VEGFD
protein-codingvascular endothelial growth factor D, 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 and is active in angiogenesis, lymphangiogenesis, and endothelial cell growth. This secreted protein undergoes a complex proteolytic maturation, generating multiple processed forms which bind and activate VEGFR-2 and VEGFR-3 receptors. This protein is structurally and functionally similar to vascular endothelial growth factor C. Read-through transcription has been observed between this locus and the upstream PIR (GeneID 8544) locus. [provided by RefSeq, Feb 2011]
- FIGF
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~38.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to VEGFD variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004469.5. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 3 | |||
| missense | 1 | 1 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 1 | 2 | 1 | 4 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004460.1 | 7 | MANE Select | |
| Ensembl | ENSP00000297904.3 | 7 | MANE Select | |
| Ensembl | ENSP00000618623.1 | 7 | Standard | |
| Ensembl | ENSP00000618623.1 | 7 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| vegfd | Danio rerio | Structure: medial facial lymph vessel 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)
- Rap1 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
- platelet-derived growth factor receptor binding
- vascular endothelial growth factor receptor binding
- protein binding
- growth factor activity
- chemoattractant activity
Cellular Component
- extracellular region
- extracellular space
- membrane
- platelet alpha granule lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000297904
- Coding exons
- 7
- Length
- 38786
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 8
- Heterozygous LoFs
- 22
- Defined
- 125745
- p
- 0.000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.499 | 121 | 137 | 0.880 | 0.0000104 | 2348 |
| Missense (PolyPhen) | 32 | 42.436 | 0.75408 | 697 | ||
| Synonymous | -0.662 | 55 | 49.1 | 1.12 | 0.00000378 | 643 |
| Loss of Function | 1.16 | 9 | 13.6 | 0.662 | 0.00000114 | 211 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00017 | 0.00012 | rare |
| Latino/Admixed American | 0.00029 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00044 | 0.00033 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.000079 | rare |
| South Asian | 0.00022 | 0.00013 | rare |
| Other | 0.00022 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Growth factor active in angiogenesis, lymphangiogenesis and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May function in the formation of the venous and lymphatic vascular systems during embryogenesis, and also in the maintenance of differentiated lymphatic endothelium in adults. Binds and activates VEGFR-2 (KDR/FLK1) and VEGFR-3 (FLT4) receptors. {ECO:0000269|PubMed:21148085}.;
Recessive Scores
- pRec
- 0.182
Intolerance Scores
- RVIS EVS
- -0.43
- RVIS percentile EVS
- 25.15
Essentials
- Essential (gene trap)
- N