CCDC88C

coiled-coil domain containing 88C

Basic information

Region (hg38): 14:91271322-91417844

Previous symbols: [ "KIAA1509" ]

Links

ENSG00000015133 ∙ NCBI:440193 ∙ OMIM:611204 ∙ HGNC:19967 ∙ Uniprot:Q9P219 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hydrocephalus, nonsyndromic, autosomal recessive 1 (Strong), mode of inheritance: AR
• spinocerebellar ataxia type 40 (Moderate), mode of inheritance: AD
• hydrocephalus, nonsyndromic, autosomal recessive 1 (Strong), mode of inheritance: AR
• hydrocephalus, nonsyndromic, autosomal recessive 1 (Moderate), mode of inheritance: AR
• spinocerebellar ataxia type 40 (Limited), mode of inheritance: AD
• spinocerebellar ataxia type 40 (Supportive), mode of inheritance: AD
• hydrocephalus, nonsyndromic, autosomal recessive 1 (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
Spinocerebellar ataxia 40; Hydrocephalus, congenital, 1	AD/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	Neurologic	21031079; 23042809; 25062847

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCDC88C gene.

• not provided (571 variants)
• Inborn genetic diseases (139 variants)
• not specified (64 variants)
• Spinocerebellar ataxia type 40 (24 variants)
• Hydrocephalus, nonsyndromic, autosomal recessive 1 (23 variants)
• Hydrocephalus, nonsyndromic, autosomal recessive 1;Spinocerebellar ataxia type 40 (9 variants)
• Spinocerebellar ataxia type 40;Hydrocephalus, nonsyndromic, autosomal recessive 1 (6 variants)
• CCDC88C-related condition (3 variants)
• Spastic ataxia (2 variants)
• Hydrocephalus (2 variants)
• Congenital hydrocephalus (1 variants)
• CCDC88C-Related Disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCDC88C 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	164	24	189
missense		3	247	27	19	296
nonsense	11	1	1			13
start loss						0
frameshift	13	2	3			18
inframe indel			4			4
splice donor/acceptor (+/-2bp)		8				8
splice region		1	5	36	8	50
non coding			3	42	49	94
Total	24	14	259	233	92

Highest pathogenic variant AF is 0.00000659

Variants in CCDC88C

This is a list of pathogenic ClinVar variants found in the CCDC88C region.

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

Position	Type	Phenotype	Significance	ClinVar
14-91272631-A-G			Likely benign (Nov 21, 2023)
14-91272634-G-A			Likely benign (Nov 10, 2023)
14-91272637-G-A			Likely benign (Nov 29, 2023)
14-91272652-G-A			Likely benign (Oct 25, 2023)
14-91272658-C-A			Likely benign (Oct 12, 2023)
14-91272658-C-T			Likely benign (Jan 04, 2024)
14-91272666-C-T			Uncertain significance (Jan 25, 2019)
14-91272667-G-A			Likely benign (Dec 19, 2023)
14-91272667-G-C			Likely benign (May 17, 2023)
14-91272669-C-T			Likely benign (Jan 31, 2024)
14-91272670-G-A			Likely benign (Oct 14, 2023)
14-91272676-C-T			Likely benign (Jan 04, 2024)
14-91272677-G-A		Spinocerebellar ataxia type 40	Uncertain significance (Sep 08, 2021)
14-91272680-G-C		Inborn genetic diseases	Uncertain significance (Aug 25, 2021)
14-91272685-C-T		Spinocerebellar ataxia type 40;Hydrocephalus, nonsyndromic, autosomal recessive 1	Benign/Likely benign (Jan 31, 2024)
14-91272686-G-A		Hydrocephalus, nonsyndromic, autosomal recessive 1;Spinocerebellar ataxia type 40 • Spinocerebellar ataxia type 40 • Inborn genetic diseases	Uncertain significance (Oct 01, 2023)
14-91272688-A-G		not specified	Likely benign (Jan 31, 2024)
14-91272694-C-T			Likely benign (Jun 15, 2023)
14-91272694-CTT-C		Hydrocephalus, nonsyndromic, autosomal recessive 1	Uncertain significance (Mar 25, 2024)
14-91272700-G-T			Likely benign (Jan 29, 2024)
14-91272702-C-T			Uncertain significance (May 24, 2022)
14-91272703-G-A			Likely benign (May 11, 2023)
14-91272711-G-A		Inborn genetic diseases	Uncertain significance (Sep 02, 2021)
14-91272715-G-A			Likely benign (Mar 26, 2023)
14-91272724-C-T			Likely benign (Dec 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCDC88C	protein_coding	protein_coding	ENST00000389857	30	146522

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.30e-8	1.00	124702	0	66	124768	0.000265

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.708	1104	1.17e+3	0.942	0.0000759	13061
Missense in Polyphen		350	392.88	0.89086		4753
Synonymous	-0.725	552	531	1.04	0.0000369	4022
Loss of Function	5.91	31	92.2	0.336	0.00000480	1064

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000901	0.000893
Ashkenazi Jewish	0.000697	0.000696
East Asian	0.000224	0.000222
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.000245	0.000230
Middle Eastern	0.000224	0.000222
South Asian	0.000171	0.000163
Other	0.000521	0.000495

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Negative regulator of the canonical Wnt signaling pathway, acting downstream of DVL to inhibit CTNNB1/Beta-catenin stabilization (By similarity). May also activate the JNK signaling pathway (PubMed:25062847). {ECO:0000250|UniProtKB:Q6VGS5, ECO:0000269|PubMed:25062847}.
• Disease: DISEASE: Hydrocephalus, congenital, 1 (HYC1) [MIM:236600]: A form of congenital hydrocephalus, a disease characterized by onset in utero of enlarged ventricles due to accumulation of ventricular cerebrospinal fluid. Affected individuals may have neurologic impairment. HYC1 inheritance is autosomal recessive. {ECO:0000269|PubMed:21031079, ECO:0000269|PubMed:23042809}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spinocerebellar ataxia 40 (SCA40) [MIM:616053]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA40 is an autosomal dominant, slowly progressive form. Brain MRI shows pontocerebellar atrophy along with a global reduction in brain volume. {ECO:0000269|PubMed:25062847}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ectoderm Differentiation;Signaling by WNT;Signal Transduction;Negative regulation of TCF-dependent signaling by DVL-interacting proteins;TCF dependent signaling in response to WNT (Consensus)

Recessive Scores

• pRec: 0.102

Intolerance Scores

• loftool: 0.504
• rvis_EVS: 1.14
• rvis_percentile_EVS: 92.38

Haploinsufficiency Scores

• pHI: 0.124
• hipred: N
• hipred_score: 0.414
• ghis: 0.463

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.135

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ccdc88c

Gene ontology

• Biological process: regulation of protein phosphorylation;Wnt signaling pathway;cytoskeleton-dependent intracellular transport;stress-activated protein kinase signaling cascade;cytoplasmic microtubule organization;protein destabilization;protein homooligomerization
• Cellular component: cytoplasm;centrosome
• Molecular function: microtubule binding;PDZ domain binding;protein self-association;dynein light intermediate chain binding