FLT4
fms related receptor tyrosine kinase 4, the group of Receptor tyrosine kinases|I-set domain containing
Basic information
Region (hg38): 5:180601505-180649624
Links
Phenotypes
GenCC
Source:
- lymphatic malformation 1 (Definitive), mode of inheritance: AD
- capillary infantile hemangioma (Strong), mode of inheritance: AD
- lymphatic malformation 1 (Definitive), mode of inheritance: AD
- tetralogy of fallot (Supportive), mode of inheritance: AD
- lymphatic malformation (Supportive), mode of inheritance: AD
- lymphatic malformation 1 (Strong), mode of inheritance: AD
- congenital heart defects, multiple types, 7 (Strong), mode of inheritance: AD
- lymphatic malformation 1 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Lymphatic malformation 1 | AD/AR | Allergy/Immunology/Infectious; Cardiovascular | Individuals with congenital cardiac anomalies may benefit from early diagnosis to enable early surgical and other interventions; In Lymphatic malformation, treatment includes early and aggressive treatment of infections, as well as prophylactic antibiotics in some instances | Allergy/Immunology/Infectious; Cardiovascular | 14295660; 9817924; 10835628; 12960217; 15689446; 16965327; 16924388; 19002718; 19289394; 20301417; 22768468; 28991257; 30232381 |
| Biallelic inheritance has been described |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (201 variants)
- not specified (68 variants)
- Inborn genetic diseases (35 variants)
- Hereditary lymphedema type I (24 variants)
- FLT4-related condition (21 variants)
- Congenital heart defects, multiple types, 7 (13 variants)
- Carcinoma of colon (2 variants)
- Capillary infantile hemangioma (1 variants)
- Colorectal cancer (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FLT4 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 | 20 | 12 | 32 | |||
| missense | 10 | 88 | 16 | 10 | 126 | |
| nonsense | 4 | |||||
| start loss | 0 | |||||
| frameshift | 5 | |||||
| inframe indel | 3 | |||||
| splice donor/acceptor (+/-2bp) | 4 | |||||
| splice region ? | 1 | 3 | 4 | |||
| non coding ? | 18 | 91 | 110 | |||
| Total | 7 | 15 | 94 | 54 | 114 |
Highest pathogenic variant AF is 0.0000131
Variants in FLT4
This is a list of pathogenic ClinVar variants found in the FLT4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FLT4 | protein_coding | protein_coding | ENST00000261937 | 30 | 48119 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 1.72e-8 | 125739 | 0 | 9 | 125748 | 0.0000358 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.83 | 626 | 860 | 0.728 | 0.0000590 | 8853 |
| Missense in Polyphen | 168 | 328.31 | 0.5117 | 3481 | ||
| Synonymous | -1.77 | 440 | 395 | 1.11 | 0.0000310 | 2716 |
| Loss of Function | 7.28 | 5 | 71.4 | 0.0700 | 0.00000357 | 764 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000579 | 0.0000579 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000559 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000444 | 0.0000352 |
| Middle Eastern | 0.0000559 | 0.0000544 |
| South Asian | 0.0000653 | 0.0000653 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3- kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr- 185', and of AKT1 at 'Ser-473'. {ECO:0000269|PubMed:11532940, ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:15474514, ECO:0000269|PubMed:16076871, ECO:0000269|PubMed:16452200, ECO:0000269|PubMed:17210781, ECO:0000269|PubMed:19610651, ECO:0000269|PubMed:19779139, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20431062, ECO:0000269|PubMed:20445537, ECO:0000269|PubMed:21273538, ECO:0000269|PubMed:7675451, ECO:0000269|PubMed:8700872, ECO:0000269|PubMed:9435229}.;
- Disease
- DISEASE: Lymphedema, hereditary, 1A (LMPH1A) [MIM:153100]: 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:10835628, ECO:0000269|PubMed:10856194, ECO:0000269|PubMed:12881528, ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:16924388, ECO:0000269|PubMed:16965327, ECO:0000269|PubMed:17458866, ECO:0000269|PubMed:19289394, ECO:0000269|PubMed:26091405, ECO:0000269|PubMed:9817924}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hemangioma, capillary infantile (HCI) [MIM:602089]: A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring. {ECO:0000269|PubMed:11807987}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Note=Plays an important role in tumor lymphangiogenesis, in cancer cell survival, migration, and formation of metastases.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Breast cancer - 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);Pathway_PA165959425;Sorafenib Pharmacodynamics;Vemurafenib Pathway, Pharmacodynamics;update your name in edit mode;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Ras Signaling;Signal Transduction;vegf hypoxia and angiogenesis;actions of nitric oxide in the heart;VEGF ligand-receptor interactions;IL-7 signaling;JAK STAT pathway and regulation;VEGFR3 signaling in lymphatic endothelium;EPO signaling;VEGF binds to VEGFR leading to receptor dimerization;Signaling by VEGF;Signaling by Receptor Tyrosine Kinases;VEGF;VEGF and VEGFR signaling network
(Consensus)
Recessive Scores
- pRec
- 0.236
Intolerance Scores
- loftool
- 0.0227
- rvis_EVS
- 0.71
- rvis_percentile_EVS
- 85.53
Haploinsufficiency Scores
- pHI
- 0.200
- hipred
- Y
- hipred_score
- 0.822
- ghis
- 0.550
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.766
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Flt4
- Phenotype
- embryo phenotype; liver/biliary system phenotype; normal 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); digestive/alimentary phenotype; immune system 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); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- flt4
- Affected structure
- vascular lymphangioblast
- Phenotype tag
- abnormal
- Phenotype quality
- absent
Gene ontology
- Biological process
- positive regulation of protein phosphorylation;positive regulation of endothelial cell proliferation;vasculature development;lymph vessel development;lymphangiogenesis;sprouting angiogenesis;respiratory system process;transmembrane receptor protein tyrosine kinase signaling pathway;positive regulation of cell population proliferation;positive regulation of vascular endothelial growth factor production;positive regulation of endothelial cell migration;positive regulation of phosphatidylinositol 3-kinase signaling;peptidyl-tyrosine phosphorylation;cellular response to vascular endothelial growth factor stimulus;vascular endothelial growth factor signaling pathway;negative regulation of apoptotic process;positive regulation of MAPK cascade;positive regulation of JNK cascade;protein autophosphorylation;vascular endothelial growth factor receptor signaling pathway;lung alveolus development;blood vessel morphogenesis;regulation of blood vessel remodeling;positive regulation of ERK1 and ERK2 cascade;positive regulation of protein kinase C signaling
- Cellular component
- extracellular region;nucleoplasm;plasma membrane;integral component of plasma membrane;receptor complex
- Molecular function
- transmembrane receptor protein tyrosine kinase activity;vascular endothelial growth factor-activated receptor activity;protein binding;ATP binding;growth factor binding;protein phosphatase binding;VEGF-C-activated receptor activity;vascular endothelial growth factor binding;protein homodimerization activity