CSF3R

Chr 1ADAR

colony stimulating factor 3 receptor

Also known as: CD114, GCSFR, SCN7

NCBI Gene: 1441ENSG00000119535UniProt: Q99062

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]

Primary Disease Associations & Inheritance

?Neutrophilia, hereditaryMIM #162830
AD
Neutropenia, severe congenital, 7, autosomal recessiveMIM #617014
AR
UniProtHereditary neutrophilia
1
Active trials
31
Pathogenic / LP
483
ClinVar variants
57
Pubs (1 yr)
1.2
Missense Z
0.77
LOEUF
Clinical Summary— CSF3R
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 279 VUS of 483 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.77LOEUF
pLI 0.000
Z-score 2.78
OE 0.54 (0.39–0.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.20Z-score
OE missense 0.85 (0.78–0.92)
412 obs / 486.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.54 (0.39–0.77)
0≤0.351.4
Missense OE0.85 (0.78–0.92)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 23 / 42.5Missense obs/exp: 412 / 486.5Syn Z: -0.07
GOFDN
DN
0.74top 25%
GOF
0.75top 25%
LOF
0.2679th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median · 1 literature citation
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

GOFThis variant is located between the extracellular immunoglobulin-like and cytokine receptor homology domains and results in decreased G-CSF sensitivity. p.Pro784Thr was identified in a 67-year-old man with multiple myeloma. p.Pro784Thr is a missense variant in the cytoplasmic domain that inhibits CSPMID:33108454

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

483 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic14
VUS279
Likely Benign165
Conflicting8
17
Pathogenic
14
Likely Pathogenic
279
VUS
165
Likely Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
1
8
0
17
Likely Pathogenic
10
0
4
0
14
VUS
4
248
25
2
279
Likely Benign
0
6
47
112
165
Benign
0
0
0
0
0
Conflicting
—8
Total2225584114483

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

CSF3R · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
The MPL mutation.
Guglielmelli P et al.·Int Rev Cell Mol Biol
2021Review
Chronic neutrophilic leukemia and atypical chronic myeloid leukemia: 2024 update on diagnosis, genetics, risk stratification, and management.
Szuber N et al.·Am J Hematol
2024Review
Severe congenital neutropenias.
Skokowa J et al.·Nat Rev Dis Primers
2017Review
Chronic neutrophilic leukaemia.
Uppal G et al.·J Clin Pathol
2015Review
The spectrum of Ph-negative disease: CNL and CSF3R-related disorders.
Hasserjian RP·Hematology Am Soc Hematol Educ Program
2024Review
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
CSF3R Mutations Imply Adverse Prognostic Impact in Adult Acute Myeloid Leukemia Patients: A Single-Center Retrospective Study.
Yang J et al.·Cancer Med
2025Open AccessCohort
Abnormal RH antigen expression in myeloid malignancies with MPL mutation, CSF3R mutation, or 1p deletion: Evidence of two distinct mechanisms.
Bourgeois R et al.·Transfusion
2025Functional
Research progress on the mechanisms of CSF3R mutations in leukemogenesis and treatment strategies.
Wang N et al.·Cancer Cell Int
2025Open AccessFunctional
Expanding the Spectrum of CSF3R-Mutated Myeloid Neoplasm Beyond Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia: A Comprehensive Analysis of 13 Cases.
Seth N et al.·J Clin Med
2025Open AccessCohort
Dual ASXL1 and CSF3R mutations drive myeloid-biased stem cell expansion and enhance neutrophil differentiation.
Darmusey L et al.·Blood Adv
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients