBL6102816
8.21	IC50	6.2	nM	CHEMBL4639022
8.21	IC50	6.1	nM	CHEMBL6143967
8.15	IC50	7	nM	CEP-32496
8.07	IC50	8.5	nM	CHEMBL6149497
8.03	IC50	9.4	nM	CHEMBL6078080
8.00	IC50	10	nM	LENVATINIB
7.96	IC50	11	nM	CHEMBL6132683
7.95	IC50	11.2	nM	CHEMBL6133093
7.90	IC50	12.5	nM	CHEMBL6078415
7.89	IC50	13	nM	CHEMBL6103486
7.82	IC50	15	nM	CHEMBL4643578
7.82	IC50	15.2	nM	CHEMBL6132745
7.82	IC50	15.3	nM	CHEMBL6102760
7.81	IC50	15.5	nM	CHEMBL6102816
7.80	IC50	16	nM	CHEMBL4636056
7.80	IC50	15.7	nM	CHEMBL6078524
7.76	IC50	17.5	nM	CHEMBL6091882
7.75	IC50	17.6	nM	CHEMBL5430810

PubChem BioAssay actives

27 with measured affinity, of 89 total; 23 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
1-[3-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-[5-(1,1,1-trifluoro-2-methylpropan-2-yl)-1,2-oxazol-3-yl]urea	1895750: Inhibition of CCDC6-RET (unknown origin)	ic50	0.0003	uM
N-[(1S)-1-[6-(4-fluoropyrazol-1-yl)-3-pyridinyl]ethyl]-1-methoxy-4-[4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]cyclohexane-1-carboxamide	1895760: Inhibition of recombinant CCDC6-RET (unknown origin) incubated for 120 mins by Perkin Elmer electrophoretic mobility shift platform method	ic50	0.0004	uM
N-(5-tert-butyl-1,2-oxazol-3-yl)-2-[4-[5-(4-methylsulfonylphenyl)benzimidazol-1-yl]phenyl]acetamide	1561830: Inhibition of CCDC6/RET in human TPC1 cells assessed as reduction in cell proliferation supplemented with fresh medium containing compound for every 2 to 3 days and measured during compound dosing	ic50	0.0007	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1704868: Inhibition of human N-terminal GST-HIS6 fused CCDC6-RET fusion protein (Met1 to Ser503 residues) expressed in Sf9 insect cells using TRK-C-derived peptide as substrate in presence of [33P]-ATP by filter binding assay	ic50	0.0022	uM
5-[2-(8-amino-1,7-naphthyridin-5-yl)ethynyl]-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]pyridine-3-carboxamide	2091123: Inhibition of CCDC6-RET (unknown origin)	ic50	0.0030	uM
3-(3,4-dimethoxyphenyl)-5-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-6-phenylpyrazolo[1,5-a]pyrimidine-5,7-diamine	1648977: Inhibition of CCDC6/RET (unknown origin) transfected in human LC2/ad cells assessed as reduction in cell viability incubated for 6 days by CellTiter Glo assay	ic50	0.0053	uM
4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[(6-pyridin-3-yl-1H-pyrazolo[5,4-d]pyrimidin-4-yl)oxy]benzamide	1704868: Inhibition of human N-terminal GST-HIS6 fused CCDC6-RET fusion protein (Met1 to Ser503 residues) expressed in Sf9 insect cells using TRK-C-derived peptide as substrate in presence of [33P]-ATP by filter binding assay	ic50	0.0054	uM
[4-[7-amino-5-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]-6-phenylpyrazolo[1,5-a]pyrimidin-3-yl]phenyl]-(4-methylsulfonylpiperazin-1-yl)methanone	1648977: Inhibition of CCDC6/RET (unknown origin) transfected in human LC2/ad cells assessed as reduction in cell viability incubated for 6 days by CellTiter Glo assay	ic50	0.0062	uM
Lenvatinib	1204919: Inhibition of CCDC6/RET (unknown origin) autophoshorylation	ic50	0.0100	uM
methyl 4-[4-[7-amino-5-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]-6-phenylpyrazolo[1,5-a]pyrimidin-3-yl]benzoyl]piperazine-1-carboxylate	1648977: Inhibition of CCDC6/RET (unknown origin) transfected in human LC2/ad cells assessed as reduction in cell viability incubated for 6 days by CellTiter Glo assay	ic50	0.0150	uM
[4-[7-amino-5-[(1,2,2,6,6-pentamethylpiperidin-4-yl)amino]-6-phenylpyrazolo[1,5-a]pyrimidin-3-yl]phenyl]-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]methanone	1648977: Inhibition of CCDC6/RET (unknown origin) transfected in human LC2/ad cells assessed as reduction in cell viability incubated for 6 days by CellTiter Glo assay	ic50	0.0160	uM
Vandetanib	1895760: Inhibition of recombinant CCDC6-RET (unknown origin) incubated for 120 mins by Perkin Elmer electrophoretic mobility shift platform method	ic50	0.0200	uM
Cabozantinib	1895760: Inhibition of recombinant CCDC6-RET (unknown origin) incubated for 120 mins by Perkin Elmer electrophoretic mobility shift platform method	ic50	0.0340	uM
methyl N-[4-[4-amino-5-(3-amino-4-chlorophenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl]carbamate	1774935: Inhibition of CCDC6-RET fusion protein (unknown origin) expressed in human LC-2-ad cells assessed as reduction in cell proliferation incubated for 6 days by d CellTiter Glo assay	ic50	0.0350	uM
6,6-dimethyl-8-[1-(oxan-4-ylmethyl)piperidin-4-yl]-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	1312492: Inhibition of CCDC6-RET (unknown origin) expressed in mouse BaF3 cells assessed as inhibition of cell proliferation after 72 hrs by SRB/CCK-8 assay	ic50	0.0436	uM
1-[4-[3-[4-amino-5-(3-amino-4-chlorophenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclobutyl]piperazin-1-yl]ethanone	1774935: Inhibition of CCDC6-RET fusion protein (unknown origin) expressed in human LC-2-ad cells assessed as reduction in cell proliferation incubated for 6 days by d CellTiter Glo assay	ic50	0.0460	uM
methyl N-[4-[4-amino-5-(5-amino-4-chloro-2-fluorophenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-1-bicyclo[2.2.2]octanyl]carbamate	1774935: Inhibition of CCDC6-RET fusion protein (unknown origin) expressed in human LC-2-ad cells assessed as reduction in cell proliferation incubated for 6 days by d CellTiter Glo assay	ic50	0.0510	uM
3-(3,4-dimethoxyphenyl)-5-N-(1-methylpiperidin-4-yl)-6-phenylpyrazolo[1,5-a]pyrimidine-5,7-diamine	1648977: Inhibition of CCDC6/RET (unknown origin) transfected in human LC2/ad cells assessed as reduction in cell viability incubated for 6 days by CellTiter Glo assay	ic50	0.0560	uM
3-(3,4-dimethoxyphenyl)-5-(1-methylpiperidin-4-yl)oxy-6-phenylpyrazolo[1,5-a]pyrimidin-7-amine	1648977: Inhibition of CCDC6/RET (unknown origin) transfected in human LC2/ad cells assessed as reduction in cell viability incubated for 6 days by CellTiter Glo assay	ic50	0.0950	uM
methyl N-[4-[4-amino-5-(3-amino-4-chlorophenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-1-bicyclo[2.2.2]octanyl]carbamate	1774935: Inhibition of CCDC6-RET fusion protein (unknown origin) expressed in human LC-2-ad cells assessed as reduction in cell proliferation incubated for 6 days by d CellTiter Glo assay	ic50	0.1100	uM
3-(3,4-dimethoxyphenyl)-6-phenyl-5-piperidin-4-yloxypyrazolo[1,5-a]pyrimidin-7-amine	1648977: Inhibition of CCDC6/RET (unknown origin) transfected in human LC2/ad cells assessed as reduction in cell viability incubated for 6 days by CellTiter Glo assay	ic50	0.1600	uM
Ponatinib	1328572: Inhibition of CCDC6/RET (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation after 72 hrs by MTT assay	ic50	0.1804	uM
4-chloro-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[5-[5-(1-methylpyrazol-4-yl)-3-pyridinyl]-1,2,4-oxadiazol-3-yl]benzamide	1328572: Inhibition of CCDC6/RET (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation after 72 hrs by MTT assay	ic50	0.4069	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases expression	4
Arsenic	increases abundance, increases expression, affects methylation	2
Etoposide	decreases response to substance, increases response to substance	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
lead acetate	affects cotreatment, decreases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
zinc protoporphyrin	affects cotreatment, decreases expression	1
sodium arsenite	increases abundance, increases expression	1
cobaltous chloride	increases expression	1
coumarin	decreases phosphorylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
beta-methylcholine	affects expression	1
chloropicrin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
LDN 193189	decreases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Bortezomib	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Cannabinoids	affects methylation, increases abundance	1

ChEMBL screening assays

74 unique, capped per target: 74 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3428924	Binding	Inhibition of CCDC6/RET (unknown origin) autophoshorylation	Progress in Discovery of KIF5B-RET Kinase Inhibitors for the Treatment of Non-Small-Cell Lung Cancer. — J Med Chem

Cellosaurus cell lines

15 cell lines: 15 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1373	LC-2/ad	Cancer cell line	Female
CVCL_4W01	BHP2-7 Pazopanib selected	Cancer cell line	Female
CVCL_6278	BHP 10-3	Cancer cell line	Female
CVCL_6283	BHP 2-7	Cancer cell line	Female
CVCL_6285	BHP 7-13	Cancer cell line	Female
CVCL_6298	TPC-1	Cancer cell line	Female
CVCL_9917	FB-2	Cancer cell line	Female
CVCL_B1MG	Abcam HeLa CCDC6 KO	Cancer cell line	Female
CVCL_C4AM	LC-2/ad-cis	Cancer cell line	Female
CVCL_E3IT	HyCyte TPC-1-Luc	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice