This gene encodes a ubiquitously expressed coiled-coil domain-containing protein that interacts with the dishevelled protein and is a negative regulator of the Wnt signalling pathway. The protein encoded by this gene has a PDZ-domain binding motif in its C-terminus with which it interacts with the dishevelled protein. Dishevelled is a scaffold protein involved in the regulation... See more...

Aliases for CCDC88C Gene

Aliases for CCDC88C Gene

  • Coiled-Coil Domain Containing 88C 2 3 5
  • Dvl-Associating Protein With A High Frequency Of Leucine Residues 2 3 4
  • KIAA1509 2 3 4
  • Spinocerebellar Ataxia 40 2 3
  • Hook-Related Protein 2 3 4
  • Protein Daple 3 4
  • DAPLE 3 4
  • Coiled-Coil Domain-Containing Protein 88C 4
  • HDaple 4
  • HKRP2 3
  • SCA40 3
  • HkRP2 4
  • HYC1 3

External Ids for CCDC88C Gene

Previous HGNC Symbols for CCDC88C Gene

  • KIAA1509

Previous GeneCards Identifiers for CCDC88C Gene

  • GC14M090809
  • GC14M091737
  • GC14M071913

Summaries for CCDC88C Gene

Entrez Gene Summary for CCDC88C Gene

  • This gene encodes a ubiquitously expressed coiled-coil domain-containing protein that interacts with the dishevelled protein and is a negative regulator of the Wnt signalling pathway. The protein encoded by this gene has a PDZ-domain binding motif in its C-terminus with which it interacts with the dishevelled protein. Dishevelled is a scaffold protein involved in the regulation of the Wnt signaling pathway. The Wnt signaling pathway plays an important role in embryonic development, tissue maintenance, and cancer progression. Mutations in this gene cause autosomal recessive, primary non-syndromic congenital hydrocephalus; a condition characterized by excessive accumulation of cerebrospinal fluid in the ventricles of the brain. [provided by RefSeq, Jan 2013]

GeneCards Summary for CCDC88C Gene

CCDC88C (Coiled-Coil Domain Containing 88C) is a Protein Coding gene. Diseases associated with CCDC88C include Hydrocephalus, Congenital, 1 and Spinocerebellar Ataxia 40. Among its related pathways are Signaling by Wnt and Ectoderm Differentiation. Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and protein self-association. An important paralog of this gene is CCDC88A.

UniProtKB/Swiss-Prot Summary for CCDC88C Gene

  • Required for activation of guanine nucleotide-binding proteins (G-proteins) during non-canonical Wnt signaling (PubMed:26126266). Binds to ligand-activated Wnt receptor FZD7, displacing DVL1 from the FZD7 receptor and leading to inhibition of canonical Wnt signaling (PubMed:26126266). Acts as a non-receptor guanine nucleotide exchange factor by also binding to guanine nucleotide-binding protein G(i) alpha (Gi-alpha) subunits, leading to their activation (PubMed:26126266). Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex, triggering non-canonical Wnt responses such as activation of RAC1 and PI3K-AKT signaling (PubMed:26126266). Promotes apical constriction of cells via ARHGEF18 (PubMed:30948426).

Additional gene information for CCDC88C Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CCDC88C Gene

Genomics for CCDC88C Gene

GeneHancer (GH) Regulatory Elements for CCDC88C Gene

Promoters and enhancers for CCDC88C Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CCDC88C on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CCDC88C

Top Transcription factor binding sites by QIAGEN in the CCDC88C gene promoter:
  • AML1a
  • ATF-2
  • ATF6
  • FOXO1
  • FOXO1a
  • Ik-3
  • MyoD
  • PPAR-gamma1
  • PPAR-gamma2
  • Sox5

Genomic Locations for CCDC88C Gene

Genomic Locations for CCDC88C Gene
chr14:91,271,323-91,417,844
(GRCh38/hg38)
Size:
146,522 bases
Orientation:
Minus strand
chr14:91,737,667-91,884,188
(GRCh37/hg19)
Size:
146,522 bases
Orientation:
Minus strand

Genomic View for CCDC88C Gene

Genes around CCDC88C on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CCDC88C Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CCDC88C Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CCDC88C Gene

Proteins for CCDC88C Gene

  • Protein details for CCDC88C Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9P219-DAPLE_HUMAN
    Recommended name:
    Protein Daple
    Protein Accession:
    Q9P219
    Secondary Accessions:
    • Q69YK1
    • Q7L1M2
    • Q86SX7
    • Q8IYG8

    Protein attributes for CCDC88C Gene

    Size:
    2028 amino acids
    Molecular mass:
    228230 Da
    Quaternary structure:
    • Homooligomer (By similarity). Interacts with DVL1 (via PDZ domain); dissociates following initiation of non-canonical Wnt signaling (PubMed:26126266). Interacts (via C-terminus) with ligand-activated Wnt receptor FZD7; competes with DVL1 for binding to FZD7 and displaces DVL1 from ligand-activated FZD7 (PubMed:26126266). Interacts (via GBA motif) with guanine nucleotide-binding protein G(i) alpha subunits GNAI1, GNAI2 and GNAI3 (inactive GDP-bound form); interacts with higher affinity with GNAI1 and GNAI3 than with GNAI2 and interaction leads to G(i) alpha subunit activation (PubMed:26126266). Does not interact with GNAO1 (PubMed:26126266).
    Miscellaneous:
    • [Isoform 3]: Due to intron retention.
    SequenceCaution:
    • Sequence=BAA96033.2; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; Sequence=CAH10602.1; Type=Frameshift; Evidence={ECO:0000305};

    Alternative splice isoforms for CCDC88C Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CCDC88C Gene

Post-translational modifications for CCDC88C Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for CCDC88C Gene

Domains & Families for CCDC88C Gene

Gene Families for CCDC88C Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for CCDC88C Gene

Suggested Antigen Peptide Sequences for CCDC88C Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ59076, highly similar to Mus musculus coiled-coil domain containing 88C (Ccdc88c), mRNA (B4DZB8_HUMAN)
  • Hook-related protein 2 (DAPLE_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9P219

UniProtKB/Swiss-Prot:

DAPLE_HUMAN :
  • The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins).
  • Belongs to the CCDC88 family.
Domain:
  • The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins).
  • The PDZ domain is required for localization to apical junctions.
Family:
  • Belongs to the CCDC88 family.
genes like me logo Genes that share domains with CCDC88C: view

Function for CCDC88C Gene

Molecular function for CCDC88C Gene

UniProtKB/Swiss-Prot Function:
Required for activation of guanine nucleotide-binding proteins (G-proteins) during non-canonical Wnt signaling (PubMed:26126266). Binds to ligand-activated Wnt receptor FZD7, displacing DVL1 from the FZD7 receptor and leading to inhibition of canonical Wnt signaling (PubMed:26126266). Acts as a non-receptor guanine nucleotide exchange factor by also binding to guanine nucleotide-binding protein G(i) alpha (Gi-alpha) subunits, leading to their activation (PubMed:26126266). Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex, triggering non-canonical Wnt responses such as activation of RAC1 and PI3K-AKT signaling (PubMed:26126266). Promotes apical constriction of cells via ARHGEF18 (PubMed:30948426).

Phenotypes From GWAS Catalog for CCDC88C Gene

Gene Ontology (GO) - Molecular Function for CCDC88C Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IEA --
GO:0008017 microtubule binding IBA 21873635
GO:0030165 PDZ domain binding IEA,ISS 14750955
GO:0043621 protein self-association IEA,ISS 14750955
GO:0051959 dynein light intermediate chain binding IBA 21873635
genes like me logo Genes that share ontologies with CCDC88C: view
genes like me logo Genes that share phenotypes with CCDC88C: view

Human Phenotype Ontology for CCDC88C Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CCDC88C

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for CCDC88C Gene

Localization for CCDC88C Gene

Subcellular locations from UniProtKB/Swiss-Prot for CCDC88C Gene

Cytoplasm. Cell junction. Note=Enriched at apical cell junctions. {ECO:0000269 PubMed:30948426}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CCDC88C gene
Compartment Confidence
cytoskeleton 4
nucleus 4
cytosol 2
plasma membrane 1
extracellular 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoli fibrillar center (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CCDC88C Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA,IBA 25062847
GO:0005813 centrosome IBA 21873635
genes like me logo Genes that share ontologies with CCDC88C: view

Pathways & Interactions for CCDC88C Gene

genes like me logo Genes that share pathways with CCDC88C: view

Pathways by source for CCDC88C Gene

SIGNOR curated interactions for CCDC88C Gene

Is activated by:

Gene Ontology (GO) - Biological Process for CCDC88C Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001932 regulation of protein phosphorylation ISS 14750955
GO:0016055 Wnt signaling pathway IEA --
GO:0030705 cytoskeleton-dependent intracellular transport IBA 21873635
GO:0031098 stress-activated protein kinase signaling cascade IMP 25062847
GO:0031122 cytoplasmic microtubule organization IBA 21873635
genes like me logo Genes that share ontologies with CCDC88C: view

Drugs & Compounds for CCDC88C Gene

No Compound Related Data Available

Transcripts for CCDC88C Gene

mRNA/cDNA for CCDC88C Gene

1 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
14 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CCDC88C

Alternative Splicing Database (ASD) splice patterns (SP) for CCDC88C Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11a · 11b · 11c · 11d · 11e ^ 12a · 12b · 12c ^ 13a · 13b ^ 14 ^ 15a · 15b ^ 16 ^ 17 ^
SP1: - - - - - - -
SP2: - - -
SP3:
SP4:
SP5: - -
SP6:
SP7: - -

ExUns: 18a · 18b · 18c
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:

Relevant External Links for CCDC88C Gene

GeneLoc Exon Structure for
CCDC88C

Expression for CCDC88C Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CCDC88C Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CCDC88C Gene

This gene is overexpressed in Whole Blood (x4.8).

Protein differential expression in normal tissues from HIPED for CCDC88C Gene

This gene is overexpressed in Frontal cortex (43.4) and Brain (7.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CCDC88C Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CCDC88C

SOURCE GeneReport for Unigene cluster for CCDC88C Gene:

Hs.525536

Evidence on tissue expression from TISSUES for CCDC88C Gene

  • Stomach(4.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CCDC88C Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • nervous
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cerebellum
  • cerebrospinal fluid
  • head
  • meninges
  • skull
Limb:
  • lower limb
General:
  • peripheral nerve
  • peripheral nervous system
  • spinal cord
genes like me logo Genes that share expression patterns with CCDC88C: view

No data available for Protein tissue co-expression partners and mRNA Expression by UniProt/SwissProt for CCDC88C Gene

Orthologs for CCDC88C Gene

This gene was present in the common ancestor of animals.

Orthologs for CCDC88C Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CCDC88C 31 30
  • 99.56 (n)
OneToOne
dog
(Canis familiaris)
Mammalia CCDC88C 31 30
  • 86.33 (n)
OneToOne
cow
(Bos Taurus)
Mammalia CCDC88C 31
  • 85 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Ccdc88c 17 31 30
  • 84 (n)
rat
(Rattus norvegicus)
Mammalia Ccdc88c 30
  • 83.88 (n)
oppossum
(Monodelphis domestica)
Mammalia CCDC88C 31
  • 72 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CCDC88C 31
  • 66 (a)
OneToOne
chicken
(Gallus gallus)
Aves CCDC88C 31 30
  • 68.65 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CCDC88C 31
  • 65 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100485260 30
  • 61.83 (n)
zebrafish
(Danio rerio)
Actinopterygii LOC553231 30
  • 60.04 (n)
ccdc88c 31
  • 54 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Girdin 31
  • 30 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea grdn-1 31
  • 24 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3137 31
  • 36 (a)
OneToMany
Species where no ortholog for CCDC88C was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for CCDC88C Gene

ENSEMBL:
Gene Tree for CCDC88C (if available)
TreeFam:
Gene Tree for CCDC88C (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CCDC88C: view image

Paralogs for CCDC88C Gene

Paralogs for CCDC88C Gene

(2) SIMAP similar genes for CCDC88C Gene using alignment to 4 proteins:

  • DAPLE_HUMAN
  • G3V3S0_HUMAN
  • H0YJX5_HUMAN
  • Q0P665_HUMAN
genes like me logo Genes that share paralogs with CCDC88C: view

Variants for CCDC88C Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CCDC88C Gene

SNP ID Clinical significance and condition Chr 14 pos Variation AA Info Type
585626 Uncertain Significance: not provided 91,308,399(-) C/T MISSENSE_VARIANT
587642 Uncertain Significance: Hydrocephalus; Spinocerebellar ataxia 40 91,273,461(-) C/T MISSENSE_VARIANT
638322 Uncertain Significance: not specified 91,313,262(-) C/G MISSENSE_VARIANT
rs1064794398 Uncertain Significance: not provided 91,303,948(-) C/T MISSENSE_VARIANT
rs1064795357 Uncertain Significance: not provided 91,339,401(-) A/G MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for CCDC88C Gene

Structural Variations from Database of Genomic Variants (DGV) for CCDC88C Gene

Variant ID Type Subtype PubMed ID
esv1637561 CNV insertion 17803354
esv1730768 CNV insertion 17803354
esv25253 CNV loss 19812545
esv2749015 CNV deletion 23290073
esv2749016 CNV deletion 23290073
esv3308271 CNV mobile element insertion 20981092
esv3333557 CNV insertion 20981092
nsv1046924 CNV gain 25217958
nsv1069814 CNV deletion 25765185
nsv1118285 CNV deletion 24896259
nsv1126371 CNV deletion 24896259
nsv1395 CNV insertion 18451855
nsv456393 CNV loss 19166990
nsv456394 CNV loss 19166990
nsv517700 CNV loss 19592680
nsv519459 CNV loss 19592680
nsv565517 CNV loss 21841781
nsv565518 CNV loss 21841781
nsv817642 CNV gain 17921354
nsv832857 CNV loss 17160897
nsv983851 CNV duplication 23825009

Variation tolerance for CCDC88C Gene

Residual Variation Intolerance Score: 98.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.86; 74.05% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CCDC88C Gene

Human Gene Mutation Database (HGMD)
CCDC88C
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CCDC88C

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CCDC88C Gene

Disorders for CCDC88C Gene

MalaCards: The human disease database

(7) MalaCards diseases for CCDC88C Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
hydrocephalus, congenital, 1
  • hyc1
spinocerebellar ataxia 40
  • sca40
congenital hydrocephalus
  • hydrocephalus
hydrocephalus
  • hydrocephalus, nonsyndromic, autosomal recessive
hereditary ataxia
  • ataxias hereditary
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

DAPLE_HUMAN
  • 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.
  • 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.

Additional Disease Information for CCDC88C

genes like me logo Genes that share disorders with CCDC88C: view

No data available for Genatlas for CCDC88C Gene

Publications for CCDC88C Gene

  1. A novel missense mutation in CCDC88C activates the JNK pathway and causes a dominant form of spinocerebellar ataxia. (PMID: 25062847) Tsoi H … Chan HY (Journal of medical genetics 2014) 2 3 4 54
  2. Daple is a novel non-receptor GEF required for trimeric G protein activation in Wnt signaling. (PMID: 26126266) Aznar N … Ghosh P (eLife 2015) 3 4 54
  3. Two novel CCDC88C mutations confirm the role of DAPLE in autosomal recessive congenital hydrocephalus. (PMID: 23042809) Drielsma A … Edvardson S (Journal of medical genetics 2012) 3 4 54
  4. Disturbed Wnt Signalling due to a Mutation in CCDC88C Causes an Autosomal Recessive Non-Syndromic Hydrocephalus with Medial Diverticulum. (PMID: 21031079) Ekici AB … Rauch A (Molecular syndromology 2010) 3 4 54
  5. Girdin, a novel actin-binding protein, and its family of proteins possess versatile functions in the Akt and Wnt signaling pathways. (PMID: 17185515) Enomoto A … Takahashi M (Annals of the New York Academy of Sciences 2006) 2 3 54

Products for CCDC88C Gene

Sources for CCDC88C Gene