CSF3R

protein-coding

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

Gene summary

The protein encoded by this gene is the receptor for colony stimulating factor 3, a cytokine that controls the production, differentiation, and function of granulocytes. The encoded protein, which is a member of the family of cytokine receptors, may also function in some cell surface adhesion or recognition processes. Alternatively spliced transcript variants have been described. Mutations in this gene are a cause of Kostmann syndrome, also known as severe congenital neutropenia. [provided by RefSeq, Aug 2010]

Previous symbols:

CD114

MANE transcript

NM_000760.4

Inheritance

AD, AR

ClinVar variants

P:65U:390B:219

Top phenotype

Neutropenia, severe congenital, 7, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.54

Max pathogenic AF

—

Genomic locus

chr1:36,466,043-36,483,278

External References & Databases

Ensembl (ENSG00000119535)

Transcript & Mutation Effects

hg38 • Region Span ~17.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary neutrophiliaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008092

Submitter: Orphanet

autosomal recessive severe congenital neutropenia due to CSF3R deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014865

Submitter: Orphanet

autosomal recessive severe congenital neutropenia due to CSF3R deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014865

Submitter: Labcorp Genetics (formerly Invitae)

autosomal recessive severe congenital neutropenia due to CSF3R deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014865

Submitter: Ambry Genetics

hereditary neutrophiliaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008092

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Neutropenia, severe congenital, 7, autosomal recessiveAR

Manifestation: Allergy/Immunology/Infectious; Hematologic

Intervention: Allergy/Immunology/Infectious

Rationale: 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

Comments: One individual with Neutrophilia has been described as developing a myelodysplastic syndrome with refractory anemia

Refs: 4825608; 19620628; 24753537; 26324699

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CSF3R variants in ClinVar

12 Conditions Cataloged

Autosomal recessive severe congenital neutropenia due to CSF3R deficiencyTotal: 690

not specifiedTotal: 130

not providedTotal: 117

Inborn genetic diseasesTotal: 84

CSF3R-related disorderTotal: 60

Hereditary neutrophiliaTotal: 10

CSF3R-Related DisordersTotal: 6

Severe congenital neutropeniaTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000760.4. 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			4 clinvar	182 clinvar	3 clinvar	189
missense	2 clinvar	4 clinvar	374 clinvar	32 clinvar	2 clinvar	414
nonsense	13 clinvar	9 clinvar	4 clinvar			26
start loss						0
frameshift	16 clinvar	6 clinvar	4 clinvar			26
splice donor/acceptor (+/-2bp)	1 clinvar	14 clinvar	4 clinvar			19
Total	32	33	390	214	5	674

Highest pathogenic variant AF is 0.00046055357

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000760.4	RefSeq	NP_000751.1	15	MANE Select
ENST00000373106.6	Ensembl	ENSP00000362198.2	15	MANE Select
NM_156039.3	RefSeq	NP_724781.1	15	Standard
NM_172313.3	RefSeq	NP_758519.1	16	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
csf3r	Danio rerio	Structure: neutrophil Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

csf3r

Danio rerio

Structure: neutrophil

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

defense response
cell adhesion
signal transduction
cytokine-mediated signaling pathway
neutrophil chemotaxis

Molecular Function

cytokine receptor activity
interleukin-3 receptor activity
protein binding
cytokine binding
interleukin-3 binding

Cellular Component

extracellular region
plasma membrane
integral component of plasma membrane
external side of plasma membrane
receptor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373103
Coding exons: 15
Length: 17236
Individuals with no LoFs: 125634
Homozygous LoFs: 0
Heterozygous LoFs: 114
Defined: 125748
p: 0.000453

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.20	412	486	0.847	0.0000271	5575
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00062	0.00062	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00078	0.00077	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.336

Intolerance Scores

LoFtool: 0.786
RVIS EVS: 1.79
RVIS percentile EVS: 96.87

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.952

Gene Damage Prediction

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