CCBE1

Chr 18AR

collagen and calcium binding EGF domains 1

NCBI Gene: 147372ENSG00000183287UniProt: Q6UXH8

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

Primary Disease Associations & Inheritance

Hennekam lymphangiectasia-lymphedema syndrome 1MIM #235510
AR
645
ClinVar variants
55
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CCBE1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
55 Pathogenic / Likely Pathogenic· 210 VUS of 645 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.01LOEUF
pLI 0.000
Z-score 1.54
OE 0.64 (0.42–1.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.69Z-score
OE missense 1.13 (1.02–1.25)
265 obs / 235.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.64 (0.42–1.01)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.13 (1.02–1.25)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 14 / 21.8Missense obs/exp: 265 / 235.2Syn Z: -0.48

ClinVar Variant Classifications

645 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic8
VUS210
Likely Benign171
Benign34
Conflicting25
47
Pathogenic
8
Likely Pathogenic
210
VUS
171
Likely Benign
34
Benign
25
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
44
0
47
Likely Pathogenic
4
1
3
0
8
VUS
3
152
53
2
210
Likely Benign
0
4
75
92
171
Benign
0
1
32
1
34
Conflicting
—25
Total915920795495

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CCBE1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

CCBE1-related Hennekam lymphangiectasia-lymphedema syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hennekam lymphangiectasia-lymphedema syndrome 1

MIM #235510

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Apelin-VEGF-C mRNA delivery as therapeutic for the treatment of secondary lymphedema.
Creff J et al.·EMBO Mol Med
2024
A novel CCBE1 mutation leading to a mild form of hennekam syndrome: case report and review of the literature.
Frosk P et al.·BMC Med Genet
2015Review
Clinical significance of CCBE1 expression in lung cancer.
Li P et al.·Mol Med Rep
2018
Expression of SLP-2 gene and CCBE1 are associated with prognosis of rectal cancer.
Zhang L et al.·Eur Rev Med Pharmacol Sci
2017
Circ_0006174 promotes the malignancy of colorectal cancer cell via the miR‑1205/CCBE1/Wnt pathway.
Zhao X et al.·Mol Med Rep
2022
miR-942-5p Inhibits Proliferation, Metastasis, and Epithelial-Mesenchymal Transition in Colorectal Cancer by Targeting CCBE1.
Zhou L et al.·Biomed Res Int
2021
Predicting the Most Deleterious Missense Nonsynonymous Single-Nucleotide Polymorphisms of Hennekam Syndrome-Causing CCBE1 Gene, In Silico Analysis.
Shinwari K et al.·ScientificWorldJournal
2021
Expanding the genotypic spectrum of CCBE1 mutations in Hennekam syndrome.
Crawford J et al.·Am J Med Genet A
2016Case report
A Multiplex Kindred with Hennekam Syndrome due to Homozygosity for a CCBE1 Mutation that does not Prevent Protein Expression.
Jackson CC et al.·J Clin Immunol
2016Case report
CCBE1 mutation in two siblings, one manifesting lymphedema-cholestasis syndrome, and the other, fetal hydrops.
Shah S et al.·PLoS One
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools