CCDC25

Summary

CCDC25 (coiled-coil domain containing 25, HGNC:25591) is a protein-coding gene on chromosome 8p21.1, encoding Coiled-coil domain-containing protein 25 (Q86WR0). Transmembrane receptor that senses neutrophil extracellular traps (NETs) and triggers the ILK-PARVB pathway to enhance cell motility.

Enables DNA binding activity. Involved in positive regulation of cell motility. Located in endomembrane system and plasma membrane.

Source: NCBI Gene 55246 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 49 total
• MANE Select transcript: NM_018246

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25591
Approved symbol	CCDC25
Name	coiled-coil domain containing 25
Location	8p21.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10853
Ensembl gene	ENSG00000147419
Ensembl biotype	protein_coding
OMIM	619100
Entrez	55246

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 6 protein_coding, 5 nonsense_mediated_decay, 3 retained_intron

ENST00000356537, ENST00000517979, ENST00000519299, ENST00000519509, ENST00000519843, ENST00000520202, ENST00000520486, ENST00000521220, ENST00000522915, ENST00000523841, ENST00000524084, ENST00000869301, ENST00000931261, ENST00000931262

RefSeq mRNA: 4 — MANE Select: NM_018246 NM_001304529, NM_001304530, NM_001304532, NM_018246

CCDS: CCDS6062, CCDS78323, CCDS78324

Canonical transcript exons

ENST00000356537 — 9 exons

Exon	Start	End
ENSE00003485194	27772513	27772640
ENSE00003505472	27765204	27765251
ENSE00003551718	27762419	27762458
ENSE00003553972	27752512	27752587
ENSE00003554117	27756719	27756770
ENSE00003639429	27748495	27748598
ENSE00003671453	27748077	27748279
ENSE00003683810	27740472	27740517
ENSE00003694097	27733316	27736245

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 98.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.5974 / max 775.5929, expressed in 1800 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92511	22.5353	1800
92508	0.0386	19
92507	0.0235	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.47	gold quality
secondary oocyte	CL:0000655	98.47	gold quality
calcaneal tendon	UBERON:0003701	97.66	gold quality
tendon	UBERON:0000043	95.86	gold quality
duodenum	UBERON:0002114	94.99	gold quality
jejunal mucosa	UBERON:0000399	94.50	gold quality
sural nerve	UBERON:0015488	93.08	gold quality
adrenal tissue	UBERON:0018303	92.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.27	gold quality
tendon of biceps brachii	UBERON:0008188	92.27	gold quality
corpus epididymis	UBERON:0004359	92.11	gold quality
jejunum	UBERON:0002115	91.97	gold quality
spinal cord	UBERON:0002240	91.48	gold quality
islet of Langerhans	UBERON:0000006	91.41	gold quality
rectum	UBERON:0001052	91.33	gold quality
adrenal gland	UBERON:0002369	91.11	gold quality
left adrenal gland	UBERON:0001234	91.08	gold quality
right adrenal gland cortex	UBERON:0035827	91.07	gold quality
muscle of leg	UBERON:0001383	91.03	gold quality
colonic epithelium	UBERON:0000397	90.98	gold quality
prefrontal cortex	UBERON:0000451	90.94	gold quality
substantia nigra	UBERON:0002038	90.93	gold quality
anterior cingulate cortex	UBERON:0009835	90.91	gold quality
right adrenal gland	UBERON:0001233	90.86	gold quality
cingulate cortex	UBERON:0003027	90.84	gold quality
gastrocnemius	UBERON:0001388	90.80	gold quality
pons	UBERON:0000988	90.64	gold quality
midbrain	UBERON:0001891	90.62	gold quality
caput epididymis	UBERON:0004358	90.60	gold quality
putamen	UBERON:0001874	90.58	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	382.28
E-ANND-3	yes	8.43
E-GEOD-100618	no	601.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting CCDC25, 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-4795-3P	100.00	74.62	4024
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-10393-3P	99.72	66.56	961

Literature-anchored findings (GeneRIF, showing 6)

• DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25. (PMID:32528174)
• CCDC25: precise navigator for neutrophil extracellular traps on the prometastatic road. (PMID:32839429)
• Kallikrein-11, in Association with Coiled-Coil Domain Containing 25, as a Potential Prognostic Marker for Cholangiocarcinoma with Lymph Node Metastasis. (PMID:34067437)
• Enhanced CHOLESTEROL biosynthesis promotes breast cancer metastasis via modulating CCDC25 expression and neutrophil extracellular traps formation. (PMID:36253427)
• Coiled-coil domain containing 25 (CCDC25) regulates cell proliferation, migration, and invasion in clear cell renal cell carcinoma by targeting the ILK-NF-kappaB signaling pathway. (PMID:38236371)
• Serum CCDC25 Levels as a Potential Marker for Metabolic Syndrome. (PMID:38418150)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc25	ENSDARG00000021753
mus_musculus	Ccdc25	ENSMUSG00000022035
rattus_norvegicus	Ccdc25	ENSRNOG00000015939
drosophila_melanogaster	CG4593	FBGN0029929
caenorhabditis_elegans		WBGENE00013213
caenorhabditis_elegans		WBGENE00023423

Protein

Protein identifiers

Coiled-coil domain-containing protein 25 — Q86WR0 (reviewed: Q86WR0)

All UniProt accessions (5): Q86WR0, B7Z2L8, E5RI21, G3V121, Q0VGD4

UniProt curated annotations — full annotation on UniProt →

Function. Transmembrane receptor that senses neutrophil extracellular traps (NETs) and triggers the ILK-PARVB pathway to enhance cell motility. NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation. Formation of NETs is also associated with cancer metastasis, NET-DNA acting as a chemotactic factor to attract cancer cells. Specifically binds NETs on its extracellular region, in particular the 8-OHdG-enriched DNA present in NETs, and recruits ILK, initiating the ILK-PARVB cascade to induce cytoskeleton rearrangement and directional migration of cells. In the context of cancer, promotes cancer metastasis by sensing NETs and promoting migration of tumor cells.

Subunit / interactions. Interacts (via cytoplasmic region) with ILK.

Subcellular location. Cell membrane. Endomembrane system.

Similarity. Belongs to the CCDC25 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86WR0-1	1	yes
Q86WR0-2	2

RefSeq proteins (4): NP_001291458, NP_001291459, NP_001291461, NP_060716* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008532	NFACT_RNA-bd	Domain
IPR039730	Jlp2/Ccd25	Family

Pfam: PF05670

UniProt features (28 total): strand 8, helix 6, topological domain 2, mutagenesis site 2, region of interest 2, modified residue 2, chain 1, splice variant 1, transmembrane region 1, turn 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7EOF	X-RAY DIFFRACTION	2.73
7EOE	X-RAY DIFFRACTION	2.9
8WOH	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86WR0-F1	82.83	0.28

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): 23, 204

Mutagenesis-validated functional residues (2):

Position	Phenotype
16–20	does not affect binding to neutrophil extracellular traps (nets).
21–25	abolished binding to neutrophil extracellular traps (nets).

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 112 (showing top): AACYNNNNTTCCS_UNKNOWN, AACWWCAANK_UNKNOWN, chr8p21, DOUGLAS_BMI1_TARGETS_DN, YRTCANNRCGC_UNKNOWN, YY1_01, HAN_SATB1_TARGETS_DN, AACTGGA_MIR145, TCCCRNNRTGC_UNKNOWN, MARSON_BOUND_BY_E2F4_UNSTIMULATED, SCGGAAGY_ELK1_02, STAT5A_01, MGGAAGTG_GABP_B, GCM_IL6ST, ELK1_02

GO Biological Process (1): positive regulation of cell motility (GO:2000147)

GO Molecular Function (2): DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
positive regulation of locomotion	1
positive regulation of cellular process	1
cell motility	1
regulation of cell motility	1
nucleic acid binding	1
binding	1
membrane	1
cell periphery	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

844 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC25	PARVB	Q9HBI1	632
CCDC25	SH2D4A	Q9H788	453
CCDC25	ILK	P57043	446
CCDC25	IWS1	Q96ST2	435
CCDC25	SRD5A3	Q9H8P0	427
CCDC25	ROM1	Q03395	403
CCDC25	RNASEH2A	O75792	399
CCDC25	PLPBP	O94903	380
CCDC25	CYTH3	O43739	365
CCDC25	PADI4	Q9UM07	359
CCDC25	ELP3	Q9H9T3	316
CCDC25	KLK11	Q9UBX7	314
CCDC25	ELANE	P08246	312
CCDC25	SORBS3	O60504	310
CCDC25	DNAJA3	Q96EY1	306
CCDC25	CYTH1	Q15438	306

IntAct

29 interactions, top by confidence:

A	B	Type	Score
CCDC25	TRIM23	psi-mi:“MI:0915”(physical association)	0.560
FLJ13057	CCDC25	psi-mi:“MI:0915”(physical association)	0.560
CCDC25	FLJ13057	psi-mi:“MI:0915”(physical association)	0.560
CCDC25	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
OR5F1	UBA6	psi-mi:“MI:0914”(association)	0.530
MCRIP2	CASC3	psi-mi:“MI:0914”(association)	0.530
CCDC25	AGTR1	psi-mi:“MI:0915”(physical association)	0.370
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC25A32	NEDD8-MDP1	psi-mi:“MI:0914”(association)	0.350
SLC25A32	AKR1A1	psi-mi:“MI:0914”(association)	0.350
BCAR3	CREB1	psi-mi:“MI:0914”(association)	0.350
AZU1	UBA6	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
KIAA1191	UBA6	psi-mi:“MI:0914”(association)	0.350
OAS1	UBA6	psi-mi:“MI:0914”(association)	0.350
RPF1	CAPG	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
WNT10B	VWA8	psi-mi:“MI:0914”(association)	0.350
ESR2	PSMD11	psi-mi:“MI:0914”(association)	0.350
H2BC10	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
EGFR	FAM171A2	psi-mi:“MI:2364”(proximity)	0.270
RYK	FAM171A2	psi-mi:“MI:2364”(proximity)	0.270
PLEKHF2	CCDC25	psi-mi:“MI:0915”(physical association)	0.000
SMAD2	CCDC25	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (45): CCDC25 (Two-hybrid), GMCL1 (Two-hybrid), CCDC25 (Affinity Capture-RNA), CCDC25 (Affinity Capture-RNA), CCDC25 (Affinity Capture-MS), CCDC25 (Affinity Capture-MS), CCDC25 (Affinity Capture-MS), CCDC25 (Co-fractionation), CCDC25 (Co-fractionation), NPEPL1 (Co-fractionation), CCDC25 (Proximity Label-MS), CCDC25 (Affinity Capture-MS), CCDC25 (Affinity Capture-MS), CCDC25 (Proximity Label-MS), CCDC25 (Proximity Label-MS)

ESM2 similar proteins: A0JN39, B9N1F9, D2SW95, E0CSI1, F1QH17, O48556, O60832, O60942, O82597, O82793, P11029, P11497, P21343, P23514, P50502, P53618, Q0J035, Q13085, Q28559, Q2YDN6, Q3SZX8, Q43187, Q5R4J9, Q5R922, Q5R9S1, Q5RF31, Q5SWU9, Q5XGY9, Q5ZIA5, Q5ZID6, Q5ZJH9, Q66HV4, Q6GLE1, Q78PG9, Q7T312, Q80UM3, Q86WR0, Q8IZH2, Q8K396, Q8L5Y9

Diamond homologs: P40206, Q3SZX8, Q55D55, Q5R9S1, Q6GLE1, Q78PG9, Q7T312, Q86WR0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

49 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	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1399 predictions. Top by Δscore:

Variant	Effect	Δscore
8:27745637:AGAG:A	donor_gain	1.0000
8:27752507:CTGA:C	donor_loss	1.0000
8:27752508:TGACC:T	donor_loss	1.0000
8:27752509:GACCT:G	donor_loss	1.0000
8:27752510:A:AG	donor_loss	1.0000
8:27752511:CCT:C	donor_loss	1.0000
8:27756714:GTTA:G	donor_loss	1.0000
8:27756715:TTAC:T	donor_loss	1.0000
8:27756716:TA:T	donor_loss	1.0000
8:27756717:A:C	donor_loss	1.0000
8:27756718:CCTTA:C	donor_loss	1.0000
8:27762415:TTA:T	donor_loss	1.0000
8:27762417:A:AC	donor_gain	1.0000
8:27762417:AC:A	donor_gain	1.0000
8:27762417:ACC:A	donor_loss	1.0000
8:27762418:C:CC	donor_gain	1.0000
8:27762418:CC:C	donor_gain	1.0000
8:27762418:CCA:C	donor_gain	1.0000
8:27762418:CCAG:C	donor_gain	1.0000
8:27762418:CCAGA:C	donor_gain	1.0000
8:27762458:TCT:T	acceptor_loss	1.0000
8:27762459:CT:C	acceptor_loss	1.0000
8:27762469:A:AC	acceptor_gain	1.0000
8:27762469:A:C	acceptor_gain	1.0000
8:27762471:A:AC	acceptor_gain	1.0000
8:27762471:A:C	acceptor_gain	1.0000
8:27765248:TTAA:T	acceptor_gain	1.0000
8:27765249:TAA:T	acceptor_gain	1.0000
8:27765250:AA:A	acceptor_gain	1.0000
8:27765252:C:CC	acceptor_gain	1.0000

AlphaMissense

1413 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:27748510:A:C	F111L	1.000
8:27748510:A:T	F111L	1.000
8:27748512:A:G	F111L	1.000
8:27748523:C:T	G107E	1.000
8:27748524:C:A	G107W	1.000
8:27748524:C:G	G107R	1.000
8:27748524:C:T	G107R	1.000
8:27748550:A:G	L98P	1.000
8:27752512:C:G	G82R	1.000
8:27752535:A:G	L74P	1.000
8:27756732:A:G	L52P	1.000
8:27756738:A:T	V50E	1.000
8:27756740:A:C	H49Q	1.000
8:27756740:A:T	H49Q	1.000
8:27756742:G:C	H49D	1.000
8:27756744:G:T	A48D	1.000
8:27756764:A:C	H41Q	1.000
8:27756764:A:T	H41Q	1.000
8:27756766:G:C	H41D	1.000
8:27756766:G:T	H41N	1.000
8:27762449:A:G	L29P	1.000
8:27765221:C:A	G20V	1.000
8:27765221:C:T	G20E	1.000
8:27765222:C:G	G20R	1.000
8:27765222:C:T	G20R	1.000
8:27748511:A:G	F111S	0.999
8:27748517:A:C	I109R	0.999
8:27748517:A:T	I109K	0.999
8:27748520:T:G	Q108P	0.999
8:27748523:C:A	G107V	0.999

dbSNP variants (sampled 300 via entrez): RS1000004034 (8:27773632 G>A,T), RS1000041324 (8:27745605 T>C), RS1000209115 (8:27746810 G>A), RS1000255792 (8:27769935 A>G), RS1000447632 (8:27743886 T>C), RS1000519015 (8:27765259 A>T), RS1000571635 (8:27765009 A>G), RS1000582921 (8:27750669 T>C), RS1000684632 (8:27763130 A>T), RS1000736125 (8:27770854 A>G), RS1001106782 (8:27758393 G>C), RS1001168354 (8:27757168 G>T), RS1001196733 (8:27754627 A>G), RS1001304436 (8:27768590 A>G), RS1001320726 (8:27760532 C>T)

Disease associations

OMIM: gene MIM:619100 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008839_257	Height	1.000000e-07
GCST008839_535	Height	1.000000e-11
GCST010002_272	Refractive error	3.000000e-16

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment	5
Cadmium Chloride	decreases expression, increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
beta-methylcholine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	increases expression, decreases reaction	1
Benzo(a)pyrene	affects methylation	1
Paraquat	increases expression	1
Phthalic Acids	decreases methylation	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Genistein	increases expression, increases reaction	1
tert-Butylhydroperoxide	decreases expression	1
Particulate Matter	decreases reaction, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8IK	Ubigene HCT 116 CCDC25 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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