CCDC181

Summary

CCDC181 (coiled-coil domain containing 181, HGNC:28051) is a protein-coding gene on chromosome 1q24.2, encoding Coiled-coil domain-containing protein 181 (Q5TID7). Microtubule-binding protein that is essential for the integrity and function of the manchette, facilitating proper sperm head shaping and subsequent flagellum formation during spermatogenesis.

Predicted to enable microtubule binding activity. Predicted to be located in manchette and sperm flagellum.

Source: NCBI Gene 57821 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_001300969

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28051
Approved symbol	CCDC181
Name	coiled-coil domain containing 181
Location	1q24.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25846
Ensembl gene	ENSG00000117477
Ensembl biotype	protein_coding
OMIM	620891
Entrez	57821

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000367805, ENST00000367806, ENST00000437857, ENST00000445428, ENST00000456107, ENST00000491570, ENST00000545005, ENST00000929705, ENST00000929706, ENST00000929707, ENST00000929708, ENST00000947028, ENST00000947029, ENST00000947030, ENST00000947031

RefSeq mRNA: 6 — MANE Select: NM_001300969 NM_001300968, NM_001300969, NM_001394007, NM_001394008, NM_001394009, NM_021179

CCDS: CCDS1279, CCDS72979

Canonical transcript exons

ENST00000367806 — 6 exons

Exon	Start	End
ENSE00000789589	169419013	169419159
ENSE00001445654	169397237	169397391
ENSE00001510702	169394870	169395206
ENSE00001812067	169427288	169427474
ENSE00003788752	169421363	169422313
ENSE00003933008	169424811	169424950

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 94.35.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6262 / max 215.3042, expressed in 540 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15835	1.3536	517
15834	0.2537	96
15836	0.0188	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	94.35	gold quality
male germ cell	CL:0000015	92.20	gold quality
bronchial epithelial cell	CL:0002328	91.88	gold quality
epithelium of bronchus	UBERON:0002031	90.82	gold quality
bronchus	UBERON:0002185	89.59	gold quality
left testis	UBERON:0004533	89.30	gold quality
right testis	UBERON:0004534	88.99	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.58	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.57	gold quality
testis	UBERON:0000473	87.56	gold quality
adenohypophysis	UBERON:0002196	87.25	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.16	gold quality
right uterine tube	UBERON:0001302	86.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.67	gold quality
pituitary gland	UBERON:0000007	86.50	gold quality
oocyte	CL:0000023	85.81	gold quality
secondary oocyte	CL:0000655	84.97	gold quality
Brodmann (1909) area 23	UBERON:0013554	84.70	gold quality
ventricular zone	UBERON:0003053	83.26	gold quality
choroid plexus epithelium	UBERON:0003911	82.92	gold quality
middle temporal gyrus	UBERON:0002771	82.59	gold quality
primary visual cortex	UBERON:0002436	81.90	gold quality
endothelial cell	CL:0000115	80.62	silver quality
cortical plate	UBERON:0005343	80.22	gold quality
hypothalamus	UBERON:0001898	80.01	gold quality
islet of Langerhans	UBERON:0000006	79.88	gold quality
pigmented layer of retina	UBERON:0001782	79.61	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.09	gold quality
nucleus accumbens	UBERON:0001882	78.55	gold quality
ganglionic eminence	UBERON:0004023	77.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.34
E-MTAB-9388	yes	6.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting CCDC181, 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-4282	99.99	75.36	6408
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-6760-3P	96.35	68.31	1001

Literature-anchored findings (GeneRIF, showing 1)

• High C1orf114 methylation was associated with biochemical recurrence in prostate cancer. (PMID:23918943)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc181	ENSDARG00000062021
mus_musculus	Ccdc181	ENSMUSG00000026578
rattus_norvegicus	Ccdc181	ENSRNOG00000002860

Protein

Protein identifiers

Coiled-coil domain-containing protein 181 — Q5TID7 (reviewed: Q5TID7)

All UniProt accessions (2): Q5TID7, X6RJ50

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule-binding protein that is essential for the integrity and function of the manchette, facilitating proper sperm head shaping and subsequent flagellum formation during spermatogenesis.

Subunit / interactions. Homodimer. Interacts with HOOK1. Interacts with HOOK2. Interacts with HOOK3. Interacts with LRRC46; interaction is essential for proper localization of LRRC46 to sperm flagella.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Cilium. Flagellum. Cilium axoneme.

Similarity. Belongs to the CCDC181 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5TID7-1	1	yes
Q5TID7-2	2
Q5TID7-3	3

RefSeq proteins (6): NP_001287897, NP_001287898, NP_001380936, NP_001380937, NP_001380938, NP_067002 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026687	CCDC181	Family

UniProt features (14 total): compositionally biased region 4, sequence variant 3, region of interest 2, splice variant 2, chain 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TID7-F1	68.92	0.28

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 100 (showing top): GOBP_MALE_GAMETE_GENERATION, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, KONDO_COLON_CANCER_HCP_WITH_H3K27ME1, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, AACTTT_UNKNOWN, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MOTILE_CILIUM_ASSEMBLY, RFX1_02, GOBP_CELL_PROJECTION_ORGANIZATION, GOCC_CYTOPLASMIC_REGION, RYTGCNWTGGNR_UNKNOWN

GO Biological Process (3): spermatid development (GO:0007286), sperm flagellum assembly (GO:0120316), manchette assembly (GO:1905198)

GO Molecular Function (1): microtubule binding (GO:0008017)

GO Cellular Component (9): manchette (GO:0002177), microtubule (GO:0005874), cilium (GO:0005929), axoneme (GO:0005930), sperm flagellum (GO:0036126), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
spermatid development	2
microtubule cytoskeleton	2
germ cell development	1
spermatid differentiation	1
developmental process involved in reproduction	1
flagellated sperm motility	1
motile cilium assembly	1
cellular component assembly	1
tubulin binding	1
polymeric cytoskeletal fiber	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
9+2 motile cilium	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cilium	1

Protein interactions and networks

STRING

526 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC181	HAPLN3	Q96S86	699
CCDC181	HOOK1	Q9UJC3	664
CCDC181	AOX1	Q06278	625
CCDC181	ZNF660	Q6AZW8	608
CCDC181	SAXO4	Q7Z5V6	574
CCDC181	IQCF1	Q8N6M8	523
CCDC181	ANKRD9	Q96BM1	490
CCDC181	MRPL30	Q8TCC3	490
CCDC181	ST6GALNAC3	Q8NDV1	475
CCDC181	BLZF1	Q9H2G9	469
CCDC181	NME7	Q9Y5B8	465
CCDC181	MOB3B	Q86TA1	447
CCDC181	OR6S1	Q8NH40	447
CCDC181	ZNF706	Q9Y5V0	434
CCDC181	ZNF454	Q8N9F8	432

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CCDC181	LMNB1	psi-mi:“MI:0915”(physical association)	0.400
CCDC181	ABCF1	psi-mi:“MI:0915”(physical association)	0.400
CCDC181	PPP1R7	psi-mi:“MI:0915”(physical association)	0.400
CCDC181		psi-mi:“MI:0915”(physical association)	0.370
CCDC181	PPP1CA	psi-mi:“MI:0915”(physical association)	0.370
FMOD	SERPINB3	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): ABCF1 (Proximity Label-MS), CCDC181 (Proximity Label-MS), CCDC181 (Affinity Capture-MS), PPP1R7 (Affinity Capture-MS), CCDC181 (Affinity Capture-MS), NAV3 (Cross-Linking-MS (XL-MS)), CCDC181 (Protein-peptide), CCDC181 (Affinity Capture-MS), CCDC181 (Two-hybrid)

ESM2 similar proteins: A2BDB7, A2CE83, B2ZX90, D3IUT5, E1BXS0, F4IDY7, P0DPK0, P49069, P58501, Q07532, Q0P4A6, Q1JQE2, Q28GJ0, Q28GL6, Q2KJD6, Q2MJV9, Q2TBJ0, Q2WG79, Q2WG80, Q5F3D1, Q5R789, Q5TID7, Q5U3I2, Q5ZHQ6, Q640U0, Q641E3, Q66H73, Q67W65, Q68F53, Q6AYN9, Q6DRL4, Q6NZY4, Q7TPE5, Q7Z2Z1, Q7ZX27, Q80YR7, Q80ZU5, Q86XK3, Q8BQ33, Q8C6C7

Diamond homologs: Q4R6Q9, Q5NVK0, Q5TID7, Q6AYN9, Q80ZU5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1108 predictions. Top by Δscore:

Variant	Effect	Δscore
1:169395203:CCAT:C	acceptor_gain	1.0000
1:169395204:CATC:C	acceptor_gain	1.0000
1:169397235:A:AC	donor_gain	1.0000
1:169397235:A:C	donor_loss	1.0000
1:169397236:C:CC	donor_gain	1.0000
1:169397236:C:CG	donor_loss	1.0000
1:169397236:CT:C	donor_gain	1.0000
1:169397236:CTG:C	donor_gain	1.0000
1:169397288:T:A	donor_gain	1.0000
1:169397389:CTG:C	acceptor_gain	1.0000
1:169397390:TGCTG:T	acceptor_loss	1.0000
1:169397391:GC:G	acceptor_loss	1.0000
1:169397392:C:A	acceptor_loss	1.0000
1:169397392:C:CC	acceptor_gain	1.0000
1:169397393:T:G	acceptor_loss	1.0000
1:169419011:A:AC	donor_gain	1.0000
1:169419012:C:CC	donor_gain	1.0000
1:169419012:CT:C	donor_gain	1.0000
1:169419012:CTCT:C	donor_gain	1.0000
1:169419012:CTCTA:C	donor_gain	1.0000
1:169419173:A:C	acceptor_gain	1.0000
1:169421357:TCTCA:T	donor_loss	1.0000
1:169421358:CTCA:C	donor_loss	1.0000
1:169421359:TCACC:T	donor_loss	1.0000
1:169421360:CACCT:C	donor_loss	1.0000
1:169421362:CCT:C	donor_gain	1.0000
1:169421362:CCTCT:C	donor_gain	1.0000
1:169422309:GCCAT:G	acceptor_gain	1.0000
1:169422310:CCAT:C	acceptor_gain	1.0000
1:169422310:CCATC:C	acceptor_gain	1.0000

AlphaMissense

3405 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:169397355:A:G	W418R	0.995
1:169397355:A:T	W418R	0.995
1:169421969:G:C	F154L	0.995
1:169421969:G:T	F154L	0.995
1:169421971:A:G	F154L	0.995
1:169419093:A:G	W379R	0.994
1:169419093:A:T	W379R	0.994
1:169397351:A:G	L419P	0.993
1:169421970:A:G	F154S	0.993
1:169397353:C:A	W418C	0.992
1:169397353:C:G	W418C	0.992
1:169421756:A:C	F225L	0.992
1:169421756:A:T	F225L	0.992
1:169421758:A:G	F225L	0.992
1:169395205:A:G	W458R	0.991
1:169395205:A:T	W458R	0.991
1:169397362:A:C	F415L	0.991
1:169397362:A:T	F415L	0.991
1:169397364:A:G	F415L	0.991
1:169422031:C:G	A134P	0.991
1:169419091:C:A	W379C	0.989
1:169419091:C:G	W379C	0.989
1:169395203:C:A	W458C	0.988
1:169395203:C:G	W458C	0.988
1:169419042:C:G	A396P	0.988
1:169419100:A:C	F376L	0.986
1:169419100:A:T	F376L	0.986
1:169419102:A:G	F376L	0.986
1:169397341:C:A	K422N	0.984
1:169397341:C:G	K422N	0.984

dbSNP variants (sampled 300 via entrez): RS1000065245 (1:169431081 G>C,T), RS1000101747 (1:169455871 T>G), RS1000107271 (1:169413374 G>A), RS1000158049 (1:169404471 T>C), RS1000218102 (1:169420340 T>A,C), RS1000331795 (1:169447452 A>G), RS1000401601 (1:169434316 C>A), RS1000432081 (1:169437158 G>T), RS1000461737 (1:169441015 A>G), RS1000521711 (1:169413025 G>T), RS1000614237 (1:169408493 C>G), RS1000646367 (1:169461785 T>C), RS1000732243 (1:169434055 T>C), RS1000739354 (1:169440942 A>C), RS1000790923 (1:169428108 G>T)

Disease associations

OMIM: gene MIM:620891 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	2
Air Pollutants	increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, decreases methylation	2
titanium dioxide	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Vorinostat	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Silicon Dioxide	decreases expression	1
Smoke	increases abundance, increases expression	1
Theophylline	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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