CCDC61

Summary

CCDC61 (coiled-coil domain containing 61, HGNC:33629) is a protein-coding gene on chromosome 19q13.32, encoding Centrosomal protein CCDC61 (Q9Y6R9). Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker.

Enables identical protein binding activity and microtubule binding activity. Involved in centriole assembly and mitotic spindle assembly. Located in centriolar satellite and ciliary basal body. Part of centriolar subdistal appendage.

Source: NCBI Gene 729440 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 21 total — 1 pathogenic
• MANE Select transcript: NM_001267723

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33629
Approved symbol	CCDC61
Name	coiled-coil domain containing 61
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	VFL3, hVFL3
Ensembl gene	ENSG00000104983
Ensembl biotype	protein_coding
OMIM	620676
Entrez	729440

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 21 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000536603, ENST00000594087, ENST00000594672, ENST00000595358, ENST00000596161, ENST00000596687, ENST00000599044, ENST00000601763, ENST00000897318, ENST00000897319, ENST00000897320, ENST00000897321, ENST00000897322, ENST00000897323, ENST00000897324, ENST00000916385, ENST00000916386, ENST00000916387, ENST00000916388, ENST00000959914, ENST00000959915, ENST00000959916, ENST00000959917, ENST00000959918, ENST00000959919

RefSeq mRNA: 1 — MANE Select: NM_001267723 NM_001267723

CCDS: CCDS46120

Canonical transcript exons

ENST00000595358 — 14 exons

Exon	Start	End
ENSE00000713753	46017247	46017304
ENSE00000713785	46018078	46018150
ENSE00000713800	46018290	46018616
ENSE00000858273	46015345	46015427
ENSE00000858275	46016318	46016393
ENSE00000858276	46016694	46016833
ENSE00000858277	46016991	46017069
ENSE00003054228	45995467	45995504
ENSE00003217843	46016054	46016223
ENSE00003531910	46006559	46006716
ENSE00003596671	46003008	46003166
ENSE00003674844	46015049	46015259
ENSE00003686281	46008140	46008301
ENSE00003790586	46003419	46003501

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 95.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1160 / max 81.2498, expressed in 1734 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176518	6.1160	1734

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	95.94	gold quality
right testis	UBERON:0004534	90.84	gold quality
left testis	UBERON:0004533	90.65	gold quality
granulocyte	CL:0000094	87.83	gold quality
mucosa of transverse colon	UBERON:0004991	87.72	gold quality
testis	UBERON:0000473	86.98	gold quality
adenohypophysis	UBERON:0002196	86.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.78	gold quality
lower esophagus mucosa	UBERON:0035834	84.99	gold quality
cerebellar hemisphere	UBERON:0002245	84.75	gold quality
cerebellar cortex	UBERON:0002129	84.51	gold quality
right lobe of thyroid gland	UBERON:0001119	84.33	gold quality
pituitary gland	UBERON:0000007	84.11	gold quality
right adrenal gland	UBERON:0001233	83.91	gold quality
right adrenal gland cortex	UBERON:0035827	83.71	gold quality
left ovary	UBERON:0002119	83.70	gold quality
right ovary	UBERON:0002118	83.37	gold quality
left adrenal gland cortex	UBERON:0035825	83.33	gold quality
body of stomach	UBERON:0001161	83.25	gold quality
left adrenal gland	UBERON:0001234	83.13	gold quality
transverse colon	UBERON:0001157	83.07	gold quality
left lobe of thyroid gland	UBERON:0001120	82.92	gold quality
left uterine tube	UBERON:0001303	82.84	gold quality
spleen	UBERON:0002106	82.72	gold quality
body of uterus	UBERON:0009853	82.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.66	gold quality
cerebellum	UBERON:0002037	82.51	gold quality
lower esophagus	UBERON:0013473	82.34	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.33	gold quality
right lobe of liver	UBERON:0001114	82.24	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.26

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• Ccdc61 controls centrosomal localization of Cep170 and is required for spindle assembly and symmetry. (PMID:30354798)
• hVFL3/CCDC61 is the human orthologue of proteins required for anchoring distinct sets of cytoskeletal fibers to centrioles in unicellular eukaryotes. (PMID:31789463)
• CCDC61/VFL3 Is a Paralog of SAS6 and Promotes Ciliary Functions. (PMID:32375023)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc61	ENSDARG00000062307
mus_musculus	Ccdc61	ENSMUSG00000074358
rattus_norvegicus	Ccdc61	ENSRNOG00000013767

Paralogs (1): SPTY2D1 (ENSG00000179119)

Protein

Protein identifiers

Centrosomal protein CCDC61 — Q9Y6R9 (reviewed: Q9Y6R9)

Alternative names: Coiled-coil domain-containing protein 61, VFL3 homolog

All UniProt accessions (3): Q9Y6R9, M0QY15, M0QYL5

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker. In interphase, required for anchoring microtubule at the mother centriole subdistal appendages and for centrosome positioning. During mitosis, may be involved in spindle assembly and chromatin alignment by regulating the organization of spindle microtubules into a symmetrical structure. Has been proposed to play a role in CEP170 recruitment to centrosomes. However, this function could not be confirmed. Plays a non-essential role in ciliogenesis.

Subunit / interactions. Forms homodimers (via head domain). Interacts with CEP170. Interacts with PCM1 and CEP131. Binds tubulin.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriolar satellite. Cilium basal body.

Domain organisation. The coiled-coil domains are involved in microtubule-binding.

Miscellaneous. The N-terminal 3D structure (head domain) resembles that of NHEJ1/XLF, PAXX, SASS6 and XRCC4.

Similarity. Belongs to the CCDC61 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y6R9-1	1	yes
Q9Y6R9-2	2

RefSeq proteins (1): NP_001254652* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR049733	CCDC61_N	Domain

UniProt features (35 total): modified residue 8, strand 7, mutagenesis site 6, helix 3, region of interest 2, sequence conflict 2, coiled-coil region 2, compositionally biased region 2, chain 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6HXT	X-RAY DIFFRACTION	2.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6R9-F1	71.97	0.40

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 (8): 336, 373, 376, 447, 473, 1, 285, 334

Mutagenesis-validated functional residues (6):

Position	Phenotype
128–129	loss of dimerization.
259	loss of microtubule-binding; when associated with e-263, e-266, e-268 and e-270.
263	loss of microtubule-binding; when associated with e-259, e-266, e-268 and e-270.
266	loss of microtubule-binding; when associated with e-259, e-263, e-268 and e-270.
268	loss of microtubule-binding; when associated with e-259, e-263, e-266 and e-270.
270	loss of microtubule-binding; when associated with e-259, e-263, e-266 and e-268.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 80 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_CHROMOSOME_ORGANIZATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_CENTRIOLE_ASSEMBLY, GOBP_MITOTIC_SPINDLE_ASSEMBLY, GOBP_ORGANELLE_FISSION, GOCC_CENTROSOME, GOBP_MITOTIC_NUCLEAR_DIVISION, GOBP_ORGANELLE_ASSEMBLY, GOBP_MITOTIC_CELL_CYCLE, GOBP_SPINDLE_ASSEMBLY, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_NUCLEAR_CHROMOSOME_SEGREGATION, GOCC_CILIUM, GOBP_CELL_CYCLE_PROCESS

GO Biological Process (3): cell projection organization (GO:0030030), mitotic spindle assembly (GO:0090307), centriole assembly (GO:0098534)

GO Molecular Function (3): microtubule binding (GO:0008017), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (8): centrosome (GO:0005813), microtubule organizing center (GO:0005815), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), centriolar subdistal appendage (GO:0120103), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
microtubule organizing center	2
cilium	2
cellular component organization	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1
mitotic nuclear division	1
microtubule organizing center organization	1
membraneless organelle assembly	1
tubulin binding	1
protein binding	1
binding	1
centriole	1
microtubule cytoskeleton	1
centrosome	1
intracellular protein-containing complex	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

696 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC61	CEP20	Q96NB1	626
CCDC61	CCDC138	Q96M89	591
CCDC61	LRRCC1	Q9C099	586
CCDC61	TBC1D31	Q96DN5	553
CCDC61	HIC2	Q96JB3	542
CCDC61	TTLL5	Q6EMB2	539
CCDC61	FNDC4	Q9H6D8	536
CCDC61	ERGIC2	Q96RQ1	531
CCDC61	PIBF1	Q8WXW3	498
CCDC61	PNPO	Q9NVS9	476
CCDC61	BRICD5	Q6PL45	468
CCDC61	ZNF382	Q96SR6	458
CCDC61	PNKP	Q96T60	428
CCDC61	VSX2	P58304	416
CCDC61	CCDC63	Q8NA47	415

IntAct

43 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
CSNK1E	PER1	psi-mi:“MI:0914”(association)	0.840
CEP170	CCDC61	psi-mi:“MI:0915”(physical association)	0.540
CEP170	CCDC61	psi-mi:“MI:0403”(colocalization)	0.540
CCDC13	CEP290	psi-mi:“MI:0914”(association)	0.460
PCM1	CCDC61	psi-mi:“MI:0915”(physical association)	0.460
CEP131	CCDC61	psi-mi:“MI:0915”(physical association)	0.460
CCDC61	PCM1	psi-mi:“MI:0403”(colocalization)	0.460
Cep135		psi-mi:“MI:0914”(association)	0.350
Nedd1		psi-mi:“MI:0914”(association)	0.350
Cep152	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
Cep120	TBC1D31	psi-mi:“MI:0914”(association)	0.350
CEP43	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Cep131	WBP2	psi-mi:“MI:0914”(association)	0.350
Cep55	UMAD1	psi-mi:“MI:0914”(association)	0.350
OFD1	CCDC14	psi-mi:“MI:0914”(association)	0.350
CEP135	TBC1D31	psi-mi:“MI:0914”(association)	0.350
PPP2CB	DKFZP586J0619	psi-mi:“MI:0914”(association)	0.350
ZBTB33	SF3B1	psi-mi:“MI:0914”(association)	0.350
Cep43	TBC1D31	psi-mi:“MI:0914”(association)	0.350
Ankrd26	TBC1D31	psi-mi:“MI:0914”(association)	0.350
Mib1	TBC1D31	psi-mi:“MI:0914”(association)	0.350
Prkar2a	TBC1D31	psi-mi:“MI:0914”(association)	0.350
Sdccag8	EEF1E1	psi-mi:“MI:0914”(association)	0.350
Lrrcc1	CCDC14	psi-mi:“MI:0914”(association)	0.350
Cep72	TBC1D31	psi-mi:“MI:0914”(association)	0.350
PPP2R5D	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Pcm1	TBC1D31	psi-mi:“MI:0914”(association)	0.350
KIF7	TBC1D31	psi-mi:“MI:0914”(association)	0.350

BioGRID (46): CCDC61 (Proximity Label-MS), CCDC61 (Affinity Capture-MS), CCDC61 (Proximity Label-MS), CCDC61 (Affinity Capture-MS), CCDC61 (Affinity Capture-MS), CCDC61 (Affinity Capture-MS), CCDC61 (Affinity Capture-MS), CCDC61 (Affinity Capture-MS), CCDC61 (Affinity Capture-MS), CCDC61 (Affinity Capture-MS), CCDC61 (Affinity Capture-MS), CCDC61 (Affinity Capture-MS), CCDC61 (Affinity Capture-MS), CCDC61 (Affinity Capture-MS), CCDC61 (Affinity Capture-MS)

ESM2 similar proteins: A0JNT9, A0JPP8, A1X157, O15169, O75145, O75335, P39880, P60469, Q07DZ5, Q08CF3, Q08E13, Q09YM8, Q2M1P5, Q2QLG9, Q2VUH7, Q32PN7, Q3TMW1, Q3UHC7, Q3UIL6, Q3UIW5, Q3UJV1, Q5DU25, Q5FWS6, Q5JU85, Q5PRF9, Q5XI59, Q5ZJ07, Q674X7, Q68UI8, Q69ZS8, Q6IPM2, Q6NZT2, Q6P402, Q6P730, Q6ZP65, Q80XS6, Q80Y83, Q8JZP9, Q8K1S6, Q8R4R9

Diamond homologs: A0JPP8, Q08CF3, Q3UJV1, Q5ZJ07, Q68UI8, Q9Y6R9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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
Loss of Nlp from mitotic centrosomes	8	47.0×	2e-10
Loss of proteins required for interphase microtubule organization from the centrosome	8	47.0×	2e-10
AURKA Activation by TPX2	8	45.1×	2e-10
Recruitment of mitotic centrosome proteins and complexes	8	40.3×	5e-10
Anchoring of the basal body to the plasma membrane	9	37.7×	2e-10
Regulation of PLK1 Activity at G2/M Transition	8	37.6×	7e-10
Recruitment of NuMA to mitotic centrosomes	8	34.5×	1e-09
Mitotic Prometaphase	6	15.4×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
cilium assembly	7	14.3×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	4
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57097	GRCh38/hg38 19q13.32(chr19:45595873-46600026)x1	Pathogenic

SpliceAI

2167 predictions. Top by Δscore:

Variant	Effect	Δscore
19:46003150:C:T	donor_gain	1.0000
19:46003162:TGGCT:T	donor_gain	1.0000
19:46003163:GGCT:G	donor_gain	1.0000
19:46003163:GGCTG:G	donor_gain	1.0000
19:46003164:GCT:G	donor_gain	1.0000
19:46003164:GCTG:G	donor_gain	1.0000
19:46003167:G:GG	donor_gain	1.0000
19:46003417:A:AG	acceptor_gain	1.0000
19:46003418:G:GG	acceptor_gain	1.0000
19:46003418:GTC:G	acceptor_gain	1.0000
19:46003498:TCAG:T	donor_loss	1.0000
19:46003499:CAGG:C	donor_loss	1.0000
19:46003500:AGG:A	donor_loss	1.0000
19:46003501:GGTA:G	donor_loss	1.0000
19:46003502:GTAGG:G	donor_loss	1.0000
19:46003503:T:A	donor_loss	1.0000
19:46006558:GA:G	acceptor_gain	1.0000
19:46006558:GAGTA:G	acceptor_gain	1.0000
19:46006713:ACAG:A	donor_loss	1.0000
19:46006714:CAG:C	donor_loss	1.0000
19:46006715:AG:A	donor_loss	1.0000
19:46006717:G:A	donor_loss	1.0000
19:46008297:GAGCA:G	donor_gain	1.0000
19:46008299:GCA:G	donor_gain	1.0000
19:46008302:G:GG	donor_gain	1.0000
19:46015045:CCAGG:C	acceptor_loss	1.0000
19:46015046:CAG:C	acceptor_loss	1.0000
19:46015047:A:AG	acceptor_gain	1.0000
19:46015047:A:T	acceptor_loss	1.0000
19:46015047:AG:A	acceptor_gain	1.0000

AlphaMissense

3261 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:46003142:T:A	W42R	1.000
19:46003142:T:C	W42R	1.000
19:46003144:G:C	W42C	1.000
19:46003144:G:T	W42C	1.000
19:46003445:G:T	G59W	1.000
19:46003446:G:A	G59E	1.000
19:46003446:G:T	G59V	1.000
19:46003450:C:A	N60K	1.000
19:46003450:C:G	N60K	1.000
19:46003454:A:G	K62E	1.000
19:46003456:A:C	K62N	1.000
19:46003456:A:T	K62N	1.000
19:46003469:T:C	F67L	1.000
19:46003470:T:C	F67S	1.000
19:46003471:C:A	F67L	1.000
19:46003471:C:G	F67L	1.000
19:46003479:T:C	M70T	1.000
19:46003480:G:A	M70I	1.000
19:46003480:G:C	M70I	1.000
19:46003480:G:T	M70I	1.000
19:46003491:C:A	A74D	1.000
19:46006572:T:A	V82D	1.000
19:46006584:T:C	L86P	1.000
19:46006587:T:C	L87P	1.000
19:46006602:T:A	L92Q	1.000
19:46006602:T:C	L92P	1.000
19:46006682:T:C	Y119H	1.000
19:46006682:T:G	Y119D	1.000
19:46006686:T:C	L120P	1.000
19:46006689:T:A	I121N	1.000

dbSNP variants (sampled 300 via entrez): RS1000157749 (19:46004180 T>C), RS1000208906 (19:46002047 G>A), RS1000233963 (19:46011954 C>T), RS1000373208 (19:46002067 C>T), RS1000468994 (19:46012679 A>G), RS1000594254 (19:46008557 C>T), RS1000645324 (19:46008373 G>A,T), RS1000675954 (19:46018004 T>C), RS1000757134 (19:46014296 C>T), RS1000767395 (19:46011611 G>A,T), RS1000861953 (19:45997002 G>A,C), RS1000942758 (19:45997389 A>G,T), RS1000946379 (19:46003480 G>C), RS1001003323 (19:45997195 C>G), RS1001162331 (19:46003809 G>A,C)

Disease associations

OMIM: gene MIM:620676 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007576_412	Chronotype	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
pirinixic acid	affects binding, decreases expression, increases activity	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol S	decreases expression, affects cotreatment	1
jinfukang	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Caffeine	affects phosphorylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	decreases expression	1
Ozone	affects expression, increases abundance	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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