FLT1

fms related receptor tyrosine kinase 1, the group of I-set domain containing|Receptor tyrosine kinases

Basic information

Region (hg38): 13:28300345-28495145

Previous symbols: [ "FLT" ]

Links

ENSG00000102755 ∙ NCBI:2321 ∙ OMIM:165070 ∙ HGNC:3763 ∙ Uniprot:P17948 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FLT1 gene.

• Inborn genetic diseases (33 variants)
• not provided (22 variants)
• Carcinoma of colon (10 variants)
• Lung adenocarcinoma (6 variants)
• Squamous cell carcinoma (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FLT1 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				6	8	14
missense			32	5	1	38
nonsense						0
start loss						0
frameshift						0
inframe indel					1	1
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			8		2	10
Total	0	0	40	11	12

Variants in FLT1

This is a list of pathogenic ClinVar variants found in the FLT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-28303200-G-T		not specified	Uncertain significance (Dec 17, 2023)
13-28303215-C-T			Likely benign (Jun 18, 2018)
13-28303258-T-C		not specified	Uncertain significance (Jun 22, 2023)
13-28306519-T-C		Squamous cell carcinoma	Benign (Jun 06, 2022)
13-28306688-G-A		not specified	Uncertain significance (Jul 13, 2022)
13-28306693-G-C		not specified	Uncertain significance (Nov 17, 2023)
13-28306723-C-T		not specified	Uncertain significance (Dec 13, 2022)
13-28306850-G-T		Lung adenocarcinoma	Uncertain significance (Jun 06, 2022)
13-28311623-G-A			Likely benign (Jul 01, 2023)
13-28311626-G-A		not specified	Uncertain significance (Aug 02, 2021)
13-28311662-G-T		not specified	Uncertain significance (Oct 06, 2022)
13-28311667-A-G			Likely benign (Jan 08, 2018)
13-28311673-G-A			Likely benign (Dec 01, 2022)
13-28311732-C-T		not specified	Uncertain significance (Mar 07, 2024)
13-28312014-C-G		not specified	Uncertain significance (Feb 22, 2024)
13-28317555-C-G		Carcinoma of colon	not provided (-)
13-28317577-C-G		not specified	Uncertain significance (Jan 02, 2024)
13-28317595-C-T		not specified	Uncertain significance (Mar 07, 2024)
13-28317597-C-T		not specified	Uncertain significance (Nov 14, 2023)
13-28317613-T-G		Carcinoma of colon	not provided (-)
13-28319505-A-G		Carcinoma of colon	Benign (Jul 13, 2018)
13-28319512-A-G		not specified	Uncertain significance (Dec 16, 2023)
13-28319544-G-A			Benign (Jul 18, 2018)
13-28319603-T-A		Carcinoma of colon	not provided (-)
13-28321238-A-C		Lung adenocarcinoma	Uncertain significance (Jun 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FLT1	protein_coding	protein_coding	ENST00000282397	30	194777

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000168	125721	0	27	125748	0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.45	611	721	0.848	0.0000401	8820
Missense in Polyphen		190	285.86	0.66466		3511
Synonymous	-0.0752	270	268	1.01	0.0000163	2517
Loss of Function	6.57	10	68.9	0.145	0.00000351	858

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000203	0.000203
Ashkenazi Jewish	0.000397	0.000397
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000792	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion. {ECO:0000269|PubMed:11141500, ECO:0000269|PubMed:11312102, ECO:0000269|PubMed:11811792, ECO:0000269|PubMed:12796773, ECO:0000269|PubMed:14633857, ECO:0000269|PubMed:15735759, ECO:0000269|PubMed:16685275, ECO:0000269|PubMed:18079407, ECO:0000269|PubMed:18515749, ECO:0000269|PubMed:18583712, ECO:0000269|PubMed:18593464, ECO:0000269|PubMed:20512933, ECO:0000269|PubMed:20551949, ECO:0000269|PubMed:21752276, ECO:0000269|PubMed:7824266, ECO:0000269|PubMed:8248162, ECO:0000269|PubMed:8605350, ECO:0000269|PubMed:9299537}.
• Disease: DISEASE: Note=Can contribute to cancer cell survival, proliferation, migration, and invasion, and tumor angiogenesis and metastasis. May contribute to cancer pathogenesis by promoting inflammatory responses and recruitment of tumor-infiltrating macrophages.; DISEASE: Note=Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Focal adhesion - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Pathway_PA165959425;Sorafenib Pharmacodynamics;Vemurafenib Pathway, Pharmacodynamics;update your name in edit mode;VEGF Signaling Pathway;Bevacizumab Action Pathway;Angiogenesis;Focal Adhesion;Imatinib and Chronic Myeloid Leukemia;VEGFA-VEGFR2 Signaling Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Pathways in clear cell renal cell carcinoma;PI3K-Akt Signaling Pathway;Ras Signaling;Signal Transduction;vegf hypoxia and angiogenesis;Neurophilin interactions with VEGF and VEGFR;HIF-2-alpha transcription factor network;actions of nitric oxide in the heart;VEGF ligand-receptor interactions;IL-7 signaling;JAK STAT pathway and regulation;EPO signaling;VEGF binds to VEGFR leading to receptor dimerization;Signaling by VEGF;Signaling by Receptor Tyrosine Kinases;VEGF;VEGF and VEGFR signaling network;Glypican 1 network;S1P3 pathway;Signaling events mediated by VEGFR1 and VEGFR2;VEGFR1 specific signals (Consensus)

Recessive Scores

• pRec: 0.648

Intolerance Scores

• loftool: 0.463
• rvis_EVS: -1.52
• rvis_percentile_EVS: 3.44

Haploinsufficiency Scores

• pHI: 0.241
• hipred: Y
• hipred_score: 0.756
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.956

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Flt1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype; embryo phenotype; immune system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); 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); hematopoietic 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); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: flt1
• Affected structure: blood vessel endothelial cell
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: angiogenesis;sprouting angiogenesis;monocyte chemotaxis;transmembrane receptor protein tyrosine kinase signaling pathway;positive regulation of cell population proliferation;positive regulation of phospholipase C activity;positive regulation of phosphatidylinositol 3-kinase signaling;cell migration;peptidyl-tyrosine phosphorylation;positive regulation of cell migration;positive regulation of vascular endothelial growth factor receptor signaling pathway;cellular response to vascular endothelial growth factor stimulus;vascular endothelial growth factor receptor-1 signaling pathway;vascular endothelial growth factor signaling pathway;positive regulation of MAP kinase activity;positive regulation of MAPK cascade;positive regulation of phosphatidylinositol 3-kinase activity;positive regulation of angiogenesis;protein autophosphorylation;vascular endothelial growth factor receptor signaling pathway;blood vessel morphogenesis;embryonic morphogenesis;positive regulation of ERK1 and ERK2 cascade;negative regulation of vascular endothelial cell proliferation
• Cellular component: extracellular space;endosome;plasma membrane;integral component of plasma membrane;focal adhesion;actin cytoskeleton;receptor complex
• Molecular function: transmembrane receptor protein tyrosine kinase activity;vascular endothelial growth factor-activated receptor activity;protein binding;ATP binding;growth factor binding;VEGF-A-activated receptor activity;VEGF-B-activated receptor activity;placental growth factor-activated receptor activity;vascular endothelial growth factor binding