CSF3R

Summary

CSF3R (colony stimulating factor 3 receptor, HGNC:2439) is a protein-coding gene on chromosome 1p34.3, encoding Granulocyte colony-stimulating factor receptor (Q99062). Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. In precision oncology, CSF3R T618I confers sensitivity to Ruxolitinib in Chronic Neutrophilic Leukemia (CIViC Level C).

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.

Source: NCBI Gene 1441 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive severe congenital neutropenia due to CSF3R deficiency (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 38 (top 3% of genes corpus-wide)
• Clinical variants (ClinVar): 810 total — 30 pathogenic, 17 likely-pathogenic (top 4% of genes corpus-wide)
• GTEx eGene: eQTL in 8 tissues, sQTL in 21 (q < 0.05)
• Phenotypes (HPO): 13
• Drug target: yes — 10 curated mechanism-of-action drugs
• Approved drugs (ChEMBL mechanism of action): 6 — Efbemalenograstim Alfa, Eflapegrastim, Filgrastim, +3 more
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 3 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.73 (unconstrained)
• MANE Select transcript: NM_000760
• Interaction hub: 2,298 STRING partners (top 5% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2439
Approved symbol	CSF3R
Name	colony stimulating factor 3 receptor
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	GCSFR, G-CSF-R
Ensembl gene	ENSG00000119535
Ensembl biotype	protein_coding
OMIM	138971
Entrez	1441

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 19 protein_coding, 7 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000373106

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 3, TSL 3: 2, TSL 5: 4

ENST00000373106, ENST00000373103, ENST00000373104, ENST00000464365, ENST00000464465, ENST00000466138, ENST00000469380, ENST00000480825, ENST00000484762, ENST00000487540, ENST00000489551, ENST00000526980, ENST00000533491, ENST00000699089, ENST00000699090, ENST00000699160, ENST00000909337, ENST00000909338, ENST00000909339, ENST00000944959, ENST00000944960, ENST00000944961, ENST00000944962, ENST00000944963, ENST00001052183, ENST00001052185, ENST00001111087, ENST00001115469, ENST00001115470, ENST00001126432, ENST00001141668

RefSeq mRNA: 3 — MANE Select: NM_000760 NM_000760, NM_156039, NM_172313

CCDS: CCDS412, CCDS413, CCDS414

Canonical transcript exons

ENST00000373106 — 17 exons

Exon	Start	End
ENSE00000000237	36482811	36482913
ENSE00000807433	36475377	36475673
ENSE00000807443	36467822	36467962
ENSE00001459523	36481478	36481537
ENSE00001633459	36466043	36466827
ENSE00003491116	36469156	36469257
ENSE00003501963	36467230	36467311
ENSE00003536478	36471433	36471646
ENSE00003548006	36479433	36479516
ENSE00003557128	36472238	36472391
ENSE00003565017	36473435	36473622
ENSE00003591626	36468075	36468221
ENSE00003600643	36469652	36469840
ENSE00003616645	36467558	36467651
ENSE00003618385	36472517	36472686
ENSE00003618998	36472066	36472139
ENSE00003631581	36473764	36473887

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 99.53.

FANTOM5 (CAGE): breadth broad, TPM avg 30.9174 / max 5737.9647, expressed in 489 samples.

Highest expression (Bgee): granulocyte, monocyte, blood, leukocyte, mononuclear cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CSF3R is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 8 tissues and its splicing (sQTL) in 21 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 29 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	sqtl	2.7e-74	-2.90	1:36480112:C:T
Spleen	sqtl	7.0e-49	-3.04	1:36480112:C:T
Whole Blood	sqtl	1.3e-46	+0.45	1:36478697:C:A
Breast Mammary Tissue	sqtl	1.8e-39	-2.84	1:36480112:C:T
Cells Cultured fibroblasts	eqtl	1.6e-36	+0.88	1:36495025:G:A
Adipose Visceral Omentum	sqtl	1.2e-34	-2.93	1:36480112:C:T
Heart Atrial Appendage	sqtl	4.1e-27	-2.90	1:36480112:C:T
Artery Aorta	sqtl	1.0e-25	-2.36	1:36480112:C:T
Esophagus Mucosa	sqtl	9.6e-23	-2.14	1:36480112:C:T
Colon Transverse	sqtl	5.1e-21	-2.27	1:36480112:C:T
Colon Sigmoid	sqtl	1.0e-18	-2.18	1:36480112:C:T
Liver	sqtl	1.0e-16	-3.10	1:36480112:C:T
Heart Left Ventricle	sqtl	5.3e-15	-2.65	1:36480112:C:T
Small Intestine Terminal Ileum	sqtl	7.0e-13	-2.40	1:36480112:C:T
Lung	sqtl	1.8e-12	+0.33	1:36478315:C:G
Prostate	sqtl	3.5e-11	-2.91	1:36480112:C:T
Stomach	sqtl	2.0e-09	-2.08	1:36480112:C:T
Brain Spinal cord cervical c-1	sqtl	3.3e-09	-3.66	1:36480112:C:T
Pituitary	sqtl	1.8e-06	-2.03	1:36480112:C:T
Artery Coronary	sqtl	7.4e-04	-2.51	1:36480112:C:T

FANTOM5 promoters

showing 10 of 12 alternative TSS:

Promoter ID	TPM avg	Samples expressed
11754	17.1657	430
11752	8.3156	364
11753	4.1789	280
11743	0.4534	84
11750	0.1817	41
11747	0.1534	60
201469	0.1132	29
11749	0.1105	38
11748	0.0977	37
11751	0.0720	25

Top tissues by expression

showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.53	gold quality
monocyte	CL:0000576	99.20	gold quality
blood	UBERON:0000178	98.93	gold quality
leukocyte	CL:0000738	98.86	gold quality
mononuclear cell	CL:0000842	98.81	gold quality
upper lobe of left lung	UBERON:0008952	98.40	gold quality
right lung	UBERON:0002167	98.18	gold quality
upper lobe of lung	UBERON:0008948	97.94	gold quality
spleen	UBERON:0002106	97.64	gold quality
bone marrow cell	CL:0002092	94.43	gold quality
bone marrow	UBERON:0002371	94.13	gold quality
placenta	UBERON:0001987	93.42	gold quality
lower lobe of lung	UBERON:0008949	92.15	gold quality
trabecular bone tissue	UBERON:0002483	90.65	gold quality
vermiform appendix	UBERON:0001154	90.47	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.77	gold quality
gall bladder	UBERON:0002110	89.67	gold quality
omental fat pad	UBERON:0010414	89.22	gold quality
peritoneum	UBERON:0002358	89.16	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.46	gold quality
spinal cord	UBERON:0002240	87.35	gold quality
lung	UBERON:0002048	87.33	gold quality
caecum	UBERON:0001153	86.55	gold quality
right lobe of liver	UBERON:0001114	86.41	gold quality
left uterine tube	UBERON:0001303	85.95	gold quality
periodontal ligament	UBERON:0008266	84.13	gold quality
right coronary artery	UBERON:0001625	84.02	gold quality
apex of heart	UBERON:0002098	82.88	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.81	gold quality
right atrium auricular region	UBERON:0006631	82.79	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.13	gold quality
descending thoracic aorta	UBERON:0002345	81.89	gold quality
heart left ventricle	UBERON:0002084	81.77	gold quality
adipose tissue	UBERON:0001013	81.74	gold quality
left adrenal gland cortex	UBERON:0035825	81.74	gold quality
cardiac ventricle	UBERON:0002082	81.23	gold quality
cardiac atrium	UBERON:0002081	81.15	gold quality
tibial nerve	UBERON:0001323	81.11	gold quality
lower esophagus mucosa	UBERON:0035834	80.95	gold quality
smooth muscle tissue	UBERON:0001135	80.85	gold quality
connective tissue	UBERON:0002384	80.77	gold quality
left adrenal gland	UBERON:0001234	80.66	gold quality
substantia nigra	UBERON:0002038	80.50	gold quality
adrenal cortex	UBERON:0001235	80.24	gold quality
lymph node	UBERON:0000029	80.00	gold quality
mucosa of stomach	UBERON:0001199	79.91	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.84	gold quality
liver	UBERON:0002107	79.78	gold quality
left coronary artery	UBERON:0001626	79.76	gold quality
right adrenal gland cortex	UBERON:0035827	79.59	gold quality
amygdala	UBERON:0001876	79.54	gold quality
heart	UBERON:0000948	79.51	gold quality
coronary artery	UBERON:0001621	79.51	gold quality
midbrain	UBERON:0001891	79.46	gold quality
ascending aorta	UBERON:0001496	79.25	gold quality
thoracic aorta	UBERON:0001515	79.25	gold quality
right adrenal gland	UBERON:0001233	79.20	gold quality
right lobe of thyroid gland	UBERON:0001119	79.02	gold quality
small intestine Peyer’s patch	UBERON:0003454	78.95	gold quality
minor salivary gland	UBERON:0001830	78.73	gold quality
body of stomach	UBERON:0001161	78.20	gold quality
adrenal gland	UBERON:0002369	78.07	gold quality
left lobe of thyroid gland	UBERON:0001120	77.61	gold quality
superficial temporal artery	UBERON:0001614	77.57	silver quality
hypothalamus	UBERON:0001898	77.54	gold quality
palpebral conjunctiva	UBERON:0001812	77.45	gold quality
gastrocnemius	UBERON:0001388	77.44	gold quality
caudate nucleus	UBERON:0001873	77.14	gold quality
small intestine	UBERON:0002108	76.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	76.77	gold quality
adenohypophysis	UBERON:0002196	76.72	gold quality
sural nerve	UBERON:0015488	76.71	gold quality
aorta	UBERON:0000947	76.29	gold quality
thyroid gland	UBERON:0002046	76.27	gold quality
right frontal lobe	UBERON:0002810	76.14	gold quality
urinary bladder	UBERON:0001255	76.06	gold quality
saliva-secreting gland	UBERON:0001044	76.04	gold quality
putamen	UBERON:0001874	75.96	gold quality
endocervix	UBERON:0000458	75.91	gold quality
mouth mucosa	UBERON:0003729	75.90	gold quality
transverse colon	UBERON:0001157	75.80	gold quality
nucleus accumbens	UBERON:0001882	75.50	gold quality
muscle of leg	UBERON:0001383	75.48	gold quality
Ammon’s horn	UBERON:0001954	75.45	gold quality
lower esophagus	UBERON:0013473	75.45	gold quality
lower esophagus muscularis layer	UBERON:0035833	75.40	gold quality
anatomical system	UBERON:0000467	75.36	gold quality
stomach	UBERON:0000945	75.34	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	75.33	gold quality
multicellular organism	UBERON:0000468	75.25	gold quality
material anatomical entity	UBERON:0000465	75.23	gold quality
visceral pleura	UBERON:0002401	75.17	gold quality
myometrium	UBERON:0001296	75.12	gold quality
cingulate cortex	UBERON:0003027	75.03	gold quality
metanephros cortex	UBERON:0010533	74.78	gold quality
anterior cingulate cortex	UBERON:0009835	74.70	gold quality
inferior vagus X ganglion	UBERON:0005363	74.67	silver quality
right ovary	UBERON:0002118	74.40	gold quality
esophagus	UBERON:0001043	74.39	gold quality
subthalamic nucleus	UBERON:0001906	74.31	silver quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	3737.40
E-MTAB-6678	yes	2607.46
E-MTAB-9221	yes	2032.99
E-GEOD-149689	yes	1912.26
E-GEOD-130473	yes	1564.80
E-GEOD-150728	yes	1465.91
E-MTAB-9067	yes	955.32
E-MTAB-8884	yes	820.09
E-ANND-2	yes	362.32
E-HCAD-6	yes	184.63
E-MTAB-6701	yes	129.29
E-HCAD-1	yes	75.60
E-CURD-122	yes	65.73
E-HCAD-4	yes	62.03
E-GEOD-84465	yes	36.38

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 74 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	183.7	low
Placenta	tissue	74.7	high
Appendix	tissue	72.9	not detected
Spleen	tissue	30.4	not detected
Lung	tissue	19.8	low
Adipose tissue	tissue	16.0	not detected
Urinary bladder	tissue	13.6	not detected
Tongue	tissue	9.7
Gallbladder	tissue	7.5	not detected
Smooth muscle	tissue	7.4	not detected
Vagina	tissue	6.1	not detected
Pituitary gland	tissue	5.5
Periaqueductal gray	tissue	5.5
Lymph node	tissue	5.3	low
Corpus callosum	tissue	5.3
Spinal cord	tissue	5.2
Medulla oblongata	tissue	5.1
Hypothalamus	tissue	4.9
Substantia nigra	tissue	4.5
Pons	tissue	4.2
Midbrain	tissue	4.1
Choroid plexus	tissue	4.0
Thymus	tissue	3.7
Breast	tissue	3.5	not detected
Liver	tissue	3.4	not detected
Septum	tissue	3.4
Pancreas	tissue	3.2	not detected
Thalamus	tissue	3.2
Fallopian tube	tissue	3.2	not detected
Adrenal gland	tissue	3.1	not detected
Superior colliculi	tissue	2.7
Esophagus	tissue	2.6	not detected
Small intestine	tissue	2.6	not detected
Putamen	tissue	2.3
Locus coeruleus	tissue	2.2
Ventral forebrain	tissue	2.2
Caudate putamen	tissue	2.2
Frontal cortex	tissue	2.1
Cervix	tissue	2.0	not detected
Amygdala	tissue	2.0
Hippocampus	tissue	2.0	not detected
Hippocampal formation	tissue	2.0
Basal ganglia	tissue	1.7	not detected
Colon	tissue	1.5	not detected
Duodenum	tissue	1.5	not detected
Salivary gland	tissue	1.3	not detected
Tonsil	tissue	1.3	not detected
Olfactory bulb	tissue	1.3
Heart muscle	tissue	1.2	medium
Cerebral cortex	tissue	1.1	medium
Insular cortex	tissue	1.1
Motor cortex	tissue	1.0
Entorhinal cortex	tissue	1.0
Retrosplenial cortex	tissue	1.0
Prefrontal cortex	tissue	0.9
Stomach 1	tissue	0.9	not detected
Seminal vesicle	tissue	0.9	not detected
Parathyroid gland	tissue	0.9	not detected
Nucleus accumbens	tissue	0.9
Thyroid gland	tissue	0.9	not detected

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Area parastriata, superior (22.9), Blood vessel (9.8), Lateral funiculus (white matter) (9.1), Ventrolateral tegmental area, A5 NE cell group (8.5), Nucleus rhomboideus (6.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CEBPE, ETS1, ETS2, MAX, MYB, NFIA, SPI1, STAT5A

miRNA regulators (miRDB)

Targeting CSF3R by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

29 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-4670-3P	97.37	68.35	1378
HSA-MIR-3663-5P	97.01	64.84	713

Functional genomics

gnomAD constraint: pLI 3.61e-09, LOEUF 0.726, missense Z 2.41 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000373106 — one region, missense o/e 0.84.

Literature-anchored findings (GeneRIF, showing 40)

• the dimerization interface of the complete receptor complex is different from that in the x-ray structure of a partial complex. A model of the tetrameric G-CSF.G-CSF-R complex was prepared (PMID:11468284)
• The C-terminus of the G-CSF receptor, truncated in patients with severe congenital neutropenia/acute myeloid leukemia, is required for SH2-containing phosphatase-1 suppression of G-CSF-stimulated Stat activation. (PMID:11714811)
• Lack of STAT3beta function in a differentiation-competent murine cell line expressing human G-CSFR argues against its having a role in Kip1 expression or neutrophil differentiation. (PMID:11920194)
• Novel variant involved in induction of cell proliferation; myelodysplastic syndrome; a deletion of three nucleotides (2128-2130) in the juxtamembrane domain of the G-CSFR resulted in a conversion of Asn(630)Arg(631) to Lys(630). (PMID:12012328)
• abnormalities of primitive myeloid progenitor cells expressing G-CSFR may play an important role in the impairment of granulopoiesis in patients with severe congenital neutropenia (PMID:12422946)
• the carboxy-terminal region of hGCSFR plays a role in the phagocytosis and Syk and Hck kinase tyrosine phosphorylation is involved. (PMID:12586631)
• selective inhibition of G-CSF receptor expression by C/EBPalphap30-ER is due in part to its variable affinity for C/EBP sites (PMID:14737106)
• G-CSFR expression in some bladder cancers appears to be an early event during malignant transformation that increases beta1-integrin expression and adhesion and thereby may promote tissue invasion. (PMID:14751388)
• Thermodynamic data for the interaction of GCSF-GCSFR induced by GCSF binding suggest that the activated structure of GCSFR is a 2:2 complex structure. (PMID:14992583)
• reviewed the knowledge of the expression of G-CSFR and its role in the disorders of granulopoiesis, including myelodysplastic syndrome, and neutropenia in myelodysplastic patients (PMID:15370243)
• lifelong altered G-CSF response by the G-CSF-R_785Lys may render individuals susceptible to development of high-risk M (PMID:15644419)
• The Tyr 729 of the G-CSF-R is required for SOCS3-mediated negative regulation of G-CSF-R signaling and that the duration and intensity of G-CSF-induced Stat5 activation are regulated by two distinct mechanisms. (PMID:16033816)
• crystal structure of the signaling complex between human granulocyte colony-stimulating factor (GCSF) and a ligand binding region of GCSF receptor (GCSF-R), has been determined to 2.8 A resolution (PMID:16492764)
• Deleterious G-CSFR-mediated signaling events, such as aberrant Stat3 activation demonstrated in a subset of acute myeloid leukemia (AML) patients with poor prognosis, could be exploited for the treatment of AML patients. (PMID:16493051)
• CSF3R nonsense mutations (10 new) in SCN at 17 sites lead to a loss Tyr residues in the intracellular domain of the receptor. CSF3R mutation is an early event in leukemogenesis that has to be accompanied by as yet undefined cooperating molecular events (PMID:16985178)
• single-nucleotide polymorphism (Glu785Lys) is associated with myelodysplastic syndromes and acute myeloid leukemia with multlineage dysplasia (PMID:17024119)
• The observed up-regulation of G-CSF receptors towards a role in the pathophysiology of human ischemic stroke. (PMID:17047971)
• that mutations of CSF3R may provide the “activated tyrosine kinase signal” that is thought to be important for leukemogenesis. (PMID:17494858)
• The G-CSF/G-CSFR autocrine/paracrine signaling loop significantly promotes survival and growth of bladder cancer cells. (PMID:17572226)
• REVIEW: Congenital neutropenia patients with acquired CSF3R mutations define a group with high risk for development of leukemia; discussion of possible pathomechanism (PMID:18536571)
• results indicate ubiquitination required for regulation of G-CSFR-mediated proliferation & cell survival; mutation disrupting G-CSFR ubiquitination induce aberrant signaling & proliferative response to G-CSF; this may contribute to leukemic transformation (PMID:18923646)
• There was no significant difference in expression rate of G-CSFR on CD34+ cells between aplastic anemia, myelodysplastic syndrome, and controls. (PMID:19099633)
• Data show that a lysine within the membrane-proximal region of the granulocyte colony-stimulating factor receptor is indispensable for ubiquitination and lysosomal sorting of the receptor. (PMID:19453968)
• identify an autosomal mutation in the CSF3R gene in a family with a chronic neutrophilia. This T617N mutation energetically favors dimerization of the granulocyte colony-stimulating factor (G-CSF) receptor transmembrane domain. (PMID:19620628)
• Two cases of X-linked neutropenia are reported that evolved to acute myeloid leukemia or myelodysplasia, with acquisition of G-CSF receptor mutations. (PMID:19794089)
• RAS and CSF3R mutations in severe congenital neutropenia. (PMID:19833857)
• a possible role of G-CSF in malignant transformation, particularly in patients with neutropenia harboring mutations in the gene encoding the G-CSF receptor. (PMID:20237318)
• G-CSF-induced upregulation of MT1-MMP in hematopoietic cells and its enhanced incorporation into membrane lipid rafts contributes to proMMP-2 activation, which facilitates mobilization of HSPC. (PMID:20471446)
• Transgenic Fn14/TWEAK receptor pathway in a mouse model is adversely involved in inflammatory and ischemic brain disease associated with the strongest increase of the endogenous neuroprotective G-CSF and the G-CSF receptor system. (PMID:20557950)
• The results reported in this study suggest a role for CSF3R in the determination of bone density in women. (PMID:20654748)
• Data from rna interference of G-CSFR messenger RNA demonstrated the limited specificity of antibodies for HuG-CSFR expressed on the cell surface. (PMID:20696205)
• CD123+CD34+CD38- cells exhibited lower expression of G-CSF receptors, which might partly explain why MDS clone responds worse to G-CSF in vitro and in vivo. (PMID:20819538)
• Gemcitabine can enhance in vitro the expression rate of bone marrow G-CSFR in chronic myeloid leukemia patients at chronic or blastic phases. (PMID:21129254)
• Pretreatment of PMNs with IFN-gamma or G-CSF for a long-time (22 h)induced a significant lower fungal damage against biofilms compared with planktonic cells. (PMID:21641233)
• An acquired CSF3R mutation in an adult chronic idiopathic neutropenia patient who developed acute myeloid leukaemia. (PMID:22146088)
• CSF3R gene polymorphism plays a significant role in hematopoietic stem and progenitor cells for transplantation. (PMID:22796466)
• Certain missense single nucleotide polymorphisms, especially which are placed in the conserved regions of G-CSFR may possess the capacity to influence the response to G-CSF treatment. (PMID:23159284)
• The stimulating factor 3 receptor mutation (CSF3R-T595I) found in acute myeloid leukemia patients was found to have ligand independent activation properties. (PMID:23508011)
• Mutations in CSF3R are common in patients with CNL or atypical CML and represent a potentially useful criterion for diagnosing these neoplasms. (PMID:23656643)
• A subpopulation of GCSFR positive neuroblastoma cells exhibit enhanced tumorigenicity and a stem cell phenotype. (PMID:23687340)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	csf3r	ENSDARG00000045959
mus_musculus	Csf3r	ENSMUSG00000028859
rattus_norvegicus	Csf3r	ENSRNOG00000008759

Paralogs (23): CRLF1 (ENSG00000006016), IL12RB2 (ENSG00000081985), IL5RA (ENSG00000091181), IL12RB1 (ENSG00000096996), IL27RA (ENSG00000104998), EBI3 (ENSG00000105246), GHR (ENSG00000112964), PRLR (ENSG00000113494), LIFR (ENSG00000113594), LEPR (ENSG00000116678), CNTFR (ENSG00000122756), IL13RA2 (ENSG00000123496), IL13RA1 (ENSG00000131724), IL6ST (ENSG00000134352), IL11RA (ENSG00000137070), OSMR (ENSG00000145623), IL2RG (ENSG00000147168), IL6R (ENSG00000160712), IL23R (ENSG00000162594), IL31RA (ENSG00000164509), IL3RA (ENSG00000185291), CSF2RA (ENSG00000198223), CRLF2 (ENSG00000205755)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1339755) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 16 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased neutrophil cell number	4
impaired neutrophil chemotaxis	2
decreased monocyte cell number	1
increased bone marrow cell number	1
decreased bone marrow cell number	1
abnormal testis morphology	1
small testis	1
abnormal hematopoietic system morphology/development	1
abnormal bone marrow cell morphology/development	1
abnormal myeloblast morphology/development	1
abnormal neutrophil differentiation	1
abnormal neutrophil physiology	1
abnormal monocyte morphology	1
decreased hematopoietic stem cell number	1
abnormal common myeloid progenitor cell morphology	1
preweaning lethality, incomplete penetrance	1

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MRPS15	protein-coding	64960
GRIK3	protein-coding	2899
SNORA63C	snoRNA	109616970
OSCP1	protein-coding	127700
LSM10	protein-coding	84967

Protein

Protein identifiers

Granulocyte colony-stimulating factor receptor — Q99062 (reviewed: Q99062)

All UniProt accessions (5): A0A8V8TNA4, A0A8V8TP76, E9PK56, Q99062, H0YE86

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differentiation and survival of cells along the neutrophilic lineage. In addition it may function in some adhesion or recognition events at the cell surface.

Subunit / interactions. Homodimer. The dimeric receptor binds two CSF3 molecules. Interacts with CEACAM1; down-regulates the CSF3R-STAT3 pathway through recruitment of PTPN6 that dephosphorylates CSF3R.

Subcellular location. Secreted Cell membrane.

Tissue specificity. One or several isoforms have been found in myelogenous leukemia cell line KG-1, leukemia U-937 cell line, in bone marrow cells, placenta, and peripheral blood granulocytes. Isoform GCSFR-2 is found only in leukemia U-937 cells. Isoform GCSFR-3 is highly expressed in placenta.

Post-translational modifications. N-glycosylated.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. The box 1 motif is required for JAK interaction and/or activation.

Miscellaneous. Mutations in CSF3R acquired in multipotent hematopoietic progenitor cells and resulting in truncated hyper-responsive forms of the receptor, have been identified in most cases of severe congenital neutropenia (SCN). Patients carrying these mutations are at risk for developing myelodysplastic syndromes and/or acute myeloid leukemia. Constitutive mutations leading to hyporesponsive forms of the receptor are responsible for the refractoriness to CSF3 treatment observed in some SCN patients.

Similarity. Belongs to the type I cytokine receptor family. Type 2 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q99062-1	1, GCSFR-1	yes
Q99062-2	2, GCSFR-2
Q99062-3	3, GCSFR-3
Q99062-4	4, GCSFR-4, D7

RefSeq proteins (3): NP_000751, NP_724781, NP_758519 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003529	Hematopoietin_rcpt_Gp130_CS	Conserved_site
IPR003961	FN3_dom	Domain
IPR010457	IgC2-like_lig-bd	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR052672	Type1_Cytokine_Rcpt_Type2	Family

Pfam: PF00041, PF06328

UniProt features (75 total): strand 23, sequence variant 11, glycosylation site 8, helix 8, disulfide bond 7, domain 6, splice variant 4, short sequence motif 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, turn 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
2D9Q	Crystal Structure of the Human GCSF-Receptor Signaling Complex	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99062-F1	74.29	0.37

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Predicted intracellular proteins, Cancer-related genes, Disease related genes, FDA approved drug targets, Biotech drugs, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (7)

Type	Positions
Disulfide bond	26–52, 46–101, 131–142, 167–218, 177–186, 248–295, 266–309

Glycosylation sites (8)

Type	Positions
N-linked (glcnac…) asparagine	51, 93, 128, 134, 389, 474, 579, 610

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-449836	Other interleukin signaling	curated
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-1266738	Developmental Biology	—
R-HSA-168256	Immune System	—
R-HSA-9705462	Inactivation of CSF3 (G-CSF) signaling	electronic
R-HSA-9674555	Signaling by CSF3 (G-CSF)	electronic
R-HSA-449147	Signaling by Interleukins	—
R-HSA-9616222	Transcriptional regulation of granulopoiesis	electronic

MSigDB gene sets: 310 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_CD11B_DC_DN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, GOCC_VACUOLAR_MEMBRANE, MODULE_45, MODULE_64, GOCC_CELL_SURFACE, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_TAXIS

GO Biological Process (6): defense response (GO:0006952), cell adhesion (GO:0007155), signal transduction (GO:0007165), positive regulation of cell population proliferation (GO:0008284), cytokine-mediated signaling pathway (GO:0019221), amelogenesis (GO:0097186)

GO Molecular Function (5): cytokine receptor activity (GO:0004896), cytokine binding (GO:0019955), signaling receptor activity (GO:0038023), granulocyte colony-stimulating factor binding (GO:0051916), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), endocytic vesicle membrane (GO:0030666), signaling receptor complex (GO:0043235), membrane (GO:0016020)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Cytokine Signaling in Immune system	2
Signaling by Interleukins	1
Developmental Biology	1
Signaling by CSF3 (G-CSF)	1
Immune System	1

GO top-level categories

32 GO namespaces:

Category	Terms
cellular process	2
cytokine binding	2
cellular anatomical structure	2
response to stress	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
odontogenesis of dentin-containing tooth	1
anatomical structure formation involved in morphogenesis	1
transmembrane signaling receptor activity	1
cytokine-mediated signaling pathway	1
immune receptor activity	1
protein binding	1
molecular transducer activity	1
binding	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
endocytic vesicle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

showing 15 of 2,298 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSF3R	CSF3	P09919	920
CSF3R	CSF2RA	P15509	794
CSF3R	ELANE	P08246	769
CSF3R	CEBPA	P49715	766
CSF3R	HAX1	O00165	753
CSF3R	SETBP1	Q9Y6X0	735
CSF3R	ASXL1	Q8IXJ9	679
CSF3R	CSF2	P04141	677
CSF3R	CSF2RB	P32927	667
CSF3R	ZRSR2	Q15696	654
CSF3R	ABL1	P00519	652
CSF3R	U2AF1	Q01081	650
CSF3R	SRSF2	Q01130	649
CSF3R	CSF1R	P07333	629
CSF3R	JAK2	O60674	622

IntAct

Human interaction partners of CSF3R in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
UBC	physical association	0.520	2
STAT3	association	0.460	4

BioGRID (36 interactions; top human partners by supporting records): GRB2 (Reconstituted Complex; 5 records), SHC1 (Reconstituted Complex; 5 records), WSB2 (Affinity Capture-Western; 3 records), CISH (Reconstituted Complex; 2 records), GSK3B (Affinity Capture-Western; 2 records), HCK (Affinity Capture-Western; 2 records), WSB1 (Affinity Capture-Western; 2 records), AXL (Negative Genetic), CDKN1A (Negative Genetic), DMPK (Negative Genetic), FBXW7 (Affinity Capture-Western), FZR1 (Affinity Capture-Western), GCK (Negative Genetic), HMGA1 (Negative Genetic), JAK1 (Affinity Capture-Western)

SIGNOR signaling

showing 4 of 6 signaling interactions:

A	Effect	B	Mechanism
CSF1	up-regulates	CSF3R	binding
CSF2	up-regulates	CSF3R	binding
CSF3	up-regulates	CSF3R	binding
HCK	“up-regulates activity”	CSF3R	phosphorylation

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
★ CSF3R-FBXW7-GSK3B complex	3	GSK3B, CSF3R, FBXW7
★ CSF3R-LYN-SYK complex	3	CSF3R, LYN, SYK
★ CSF3-CSF3R complex	2	CSF3, CSF3R
★ FTH1-CSF3R complex	2	CSF3R, FTH1

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
CSF3	receptor	Signaling by Colony-Stimulating factor

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 3 cancer types — AML, BLADDER, HNSC.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for CSF3R: 810 ClinVar records (47 pathogenic / likely pathogenic); 2 CIViC cancer variants; 38 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

810 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	17
Uncertain significance	407
Likely benign	259
Benign	22

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 47 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1322165	NM_000760.4(CSF3R):c.189G>A (p.Trp63Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
4741276	NM_000760.4(CSF3R):c.1318C>T (p.Arg440Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
242835	NM_000760.4(CSF3R):c.998-2A>T	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1410136	NM_000760.4(CSF3R):c.218dup (p.Arg74fs)	Pathogenic	criteria provided, single submitter	2
542855	NM_000760.4(CSF3R):c.1216dup (p.Val406fs)	Pathogenic	criteria provided, single submitter	1
542856	NM_000760.4(CSF3R):c.799del (p.Glu267fs)	Pathogenic	criteria provided, single submitter	1
649220	NM_000760.4(CSF3R):c.935_963del (p.Arg311_Trp312insTer)	Pathogenic	criteria provided, single submitter	1
655386	NM_000760.4(CSF3R):c.203_221del (p.Glu68fs)	Pathogenic	criteria provided, single submitter	1
971335	NM_000760.4(CSF3R):c.1404del (p.Ser469fs)	Pathogenic	criteria provided, single submitter	1
988352	NM_000760.4(CSF3R):c.2134C>T (p.His712Tyr)	Pathogenic	criteria provided, single submitter	1
988435	NM_000760.4(CSF3R):c.2260C>T (p.Gln754Ter)	Pathogenic	criteria provided, single submitter	1
1070139	NM_000760.4(CSF3R):c.32G>A (p.Trp11Ter)	Pathogenic	criteria provided, single submitter	1
1073345	NM_000760.4(CSF3R):c.1388G>A (p.Trp463Ter)	Pathogenic	criteria provided, single submitter	1
1372222	NM_000760.4(CSF3R):c.642_650delinsTTGATCCCATGGATGTTGGTGTCTTGATCCCATGGATGTTG (p.Pro215_Leu217delinsTer)	Pathogenic	criteria provided, single submitter	1
1416044	NM_000760.4(CSF3R):c.78C>A (p.Cys26Ter)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CSF3R’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 1,275):

Position(s)	Effect	Δscore	Sites
1:36472068	donor_gain	1.0000
1:36467670–36467671	acceptor_gain	0.9900	2
1:36467820–36467821	donor_loss	0.9900	5
1:36467922	acceptor_gain	0.9900
1:36472236–36472237	donor_loss	0.9900	6
1:36472256	donor_gain	0.9900
1:36472392–36472393	acceptor_loss	0.9900	6
1:36472395	acceptor_gain	0.9900
1:36482809–36482810	donor_loss	0.9900	5
1:36467556–36467557	donor_loss	0.9800	5

AlphaMissense

651 missense substitutions predicted likely pathogenic (of 5,441 scored), across 215 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
N207	8	0.875	0.979
C142	7	0.957	0.984
C46	7	0.948	0.975
C131	7	0.946	0.974
W144	7	0.942	0.996
C101	7	0.933	0.960
W321	7	0.926	0.990
W63	7	0.920	0.985
W356	7	0.916	0.974
W547	7	0.912	0.984
W449	7	0.906	0.972
C395	7	0.894	0.939
S319	7	0.893	0.984
C388	7	0.888	0.951
C309	7	0.861	0.923
W463	7	0.850	0.959
W477	7	0.844	0.947
W318	7	0.843	0.959
W673	7	0.840	0.932
C218	7	0.796	0.877

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Testicular Germ Cell Tumor (TCGA)	unfavorable	0.000226

Disease associations

OMIM: gene MIM:138971 | disease phenotypes: MIM:162830, MIM:617014, MIM:202700

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
autosomal recessive severe congenital neutropenia due to CSF3R deficiency	Strong	Autosomal recessive	3
hereditary neutrophilia	Strong	Autosomal dominant	2

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (5 panels, 5 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

5 panels:

Panel	Rating
COVID-19 research	green
Cytopenia - NOT Fanconi anaemia	green
Cytopenias and congenital anaemias	green
Monitoring for G(M)CSF escape variants	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green

Mondo (4): hereditary neutrophilia (MONDO:0008092), autosomal recessive severe congenital neutropenia due to CSF3R deficiency (MONDO:0014865), severe congenital neutropenia (MONDO:0018542), early T cell progenitor acute lymphoblastic leukemia (MONDO:0100291)

Orphanet (3): Hereditary neutrophilia (Orphanet:279943), Autosomal recessive severe congenital neutropenia due to CSF3R deficiency (Orphanet:420702), Severe congenital neutropenia (Orphanet:42738)

HPO phenotypes

13 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001744	Splenomegaly
HP:0001875	Decreased total neutrophil count
HP:0002719	Recurrent infections
HP:0002863	Myelodysplasia
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0008318	Elevated leukocyte alkaline phosphatase
HP:0011463	Childhood onset
HP:0011897	Increased total neutrophil count
HP:0012138	Granulocytic hyperplasia
HP:0033606	Bone marrow maturation arrest

GWAS associations

showing 30 of 38 associations:

Study	Trait	p-value
GCST90002398_219	Neutrophil count	2e-99
GCST90002407_538	White blood cell count	2e-74
GCST90002399_81	Neutrophil percentage of white cells	1e-55
GCST90002389_8	Lymphocyte percentage of white cells	5e-40
GCST004629_3	Neutrophil count	2e-39
GCST004620_122	Sum basophil neutrophil counts	7e-39
GCST004613_57	Sum neutrophil eosinophil counts	1e-38
GCST004614_128	Granulocyte count	6e-38
GCST004626_157	Myeloid white cell count	1e-36
GCST004610_179	White blood cell count	3e-31
GCST90002398_424	Neutrophil count	2e-28
GCST004633_12	Neutrophil percentage of white cells	1e-23
GCST90002407_539	White blood cell count	2e-22
GCST004620_123	Sum basophil neutrophil counts	1e-21
GCST004629_4	Neutrophil count	1e-21
GCST90002394_269	Monocyte percentage of white cells	1e-21
GCST004613_58	Sum neutrophil eosinophil counts	2e-21
GCST004614_129	Granulocyte count	2e-21
GCST004626_158	Myeloid white cell count	2e-20
GCST004608_4	Granulocyte percentage of myeloid white cells	1e-19
GCST004632_1	Lymphocyte percentage of white cells	2e-17
GCST005973_36	White blood cell count	5e-17
GCST004610_180	White blood cell count	2e-16
GCST90002399_82	Neutrophil percentage of white cells	2e-15
GCST004633_13	Neutrophil percentage of white cells	1e-14
GCST004632_2	Lymphocyte percentage of white cells	3e-13
GCST004609_105	Monocyte percentage of white cells	4e-12
GCST90002382_19	Eosinophil percentage of white cells	5e-12
GCST90002389_9	Lymphocyte percentage of white cells	5e-12
GCST90002379_104	Basophil count	1e-11

EFO canonical traits (from GWAS)

13 canonical traits:

EFO ID	Trait name
EFO:0006334	total iron binding capacity
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004760	t-tau measurement
EFO:0004763	p-tau measurement
EFO:0010462	aspartate measurement
EFO:0007991	eosinophil percentage of leukocytes

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C563010	Neutrophilia, Hereditary *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1996 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the CSF3R protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

10 curated-mechanism drugs:

Drug	Modality	Max phase
EFBEMALENOGRASTIM ALFA	Protein	4
EFLAPEGRASTIM	Protein	4
FILGRASTIM	Protein	4
LENOGRASTIM	Protein	4
LIPEGFILGRASTIM	Protein	4
PEGFILGRASTIM	Protein	4
REGRAMOSTIM	Protein	3
ANUMIGILIMAB	Antibody	2
BALUGRASTIM	Protein	2
PEGTEOGRASTIM	Protein	2

Clinical evidence (CIViC)

Drug × variant × indication, from 2 curated evidence items; also 2 diagnostic, 1 prognostic. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

1 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
CSF3R T618I	Ruxolitinib	Chronic Neutrophilic Leukemia	Sensitivity/Response	CIViC C	EID6381 +1

CIViC column: a representative evidence item (EID); +N = additional CIViC items supporting the same association.

CIViC curated variants (2)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

T618I (missense variant), Mutation (protein altering variant).

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Prolactin receptor family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
anumigilimab	Binding	8.85	pKd

Binding affinities (BindingDB)

2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
3-(3-(3-amino-3-oxopropyl)-3’-(3-aminopropoxy)-5’-(isopentyloxy)biphenyl-4-yl)propanoic acid	KD	20000 nM
3-((3-(3-amino-3-oxopropyl)phenyl)(3-(3-aminopropoxy)-5-(isopentyloxy)benzyl)amino)propanoic acid	KD	47000 nM

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases reaction, increases expression	5
Air Pollutants	affects expression, increases abundance, increases expression, decreases expression	4
Acetaminophen	increases expression, decreases expression	2
Ozone	affects expression, increases abundance, increases expression	2
Valproic Acid	increases expression, increases methylation	2
triphenyl phosphate	affects expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
cypermethrin	decreases reaction, increases expression	1
3-phenoxybenzoic acid	increases expression, decreases reaction	1
tetrathiomolybdate	increases expression	1
indirubin	increases expression	1
nickel sulfate	increases expression	1
triphenyltin	increases expression	1
fluorotelomer alcohols	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
(+)-JQ1 compound	decreases expression	1
Acetylcysteine	decreases reaction, increases expression	1
Arsenates	affects cotreatment, increases expression	1
Aspirin	decreases expression	1
Atrazine	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression	1
Cisplatin	decreases expression	1
Coal	increases abundance, increases expression	1
Methotrexate	decreases expression	1
Mustard Gas	decreases expression	1
Naled	affects expression	1
Paraquat	decreases expression	1
Quercetin	decreases expression	1
Rotenone	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1069757	Binding	Binding affinity to granulocyte colony stimulating factor receptor by SPR biosensor technique	Molecular design of small organic molecules based on structural information for a conformationally constrained peptide that binds to G-CSF receptor. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

13 cell lines: 8 factor-dependent cell line, 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1236	GR-ST	Cancer cell line	Male
CVCL_A0UA	32D/G-CSF-R	Factor-dependent cell line	Male
CVCL_A0UB	32D/G-CSF-R p.Gln741Ter	Factor-dependent cell line	Male
CVCL_A0UC	32D/G-CSF-R p.Gln754Ter	Factor-dependent cell line	Male
CVCL_A0UD	32D/G-CSF-R p.Gln739Ter	Factor-dependent cell line	Male
CVCL_A0UE	32D/G-CSF-R p.Tyr727Phe	Factor-dependent cell line	Male
CVCL_A0UF	32D/G-CSF-R p.Tyr752Phe	Factor-dependent cell line	Male
CVCL_A0UG	32D/G-CSF-R p.Tyr767Phe	Factor-dependent cell line	Male
CVCL_A0UH	32D/G-CSF-R p.Tyr787Phe	Factor-dependent cell line	Male
CVCL_A8QX	MDS-L/GR-GFP-N	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

18 trials:

NCT	Phase	Status	Title
NCT01859637	Phase 4	TERMINATED	Immunogenicity, Safety, and Efficacy of Zarzio®/Filgrastim HEXAL® in Patients With Severe Chronic Neutropenia
NCT06361329	Phase 3	RECRUITING	Comparing the Efficacy of VHAG and Traditional Chemotherapy Regimens in Newly Diagnosed ETP-ALL
NCT00301834	Phase 2	COMPLETED	Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders
NCT00909584	Phase 2	TERMINATED	Study of Ezatiostat (Telintra Tablets) for Treatment of Severe Chronic Neutropenia
NCT01529827	Phase 2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT04844177	Phase 2	UNKNOWN	Total Lymphoid Irradiation Pre-HSCT in Severe Congenital Neutropenia
NCT07012447	Phase 2	RECRUITING	Venetoclax + Azacytidine for Newly Diagnosed ETP-like ALL and T-ALL With Myeloid Mutations
NCT00295971	Phase 1	COMPLETED	Donor Stem Cell Transplant in Treating Young Patients With Myelodysplastic Syndrome, Leukemia, Bone Marrow Failure Syndrome, or Severe Immunodeficiency Disease
NCT01917708	Phase 1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT00176852	Phase 2/3	COMPLETED	Stem Cell Transplant for Hemoglobinopathy
NCT00305708	Phase 1/2	COMPLETED	Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission
NCT01852370	Phase 1/2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT01966367	Phase 1/2	ACTIVE_NOT_RECRUITING	CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation
NCT01319851	Not specified	TERMINATED	Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
NCT02179359	Not specified	TERMINATED	Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies
NCT02720679	Not specified	RECRUITING	Investigation of the Genetics of Hematologic Diseases
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT04582487	Not specified	UNKNOWN	Advancing Chemical and Genomic Strategies for Relapsed/Refractory T-ALL and ETP-ALL

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CSF3R across ~30M SureChEMBL compounds — explore on Sugi Predict.