CCBE1
protein-codingcollagen and calcium binding EGF domains 1
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~266.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009337
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0016256
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0009337
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0009337
Submitter: Genomics England PanelApp
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Neurologic; Renal
Intervention: Allergy/Immunology/Infectious; Endocrine; Gastrointestinal
Rationale: The condition can include manifestations such as protein-losing enteropathy (which may be refractory), as well as features for which treatment can be beneficial, such as infectious sequelae, for which early and aggressive treatment may be beneficial; Individuals have been described with endocrine manifestations such as hypothyroidism and growth hormone deficiency, and awareness may allow prompt recognition and treatment
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CCBE1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_133459.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 102 | 2 | 107 | ||
| missense | 3 | 4 | 159 | 12 | 2 | 180 |
| nonsense | 4 | 2 | 6 | |||
| start loss | 1 | 2 | 3 | |||
| frameshift | 3 | 1 | 5 | 9 | ||
| splice donor/acceptor (+/-2bp) | 7 | 1 | 8 | |||
| Total | 11 | 14 | 170 | 114 | 4 | 313 |
Highest pathogenic variant AF is 0.0002132109
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_597716.1 | 11 | MANE Select | |
| Ensembl | ENSP00000404464.2 | 11 | MANE Select | |
| Ensembl | ENSP00000497183.1 | 11 | Standard | |
| Ensembl | ENSP00000497183.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ccbe1 | Danio rerio | Structure: lymphangioblast cord Quality: absent abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- lymphangiogenesis
- sprouting angiogenesis
- positive regulation of vascular endothelial growth factor production
- positive regulation of protein processing
- venous blood vessel morphogenesis
Molecular Function
- protease binding
- calcium ion binding
- protein binding
- collagen binding
Cellular Component
- collagen trimer
- extracellular space
- extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000439986
- Coding exons
- 11
- Length
- 266441
- Individuals with no LoFs
- 125686
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 62
- Defined
- 125748
- p
- 0.000247
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.691 | 265 | 235 | 1.13 | 0.0000136 | 2592 |
| Missense (PolyPhen) | 108 | 102.15 | 1.0572 | 1080 | ||
| Synonymous | -0.482 | 99 | 93.1 | 1.06 | 0.00000535 | 819 |
| Loss of Function | 1.54 | 14 | 21.8 | 0.643 | 0.00000113 | 272 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00049 | 0.00049 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.0015 | 0.0015 | notable |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00022 | 0.00022 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for lymphangioblast budding and angiogenic sprouting from venous endothelium during embryogenesis. {ECO:0000269|PubMed:19935664}.;
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- LoFtool
- 0.254
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 50.34
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.403
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |