CSF3R

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

Basic information

Region (hg38): 1:36466042-36483278

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 (457 variants)
• not provided (65 variants)
• not specified (61 variants)
• Inborn genetic diseases (29 variants)
• Hereditary neutrophilia;Autosomal recessive severe congenital neutropenia due to CSF3R deficiency (6 variants)
• CSF3R-related condition (2 variants)
• Severe congenital neutropenia (2 variants)
• Autosomal recessive severe congenital neutropenia due to CSF3R deficiency;Hereditary neutrophilia (1 variants)
• Chronic myelogenous leukemia, BCR-ABL1 positive (1 variants)
• Early T cell progenitor acute lymphoblastic leukemia (1 variants)
• Acute myeloid leukemia (1 variants)
• Inherited Immunodeficiency Diseases (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.

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			4	105	7	116
missense	1	2	257	4	9	273
nonsense	11	3	2			16
start loss						0
frameshift	9	2	3			14
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	7				8
splice region			13	9	1	23
non coding			2	36	16	54
Total	22	14	270	145	32

Highest pathogenic variant AF is 0.0000329

Variants in CSF3R

This is a list of pathogenic ClinVar variants found in the CSF3R region.

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

Position	Type	Phenotype	Significance	ClinVar
1-36466184-C-A		CSF3R-related disorder	Uncertain significance (Jul 31, 2023)
1-36466196-C-T		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Uncertain significance (Oct 15, 2018)
1-36466372-C-T		not specified • Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Benign (Jan 10, 2024)
1-36466373-G-A		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Uncertain significance (Oct 22, 2023)
1-36466373-G-T		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Uncertain significance (May 21, 2020)
1-36466373-GC-TT		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Uncertain significance (Nov 11, 2020)
1-36466384-A-G		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Benign (Jan 25, 2024)
1-36466385-T-C		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Uncertain significance (Oct 04, 2018)
1-36466391-C-T		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Uncertain significance (Feb 25, 2023)
1-36466392-G-A		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Uncertain significance (Mar 29, 2024)
1-36466413-A-G		Inborn genetic diseases	Uncertain significance (Jun 21, 2023)
1-36466413-A-T		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Uncertain significance (Jan 02, 2024)
1-36466414-G-A		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Likely benign (Oct 20, 2021)
1-36466417-G-A		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Likely benign (Jan 08, 2024)
1-36466418-A-G		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Uncertain significance (Oct 25, 2023)
1-36466427-C-T		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Uncertain significance (Oct 27, 2023)
1-36466434-C-T		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Uncertain significance (Dec 23, 2023)
1-36466439-T-C		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Uncertain significance (Nov 20, 2023)
1-36466440-C-T		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency • not specified	Uncertain significance (May 10, 2022)
1-36466441-G-A		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Likely benign (Nov 24, 2023)
1-36466445-T-C		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Uncertain significance (Feb 27, 2023)
1-36466446-C-T		not specified • Autosomal recessive severe congenital neutropenia due to CSF3R deficiency • Hereditary neutrophilia;Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Benign/Likely benign (Jan 29, 2024)
1-36466448-T-C		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Uncertain significance (Sep 06, 2023)
1-36466451-C-G		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Uncertain significance (Dec 11, 2023)
1-36466461-G-A		Autosomal recessive severe congenital neutropenia due to CSF3R deficiency • CSF3R-related disorder	Likely benign (Jan 21, 2024)

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
1.52e-10	0.997	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

Haploinsufficiency Scores

• pHI: 0.149
• hipred: N
• hipred_score: 0.322
• ghis: 0.453

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

Mouse Genome Informatics

• Gene name: Csf3r
• Phenotype: immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system 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); cellular phenotype; endocrine/exocrine gland phenotype

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