FLT3LG

Summary

FLT3LG (fms related receptor tyrosine kinase 3 ligand, HGNC:3766) is a protein-coding gene on chromosome 19q13.33, encoding Fms-related tyrosine kinase 3 ligand (P49771). Stimulates the proliferation of early hematopoietic cells by activating FLT3. In precision oncology, FLT3 Overexpression AND FLT3LG Expression confers sensitivity to Quizartinib + Linifanib + Lestaurtinib + Midostaurin + Ponatinib + FLT3 Tyrosine Kinase Inhibitor TTT-3002 + Sunitinib in Cancer (CIViC Level D); 1 further curated variant–drug associations are listed below.

Dendritic cells (DCs) provide the key link between innate and adaptive immunity by recognizing pathogens and priming pathogen-specific immune responses. FLT3LG controls the development of DCs and is particularly important for plasmacytoid DCs and CD8 (see MIM 186910)-positive classical DCs and their CD103 (ITGAE; MIM 604682)-positive tissue counterparts (summary by Sathaliyawala et al., 2010 [PubMed 20933441]).

Source: NCBI Gene 2323 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 125 (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 45 total — 1 pathogenic
• Phenotypes (HPO): 48
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• MANE Select transcript: NM_001459

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3766
Approved symbol	FLT3LG
Name	fms related receptor tyrosine kinase 3 ligand
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000090554
Ensembl biotype	protein_coding
OMIM	600007
Entrez	2323

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000204637, ENST00000593422, ENST00000594009, ENST00000595510, ENST00000596435, ENST00000597551, ENST00000597914, ENST00000598472, ENST00000598555, ENST00000600084, ENST00000600429, ENST00000601800, ENST00000892347, ENST00000892348, ENST00000892349, ENST00000892350, ENST00000892351, ENST00000892352, ENST00000892353, ENST00000892354, ENST00000892355, ENST00000892356, ENST00000947101

RefSeq mRNA: 5 — MANE Select: NM_001459 NM_001204502, NM_001204503, NM_001278637, NM_001278638, NM_001459

CCDS: CCDS12767, CCDS62753

Canonical transcript exons

ENST00000597551 — 9 exons

Exon	Start	End
ENSE00003198314	49474215	49474281
ENSE00003509415	49475691	49475801
ENSE00003524443	49478909	49479047
ENSE00003564652	49476145	49476198
ENSE00003594728	49474603	49474672
ENSE00003603662	49480298	49480476
ENSE00003603745	49476423	49476566
ENSE00003612352	49480552	49480620
ENSE00003627463	49486015	49486231

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 96.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.1130 / max 824.2900, expressed in 1588 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176992	12.4677	451
176991	5.5038	1558
176993	0.1416	50

Top tissues by expression

136 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.36	gold quality
blood	UBERON:0000178	92.01	gold quality
lymph node	UBERON:0000029	88.71	gold quality
endocervix	UBERON:0000458	88.70	gold quality
vermiform appendix	UBERON:0001154	87.49	gold quality
ectocervix	UBERON:0012249	87.22	gold quality
mucosa of stomach	UBERON:0001199	87.08	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.03	gold quality
vagina	UBERON:0000996	87.00	gold quality
body of uterus	UBERON:0009853	86.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.70	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.46	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.39	gold quality
lower esophagus	UBERON:0013473	86.38	gold quality
uterine cervix	UBERON:0000002	86.29	gold quality
spleen	UBERON:0002106	86.15	gold quality
right coronary artery	UBERON:0001625	86.04	gold quality
apex of heart	UBERON:0002098	85.50	gold quality
tibial nerve	UBERON:0001323	85.48	gold quality
myometrium	UBERON:0001296	85.36	gold quality
left uterine tube	UBERON:0001303	85.28	gold quality
adipose tissue	UBERON:0001013	85.03	gold quality
left ovary	UBERON:0002119	85.00	gold quality
right ovary	UBERON:0002118	84.87	gold quality
prostate gland	UBERON:0002367	84.86	gold quality
ovary	UBERON:0000992	84.24	gold quality
tibial artery	UBERON:0007610	83.99	gold quality
popliteal artery	UBERON:0002250	83.98	gold quality
left coronary artery	UBERON:0001626	83.91	gold quality
thoracic mammary gland	UBERON:0005200	83.83	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	60.27
E-ANND-3	yes	8.56
E-CURD-77	no	402.80
E-CURD-55	no	401.58
E-MTAB-6379	no	99.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FLI1, MYOD1

miRNA regulators (miRDB)

32 targeting FLT3LG, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-6728-5P	97.79	66.33	891

Literature-anchored findings (GeneRIF, showing 40)

• Treatment with recombinant human FLT3 ligand prevents ovalbumin-induced asthma in the mouse by stimulating IL-12 secretion by dendritic cells. It may provide a useful adjuvant in the treatment of human asthma. (PMID:11710537)
• effect of recombinant human Flt-3 ligand on dendritic cell populations in mouse spleen (PMID:11877288)
• Expression of FLT3L in primary gastrointestinal non-Hodgkin’s lymphoma. (PMID:11956621)
• Flt3/Flk-2-ligand in synergy with thrombopoietin may slow down megakaryocyte development by causing increased proliferation of megakaryocyte progenitor cells. (PMID:11983110)
• Antiapoptotic cytokine IL-3 + SCF + FLT3L influence on proliferation of gamma-irradiated AC133+/CD34+ progenitor cells. (PMID:12002675)
• Incubation of acute stem cell leukemia cells with the flt3 ligand induced the expression of unilineage HGF receptors, allowing cell growth without differentiation . (PMID:12036900)
• Flt3L-mobilized DC from cancer patients require a sequence of specific signals for maturation, including initial treatment with granulocyte macrophage-colony stimulating factor followed by a combination of maturation signals such as CD40L and IFN-gamma. (PMID:12223523)
• The striking difference in flt3 and c-kit expression on hematopoietic stem cells translated into a corresponding difference in flt3 and c-kit function because FL was more efficient than SCF at supporting the survival of HSCs (PMID:12676789)
• Administration of Flt3-L enhances a Th1-type response against mouse thyroglobulin by selective expansion of mouse dendritic cell subsets that results in induction of a severe type of murine autoimmune thyroiditis. (PMID:12759428)
• A single dose of recombinant human Flt3L locally applied in the trachea of rats results in a dose-dependent increase of dendritic cells as well as CD4+ and CD8+ T lymphocytes with different responses in lung interstitium and bronchoalveolar space. (PMID:12817014)
• wtFLT3 is often constitutively activated by FLT3 ligand in AML and thus, like its mutated form, might contribute to the altered signaling that characterizes leukemogenesis. (PMID:12969963)
• Thrombopoietin cooperates with FLT3-L, inducing CD34+ HPCs to undergo a 400-fold expansion in cell numbers. (PMID:14670916)
• endogenous FLT3LG has distinct effects on the kinetics of reconstitution of DCs and NK ce; speed of recovery of CD11c(+)CD123(low) DC1 exceeded that of CD11c(-) CD123(+) DC2, and correlated with plasma levels of flt3 ligand (PMID:14764540)
• flt3L is a potent immunorestorative agent that enhances both thymic-dependent and thymic-independent pathways of T-cell regeneration (PMID:15226184)
• Increased serum levels of the early hemopoietic cytokine FLT3-L could explain increased numbers of circulating dendritic cells in Langerhans cell histiocytosis. (PMID:15728521)
• Human flt3 ligand-mediated generation and mobilization of naive dendritic cells, fully responsive to infectious stimuli, accelerates recovery from endotoxin tolerance-related immunoparalysis in a murine infection model. (PMID:15905588)
• Purified recombinant FLT3 ligand had dose-dependent expansion activity on bone marrow nucleated cells. (PMID:15914030)
• Addition of Flt3-L to the optimal combination of megakaryocyte (Mk) growth factor MGDF, stem cell factor, interleukin-3, and granulocyte-macrophage colony stimulating factor GM-CSF reduces both fold expansion of Mk progenitors and Mk colony numbers. (PMID:16487027)
• Flt-3L treatment expands conventional & plasmacytoid dendritic cells in vivo, increasing antigen presentation by direct- & cross-presentation. It augments the size of an immune response but requires further adjuvant activation to alter its quality. (PMID:17949888)
• FLT3 and its ligand regulate proliferation of hematopoietic progenitor cells in an autocrine and/or paracrine manner. (PMID:18797870)
• Results indicate that Flt3-L is strongly expressed at the site of inflammation in human rheumatoid arthritis, and it exerts both pro-inflammatory and tissue destructive properties once in the joint cavity. (PMID:18982072)
• Data suggest that Flt3 Ligand(FL) gene regulated by Egr-1 promoter can protect hematopoiesis from 5-Fu injury. (PMID:19426596)
• Exogenous administration of Flt3 ligand increases the CD11c-expressing dendritic cell population, which, when expressing IL-15, significantly expands mature natural killer (NK) cells via enhanced survival and proliferation. (PMID:20142363)
• results demonstrate that hsFlt3L induces the proliferation of canine DCs and support its use in upcoming clinical trials for canine glioblastoma multiforme (PMID:20552015)
• FLT3 ligand impedes the efficacy of FLT3 inhibitors in vitro and in vivo. (PMID:21263155)
• data demonstrate that the Flt3L/TK gene therapeutic approach can induce systemic immunological memory capable of recognizing a brain tumor neoantigen in a model of recurrent GBM (PMID:21505426)
• FLT3 ligand(FL) leads to further activation of FLT3 mutants and is especially important in light of recent findings of elevated FL levels in acute myeloid leukemia patients in response to chemotherapy. (PMID:21516120)
• A novel dendritic cell(DC) progenitor regulatory pathway in which PGE(2) signaling through EP1/EP3 receptors regulates Flt3 expression and downstream STAT3 activation and survivin expression, required for optimal progenitor survival and differentiation. (PMID:22110249)
• Human bone marrow stromal cells simultaneously support B and T/NK lineage development from human haematopoietic progenitors: a principal role for flt3 ligand in lymphopoiesis. (PMID:22463758)
• Administration of the hematopoietic growth factor Flt3L to human subjects increases the frequency and absolute number of Treg cells. (PMID:23124877)
• The Flt3L/CD135 axis is active in rheumatoid arthritis (PMID:24314260)
• The immunohistochemical expression of caveolin-1 and podocalyxin in lungs from rats challenged with a 2-kDa macrophage-activating lipopeptide (MALP-2) and Flt3L, was examined. (PMID:24419512)
• Flt3L enhances global T cell and humoral immunity as well as both the numbers and antigen capture capacity of migratory dendritic cells and classical lymphoid-resident dendritic cells (PMID:25135299)
• Pre-treatment serum levels of FLT3-L were higher than controls. FLT3-L correlated positively with all soluble angiogenic factors, as well with bone marrow microvascular density. Post-treatment FLT3-L decreased significantly in responders to therapy. (PMID:26521986)
• serum levels can be a marker of cutaneous manifestation in dermatomyositis and marker of microangiopathy in systemic sclerosis (PMID:26559027)
• Results elucidated a novel resistance mechanism that FL attenuated inhibitory effects of FLT3 inhibitors mainly through the activation of Wt-FLT3, not mutated FLT3 in acute myeloid leukemia. (PMID:27331411)
• The cytokine Fms-like tyrosine kinase 3 ligand is an important regulator of hematopoiesis. Its receptor, Flt3, is expressed on myeloid, lymphoid and dendritic cell progenitors and is considered an important growth and differentiation factor for several hematopoietic lineages. [review] (PMID:28538663)
• it is likely that TGFbeta1 and FL, both abundantly produced by bone marrow stromal cells, function in a coordinated manner to render mixed-lineage leukemia gene-rearranged acute lymphoblastic leukemia cells chemoresistant (PMID:28917156)
• our study demonstrates that Flt3L acts as an important regulator of ILCs lymphopoiesis and it can be used as a tool to expand and study ILCs precursors in the BM. (PMID:29317685)
• Increased serum levels of FLT3-L are markers of disease activity in patients with multiple myeloma. (PMID:29604902)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Flt3l	ENSMUSG00000110206
rattus_norvegicus	Flt3lg	ENSRNOG00000020618

Protein

Protein identifiers

Fms-related tyrosine kinase 3 ligand — P49771 (reviewed: P49771)

Alternative names: SL cytokine

All UniProt accessions (5): P49771, M0QXI0, M0QYM9, M0R2K0, M0R3A6

UniProt curated annotations — full annotation on UniProt →

Function. Stimulates the proliferation of early hematopoietic cells by activating FLT3. Synergizes well with a number of other colony stimulating factors and interleukins. Required for the development of B cells, and dendritic cells (DCs).

Subunit / interactions. Homodimer (isoform 2).

Subcellular location. Cell membrane Secreted.

Disease relevance. Immunodeficiency 125 (IMD125) [MIM:620926] An autosomal recessive immunologic disorder characterized by failure to thrive and chronic diarrhea in infancy, and recurrent bacterial, viral, and fungal infections. Patients have severe human papilloma virus (HPV) infections with disseminated common warts, and the bone marrow is hypoplastic with low levels of CD34+ hematopoietic stem cells. Counts of B cells, monocytes, and dendritic cells are low in patients blood. The disease may be caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
P49771-1	1, Membrane-bound	yes
P49771-2	2, Soluble
P49771-3	3

RefSeq proteins (5): NP_001191431, NP_001191432, NP_001265566, NP_001265567, NP_001450* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004213	Flt3_lig	Family
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily

Pfam: PF02947

UniProt features (25 total): helix 7, disulfide bond 3, splice variant 3, strand 2, topological domain 2, glycosylation site 2, signal peptide 1, chain 1, sequence conflict 1, turn 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7NBI	X-RAY DIFFRACTION	1.65
1ETE	X-RAY DIFFRACTION	2.2
7QDP	X-RAY DIFFRACTION	3.69
3QS7	X-RAY DIFFRACTION	4.3
7ZV9	X-RAY DIFFRACTION	4.51
3QS9	X-RAY DIFFRACTION	7.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49771-F1	82.02	0.57

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (3): 119–158, 30–111, 70–153

Glycosylation sites (2): 126, 149

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-109704	PI3K Cascade
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-9607240	FLT3 Signaling
R-HSA-9645135	STAT5 Activation
R-HSA-9706369	Negative regulation of FLT3
R-HSA-9706374	FLT3 signaling through SRC family kinases
R-HSA-9706377	FLT3 signaling by CBL mutants

MSigDB gene sets: 359 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_EMBRYONIC_HEMOPOIESIS, GOBP_DENDRITIC_CELL_DIFFERENTIATION, GRUETZMANN_PANCREATIC_CANCER_DN, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_B_CELL_ACTIVATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOCC_CELL_SURFACE, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, BROWNE_HCMV_INFECTION_48HR_DN, CCANNAGRKGGC_UNKNOWN, GOBP_LEUKOCYTE_PROLIFERATION, WANG_RESPONSE_TO_BEXAROTENE_DN

GO Biological Process (6): signal transduction (GO:0007165), positive regulation of cell population proliferation (GO:0008284), B cell differentiation (GO:0030183), positive regulation of natural killer cell proliferation (GO:0032819), embryonic hemopoiesis (GO:0035162), dendritic cell differentiation (GO:0097028)

GO Molecular Function (4): signaling receptor binding (GO:0005102), cytokine activity (GO:0005125), receptor tyrosine kinase binding (GO:0030971), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
FLT3 Signaling	3
IRS-mediated signalling	1
Intracellular signaling by second messengers	1
PI3K/AKT Signaling in Cancer	1
MAPK1/MAPK3 signaling	1
Negative regulation of the PI3K/AKT network	1
Cytokine Signaling in Immune system	1
FLT3 signaling in disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
lymphocyte differentiation	1
B cell activation	1
natural killer cell proliferation	1
positive regulation of natural killer cell activation	1
regulation of natural killer cell proliferation	1
positive regulation of lymphocyte proliferation	1
hemopoiesis	1
embryonic organ development	1
mononuclear cell differentiation	1
protein binding	1
receptor ligand activity	1
signaling receptor binding	1
protein tyrosine kinase binding	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

5552 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FLT3LG	FLT3	P36888	998
FLT3LG	KITLG	P21583	972
FLT3LG	IL3	P08700	968
FLT3LG	THPO	P40225	968
FLT3LG	CSF3	P09919	960
FLT3LG	CSF2	P04141	957
FLT3LG	FGF2	P09038	916
FLT3LG	CCL11	P50877	906
FLT3LG	FGF13	Q92913	906
FLT3LG	CX3CL1	P78423	874
FLT3LG	EGF	P01133	861
FLT3LG	KIT	P10721	860
FLT3LG	IL7	P13232	840
FLT3LG	IL6	P05231	832
FLT3LG	CXCL1	P09341	824

IntAct

8 interactions, top by confidence:

A	B	Type	Score
KRTAP5-9	FLT3LG	psi-mi:“MI:0915”(physical association)	0.560
FLT3LG	FLT3LG	psi-mi:“MI:0407”(direct interaction)	0.440
FLT3	FLT3LG	psi-mi:“MI:0407”(direct interaction)	0.440
KITLG	FLT3LG	psi-mi:“MI:2364”(proximity)	0.270
FLT3LG	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.000
FLT3LG	PFN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): FLT3LG (Co-localization), KRTAP5-9 (Two-hybrid), FLT3LG (Co-crystal Structure), FLT3LG (Negative Genetic), S100A6 (Reconstituted Complex)

ESM2 similar proteins: O46633, P01562, P01563, P01566, P01567, P01568, P01569, P01570, P01571, P05000, P05002, P05003, P05004, P05005, P05006, P05007, P05008, P05009, P05010, P05013, P05014, P05015, P07348, P07352, P09235, P15696, P28169, P28171, P28172, P32881, P49771, P49772, P49876, P49877, P49878, P49879, P56828, P56829, P56830, P56831

Diamond homologs: P49771, P49772

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FLT3LG	up-regulates	FLT3	binding

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

45 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	28
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3338165	NM_001459.4(FLT3LG):c.351del (p.Ser118fs)	Pathogenic

SpliceAI

1639 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49476143:A:AG	acceptor_gain	1.0000
19:49476144:G:GA	acceptor_gain	1.0000
19:49476144:GTCT:G	acceptor_gain	1.0000
19:49476195:GGAC:G	donor_gain	1.0000
19:49476196:G:GT	donor_gain	1.0000
19:49476196:GAC:G	donor_gain	1.0000
19:49476197:ACG:A	donor_loss	1.0000
19:49476198:CGT:C	donor_loss	1.0000
19:49476198:CGTA:C	donor_loss	1.0000
19:49476199:G:GC	donor_loss	1.0000
19:49476199:G:GG	donor_gain	1.0000
19:49476200:T:G	donor_loss	1.0000
19:49476534:G:GT	donor_gain	1.0000
19:49476563:TCAG:T	donor_loss	1.0000
19:49476564:CAG:C	donor_loss	1.0000
19:49476565:AG:A	donor_loss	1.0000
19:49476566:GGTC:G	donor_loss	1.0000
19:49476567:GTC:G	donor_loss	1.0000
19:49479043:GCCCG:G	donor_gain	1.0000
19:49479045:CCGGT:C	donor_loss	1.0000
19:49479046:CGGT:C	donor_loss	1.0000
19:49479047:GGTA:G	donor_loss	1.0000
19:49479047:GGTAA:G	donor_loss	1.0000
19:49479048:G:GG	donor_gain	1.0000
19:49479048:GTAA:G	donor_loss	1.0000
19:49479049:T:G	donor_loss	1.0000
19:49480293:CCCAG:C	acceptor_loss	1.0000
19:49480295:CAGAC:C	acceptor_loss	1.0000
19:49480296:A:AG	acceptor_gain	1.0000
19:49480296:A:AT	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000017974 (19:49480770 G>A), RS1000555102 (19:49484665 T>G), RS1000786769 (19:49475127 G>A,C), RS1000976569 (19:49481177 G>A,C), RS1001036088 (19:49473377 C>G,T), RS1001088379 (19:49473084 G>A), RS1001145061 (19:49486433 C>T), RS1001246541 (19:49474319 C>T), RS1001261542 (19:49481520 G>A), RS1001300190 (19:49474102 G>A), RS1001344901 (19:49485628 C>T), RS1001415276 (19:49475860 T>A), RS1001909151 (19:49484118 C>G,T), RS1002147246 (19:49485215 C>G), RS1002250670 (19:49478601 C>T)

Disease associations

OMIM: gene MIM:600007 | disease phenotypes: MIM:620926

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 125	Moderate	Autosomal recessive

Mondo (1): immunodeficiency 125 (MONDO:0975749)

Orphanet (0):

HPO phenotypes

48 total (30 of 48 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000362	Otosclerosis
HP:0000365	Hearing impairment
HP:0000403	Recurrent otitis media
HP:0000405	Conductive hearing impairment
HP:0001217	Clubbing
HP:0001508	Failure to thrive
HP:0001882	Decreased total leukocyte count
HP:0001903	Anemia
HP:0002028	Chronic diarrhea
HP:0002110	Bronchiectasis
HP:0002254	Intermittent diarrhea
HP:0002608	Celiac disease
HP:0002716	Lymphadenopathy
HP:0002718	Recurrent bacterial infections
HP:0002783	Recurrent lower respiratory tract infections
HP:0002788	Recurrent upper respiratory tract infections
HP:0002841	Recurrent fungal infections
HP:0003261	Increased circulating IgA concentration
HP:0003493	Antinuclear antibody positivity
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0003593	Infantile onset
HP:0004429	Recurrent viral infections
HP:0005528	Bone marrow hypocellularity
HP:0006532	Recurrent pneumonia
HP:0010976	Decreased total B cell count
HP:0011273	Anisocytosis
HP:0011463	Childhood onset
HP:0011950	Bronchiolitis
HP:0012312	Decreased total monocyte count

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009066_30	Mosaic loss of chromosome Y (Y chromosome dosage)	1.000000e-08
GCST90002394_562	Monocyte percentage of white cells	9.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
FLT3 Overexpression AND FLT3LG Expression	Quizartinib + Linifanib + Lestaurtinib + Midostaurin + Ponatinib + FLT3 Tyrosine Kinase Inhibitor TTT-3002 + Sunitinib	Cancer	Sensitivity/Response	CIViC D	EID11088
FLT3 Overexpression AND FLT3LG Expression	AG1295 + Crenolanib + R406	Cancer	Sensitivity/Response	CIViC D	EID11089

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	2
Resveratrol	affects cotreatment, decreases expression, increases activity	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Nickel	increases expression	2
Plant Extracts	affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
perfluorooctanoic acid	decreases expression	1
CD 437	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
diphenylarsinic acid	increases secretion	1
jinfukang	increases expression, affects cotreatment	1
StemRegenin 1	affects cotreatment, increases activity	1
10-(octyloxy)decyl-2-(trimethylammonium)ethyl phosphate	increases phosphorylation, affects cotreatment, decreases reaction, increases expression	1
Wortmannin	decreases reaction, increases expression, increases phosphorylation, affects cotreatment	1
Acetylcysteine	decreases reaction, increases expression, increases secretion	1
Benzo(a)pyrene	affects methylation	1
Cannabidiol	decreases expression	1
Cannabinoids	affects methylation, increases abundance	1
Catechin	decreases expression	1
Cisplatin	increases expression, affects cotreatment	1
Diazinon	increases methylation	1
Diethylstilbestrol	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Flavonoids	decreases expression	1
Lipopolysaccharides	increases secretion	1
Methyl Methanesulfonate	increases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 2 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B6FI	Veggie-CHO:FLT-3L	Spontaneously immortalized cell line	Female
CVCL_B8GK	Abcam HCT 116 FLT3LG KO	Cancer cell line	Male
CVCL_B9IC	Abcam A-549 FLT3LG KO	Cancer cell line	Male
CVCL_D2FB	Abcam MCF-7 FLT3LG KO	Cancer cell line	Female
CVCL_D7Q0	Ubigene A-549 FLT3LG KO	Cancer cell line	Male
CVCL_D8LI	Ubigene HCT 116 FLT3LG KO	Cancer cell line	Male
CVCL_D9EZ	Ubigene HEK293 FLT3LG KO	Transformed cell line	Female
CVCL_E0D5	Ubigene HeLa FLT3LG KO	Cancer cell line	Female
CVCL_E4IA	CHO-DXB11 FLT-3L	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.