FLT3LG

protein-coding

fms related receptor tyrosine kinase 3 ligand, the group of Receptor ligands

Gene summary

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]).[supplied by OMIM, Jan 2011]

MANE transcript

NM_001459.4

Inheritance

ClinVar variants

P:1U:34B:4

Top phenotype

Immunodeficiency 125

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr19:49,474,207-49,486,231

External References & Databases

Ensembl (ENSG00000090554)

Transcript & Mutation Effects

hg38 • Region Span ~12.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency 125MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0975749

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Immunodeficiency 125AR

Manifestation: Allergy/Immunology/Infectious; Gastrointestinal

Intervention: Allergy/Immunology/Infectious

Rationale: The condition can include recurrent infections, and awareness may allow preventive measures and early and aggressive treatment of infections

Refs: 38701783

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FLT3LG variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 31

not providedTotal: 1

Immunodeficiency 125Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001459.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			31 clinvar	3 clinvar		34
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	0	34	3	1	39

Highest pathogenic variant AF is 0.00019413354

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 57 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001459.4	RefSeq	NP_001450.2	7	MANE Select
ENST00000597551.6	Ensembl	ENSP00000468977.1	7	MANE Select
NM_001204502.2	RefSeq	NP_001191431.1	7	Standard
NM_001204503.2	RefSeq	NP_001191432.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
Ras signaling pathway - Homo sapiens (human)
MAPK signaling pathway - Homo sapiens (human)
Pathways in cancer - Homo sapiens (human)
Hematopoietic cell lineage - Homo sapiens (human)

Biological Process

MAPK cascade
positive regulation of protein phosphorylation
signal transduction
positive regulation of cell population proliferation
regulation of signaling receptor activity

Molecular Function

Ras guanyl-nucleotide exchange factor activity
signaling receptor binding
cytokine activity
1-phosphatidylinositol-3-kinase activity
receptor tyrosine kinase binding

Cellular Component

extracellular region
extracellular space
cell surface
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000594009
Coding exons: 7
Length: 12025
Individuals with no LoFs: 124183
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 124186
p: 0.0000121

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.897	108	138	0.785	0.00000832	1462
Missense (PolyPhen)		7	14.105	0.49627		149
Synonymous	0.570	56	61.7	0.908	0.00000351	518
Loss of Function	3.13	1	13.3	0.0750	6.44e-7	136

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000038	0.000027	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Stimulates the proliferation of early hematopoietic cells by activating FLT3. Synergizes well with a number of other colony stimulating factors and interleukins.;

Recessive Scores

pRec: 0.143

Intolerance Scores

LoFtool: 0.109
RVIS EVS: -0.56
RVIS percentile EVS: 19.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.439

Gene Damage Prediction

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