VEGFC

vascular endothelial growth factor C, the group of VEGF family

Basic information

Region (hg38): 4:176683537-176792922

Links

ENSG00000150630 ∙ NCBI:7424 ∙ OMIM:601528 ∙ HGNC:12682 ∙ Uniprot:P49767 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lymphatic malformation 4 (Strong), mode of inheritance: AD
• lymphatic malformation (Supportive), mode of inheritance: AD
• lymphatic malformation 4 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lymphatic malformation 4	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic	23410910; 24744435
Individuals may be susceptible to recurrent skin infections

ClinVar

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

• not provided (15 variants)
• not specified (10 variants)
• Inborn genetic diseases (8 variants)
• Lymphatic malformation 4 (5 variants)
• VEGFC-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VEGFC 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					1	1
missense			10	1	10	21
nonsense	1		1			2
start loss						0
frameshift						0
inframe indel					1	1
splice donor/acceptor (+/-2bp)	1					1
splice region						0
non coding					10	10
Total	2	0	11	1	22

Variants in VEGFC

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

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

Position	Type	Phenotype	Significance	ClinVar
4-176684019-C-T		VEGFC-related disorder	Likely benign (Sep 17, 2019)
4-176684030-G-A		not specified	Conflicting classifications of pathogenicity (May 04, 2022)
4-176686910-T-A			Benign (Nov 12, 2018)
4-176687209-T-G		not specified	Benign (May 04, 2022)
4-176687268-G-C		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
4-176687340-T-G		Inborn genetic diseases	Uncertain significance (Jun 09, 2022)
4-176687351-T-G		Inborn genetic diseases	Uncertain significance (Feb 14, 2023)
4-176687358-G-A		not specified	Benign (May 04, 2022)
4-176687380-C-A		Inborn genetic diseases	Uncertain significance (Jun 22, 2021)
4-176687419-C-A		VEGFC-related disorder	Uncertain significance (Feb 18, 2023)
4-176687452-C-A		Inborn genetic diseases	Uncertain significance (Jul 15, 2021)
4-176687472-T-C		Inborn genetic diseases	Uncertain significance (May 27, 2022)
4-176687621-T-C			Benign (Nov 12, 2018)
4-176687721-A-C			Benign (Jun 19, 2021)
4-176687827-C-T		not specified • Inborn genetic diseases	Conflicting classifications of pathogenicity (May 04, 2022)
4-176687851-C-T		Lymphatic malformation 4	Likely benign (Feb 02, 2022)
4-176687917-C-T		Inborn genetic diseases	Uncertain significance (Feb 06, 2024)
4-176688049-G-A			Benign (Nov 12, 2018)
4-176688105-C-T			Benign (Nov 12, 2018)
4-176688110-C-T			Benign (Nov 12, 2018)
4-176711544-T-C		Inborn genetic diseases	Uncertain significance (Dec 28, 2023)
4-176711559-A-T		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
4-176711574-C-T		not specified	Benign (May 04, 2022)
4-176711575-G-A		Lymphatic malformation 4	Pathogenic (Sep 26, 2022)
4-176711598-C-T		Inborn genetic diseases	Uncertain significance (Oct 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VEGFC	protein_coding	protein_coding	ENST00000280193	7	109193

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.496	0.504	124775	0	16	124791	0.0000641

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.849	194	230	0.843	0.0000119	2757
Missense in Polyphen		58	88.444	0.65578		1048
Synonymous	-0.226	87	84.4	1.03	0.00000436	767
Loss of Function	3.21	4	19.1	0.209	9.78e-7	243

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000104	0.000104
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000560	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.000124	0.000115
Middle Eastern	0.0000560	0.0000556
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Growth factor active in angiogenesis, and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May function in angiogenesis of the venous and lymphatic vascular systems during embryogenesis, and also in the maintenance of differentiated lymphatic endothelium in adults. Binds and activates KDR/VEGFR2 and FLT4/VEGFR3 receptors. {ECO:0000269|PubMed:20145116}.
• Disease: DISEASE: Lymphedema, hereditary, 1D (LMPH1D) [MIM:615907]: A chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections and physical impairment. {ECO:0000269|PubMed:23410910, ECO:0000269|PubMed:24744435}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);VEGF Signaling Pathway;Heart Development;Focal Adhesion;miR-148a-miR-31-FIH1-HIF1α-Notch signaling in glioblastoma;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Signal Transduction;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;GPCR signaling-G alpha s Epac and ERK;VEGF ligand-receptor interactions;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;GPCR signaling-G alpha s PKA and ERK;Hemostasis;VEGFR3 signaling in lymphatic endothelium;VEGF binds to VEGFR leading to receptor dimerization;Signaling by VEGF;GPCR signaling-G alpha i;Signaling by Receptor Tyrosine Kinases;VEGF;Alpha9 beta1 integrin signaling events;VEGF and VEGFR signaling network (Consensus)

Recessive Scores

• pRec: 0.174

Intolerance Scores

• loftool: 0.229
• rvis_EVS: 0.19
• rvis_percentile_EVS: 67.03

Haploinsufficiency Scores

• pHI: 0.335
• hipred: Y
• hipred_score: 0.653
• ghis: 0.522

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.603

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vegfc
• Phenotype: homeostasis/metabolism phenotype; immune system 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: vegfc
• Affected structure: vascular lymphangioblast
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: angiogenesis;response to hypoxia;positive regulation of protein phosphorylation;positive regulation of endothelial cell proliferation;sprouting angiogenesis;positive regulation of neuroblast proliferation;platelet degranulation;substrate-dependent cell migration;signal transduction;positive regulation of cell population proliferation;animal organ morphogenesis;regulation of signaling receptor activity;morphogenesis of embryonic epithelium;regulation of vascular endothelial growth factor receptor signaling pathway;positive regulation of protein autophosphorylation;vascular endothelial growth factor signaling pathway;response to drug;positive regulation of blood vessel endothelial cell migration;positive regulation of angiogenesis;negative regulation of blood pressure;vascular endothelial growth factor receptor signaling pathway;positive regulation of protein secretion;positive chemotaxis;induction of positive chemotaxis;positive regulation of cell division;positive regulation of mast cell chemotaxis;positive regulation of lymphangiogenesis;cellular response to leukemia inhibitory factor
• Cellular component: extracellular region;extracellular space;membrane;platelet alpha granule lumen
• Molecular function: vascular endothelial growth factor receptor binding;protein binding;growth factor activity;chemoattractant activity;vascular endothelial growth factor receptor 3 binding