CCBE1

collagen and calcium binding EGF domains 1

Basic information

Region (hg38): 18:59430938-59697662

Links

ENSG00000183287 ∙ NCBI:147372 ∙ OMIM:612753 ∙ HGNC:29426 ∙ Uniprot:Q6UXH8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Hennekam lymphangiectasia-lymphedema syndrome 1 (Definitive), mode of inheritance: AR
• Hennekam lymphangiectasia-lymphedema syndrome 1 (Strong), mode of inheritance: AR
• Hennekam syndrome (Supportive), mode of inheritance: AR
• Hennekam lymphangiectasia-lymphedema syndrome 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hennekam lymphangiectasia-lymphedema syndrome 1	AR	Allergy/Immunology/Infectious; Endocrine; Gastrointestinal	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	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Neurologic; Renal	2624276; 1897580; 8465855; 7645602; 10925377; 12124738; 12376947; 14564208; 12794699; 19935664; 19911200; 22239599

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCBE1 gene.

• not provided (270 variants)
• Hennekam lymphangiectasia-lymphedema syndrome 1 (235 variants)
• Inborn genetic diseases (25 variants)
• not specified (19 variants)
• CCBE1-related condition (7 variants)
• Renal tubular acidosis, distal, 4, with hemolytic anemia (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCBE1 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			3	44	2	49
missense	1	1	125	3	2	132
nonsense	1					1
start loss			2			2
frameshift	3		3			6
inframe indel						0
splice donor/acceptor (+/-2bp)		3				3
splice region			6	8		14
non coding			111	47	75	233
Total	5	4	244	94	79

Highest pathogenic variant AF is 0.0000657

Variants in CCBE1

This is a list of pathogenic ClinVar variants found in the CCBE1 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-59430952-T-G		Hennekam lymphangiectasia-lymphedema syndrome 1	Uncertain significance (Jan 13, 2018)
18-59430963-G-T		Hennekam lymphangiectasia-lymphedema syndrome 1	Benign (Jan 13, 2018)
18-59430968-T-A		Hennekam lymphangiectasia-lymphedema syndrome 1	Uncertain significance (Jan 12, 2018)
18-59430974-C-A		Hennekam lymphangiectasia-lymphedema syndrome 1	Likely benign (Jan 01, 2023)
18-59431031-G-C		Hennekam lymphangiectasia-lymphedema syndrome 1	Uncertain significance (Jan 13, 2018)
18-59431062-C-T		Hennekam lymphangiectasia-lymphedema syndrome 1	Benign (Jan 12, 2018)
18-59431090-C-T		Hennekam lymphangiectasia-lymphedema syndrome 1	Uncertain significance (Jan 13, 2018)
18-59431109-C-T		Hennekam lymphangiectasia-lymphedema syndrome 1	Uncertain significance (Jan 12, 2018)
18-59431112-C-G		Hennekam lymphangiectasia-lymphedema syndrome 1	Uncertain significance (Jan 13, 2018)
18-59431112-C-T		Hennekam lymphangiectasia-lymphedema syndrome 1	Benign (Jan 13, 2018)
18-59431120-A-G		Hennekam lymphangiectasia-lymphedema syndrome 1	Benign (Jan 13, 2018)
18-59431135-G-C		Hennekam lymphangiectasia-lymphedema syndrome 1	Uncertain significance (Jan 13, 2018)
18-59431153-T-G		Hennekam lymphangiectasia-lymphedema syndrome 1	Uncertain significance (Jan 12, 2018)
18-59431159-G-A		Hennekam lymphangiectasia-lymphedema syndrome 1	Benign (Jan 13, 2018)
18-59431170-C-T		Hennekam lymphangiectasia-lymphedema syndrome 1	Uncertain significance (Jan 12, 2018)
18-59431193-A-C		Hennekam lymphangiectasia-lymphedema syndrome 1	Uncertain significance (Jan 13, 2018)
18-59431198-C-T		Hennekam lymphangiectasia-lymphedema syndrome 1	Uncertain significance (Jan 13, 2018)
18-59431352-CATT-C		Hennekam lymphangiectasia-lymphedema syndrome 1	Conflicting classifications of pathogenicity (Jan 01, 2023)
18-59431383-A-G		Hennekam lymphangiectasia-lymphedema syndrome 1	Uncertain significance (Jan 13, 2018)
18-59431404-C-G		Hennekam lymphangiectasia-lymphedema syndrome 1	Benign (Jan 12, 2018)
18-59431410-A-G		Hennekam lymphangiectasia-lymphedema syndrome 1	Likely benign (Jan 13, 2018)
18-59431481-TG-T		Hennekam lymphangiectasia-lymphedema syndrome 1	Benign (Jun 14, 2016)
18-59431510-G-T		Hennekam lymphangiectasia-lymphedema syndrome 1	Benign (Jan 12, 2018)
18-59431533-A-G		Hennekam lymphangiectasia-lymphedema syndrome 1	Uncertain significance (Jan 13, 2018)
18-59431626-C-T		Hennekam lymphangiectasia-lymphedema syndrome 1	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCBE1	protein_coding	protein_coding	ENST00000439986	11	266441

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.53e-7	0.849	125686	0	62	125748	0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.691	265	235	1.13	0.0000136	2592
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000552	0.000550
Ashkenazi Jewish	0.00149	0.00149
East Asian	0.000163	0.000163
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000220	0.000220
Middle Eastern	0.000163	0.000163
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.167
• hipred: N
• hipred_score: 0.350
• ghis: 0.463

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.403

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ccbe1
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; hematopoietic system phenotype; liver/biliary system phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: ccbe1
• Affected structure: lymphangioblast cord
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: lymphangiogenesis;sprouting angiogenesis;positive regulation of vascular endothelial growth factor production;positive regulation of protein processing;venous blood vessel morphogenesis;positive regulation of vascular endothelial growth factor signaling pathway
• Cellular component: collagen trimer;extracellular space;extracellular matrix
• Molecular function: protease binding;calcium ion binding;protein binding;collagen binding