FLT3

fms related receptor tyrosine kinase 3, the group of Receptor tyrosine kinases|Immunoglobulin like domain containing|CD molecules

Basic information

Region (hg38): 13:28003273-28100592

Links

ENSG00000122025 ∙ NCBI:2322 ∙ OMIM:136351 ∙ HGNC:3765 ∙ Uniprot:P36888 ∙ 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 FLT3 gene.

• not provided (116 variants)
• Inborn genetic diseases (26 variants)
• not specified (21 variants)
• Acute myeloid leukemia (2 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.

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				15	10	25
missense		1	24	11	7	43
nonsense						0
start loss						0
frameshift						0
inframe indel	1					1
splice donor/acceptor (+/-2bp)						0
splice region				8	2	10
non coding				1	65	66
Total	1	1	24	27	82

Variants in FLT3

This is a list of pathogenic ClinVar variants found in the FLT3 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-28004055-C-T			Benign (Dec 31, 2019)
13-28004063-C-T		not specified	not provided (Sep 19, 2013)
13-28004072-C-G		not specified	Benign (Dec 31, 2019)
13-28004076-C-T			Benign (Jun 09, 2021)
13-28004077-G-A		not specified	not provided (Sep 19, 2013)
13-28004116-C-T		not specified	Likely benign (Feb 26, 2018)
13-28004146-G-A		not specified	Likely benign (Dec 07, 2019)
13-28004152-C-T		not specified	Likely benign (Sep 28, 2022)
13-28004153-G-A		not specified	Uncertain significance (Sep 07, 2022)
13-28014453-G-A		not specified	not provided (Sep 19, 2013)
13-28014488-C-T			Likely benign (Jun 13, 2018)
13-28015130-C-T			Benign (Nov 11, 2018)
13-28015194-A-G		not specified	Uncertain significance (Apr 04, 2023)
13-28015231-C-T			Likely benign (Dec 31, 2019)
13-28015358-C-G			Benign (Jun 18, 2021)
13-28015372-C-T			Benign (Jun 18, 2021)
13-28015525-C-G			Benign (Nov 11, 2018)
13-28015601-A-G		not specified	Uncertain significance (Jan 10, 2023)
13-28015621-A-G			Likely benign (Oct 29, 2018)
13-28015627-C-G		not specified	Uncertain significance (Jun 10, 2022)
13-28015689-C-T			Likely benign (Jan 30, 2020)
13-28016005-C-G			Benign (Jun 20, 2021)
13-28018409-T-C			Benign (Jun 19, 2021)
13-28018475-T-C		Acute myeloid leukemia	Likely pathogenic (-)
13-28018483-T-C		Acute myeloid leukemia	Likely pathogenic (Dec 26, 2014)

GnomAD

Source: gnomAD

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: dbNSFP

• 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