GeneBe

CSF3

protein-coding

colony stimulating factor 3, the group of Receptor ligands

Gene summary

This gene encodes a member of the IL-6 superfamily of cytokines. The encoded cytokine controls the production, differentiation, and function of granulocytes. Granulocytes are a type of white blood cell that are part of the innate immune response. A modified form of this protein is commonly administered to manage chemotherapy-induced neutropenia. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2020]

Previous symbols:
  • GCSF
  • G-CSF
  • C17orf33

MANE transcript

NM_172219.3

Inheritance

AR

ClinVar variants

P:2U:22B:5

Top phenotype

NEUTROPENIA, SEVERE CONGENITAL, 14, AUTOSOMAL RECESSIVE

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr17:40,015,361-40,017,813

External References & Databases

Ensembl (ENSG00000108342)NCBI Gene (1440)OMIM (138970)HGNC:2438GenCCUniProt (P09919)AlphaFoldClinVar (CSF3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~2.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive severe congenital neutropenia due to CSF3R deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014865

Submitter: LiferaOmics

Genetic evidence – Published: PMID: 37612131 reports 3 affected individuals from 2 consanguineous families with biallelic inactivating CSF3 variants. Family 1 includes 1 proband and 1 affected homozygous sibling (sibling counted as segregation, not independent proband); Family 2 includes 1 proband. Case-level (biallelic predicted null in AR model; homozygous scored once; consanguinity deduction applied) = 1.0 per family proband = 2.0; segregation (affected homozygous sibling in Family 1) = 0.5; case-control = 0. Published genetic evidence total = 2.5/12 Genetic evidence – our case: homozygous nonsense NM_000759.4:c.457C>T;p.(Gln153*) in a consanguineous family (predicted loss-of-function). Case-level (biallelic predicted null in AR model; homozygous scored once; consanguinity deduction applied) = 1.0; segregation = 0; case-control = 0. Current case contribution = 1.0/12 Total genetic evidence (published + our case) = 3.5/12 Experimental evidence – Published: CSF3 encodes G-CSF regulating neutrophil production (biochemical function) = 0.5. PMID: 37612131 demonstrates nonsense-mediated decay in patient-derived RNA (functional alteration in patient cells) = 1.0. Csf3 knockout mouse model shows chronic neutropenia (non-human model organism) = 2.0 Experimental evidence total = 3.5/6 Overall score = 7.0

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CSF3 variants in ClinVar

3 Conditions Cataloged
not specifiedTotal: 20
not providedTotal: 6
NEUTROPENIA, SEVERE CONGENITAL, 14, AUTOSOMAL RECESSIVETotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_172219.3. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
3
clinvar
 4
missense
21
clinvar
2
clinvar
 23
nonsense
2
clinvar
 2
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total20220529
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_172219.3RefSeqNP_757373.15MANE Select
ENST00000394149.8EnsemblENSP00000377705.45MANE Select
NM_000759.4RefSeqNP_000750.15Standard
NM_001178147.2RefSeqNP_001171618.14Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
csf3bDanio rerio

Structure: blood island

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)
  • Malaria - Homo sapiens (human)
  • IL-17 signaling pathway - Homo sapiens (human)
  • Hematopoietic cell lineage - Homo sapiens (human)

Biological Process

  • immune response
  • multicellular organism development
  • positive regulation of cell population proliferation
  • regulation of signaling receptor activity
  • positive regulation of phosphatidylinositol 3-kinase signaling

Molecular Function

  • cytokine activity
  • granulocyte colony-stimulating factor receptor binding
  • growth factor activity
  • enzyme binding

Cellular Component

  • extracellular region
  • extracellular space

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000225474
Coding exons
5
Length
2453
Individuals with no LoFs
125696
Homozygous LoFs
0
Heterozygous LoFs
4
Defined
125700
p
0.0000159
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.976871170.7460.000006671311
Missense (PolyPhen)2539.2280.6373488
Synonymous-0.01445554.91.000.00000351439
Loss of Function2.1829.110.2203.91e-799

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000180.000018rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This CSF induces granulocytes.;

Recessive Scores

pRec
0.850

Intolerance Scores

LoFtool
0.643
RVIS EVS
0.22
RVIS percentile EVS
68.13

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.817

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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