CSF3R

colony stimulating factor 3 receptor, the group of Fibronectin type III domain containing|CD molecules

Basic information

Region (hg38): 1:36466043-36483278

Previous symbols: [ "CD114" ]

Links

ENSG00000119535 ∙ NCBI:1441 ∙ OMIM:138971 ∙ HGNC:2439 ∙ Uniprot:Q99062 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive severe congenital neutropenia due to CSF3R deficiency (Strong), mode of inheritance: AR
• hereditary neutrophilia (Supportive), mode of inheritance: AD
• autosomal recessive severe congenital neutropenia due to CSF3R deficiency (Supportive), mode of inheritance: AR
• autosomal recessive severe congenital neutropenia due to CSF3R deficiency (Strong), mode of inheritance: AR
• hereditary neutrophilia (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neutropenia, severe congenital, 7, autosomal recessive	AR	Allergy/Immunology/Infectious	Individuals have been described with early-onset severe and recurrent infections, and prophylactic measures (eg, GM-CSF, but not G-CSF has been reported as beneficial) as well as early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious; Hematologic	4825608; 19620628; 24753537; 26324699
One individual with Neutrophilia has been described as developing a myelodysplastic syndrome with refractory anemia

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CSF3R gene.

• Autosomal_recessive_severe_congenital_neutropenia_due_to_CSF3R_deficiency (666 variants)
• not_provided (92 variants)
• Inborn_genetic_diseases (73 variants)
• not_specified (61 variants)
• CSF3R-related_disorder (34 variants)
• Hereditary_neutrophilia (9 variants)
• Severe_congenital_neutropenia (3 variants)
• Early_T_cell_progenitor_acute_lymphoblastic_leukemia (1 variants)
• Inherited_Immunodeficiency_Diseases (1 variants)
• CSF3R-Related_Disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CSF3R gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000760.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	172	4	179
missense	3	4	353	26	1	387
nonsense	12	8	4			24
start loss						0
frameshift	17	2	4			23
splice donor/acceptor (+/-2bp)	1	11	4			16
Total	33	25	368	198	5

Highest pathogenic variant AF is 0.00046055357

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CSF3R	protein_coding	protein_coding	ENST00000373103	15	17236

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125634	0	114	125748	0.000453

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.20	412	486	0.847	0.0000271	5575
Missense in Polyphen		67	115.41	0.58054		1445
Synonymous	-0.0676	204	203	1.01	0.0000117	1781
Loss of Function	2.78	23	42.5	0.541	0.00000194	441

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000822	0.000818
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000928	0.0000924
European (Non-Finnish)	0.000780	0.000774
Middle Eastern	0.0000544	0.0000544
South Asian	0.000131	0.000131
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differientation and survival of cells along the neutrophilic lineage. In addition it may function in some adhesion or recognition events at the cell surface. {ECO:0000269|PubMed:7514305}.
• Disease: DISEASE: Hereditary neutrophilia (NEUTROPHILIA) [MIM:162830]: A form of lifelong, persistent neutrophilia, a condition characterized by an increase in the number of neutrophils in the blood. {ECO:0000269|PubMed:19620628}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Neutropenia, severe congenital 7, autosomal recessive (SCN7) [MIM:617014]: A form of severe congenital neutropenia, a disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections. {ECO:0000269|PubMed:24753537, ECO:0000269|PubMed:26324699}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);JAK-STAT-Core;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Other interleukin signaling;Signaling by Interleukins;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Immune System;JAK STAT MolecularVariation 2;JAK STAT pathway and regulation (Consensus)

Recessive Scores

• pRec: 0.336

Intolerance Scores

• loftool: 0.786
• rvis_EVS: 1.79
• rvis_percentile_EVS: 96.87

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.952

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: csf3r
• Affected structure: neutrophil
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: defense response;cell adhesion;signal transduction;cytokine-mediated signaling pathway;neutrophil chemotaxis;cellular response to interleukin-3;interleukin-3-mediated signaling pathway;regulation of myeloid cell differentiation;amelogenesis
• Cellular component: extracellular region;plasma membrane;integral component of plasma membrane;external side of plasma membrane;receptor complex
• Molecular function: cytokine receptor activity;interleukin-3 receptor activity;protein binding;cytokine binding;interleukin-3 binding;signaling receptor activity;granulocyte colony-stimulating factor binding