CSF3R

Chr 1

colony stimulating factor 3 receptor

Also known as: CD114, GCSFR, SCN7

NCBI Gene: 1441 ENSG00000119535 UniProt: Q99062

The colony stimulating factor 3 receptor is essential for granulocytic maturation and controls the proliferation, differentiation and survival of cells along the neutrophilic lineage. Mutations cause severe congenital neutropenia (Kostmann syndrome) and hereditary neutrophilia, with both autosomal recessive and autosomal dominant inheritance patterns reported. This gene is extremely intolerant to loss-of-function mutations in the general population, indicating its critical importance for normal neutrophil development.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.77

Clinical Summary— CSF3R

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

50 unique Pathogenic / Likely Pathogenic· 403 VUS of 786 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.54 (0.39–0.77)

0≤0.351.4

Missense OE?0.85 (0.78–0.92)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 23 / 42.5Missense obs/exp: 412 / 486.5Syn Z: -0.07

This gene — mechanism propensity

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 CS1

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

References

1.PMID 33108454 ↗

ClinVar Variant Classifications

786 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30

Likely Pathogenic20

VUS403

Likely Benign263

Benign26

Conflicting28

Pathogenic

Likely Pathogenic

403

VUS

263

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	28	2	0	0	30
Likely Pathogenic	18	2	0	0	20
VUS	8	364	28	3	403
Likely Benign	0	16	72	175	263
Benign	0	1	19	6	26
Conflicting	—				28
Total	54	385	119	184	770

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap CSF3R — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →