CSF3R

Chr 1ADAR

colony stimulating factor 3 receptor

Also known as: CD114, GCSFR, SCN7

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAD/ARLOEUF 0.772 OMIM phenotypes
Clinical SummaryCSF3R
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.77LOEUF
pLI 0.000
Z-score 2.78
OE 0.54 (0.390.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.20Z-score
OE missense 0.85 (0.780.92)
412 obs / 486.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.54 (0.390.77)
00.351.4
Missense OE0.85 (0.780.92)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 23 / 42.5Missense obs/exp: 412 / 486.5Syn Z: -0.07
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CSF3R · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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