CCDC8

coiled-coil domain containing 8, the group of Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 19:46410329-46413564

Links

ENSG00000169515 ∙ NCBI:83987 ∙ OMIM:614145 ∙ HGNC:25367 ∙ Uniprot:Q9H0W5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 3M syndrome 3 (Strong), mode of inheritance: AR
• 3-M syndrome (Supportive), mode of inheritance: AR
• 3M syndrome 3 (Strong), mode of inheritance: AR
• spinocerebellar ataxia type 40 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Three M syndrome 3	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal	21737058

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCDC8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCDC8 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	37	5	43
missense			100	12	8	120
nonsense		1	2			3
start loss		1	1			2
frameshift		8	3			11
inframe indel			4			4
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	10	111	49	14

Variants in CCDC8

This is a list of pathogenic ClinVar variants found in the CCDC8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-46411199-G-A			Likely benign (Aug 17, 2023)
19-46411202-G-A		not specified	Uncertain significance (Mar 26, 2024)
19-46411202-G-T			Uncertain significance (Nov 27, 2023)
19-46411203-G-A			Likely benign (Apr 15, 2021)
19-46411206-T-G		not specified	Uncertain significance (Oct 25, 2022)
19-46411219-T-A			Uncertain significance (Aug 31, 2021)
19-46411222-T-G			Uncertain significance (Feb 25, 2022)
19-46411231-G-A		Inborn genetic diseases • not specified	Uncertain significance (Jun 14, 2024)
19-46411233-T-A		Inborn genetic diseases	Uncertain significance (Jan 04, 2022)
19-46411233-T-C			Likely benign (Nov 10, 2021)
19-46411255-CT-C		not specified	Uncertain significance (Aug 08, 2022)
19-46411262-T-C			Uncertain significance (May 14, 2021)
19-46411264-C-T		Inborn genetic diseases	Uncertain significance (Aug 21, 2024)
19-46411265-T-C			Uncertain significance (Mar 17, 2023)
19-46411269-C-T			Likely benign (May 15, 2023)
19-46411280-T-G			Likely benign (Aug 22, 2023)
19-46411290-C-G		not specified	Benign (Jan 31, 2024)
19-46411301-T-C		not specified	Uncertain significance (Jan 05, 2024)
19-46411305-C-T			Likely benign (Nov 12, 2022)
19-46411310-G-A		Inborn genetic diseases	Uncertain significance (May 24, 2023)
19-46411316-T-C			Uncertain significance (Jul 12, 2022)
19-46411334-G-A			Uncertain significance (Aug 16, 2022)
19-46411337-G-A		Inborn genetic diseases	Uncertain significance (Oct 06, 2021)
19-46411341-G-A			Likely benign (Oct 04, 2023)
19-46411350-C-T			Likely benign (Nov 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCDC8	protein_coding	protein_coding	ENST00000307522	1	3213

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.254	0.721	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.159	319	311	1.03	0.0000172	3455
Missense in Polyphen		85	94.144	0.90288		1061
Synonymous	-1.24	144	126	1.14	0.00000687	1129
Loss of Function	1.88	2	7.58	0.264	3.34e-7	82

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer (PubMed:24793695, PubMed:24793696). Required for localization of CUL7 to the centrosome (PubMed:24793695). {ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:24793696}.
• Disease: DISEASE: 3M syndrome 3 (3M3) [MIM:614205]: A disorder characterized by poor postnatal growth and distinctive facial features, including triangular facies, frontal bossing, fleshy tipped nose, and fleshy lips. Other features may include skeletal anomalies and prominent heels. {ECO:0000269|PubMed:21737058, ECO:0000269|PubMed:23018678}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Post-translational protein modification;Metabolism of proteins;Neddylation (Consensus)

Recessive Scores

• pRec: 0.0683

Intolerance Scores

• loftool: 0.674
• rvis_EVS: 1.44
• rvis_percentile_EVS: 95.09

Haploinsufficiency Scores

• pHI: 0.106
• hipred: N
• hipred_score: 0.233
• ghis: 0.418

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.112

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ccdc8

Gene ontology

• Biological process: microtubule cytoskeleton organization;regulation of mitotic nuclear division;negative regulation of phosphatase activity;post-translational protein modification
• Cellular component: nucleus;cytoplasm;centrosome;cytosol;plasma membrane;3M complex
• Molecular function: protein binding