FLT3
fms related receptor tyrosine kinase 3, the group of Receptor tyrosine kinases|Immunoglobulin like domain containing|CD molecules
Basic information
Region (hg38): 13:28003274-28100592
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (94 variants)
- not_provided (49 variants)
- Acute_myeloid_leukemia (9 variants)
- FLT3-related_disorder (5 variants)
- Acute_lymphoid_leukemia (3 variants)
- Multiple_myeloma (1 variants)
- Myelodysplastic_syndrome_progressed_to_acute_myeloid_leukemia (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FLT3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004119.3. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 18 | 26 | ||||
| missense | 82 | 13 | 107 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 4 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 5 | 2 | 86 | 31 | 13 |
Highest pathogenic variant AF is 6.84137e-7
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FLT3 | protein_coding | protein_coding | ENST00000241453 | 24 | 97319 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.608 | 0.392 | 125716 | 0 | 31 | 125747 | 0.000123 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.982 | 461 | 524 | 0.879 | 0.0000267 | 6539 |
| Missense in Polyphen | 116 | 167.76 | 0.69147 | 2085 | ||
| Synonymous | -0.0968 | 206 | 204 | 1.01 | 0.0000123 | 1810 |
| Loss of Function | 5.42 | 12 | 55.6 | 0.216 | 0.00000250 | 721 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000260 | 0.000260 |
| Ashkenazi Jewish | 0.000199 | 0.000198 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.000185 | 0.000185 |
| European (Non-Finnish) | 0.000106 | 0.000105 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000989 | 0.0000980 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways. {ECO:0000269|PubMed:10080542, ECO:0000269|PubMed:11090077, ECO:0000269|PubMed:14504097, ECO:0000269|PubMed:16266983, ECO:0000269|PubMed:16627759, ECO:0000269|PubMed:18490735, ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:21067588, ECO:0000269|PubMed:21262971, ECO:0000269|PubMed:21516120, ECO:0000269|PubMed:7507245}.;
- Disease
- DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. {ECO:0000269|PubMed:11090077, ECO:0000269|PubMed:11290608, ECO:0000269|PubMed:11442493, ECO:0000269|PubMed:14504097, ECO:0000269|PubMed:16266983, ECO:0000269|PubMed:18305215, ECO:0000269|PubMed:8946930, ECO:0000269|PubMed:9737679}. Note=The gene represented in this entry may be involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of FLT3 are frequent in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the activation loop of the kinase domain can result in a constitutively activated kinase.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Pathway_PA165959425;Sorafenib Pharmacodynamics;Hematopoietic Stem Cell Gene Regulation by GABP alpha-beta Complex;Wnt-beta-catenin Signaling Pathway in Leukemia;PI3K-Akt Signaling Pathway;Ras Signaling;Other interleukin signaling;Signaling by Interleukins;Cytokine Signaling in Immune system;Immune System
(Consensus)
Recessive Scores
- pRec
- 0.351
Intolerance Scores
- loftool
- 0.218
- rvis_EVS
- 0.1
- rvis_percentile_EVS
- 60.72
Haploinsufficiency Scores
- pHI
- 0.336
- hipred
- Y
- hipred_score
- 0.697
- ghis
- 0.444
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Flt3
- Phenotype
- immune system phenotype; skeleton 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); hematopoietic system phenotype; neoplasm; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype;
Gene ontology
- Biological process
- MAPK cascade;leukocyte homeostasis;hematopoietic progenitor cell differentiation;myeloid progenitor cell differentiation;pro-B cell differentiation;leukocyte differentiation;transmembrane receptor protein tyrosine kinase signaling pathway;positive regulation of cell population proliferation;response to organonitrogen compound;positive regulation of phosphatidylinositol 3-kinase signaling;viral process;peptidyl-tyrosine phosphorylation;cytokine-mediated signaling pathway;hemopoiesis;lymphocyte differentiation;B cell differentiation;animal organ regeneration;common myeloid progenitor cell proliferation;phosphatidylinositol-3-phosphate biosynthetic process;vascular endothelial growth factor signaling pathway;positive regulation of tyrosine phosphorylation of STAT protein;regulation of apoptotic process;positive regulation of MAP kinase activity;positive regulation of MAPK cascade;positive regulation of phosphatidylinositol 3-kinase activity;lymphocyte proliferation;protein autophosphorylation;positive regulation of ERK1 and ERK2 cascade;cellular response to cytokine stimulus;cellular response to glucocorticoid stimulus;dendritic cell differentiation
- Cellular component
- nucleus;endoplasmic reticulum;endoplasmic reticulum lumen;cytosol;plasma membrane;integral component of plasma membrane;receptor complex
- Molecular function
- transmembrane receptor protein tyrosine kinase activity;cytokine receptor activity;vascular endothelial growth factor-activated receptor activity;Ras guanyl-nucleotide exchange factor activity;protein binding;ATP binding;1-phosphatidylinositol-3-kinase activity;glucocorticoid receptor binding;protein homodimerization activity;protein self-association;protein-containing complex binding