CCDC68

Summary

CCDC68 (coiled-coil domain containing 68, HGNC:24350) is a protein-coding gene on chromosome 18q21.2, encoding Coiled-coil domain-containing protein 68 (Q9H2F9). Centriolar protein required for centriole subdistal appendage assembly and microtubule anchoring in interphase cells.

Involved in microtubule anchoring at centrosome and protein localization. Located in centriole. Part of centriolar subdistal appendage.

Source: NCBI Gene 80323 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 56 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_025214

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24350
Approved symbol	CCDC68
Name	coiled-coil domain containing 68
Location	18q21.2
Locus type	gene with protein product
Status	Approved
Aliases	SE57-1
Ensembl gene	ENSG00000166510
Ensembl biotype	protein_coding
OMIM	616909
Entrez	80323

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 21 protein_coding, 2 retained_intron

ENST00000337363, ENST00000432185, ENST00000587148, ENST00000591504, ENST00000592040, ENST00000592294, ENST00000878530, ENST00000878531, ENST00000878532, ENST00000878533, ENST00000878534, ENST00000878535, ENST00000878536, ENST00000878537, ENST00000878538, ENST00000878539, ENST00000878540, ENST00000971901, ENST00000971902, ENST00000971903, ENST00000971904, ENST00000971905, ENST00000971906

RefSeq mRNA: 2 — MANE Select: NM_025214 NM_001143829, NM_025214

CCDS: CCDS11959

Canonical transcript exons

ENST00000591504 — 12 exons

Exon	Start	End
ENSE00001103755	54907786	54907862
ENSE00001103759	54928800	54928882
ENSE00001103774	54936833	54936958
ENSE00001103775	54937957	54938097
ENSE00001199010	54917913	54917996
ENSE00001199014	54919271	54919376
ENSE00001260162	54945388	54945477
ENSE00001382141	54959336	54959461
ENSE00002811578	54901509	54904415
ENSE00003477014	54934820	54934948
ENSE00003532983	54940997	54941083
ENSE00003633020	54942675	54942803

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 91.44.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9524 / max 172.3860, expressed in 732 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172005	2.9524	732

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	91.44	gold quality
jejunal mucosa	UBERON:0000399	90.43	gold quality
right lung	UBERON:0002167	89.56	gold quality
duodenum	UBERON:0002114	87.34	gold quality
left ovary	UBERON:0002119	86.55	gold quality
colonic mucosa	UBERON:0000317	85.92	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.40	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.02	gold quality
small intestine	UBERON:0002108	84.49	gold quality
transverse colon	UBERON:0001157	84.45	gold quality
adrenal tissue	UBERON:0018303	84.31	gold quality
apex of heart	UBERON:0002098	83.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.16	gold quality
upper lobe of left lung	UBERON:0008952	83.03	gold quality
upper lobe of lung	UBERON:0008948	82.76	gold quality
ovary	UBERON:0000992	82.40	gold quality
mucosa of transverse colon	UBERON:0004991	82.29	gold quality
right ovary	UBERON:0002118	82.22	gold quality
lung	UBERON:0002048	81.84	gold quality
placenta	UBERON:0001987	81.40	gold quality
lower lobe of lung	UBERON:0008949	81.17	silver quality
pancreatic ductal cell	CL:0002079	81.08	gold quality
body of stomach	UBERON:0001161	81.02	gold quality
colonic epithelium	UBERON:0000397	80.92	gold quality
intestine	UBERON:0000160	80.84	gold quality
stomach	UBERON:0000945	80.59	gold quality
large intestine	UBERON:0000059	79.25	gold quality
right atrium auricular region	UBERON:0006631	79.02	gold quality
colon	UBERON:0001155	78.91	gold quality
right testis	UBERON:0004534	78.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-24	yes	456.87
E-ANND-3	yes	9.07
E-CURD-112	no	2.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

159 targeting CCDC68, 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-4776-3P	100.00	68.73	1340
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488

Literature-anchored findings (GeneRIF, showing 4)

• Data indicate coiled-coil domain containing 68 (CCDC68) as a tumor suppressor gene (TSG) in pancreatic ductal adenocarcinoma (PDAC). (PMID:25381825)
• centrosome-binding proteins, coiled-coil domain containing (CCDC) 120 and CCDC68 are two novel subdistal appendages (SDA) components required for hierarchical SDA assembly in human cells. (PMID:28422092)
• CCDC68 Upregulation by IL-6 Promotes Endometrial Carcinoma Progression. (PMID:33471616)
• CCDC68 Maintains Mitotic Checkpoint Activation by Promoting CDC20 Integration into the MCC. (PMID:39018254)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ccdc68	ENSMUSG00000038903
rattus_norvegicus	Ccdc68	ENSRNOG00000021381

Paralogs (3): TUFT1 (ENSG00000143367), POLR2M (ENSG00000255529), MYZAP (ENSG00000263155)

Protein

Protein identifiers

Coiled-coil domain-containing protein 68 — Q9H2F9 (reviewed: Q9H2F9)

Alternative names: Cutaneous T-cell lymphoma-associated antigen se57-1

All UniProt accessions (2): Q9H2F9, K7EN04

UniProt curated annotations — full annotation on UniProt →

Function. Centriolar protein required for centriole subdistal appendage assembly and microtubule anchoring in interphase cells. Together with CCDC120, cooperate with subdistal appendage components ODF2, NIN and CEP170 for hierarchical subdistal appendage assembly.

Subunit / interactions. Interacts with CEP170.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole.

Tissue specificity. Expressed in bone marrow, colon, small intestine, spleen, testis, trachea and cutaneous T-cell lymphoma (CTCL).

RefSeq proteins (2): NP_001137301, NP_079490* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR051375	Tuftelin_GRINL1A/MYZAP/CCD68	Family

UniProt features (3 total): chain 1, coiled-coil region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H2F9-F1	81.20	0.61

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 104 (showing top): GOBP_MICROTUBULE_ANCHORING, GOCC_MICROTUBULE_ORGANIZING_CENTER, FOSTER_TOLERANT_MACROPHAGE_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, YAMASHITA_METHYLATED_IN_PROSTATE_CANCER, RGAGGAARY_PU1_Q6, BOQUEST_STEM_CELL_DN, MODULE_342, GOCC_CENTRIOLE, IRF2_01, GOCC_CILIUM, chr18q21, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_GREY_UP, MODULE_495, MIKKELSEN_ES_ICP_WITH_H3K4ME3

GO Biological Process (2): intracellular protein localization (GO:0008104), microtubule anchoring at centrosome (GO:0034454)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): centriole (GO:0005814), centriolar subdistal appendage (GO:0120103), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	2
macromolecule localization	1
microtubule anchoring at microtubule organizing center	1
binding	1
microtubule organizing center	1
cilium	1
intracellular protein-containing complex	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

602 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC68	MIA2	Q96PC5	960
CCDC68	CTAGE1	Q96RT6	955
CCDC68	CCDC120	Q96HB5	919
CCDC68	CEP128	Q6ZU80	873
CCDC68	CEP170	Q5SW79	778
CCDC68	NIN	Q8N4C6	746
CCDC68	CNTRL	Q7Z7A1	667
CCDC68	CEP89	Q96ST8	571
CCDC68	CEP83	Q9Y592	542
CCDC68	STARD6	P59095	540
CCDC68	C2CD3	Q4AC94	502
CCDC68	FBF1	Q8TES7	500
CCDC68	SCLT1	Q96NL6	485
CCDC68	NINL	Q9Y2I6	469
CCDC68	CNNM2	Q9H8M5	467

IntAct

43 interactions, top by confidence:

A	B	Type	Score
CEP170	CCDC120	psi-mi:“MI:0914”(association)	0.820
CCDC68	CEP170	psi-mi:“MI:0915”(physical association)	0.810
CCDC68	CEP170	psi-mi:“MI:0403”(colocalization)	0.810
TFIP11	CCDC68	psi-mi:“MI:0915”(physical association)	0.780
CCDC68	TFIP11	psi-mi:“MI:0915”(physical association)	0.780
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CCDC68	NDC80	psi-mi:“MI:0914”(association)	0.640
KRT27	CCDC68	psi-mi:“MI:0915”(physical association)	0.560
DYNLT1	CCDC68	psi-mi:“MI:0915”(physical association)	0.560
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
OR5H8	CCDC68	psi-mi:“MI:0915”(physical association)	0.400
CCDC68	NIFK	psi-mi:“MI:0915”(physical association)	0.400
CCDC68	RPSA2	psi-mi:“MI:0914”(association)	0.350
ODF2	CCDC68	psi-mi:“MI:0403”(colocalization)	0.270
CCDC68	CCP110	psi-mi:“MI:0403”(colocalization)	0.270
CCDC68	DYNLT1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (40): CCDC68 (Two-hybrid), FYCO1 (Affinity Capture-MS), PLEC (Affinity Capture-MS), AKAP9 (Affinity Capture-MS), CENPF (Affinity Capture-MS), FBP1 (Affinity Capture-MS), CEP170 (Affinity Capture-MS), NDC80 (Affinity Capture-MS), RABGAP1 (Affinity Capture-MS), NIN (Affinity Capture-MS), FYCO1 (Affinity Capture-MS), CENPF (Affinity Capture-MS), NDC80 (Affinity Capture-MS), FBP1 (Affinity Capture-MS), NIN (Affinity Capture-MS)

ESM2 similar proteins: A0MZ66, A0MZ67, A6PWD2, A7MD70, B3DLE8, B9EKI3, F7DP49, O35550, O35551, O45420, P82094, Q05D60, Q08DR9, Q15276, Q28IH8, Q3KR99, Q3UIJ9, Q4L180, Q4R7H3, Q4V7C8, Q53EZ4, Q5BIX7, Q5R923, Q5RA03, Q5RI56, Q5U3Z6, Q6NRC9, Q6NRW2, Q6P0R8, Q6P402, Q6P6L0, Q7YS99, Q7Z7B0, Q861Q8, Q8BT07, Q8BVC4, Q8K2Q9, Q8K3K8, Q8K4T4, Q8R5M4

Diamond homologs: Q8BVC4, Q9H2F9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	43
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
148226	GRCh38/hg38 18q21.2(chr18:54468297-55949009)x1	Pathogenic
1806473	GRCh37/hg19 18q21.2(chr18:52023322-53332606)x1	Pathogenic
812695	NM_025214.3(CCDC68):c.775dup (p.Ser259fs)	Likely pathogenic

SpliceAI

1776 predictions. Top by Δscore:

Variant	Effect	Δscore
18:54917996:TC:T	acceptor_loss	1.0000
18:54917997:CTAA:C	acceptor_loss	1.0000
18:54917998:T:C	acceptor_loss	1.0000
18:54918004:T:TC	acceptor_gain	1.0000
18:54919272:T:TA	donor_gain	1.0000
18:54934815:CGTA:C	donor_loss	1.0000
18:54934816:GTAC:G	donor_loss	1.0000
18:54934817:TACC:T	donor_loss	1.0000
18:54934818:ACCTT:A	donor_loss	1.0000
18:54934819:C:A	donor_loss	1.0000
18:54934949:C:CC	acceptor_gain	1.0000
18:54937212:T:TA	donor_gain	1.0000
18:54937951:TCATA:T	donor_loss	1.0000
18:54937952:CATA:C	donor_loss	1.0000
18:54937953:ATAC:A	donor_loss	1.0000
18:54937954:TA:T	donor_loss	1.0000
18:54937955:ACC:A	donor_loss	1.0000
18:54937956:C:A	donor_loss	1.0000
18:54937973:T:TA	donor_gain	1.0000
18:54938037:CCAAA:C	acceptor_gain	1.0000
18:54938038:CAAA:C	acceptor_gain	1.0000
18:54938038:CAAAC:C	acceptor_gain	1.0000
18:54938042:C:CC	acceptor_gain	1.0000
18:54938093:CAGTG:C	acceptor_gain	1.0000
18:54940991:TATTA:T	donor_loss	1.0000
18:54940993:TTACC:T	donor_loss	1.0000
18:54940994:TA:T	donor_loss	1.0000
18:54940995:A:AG	donor_loss	1.0000
18:54941079:CGAAT:C	acceptor_gain	1.0000
18:54941080:GAAT:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000083187 (18:54961314 C>T), RS1000138302 (18:54939179 C>G), RS1000197292 (18:54951934 G>A), RS1000207365 (18:54925816 C>T), RS1000262488 (18:54929012 C>T), RS1000485666 (18:54953356 A>G), RS1000516734 (18:54935434 A>C,T), RS1000581786 (18:54934436 A>T), RS1000602318 (18:54927710 T>C), RS1000664047 (18:54926071 T>C), RS1000724850 (18:54921203 A>C), RS1000805835 (18:54957743 T>A), RS1000872097 (18:54922747 G>C), RS1000937426 (18:54941287 C>T), RS1000941287 (18:54957393 C>A,T)

Disease associations

OMIM: gene MIM:616909 | disease phenotypes: MIM:610954

GenCC curated gene-disease

Mondo (1): Pitt-Hopkins syndrome (MONDO:0012589)

Orphanet (1): Pitt-Hopkins syndrome (Orphanet:2896)

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001017_3	Diabetic retinopathy	3.000000e-06
GCST001242_21	Schizophrenia	3.000000e-08
GCST001877_29	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	3.000000e-10
GCST003989_20	Chin dimples	7.000000e-15
GCST004751_21	Serum uric acid levels in response to allopurinol in gout	2.000000e-06
GCST004751_8	Serum uric acid levels in response to allopurinol in gout	1.000000e-06
GCST005580_94	Intraocular pressure	5.000000e-11
GCST005839_20	Depression	3.000000e-08
GCST006627_74	Diastolic blood pressure	3.000000e-09
GCST007201_244	Schizophrenia	1.000000e-09
GCST007201_257	Schizophrenia	3.000000e-07
GCST012442_23	Age-related hearing impairment	3.000000e-11
GCST90002395_283	Mean platelet volume	5.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004761	uric acid measurement
EFO:0004695	intraocular pressure measurement
EFO:0006336	diastolic blood pressure

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537403	Pitt-Hopkins syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	7
Aflatoxin B1	affects expression, decreases expression, decreases methylation, increases methylation	4
sodium arsenite	affects expression, increases expression	2
Acetaminophen	increases expression, decreases expression	2
Arsenic	increases methylation	2
Benzo(a)pyrene	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression, increases expression	2
dicrotophos	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
ethyl-p-hydroxybenzoate	increases expression	1
trichostatin A	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
ormosil	affects binding, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Leflunomide	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases oxidation, affects cotreatment, increases abundance	1
Cisplatin	affects cotreatment, decreases expression	1
Demecolcine	increases expression	1
Estradiol	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04132427	PHASE2	COMPLETED	MTT for Children With Both Pitt Hopkins Syndrome and Gastrointestinal Disorders
NCT05025332	PHASE2	COMPLETED	An Open-Label Study of Oral NNZ-2591 in Pitt Hopkins Syndrome (PTHS-001)
NCT06321796	PHASE2	UNKNOWN	Microbiota Transfer Therapy for Children and Adults With Both Pitt Hopkins Syndrome and Gastrointestinal Disorders
NCT07150026	PHASE1	RECRUITING	An Exploratory Evaluation of the Safety and Efficacy of Vorinostat in Pitt Hopkins Syndrome
NCT05165017	PHASE1/PHASE2	UNKNOWN	Safety & Efficacy of AlloRx SC® in PTHS Patients
NCT07135050	PHASE1/PHASE2	RECRUITING	Phase 1/2 Study of MZ-1866, an AAV-9 Gene Therapy Delivered by Intracerebroventricular Injection to Participants With Pitt Hopkins Syndrome
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns