This gene is thought to function in extracellular matrix remodeling and migration. It is predominantly expressed in the ovary, but down regulated in ovarian cancer cell lines and primary carcinomas, suggesting its role as a tumour suppressor. Mutations in this gene have been associated with Hennekam lymphangiectasia-lymphedema syndrome, a generalized lymphatic dysplasia in huma... See more...

Aliases for CCBE1 Gene

Aliases for CCBE1 Gene

  • Collagen And Calcium Binding EGF Domains 1 2 3 5
  • Collagen And Calcium-Binding EGF Domain-Containing Protein 1 3 4
  • Full Of Fluid Protein Homolog 3 4
  • KIAA1983 4
  • HKLLS1 3

External Ids for CCBE1 Gene

Previous GeneCards Identifiers for CCBE1 Gene

  • GC18M055253
  • GC18M057101
  • GC18M053807

Summaries for CCBE1 Gene

Entrez Gene Summary for CCBE1 Gene

  • This gene is thought to function in extracellular matrix remodeling and migration. It is predominantly expressed in the ovary, but down regulated in ovarian cancer cell lines and primary carcinomas, suggesting its role as a tumour suppressor. Mutations in this gene have been associated with Hennekam lymphangiectasia-lymphedema syndrome, a generalized lymphatic dysplasia in humans. [provided by RefSeq, Mar 2010]

GeneCards Summary for CCBE1 Gene

CCBE1 (Collagen And Calcium Binding EGF Domains 1) is a Protein Coding gene. Diseases associated with CCBE1 include Hennekam Lymphangiectasia-Lymphedema Syndrome 1 and Hennekam Syndrome. Gene Ontology (GO) annotations related to this gene include calcium ion binding and collagen binding.

UniProtKB/Swiss-Prot Summary for CCBE1 Gene

  • Required for lymphangioblast budding and angiogenic sprouting from venous endothelium during embryogenesis.

Gene Wiki entry for CCBE1 Gene

Additional gene information for CCBE1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CCBE1 Gene

Genomics for CCBE1 Gene

GeneHancer (GH) Regulatory Elements for CCBE1 Gene

Promoters and enhancers for CCBE1 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH18J059695 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 750.6 -0.8 -810 6.9 CTCF RAD21 ZSCAN21 KLF14 GLIS2 ZIC2 POLR2A PRDM10 ZEB2 ZNF629 CCBE1 ENSG00000267774 ENSG00000273664
GH18J059455 Promoter 1 EPDnew 750.1 +242.4 242420 0.1 CTBP1 ZNF701 ZNF121 BCL6B SP7 ZSCAN21 GLIS2 PKNOX1 ZIC2 ZBTB8A CCBE1 ZNF532 ENSG00000267061 ENSG00000267269 ENSG00000267215 ENSG00000267462 ENTR1P1 ENSG00000267686 ENSG00000267579 ENSG00000267401
GH18J059714 Enhancer 0.9 Ensembl ENCODE dbSUPER 18.8 -20.0 -20049 6.4 POLR2A RFX1 CEBPB CHD2 JUN RCOR1 JUND SP1 ZEB1 FOS CCBE1 piR-30449-068 lnc-CCBE1-1
GH18J059513 Enhancer 1.3 Ensembl ENCODE CraniofacialAtlas 8.4 +182.0 182027 4.3 MLX RBPJ SMARCE1 NR2F1 NR2F6 CREB1 ZNF362 MIXL1 ZNF121 TEAD4 CCBE1 piR-57987 ENSG00000267000
GH18J059501 Enhancer 1.1 Ensembl ENCODE CraniofacialAtlas 9.1 +195.2 195208 3.3 ZNF362 ZNF121 ZNF384 SP7 ZSCAN21 PKNOX1 ZBTB8A CEBPB ZNF629 ZNF501 CCBE1 piR-57987 ENSG00000267000
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CCBE1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the CCBE1 gene promoter:
  • Chx10
  • FOXO1
  • FOXO1a
  • FOXO3
  • FOXO3a
  • FOXO3b
  • NF-kappaB
  • NF-kappaB1
  • RelA
  • RORalpha1

Genomic Locations for CCBE1 Gene

Genomic Locations for CCBE1 Gene
266,724 bases
Minus strand
266,474 bases
Minus strand

Genomic View for CCBE1 Gene

Genes around CCBE1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CCBE1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CCBE1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CCBE1 Gene

Proteins for CCBE1 Gene

  • Protein details for CCBE1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Collagen and calcium-binding EGF domain-containing protein 1
    Protein Accession:
    Secondary Accessions:
    • Q6MZX5
    • Q86SS2
    • Q8TF19

    Protein attributes for CCBE1 Gene

    406 amino acids
    Molecular mass:
    44103 Da
    Quaternary structure:
    No Data Available
    • Sequence=BAB85569.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for CCBE1 Gene


neXtProt entry for CCBE1 Gene

Post-translational modifications for CCBE1 Gene

  • Glycosylation at Asn142 and Asn182
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for CCBE1 Gene

Domains & Families for CCBE1 Gene

Gene Families for CCBE1 Gene

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

Suggested Antigen Peptide Sequences for CCBE1 Gene

GenScript: Design optimal peptide antigens:
  • Full of fluid protein homolog (CCBE1_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the CCBE1 family.
  • Belongs to the CCBE1 family.
genes like me logo Genes that share domains with CCBE1: view

Function for CCBE1 Gene

Molecular function for CCBE1 Gene

UniProtKB/Swiss-Prot Function:
Required for lymphangioblast budding and angiogenic sprouting from venous endothelium during embryogenesis.

Phenotypes From GWAS Catalog for CCBE1 Gene

Gene Ontology (GO) - Molecular Function for CCBE1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IPI 24552833
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding IPI 25416956
GO:0005518 collagen binding IDA 21778431
genes like me logo Genes that share ontologies with CCBE1: view
genes like me logo Genes that share phenotypes with CCBE1: view

Human Phenotype Ontology for CCBE1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CCBE1 Gene

MGI Knock Outs for CCBE1:

Animal Model Products

  • Taconic Biosciences Mouse Models for CCBE1

CRISPR Products

miRNA for CCBE1 Gene

miRTarBase miRNAs that target CCBE1

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CCBE1 Gene

Localization for CCBE1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CCBE1 Gene


Subcellular locations from

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 CCBE1 gene
Compartment Confidence
extracellular 5
plasma membrane 3
nucleus 2
cytosol 2
mitochondrion 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (4)
  • Plasma membrane (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CCBE1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005581 collagen trimer IEA --
GO:0005615 extracellular space IDA 24552833
GO:0031012 extracellular matrix IDA 21778431
genes like me logo Genes that share ontologies with CCBE1: view

Pathways & Interactions for CCBE1 Gene

PathCards logo

SuperPathways for CCBE1 Gene

No Data Available

Gene Ontology (GO) - Biological Process for CCBE1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001945 lymph vessel development IEA --
GO:0001946 lymphangiogenesis ISS,IEA --
GO:0002040 sprouting angiogenesis ISS --
GO:0003016 respiratory system process IEA --
GO:0007275 multicellular organism development IEA --
genes like me logo Genes that share ontologies with CCBE1: view

No data available for Pathways by source and SIGNOR curated interactions for CCBE1 Gene

Drugs & Compounds for CCBE1 Gene

No Compound Related Data Available

Transcripts for CCBE1 Gene

mRNA/cDNA for CCBE1 Gene

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for CCBE1 Gene

No ASD Table

Relevant External Links for CCBE1 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for CCBE1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CCBE1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CCBE1 Gene

This gene is overexpressed in Colon - Sigmoid (x5.5) and Ovary (x4.8).

Protein differential expression in normal tissues from HIPED for CCBE1 Gene

This gene is overexpressed in Heart (64.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CCBE1 Gene

Protein tissue co-expression partners for CCBE1 Gene

NURSA nuclear receptor signaling pathways regulating expression of CCBE1 Gene:


SOURCE GeneReport for Unigene cluster for CCBE1 Gene:


mRNA Expression by UniProt/SwissProt for CCBE1 Gene:

Tissue specificity: Not expressed in blood or lymphatic endothelial cells.

Evidence on tissue expression from TISSUES for CCBE1 Gene

  • Lung(4.2)
  • Liver(4.1)
  • Nervous system(4.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CCBE1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • lymphatic
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Head and neck:
  • brain
  • chin
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • middle ear
  • mouth
  • neck
  • nose
  • outer ear
  • skull
  • thyroid
  • tooth
  • chest wall
  • clavicle
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
  • abdominal wall
  • intestine
  • kidney
  • large intestine
  • small intestine
  • spleen
  • anus
  • pelvis
  • rectum
  • testicle
  • ureter
  • urinary bladder
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • nail
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
  • blood
  • blood vessel
  • hair
  • lymph node
  • lymph vessel
  • skin
  • spinal column
  • spinal cord
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with CCBE1: view

Orthologs for CCBE1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CCBE1 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia CCBE1 33 32
  • 99.59 (n)
(Ornithorhynchus anatinus)
Mammalia -- 33
  • 89 (a)
-- 33
  • 84 (a)
(Canis familiaris)
Mammalia CCBE1 33 32
  • 88.06 (n)
(Mus musculus)
Mammalia Ccbe1 17 33 32
  • 86.62 (n)
(Rattus norvegicus)
Mammalia Ccbe1 32
  • 86.45 (n)
(Bos Taurus)
Mammalia CCBE1 33 32
  • 86.29 (n)
(Monodelphis domestica)
Mammalia CCBE1 33
  • 83 (a)
(Gallus gallus)
Aves CCBE1 33 32
  • 74.56 (n)
(Anolis carolinensis)
Reptilia -- 33
  • 78 (a)
-- 33
  • 77 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia ccbe1 32
  • 72.57 (n)
(Danio rerio)
Actinopterygii ccbe1 33 32
  • 66.39 (n)
Species where no ortholog for CCBE1 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)
  • fruit fly (Drosophila melanogaster)
  • 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 squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • 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)
  • worm (Caenorhabditis elegans)

Evolution for CCBE1 Gene

Gene Tree for CCBE1 (if available)
Gene Tree for CCBE1 (if available)
Evolutionary constrained regions (ECRs) for CCBE1: view image

Paralogs for CCBE1 Gene

No data available for Paralogs for CCBE1 Gene

Variants for CCBE1 Gene

Sequence variations from dbSNP and Humsavar for CCBE1 Gene

SNP ID Clin Chr 18 pos Variation AA Info Type
rs1048006 benign, Hennekam lymphangiectasia-lymphedema syndrome 59,431,159(-) G/A 3_prime_UTR_variant, genic_downstream_transcript_variant
rs1048008 uncertain-significance, benign, Hennekam lymphangiectasia-lymphedema syndrome 59,431,112(-) C/G/T 3_prime_UTR_variant, genic_downstream_transcript_variant
rs112059725 uncertain-significance, Hennekam lymphangiectasia-lymphedema syndrome 59,432,375(-) G/T 3_prime_UTR_variant, genic_downstream_transcript_variant
rs1129748 benign, Hennekam lymphangiectasia-lymphedema syndrome 59,430,963(-) G/T 3_prime_UTR_variant, genic_downstream_transcript_variant
rs113599524 likely-benign, Hennekam lymphangiectasia-lymphedema syndrome 59,433,888(-) G/A/C 3_prime_UTR_variant, downstream_transcript_variant, genic_downstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for CCBE1 Gene

Variant ID Type Subtype PubMed ID
dgv1617n106 CNV deletion 24896259
dgv3365n100 CNV gain 25217958
dgv3366n100 CNV gain 25217958
esv1302581 CNV insertion 17803354
esv2344726 CNV deletion 18987734
esv2507425 CNV insertion 19546169
esv2578250 CNV deletion 19546169
esv2659149 CNV deletion 23128226
esv2717167 CNV deletion 23290073
esv2717168 CNV deletion 23290073
esv2717169 CNV deletion 23290073
esv274875 CNV gain+loss 21479260
esv275221 CNV loss 21479260
esv3303248 CNV mobile element insertion 20981092
esv3336754 CNV insertion 20981092
esv3391683 CNV insertion 20981092
esv3397864 CNV insertion 20981092
esv3427131 CNV duplication 20981092
esv3555474 CNV deletion 23714750
esv3642663 CNV loss 21293372
esv3642664 CNV loss 21293372
esv3642665 CNV loss 21293372
esv3642666 CNV loss 21293372
esv3642667 CNV loss 21293372
esv3893108 CNV loss 25118596
esv4345 CNV loss 18987735
esv8710 CNV loss 19470904
nsv1055437 CNV gain 25217958
nsv1055632 CNV loss 25217958
nsv1055873 CNV gain 25217958
nsv1066670 CNV loss 25217958
nsv1071853 CNV deletion 25765185
nsv1142239 CNV tandem duplication 24896259
nsv1146850 CNV deletion 26484159
nsv470420 CNV gain 18288195
nsv513499 CNV insertion 21212237
nsv522624 CNV loss 19592680
nsv577052 CNV loss 21841781
nsv577053 CNV gain 21841781
nsv828251 CNV loss 20364138

Variation tolerance for CCBE1 Gene

Residual Variation Intolerance Score: 50.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.75; 46.88% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CCBE1 Gene

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

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CCBE1 Gene

Disorders for CCBE1 Gene

MalaCards: The human disease database

(5) MalaCards diseases for CCBE1 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
hennekam lymphangiectasia-lymphedema syndrome 1
  • hklls1
hennekam syndrome
  • hennekam lymphangiectasia-lymphedema syndrome
cholestasis-lymphedema syndrome
  • chls
van maldergem syndrome
  • cerebrofacioarticular syndrome
- elite association - COSMIC cancer census association via MalaCards
Search CCBE1 in MalaCards View complete list of genes associated with diseases


  • Hennekam lymphangiectasia-lymphedema syndrome 1 (HKLLS1) [MIM:235510]: A form of Hennekam lymphangiectasia-lymphedema syndrome, a generalized lymph-vessels dysplasia characterized by intestinal lymphangiectasia with severe lymphedema of the limbs, genitalia and face. In addition, affected individuals have unusual facies and some manifest mental retardation. HKLLS1 inheritance is autosomal recessive. {ECO:0000269 PubMed:19911200, ECO:0000269 PubMed:19935664}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for CCBE1

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with CCBE1: view

No data available for Genatlas for CCBE1 Gene

Publications for CCBE1 Gene

  1. The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. (PMID: 12975309) Clark HF … Gray A (Genome research 2003) 2 3 4 56
  2. Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins. (PMID: 11853319) Nagase T … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 2001) 2 3 4 56
  3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 43 56
  4. Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia. (PMID: 19911200) Connell F … Lymphoedema Consortium (Human genetics 2010) 3 4 56
  5. Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans. (PMID: 19935664) Alders M … Hennekam RC (Nature genetics 2009) 3 4 56

Products for CCBE1 Gene

Sources for CCBE1 Gene