GeneBe

VEGFC

protein-coding

vascular endothelial growth factor C, the group of VEGF family

Gene summary

The protein encoded by this gene is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family. The encoded protein promotes angiogenesis and endothelial cell growth, and can also affect the permeability of blood vessels. The proprotein is further cleaved into a fully processed form that can bind and activate VEGFR-2 and VEGFR-3 receptors. [provided by RefSeq, Apr 2014]

MANE transcript

NM_005429.5

Inheritance

AD

ClinVar variants

P:3U:60B:17

Top phenotype

Lymphatic malformation 4

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr4:176,683,538-176,792,922

External References & Databases

Ensembl (ENSG00000150630)NCBI Gene (7424)OMIM (601528)HGNC:12682GenCCUniProt (P49767)AlphaFoldClinVar (VEGFC)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~109.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

lymphatic malformation 4STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014393

Submitter: Ambry Genetics

lymphatic malformationSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019313

Submitter: Orphanet

lymphatic malformation 4STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014393

Submitter: PanelApp Australia

lymphatic malformation 4STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014393

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Lymphatic malformation 4AD

Manifestation: Dermatologic

Intervention: General

Rationale: 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

Comments: Individuals may be susceptible to recurrent skin infections

Refs: 23410910; 24744435Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VEGFC variants in ClinVar

6 Conditions Cataloged
Inborn genetic diseasesTotal: 52
not providedTotal: 14
Lymphatic malformation 4Total: 10
not specifiedTotal: 10
VEGFC-related disorderTotal: 8
LymphedemaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005429.5. 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.

EffectPLPVUSLBBSum
synonymous
4
clinvar
1
clinvar
 5
missense
59
clinvar
4
clinvar
8
clinvar
 71
nonsense
1
clinvar
1
clinvar
 2
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total30608980
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_005429.5RefSeqNP_005420.17MANE Select
ENST00000618562.2EnsemblENSP00000480043.17MANE Select
ENST00001135725.1EnsemblENSP00000814652.17Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
vegfcDanio rerio

Structure: vascular lymphangioblast

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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)

Biological Process

  • angiogenesis
  • response to hypoxia
  • positive regulation of protein phosphorylation
  • positive regulation of endothelial cell proliferation
  • sprouting angiogenesis

Molecular Function

  • vascular endothelial growth factor receptor binding
  • protein binding
  • growth factor activity
  • chemoattractant activity
  • vascular endothelial growth factor receptor 3 binding

Cellular Component

  • extracellular region
  • extracellular space
  • membrane
  • platelet alpha granule lumen

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000280193
Coding exons
7
Length
109193
Individuals with no LoFs
124775
Homozygous LoFs
0
Heterozygous LoFs
16
Defined
124791
p
0.0000641
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.8491942300.8430.00001192757
Missense (PolyPhen)5888.4440.655781048
Synonymous-0.2268784.41.030.00000436767
Loss of Function3.21419.10.2099.78e-7243

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000650.000065rare
Latino/Admixed American0.0000390.000029rare
Ashkenazi Jewish00.0absent
East Asian0.0000560.000056rare
Finnish00.0absent
European (Non-Finnish)0.000120.00011rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.174

Intolerance Scores

LoFtool
0.229
RVIS EVS
0.19
RVIS percentile EVS
67.03

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.603

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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