CSF3

Summary

CSF3 (colony stimulating factor 3, HGNC:2438) is a protein-coding gene on chromosome 17q21.1, encoding Granulocyte colony-stimulating factor (P09919). 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 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.

Source: NCBI Gene 1440 — RefSeq curated summary.

At a glance

• GWAS associations: 37 (top 3% of genes corpus-wide)
• Clinical variants (ClinVar): 29 total
• GTEx eGene: eQTL in 9 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.24 (unconstrained)
• MANE Select transcript: NM_172219
• Interaction hub: 3,056 STRING partners (top 2% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2438
Approved symbol	CSF3
Name	colony stimulating factor 3
Location	17q21.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC45931
Ensembl gene	ENSG00000108342
Ensembl biotype	protein_coding
OMIM	138970
Entrez	1440

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000394149

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

ENST00000394149, ENST00000225474, ENST00000331769, ENST00000394148, ENST00000479880, ENST00000577675, ENST00000579852, ENST00000582798, ENST00000583218, ENST00000945857, ENST00001143015

RefSeq mRNA: 4 — MANE Select: NM_172219 NM_000759, NM_001178147, NM_172219, NM_172220

CCDS: CCDS11357, CCDS11358, CCDS42314

Canonical transcript exons

ENST00000394149 — 5 exons

Exon	Start	End
ENSE00000000154	40015440	40015514
ENSE00001517624	40015691	40015845
ENSE00003653999	40016485	40016631
ENSE00003665120	40016233	40016340
ENSE00003900839	40016795	40017813

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 92.15.

FANTOM5 (CAGE): breadth broad, TPM avg 40.4409 / max 2203.3834, expressed in 556 samples.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, olfactory segment of nasal mucosa, type B pancreatic cell, vena cava, olfactory bulb.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CSF3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 9 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Spleen	eqtl	1.6e-07	-0.45	17:40021586:A:C
Adipose Subcutaneous	eqtl	9.4e-04	-0.20	17:40032166:C:T
Breast Mammary Tissue	eqtl	1.2e-02	-0.18	17:40021586:A:C
Testis	eqtl	1.3e-02	+0.28	17:39991040:A:G
Brain Cortex	eqtl	1.4e-02	-0.32	17:40796650:T:C
Skin Not Sun Exposed Suprapubic	eqtl	2.2e-02	+0.47	17:39221731:G:A
Nerve Tibial	eqtl	2.3e-02	+0.26	17:40160437:G:A
Muscle Skeletal	eqtl	2.6e-02	+0.15	17:40041162:T:C
Brain Hippocampus	eqtl	3.4e-02	+0.39	17:40166898:T:A
Nerve Tibial	sqtl	4.7e-02	+1.24	17:40807863:GT:G
Cells Cultured fibroblasts	sqtl	4.8e-02	+0.82	17:40449766:GA:G

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
160658	39.0474	526
160657	1.1277	207
160661	0.2340	123
160660	0.0319	9

Top tissues by expression

showing 100 of 275 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.22	gold quality
type B pancreatic cell	CL:0000169	88.66	gold quality
vena cava	UBERON:0004087	87.74	gold quality
olfactory bulb	UBERON:0002264	87.30	gold quality
cervix squamous epithelium	UBERON:0006922	85.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.84	gold quality
triceps brachii	UBERON:0001509	84.61	gold quality
gastrocnemius	UBERON:0001388	83.73	gold quality
left uterine tube	UBERON:0001303	83.42	gold quality
cartilage tissue	UBERON:0002418	83.07	gold quality
diaphragm	UBERON:0001103	82.71	gold quality
tongue squamous epithelium	UBERON:0006919	81.24	gold quality
muscle of leg	UBERON:0001383	81.02	gold quality
gluteal muscle	UBERON:0002000	81.02	gold quality
vastus lateralis	UBERON:0001379	80.64	gold quality
muscle organ	UBERON:0001630	80.43	gold quality
upper lobe of left lung	UBERON:0008952	79.83	gold quality
quadriceps femoris	UBERON:0001377	79.61	gold quality
mucosa of paranasal sinus	UBERON:0005030	79.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.09	gold quality
parotid gland	UBERON:0001831	78.65	gold quality
right lung	UBERON:0002167	78.00	gold quality
upper lobe of lung	UBERON:0008948	77.96	gold quality
paraflocculus	UBERON:0005351	77.52	gold quality
skeletal muscle tissue	UBERON:0001134	77.43	gold quality
frontal pole	UBERON:0002795	77.40	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	76.64	gold quality
biceps brachii	UBERON:0001507	76.52	gold quality
middle frontal gyrus	UBERON:0002702	76.44	gold quality
endometrium epithelium	UBERON:0004811	76.24	gold quality
mucosa of urinary bladder	UBERON:0001259	75.96	gold quality
muscle tissue	UBERON:0002385	75.84	gold quality
mucosa of stomach	UBERON:0001199	75.41	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	74.88	gold quality
Brodmann (1909) area 10	UBERON:0013541	74.69	gold quality
superficial temporal artery	UBERON:0001614	73.81	silver quality
epithelial cell of pancreas	CL:0000083	73.73	gold quality
thymus	UBERON:0002370	73.36	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	73.32	gold quality
inferior olivary complex	UBERON:0002127	72.94	gold quality
lung	UBERON:0002048	72.88	gold quality
nasal cavity mucosa	UBERON:0001826	72.16	gold quality
periodontal ligament	UBERON:0008266	71.98	gold quality
left ventricle myocardium	UBERON:0006566	71.81	gold quality
myocardium	UBERON:0002349	71.62	gold quality
deltoid	UBERON:0001476	71.33	gold quality
cardiac muscle of right atrium	UBERON:0003379	71.22	gold quality
CA1 field of hippocampus	UBERON:0003881	71.19	gold quality
gall bladder	UBERON:0002110	71.05	gold quality
adenohypophysis	UBERON:0002196	70.67	gold quality
cervix epithelium	UBERON:0004801	70.66	gold quality
gingival epithelium	UBERON:0001949	70.11	silver quality
smooth muscle tissue	UBERON:0001135	70.08	gold quality
trachea	UBERON:0003126	69.97	gold quality
layer of synovial tissue	UBERON:0007616	69.68	gold quality
palpebral conjunctiva	UBERON:0001812	69.42	gold quality
cerebellar vermis	UBERON:0004720	69.15	gold quality
endothelial cell	CL:0000115	69.14	gold quality
saphenous vein	UBERON:0007318	69.04	gold quality
heart right ventricle	UBERON:0002080	68.90	gold quality
male germ cell	CL:0000015	68.87	gold quality
omental fat pad	UBERON:0010414	68.58	gold quality
peritoneum	UBERON:0002358	68.57	gold quality
Brodmann (1909) area 46	UBERON:0006483	68.30	gold quality
adipose tissue of abdominal region	UBERON:0007808	67.98	gold quality
gingiva	UBERON:0001828	67.66	silver quality
caecum	UBERON:0001153	67.58	gold quality
vermiform appendix	UBERON:0001154	67.55	gold quality
tibia	UBERON:0000979	67.20	gold quality
ventral tegmental area	UBERON:0002691	67.12	silver quality
epithelium of esophagus	UBERON:0001976	67.01	gold quality
esophagus squamous epithelium	UBERON:0006920	66.93	gold quality
sperm	CL:0000019	66.80	gold quality
entorhinal cortex	UBERON:0002728	66.77	gold quality
tibial artery	UBERON:0007610	66.65	gold quality
pericardium	UBERON:0002407	66.55	silver quality
popliteal artery	UBERON:0002250	66.51	gold quality
trabecular bone tissue	UBERON:0002483	66.39	gold quality
endocervix	UBERON:0000458	66.10	gold quality
pituitary gland	UBERON:0000007	66.05	gold quality
postcentral gyrus	UBERON:0002581	66.02	gold quality
orbitofrontal cortex	UBERON:0004167	65.89	gold quality
mammalian vulva	UBERON:0000997	65.73	gold quality
trigeminal ganglion	UBERON:0001675	65.73	silver quality
parietal lobe	UBERON:0001872	65.63	gold quality
pons	UBERON:0000988	65.37	silver quality
pharyngeal mucosa	UBERON:0000355	65.35	gold quality
superior frontal gyrus	UBERON:0002661	65.02	gold quality
aorta	UBERON:0000947	64.77	gold quality
fallopian tube	UBERON:0003889	64.76	gold quality
urinary bladder	UBERON:0001255	64.69	gold quality
cardiac atrium	UBERON:0002081	64.64	gold quality
seminal vesicle	UBERON:0000998	64.62	silver quality
substantia nigra pars reticulata	UBERON:0001966	64.26	gold quality
superior surface of tongue	UBERON:0007371	64.26	gold quality
lateral globus pallidus	UBERON:0002476	64.21	gold quality
uterine cervix	UBERON:0000002	64.00	gold quality
inferior vagus X ganglion	UBERON:0005363	63.97	gold quality
right atrium auricular region	UBERON:0006631	63.95	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-130148	yes	4.87
E-HCAD-30	no	330.65
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 67 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Urinary bladder	tissue	53.4
Cervix	tissue	23.6
Appendix	tissue	13.4
Pituitary gland	tissue	10.2
Tongue	tissue	9.8
Vagina	tissue	8.4
Adipose tissue	tissue	8.0
Skeletal muscle	tissue	6.5
Esophagus	tissue	5.8
Lung	tissue	5.3
Olfactory bulb	tissue	4.3
Cerebellum	tissue	4.0
Corpus callosum	tissue	3.9
Cerebral cortex	tissue	3.7
Retrosplenial and cingulate cortex	tissue	3.7
Insular cortex	tissue	3.7
Pancreas	tissue	3.6
Amygdala	tissue	3.6
Retrosplenial cortex	tissue	3.5
Temporal cortex	tissue	3.5
Basal ganglia	tissue	3.3
Bone marrow	tissue	3.3
Ventral forebrain	tissue	3.2
Occipital cortex	tissue	3.2
Prefrontal cortex	tissue	3.1
Hippocampal formation	tissue	3.1
Entorhinal cortex	tissue	3.1
Periaqueductal gray	tissue	3.0
Motor cortex	tissue	2.9
Somatosensory cortex	tissue	2.9
Putamen	tissue	2.8
Septum	tissue	2.7
Medulla oblongata	tissue	2.4
Placenta	tissue	2.4
Spinal cord	tissue	2.4
Midbrain	tissue	2.3
Hypothalamus	tissue	2.3
Substantia nigra	tissue	2.3
Gallbladder	tissue	2.1
Endometrium 1	tissue	1.9
Thalamus	tissue	1.9
Superior colliculi	tissue	1.8
Pons	tissue	1.7
Smooth muscle	tissue	1.5
Adrenal gland	tissue	1.4
Prostate	tissue	0.9
Locus coeruleus	tissue	0.7
Hippocampus	tissue	0.7
Colon	tissue	0.6
Postcentral gyrus	tissue	0.6
Rectum	tissue	0.5
Nucleus accumbens	tissue	0.5
Choroid plexus	tissue	0.5
Testis	tissue	0.4
Tonsil	tissue	0.4
Lymph node	tissue	0.3
Retina	tissue	0.3
Liver	tissue	0.3
Thymus	tissue	0.3
Breast	tissue	0.2

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Blood vessel (11.5), White matter (3.9), Area postrema (3.0), Subiculum (2.9), Ventral hippocampus (2.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CEBPD, CEBPG, EGR1, FOS, GFI1, HIF1A, HSF1, IRF1, IRF6, JUNB, MXD1, NFKB1, NFKB, POU2F2, PRDM16, RELA, RUNX1, SPI1, STAT3, STAT5A, TCF23, WT1

miRNA regulators (miRDB)

Targeting CSF3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

25 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-4274	98.59	66.10	630
HSA-MIR-3188	98.58	65.60	878
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-339-5P	96.73	66.01	820
HSA-MIR-3976	96.67	67.79	1187
HSA-MIR-4433B-5P	95.91	66.56	727

Functional genomics

gnomAD constraint: pLI 4.91e-06, LOEUF 1.24, missense Z 0.934 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000394149 — one region, missense o/e 0.82.

Literature-anchored findings (GeneRIF, showing 40)

• Effect of in vivo infusion of granulocyte colony-stimulating factor on immune function. (PMID:11795665)
• Induces autocrine production of epithelial cell-derived neutrophil attractant-78 in neutrophils. (PMID:11861308)
• effect of recombinant human GCSF on dendritic cell populations in mouse spleen (PMID:11877288)
• G-CSF can induce in vitro and in vivo differentiation of M2 AML t(8;21) cells. (PMID:11920209)
• Stabilizing the native state of recombinant GCSF under physiological conditions using thermodynamic stabilizers, especially high-affinity ligands binding to the native state, inhibits aggregation occurring under structurally nonperturbing conditions. (PMID:12009905)
• G-CSF increases neutrophil function in patients with severe sepsis and septic shock (PMID:12027409)
• expression in airway epithelial cells by interleukin-17 (PMID:12034575)
• Review. The synergy of granulocyte colony-stimulating factor with stem cell factor results in important biologic responses such as the down-regulation of p27kip1 and the independent phosphorylation of STAT3 on tyrosine and serine residues. (PMID:12152985)
• inhibits spontaneous cytochrome c release and mitochondria-dependent apoptosis of myelodysplastic syndrome hematopoietic progenitors. (PMID:12393561)
• Enhanced PMN survival was attributed to effects of epithelial G-CSF and granulocyte-macrophage colony-stimulating factor expression, which inhibit PMN apoptosis.Both CF and normal cells responded to bacteria with increased cytokine production (PMID:12397015)
• results demonstrate that G-CSF is produced in the human follicle shortly before the ovulatory phase and may play an important role in the mechanism of ovulation (PMID:12456601)
• granulocyte colony-stimulating factor decreased platelet-activating factor acetylhydrolase secretion by decidual macrophages (PMID:12548211)
• G-CSF-mediated antiapoptosis is mediated through protein synthesis-dependent mechanisms and involves the Janus kinase-STAT pathway. (PMID:12568301)
• In the presence of ATRA, G-CSF enhanced superoxide release stimulated by the chemotactic peptide, enhanced survival during differentiation, regulated chemotactic peptide receptors CD33 and CD10 but not of CD11b and CD11c. (PMID:12627849)
• Endogenous G-CSF levels in chemotherapy-induced neutropenia are significantly higher than non-chemotherapy related neutropenia and controls. (PMID:12636092)
• The induction of GATA-3, the master transcription factor for a Th2 immune response, can be demonstrated in T cells upon G-CSF treatment in vivo accompanied by an increase of spontaneous IL-4 secretion. G-CSF is a strong immune regulator of T cells. (PMID:12676791)
• tertiary structural perturbations in G-CSF suggest the presence of an intermediate state and possible relation to ligand binding and endocytic trafficking (PMID:12717025)
• Conformation change of an epitope of the granulocyte-colony stimulating factor after binding to receptors. (PMID:12946100)
• TNF, GM-CSF, and G-CSF induce actin depolymerization and morphological changes through activation of ERK and/or p38 MAPK, and cytokine-induced actin reorganization may affect inhibitory effect of these cytokines on neutrophil chemotaxis. (PMID:12954601)
• G-CSF 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)
• significant associations of endogenous G-CSF levels with inflammatory mediators early in the development of severe lung injury suggest an endogenous anti-inflammatory role of G-CSF in vivo (PMID:14769149)
• The significantly higher level of G-CSF in follicular fluid (FF) than in serum and the expression of G-CSF and its receptor in FF by granulosa cells suggest an important role for this growth factor in ovarian function. (PMID:15019810)
• G-CSF appears to be a suppressor of antitumor immunity (PMID:15214947)
• G-CSF is associated with the expression of proliferation vascularization in memingioma. (PMID:15218949)
• The G-CFS may provide clinically useful information, particularly regarding prognosis and response to treatment. (PMID:15576295)
• G-CSF, a promoter of tolerogenic dendritic cells, may be evaluated for the treatment of human type 1 diabetes (PMID:15616013)
• Serum G-CSF levels in 70.4% (38 of 54 cases) of the chronic aplastic anemiapatients were increased (272.76 +/- 58.39ng/L) (PMID:15622763)
• one of the major roles of Stat3 in the G-CSF signaling pathway is to augment the function of C/EBPalpha, which is essential for myeloid differentiation (PMID:15664994)
• osteoblast activity, as measured by histomorphometry and osteocalcin expression, is strongly down-regulated during G-CSF treatment (PMID:16037394)
• Correlation between endogenous G-CSF and CD34(+) cell levels supports the administration of G-CSF as an option for regeneration of myocardial tissue after acute myocardial infarct. (PMID:16051386)
• Protein kinase C plays a role in activation of granulocyte-colony stimulating factor in lung cancer. (PMID:16211258)
• 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)
• PAR2-driven upregulation of VCAM-1 cell surface expression and the release of IL-8 and G-CSF from bronchial fibroblasts may be important in promoting neutrophilic airways inflammation. (PMID:16498082)
• monocytes mobilized into the blood by G-CSF or AMD3100 stimulate angiogenesis at sites of ischemia through a paracrine mechanism (PMID:16735597)
• It appears that G-CSF mobilizes more CD34(+) cells, mature Dendritic cellswithin the same donor than does GM-CSF. (PMID:16822885)
• A progression-promoting effect of G-CSF and GM-CSF in human head and neck squamous cell carcinomas. (PMID:16912178)
• G-CSF has a role in the induction of E-selectin ligands on myeloid cells, thus providing mechanistic insight into the pathobiology of G-CSF complications (PMID:16980970)
• The observed up-regulation of G-CSF points towards a role in the pathophysiology of human ischemic stroke. (PMID:17047971)
• A comparison of the relative rates of oxidation of methionine residues in short peptides with those of corresponding methionine residues in recombinant human G-CSF yields an understanding of how protein tertiary structure affects oxidation reactions. (PMID:17176065)
• G-CSF and GM-CSF might accelerate tumor progression by directly regulating COX-2 expression, independently of an autocrine mechanism. (PMID:17342342)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	csf3b	ENSDARG00000098752
danio_rerio	csf3a	ENSDARG00000102211
mus_musculus	Csf3	ENSMUSG00000038067
rattus_norvegicus	Csf3	ENSRNOG00000008525

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1339751) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased neutrophil cell number	2
decreased leukocyte cell number	1
decreased monocyte cell number	1
impaired myelopoiesis	1
increased susceptibility to bacterial infection	1
abnormal neutrophil physiology	1
increased hematocrit	1
increased circulating alanine transaminase level	1
decreased eosinophil cell number	1
increased lymphocyte cell number	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	P35833	95.4%	Diamond
Ovis aries	Q28746	95.4%	Diamond
Felis catus	O02708	91.3%	Diamond
Canis lupus familiaris	P35834	91.3%	Diamond
Sus scrofa	O02837	87.9%	Diamond
Gallus gallus	P13854	41.2%	Diamond

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
MIR6884	ncRNA	102466757
THRA	protein-coding	7067
NR1D1	protein-coding	9572
MED24	protein-coding	9862
SNORD124	snoRNA	101340251
PSMD3-AS1	ncRNA	139432819
LRRC3C	protein-coding	100505591
GSDMA	protein-coding	284110
PSMD3	protein-coding	5709

Protein

Protein identifiers

Granulocyte colony-stimulating factor — P09919 (reviewed: P09919)

Alternative names: Pluripoietin

All UniProt accessions (6): P09919, J3KTH8, J3QRD4, J3QRX2, Q6FH65, Q8N4W3

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Monomer.

Subcellular location. Secreted.

Post-translational modifications. O-glycan consists of Gal-GalNAc disaccharide which can be modified with up to two sialic acid residues (done in recombinantly expressed G-CSF from CHO cells).

Similarity. Belongs to the IL-6 superfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P09919-1	Long	yes
P09919-2	Short
P09919-3	3

RefSeq proteins (4): NP_000750, NP_001171618, NP_757373, NP_757374 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily
IPR030473	IL6/GCSF/MGF_CS	Conserved_site
IPR030474	IL-6/GCSF/MGF	Family
IPR040117	GCSF/MGF	Family

Pfam: PF16647

UniProt features (23 total): helix 9, turn 3, strand 2, disulfide bond 2, splice variant 2, sequence variant 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

7 structures by resolution:

PDB	Title	Method	Resolution (Å)
5GW9	Crystal structure of C163, a backbone circularized G-CSF	X-RAY DIFFRACTION	1.65
5ZO6	Crystal structure of C166, a backbone circularized G-CSF	X-RAY DIFFRACTION	1.7
1RHG	THE STRUCTURE OF GRANULOCYTE-COLONY-STIMULATING FACTOR AND ITS RELATIONSHIP TO THOSE OF …	X-RAY DIFFRACTION	2.2
1CD9	2:2 COMPLEX OF G-CSF WITH ITS RECEPTOR	X-RAY DIFFRACTION	2.8
2D9Q	Crystal Structure of the Human GCSF-Receptor Signaling Complex	X-RAY DIFFRACTION	2.8
1PGR	2:2 COMPLEX OF G-CSF WITH ITS RECEPTOR	X-RAY DIFFRACTION	3.5
1GNC	STRUCTURE AND DYNAMICS OF THE HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR DETERMINED BY …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09919-F1	84.67	0.56

Human Protein Atlas

Protein class: Predicted secreted proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers

Protein evidence: Evidence at protein level

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 (2)

Type	Positions
Disulfide bond	69–75, 97–107

Glycosylation sites (1)

Type	Positions
O-linked (galnac…) threonine	166

Function

Pathways and Gene Ontology

Reactome pathways

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

8 pathways:

ID	Pathway	Evidence
R-HSA-9968734	Differentiation of Circulating Monocytes	curated
R-HSA-6783783	Interleukin-10 signaling	curated
R-HSA-449836	Other interleukin signaling	curated
R-HSA-1280215	Cytokine Signaling in Immune system	—
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	—

MSigDB gene sets: 298 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, MODULE_92, AP1_01, GOBP_RESPONSE_TO_ETHANOL, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, MODULE_64, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION

GO Biological Process (15): immune response (GO:0006955), positive regulation of cell population proliferation (GO:0008284), cytokine-mediated signaling pathway (GO:0019221), macrophage differentiation (GO:0030225), positive regulation of actin filament polymerization (GO:0030838), granulocyte differentiation (GO:0030851), granulocyte colony-stimulating factor signaling pathway (GO:0038158), response to ethanol (GO:0045471), positive regulation of myeloid cell differentiation (GO:0045639), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), cellular response to lipopolysaccharide (GO:0071222), cellular response to cytokine stimulus (GO:0071345), regulation of actin filament organization (GO:0110053), signal transduction (GO:0007165)

GO Molecular Function (6): cytokine activity (GO:0005125), granulocyte colony-stimulating factor receptor binding (GO:0005130), growth factor activity (GO:0008083), enzyme binding (GO:0019899), signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), lysosomal lumen (GO:0043202), endocytic vesicle lumen (GO:0071682)

Reactome top-level categories

5 top-level categories:

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

GO top-level categories

48 GO namespaces:

Category	Terms
myeloid leukocyte differentiation	2
receptor ligand activity	2
protein binding	2
immune system process	1
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
mononuclear cell differentiation	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
cytokine-mediated signaling pathway	1
response to alcohol	1
myeloid cell differentiation	1
positive regulation of cell differentiation	1
regulation of myeloid cell differentiation	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
response to cytokine	1
actin filament organization	1
regulation of actin cytoskeleton organization	1
regulation of supramolecular fiber organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytokine receptor binding	1
growth factor receptor binding	1
binding	1
cellular anatomical structure	1
lysosome	1
vacuolar lumen	1
endocytic vesicle	1
intracellular organelle lumen	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 25 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to cytokine stimulus	BP	direct assay
granulocyte colony-stimulating factor signaling pathway	BP	direct assay
positive regulation of actin filament polymerization	BP	direct assay
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	direct assay
regulation of actin filament organization	BP	direct assay
cytokine activity	MF	direct assay
enzyme binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 3,056 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSF3	CSF2	P04141	942
CSF3	CD34	P28906	942
CSF3	IL6	P05231	936
CSF3	IL3	P08700	924
CSF3	CSF3R	Q99062	920
CSF3	IL1B	P01584	918
CSF3	IL17A	Q16552	912
CSF3	IFNG	P01579	904
CSF3	TNF	P01375	900
CSF3	CXCL8	P10145	898
CSF3	CCL2	P13500	883
CSF3	CCL3	P10147	881
CSF3	IL10	P22301	873
CSF3	IL7	P13232	869
CSF3	CXCL1	P09341	865

IntAct

Human interaction partners of CSF3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
PTPRG	association	0.350	1

BioGRID (12 interactions; top human partners by supporting records): AHNAK2 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), MYO18A (Affinity Capture-MS), NRN1 (Affinity Capture-MS), PARVG (Two-hybrid), PTPRG (Affinity Capture-MS), PTPRJ (Affinity Capture-MS), S100A6 (Reconstituted Complex), S100P (Reconstituted Complex), SCARB1 (Affinity Capture-MS), TBX3 (Two-hybrid), TRRAP (Affinity Capture-MS)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
CSF3	up-regulates	CSF3R	binding
CSF3	up-regulates	CSF2RA	binding
CSF3	up-regulates	Angiogenesis

Protein complexes (CORUM) (1)

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

1 complexes by size:

Complex	Subunits	Members
★ CSF3-CSF3R complex	2	CSF3, CSF3R

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
CSF3R	ligand	Signaling by Colony-Stimulating factor

Disease & clinical

Genetic variants

Variant evidence for CSF3: 29 ClinVar records (0 pathogenic / likely pathogenic); 37 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	0
Benign	6

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 204):

Position(s)	Effect	Δscore	Sites
17:40015846–40015847	donor_loss	1.0000	5
17:40016231–40016232	acceptor_loss	1.0000	5
17:40016341–40016342	donor_loss	1.0000	4
17:40016353	donor_gain	1.0000
17:40016483–40016484	acceptor_loss	1.0000	6
17:40016632–40016633	donor_loss	1.0000	5
17:40015515–40015516	donor_loss	0.9900	5
17:40016226	acceptor_gain	0.9900
17:40016341	donor_loss	0.9900
17:40016793	acceptor_loss	0.9900	2

AlphaMissense

210 missense substitutions predicted likely pathogenic (of 1,301 scored), across 72 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
F177	8	0.886	0.977
D142	8	0.767	0.869
C75	7	0.892	0.939
F43	7	0.857	0.960
C107	7	0.807	0.903
C97	7	0.795	0.871
E79	7	0.762	0.842
C69	6	0.807	0.870
F193	5	0.908	0.926
F173	5	0.809	0.851
K53	5	0.745	0.855
F146	5	0.727	0.908
D145	5	0.671	0.742
G183	4	0.828	0.854
M154	4	0.768	0.793
C47	4	0.742	0.875
G114	4	0.732	0.848
E49	4	0.702	0.759
L115	3	0.895	0.907
I89	3	0.862	0.949

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma)

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	unfavorable	6.96e-05

Disease associations

OMIM: gene MIM:138970 | disease phenotypes:

GWAS associations

showing 30 of 37 associations:

Study	Trait	p-value
GCST004626_8	Myeloid white cell count	6e-191
GCST90002407_625	White blood cell count	8e-133
GCST008916_121	Asthma	2e-62
GCST005973_8	White blood cell count	9e-62
GCST001137_10	White blood cell count	9e-35
GCST001137_8	White blood cell count	2e-31
GCST90002398_312	Neutrophil count	1e-23
GCST002557_5	Neutrophil count	3e-23
GCST90002399_324	Neutrophil percentage of white cells	8e-21
GCST90002398_311	Neutrophil count	1e-18
GCST90002407_627	White blood cell count	1e-18
GCST004613_34	Sum neutrophil eosinophil counts	1e-17
GCST90002389_100	Lymphocyte percentage of white cells	1e-17
GCST004614_8	Granulocyte count	2e-17
GCST004620_20	Sum basophil neutrophil counts	6e-17
GCST004629_151	Neutrophil count	6e-17
GCST001134_16	White blood cell types	4e-16
GCST004626_9	Myeloid white cell count	4e-16
GCST000589_2	White blood cell count	3e-14
GCST004633_5	Neutrophil percentage of white cells	1e-13
GCST006959_49	Rheumatoid arthritis	3e-13
GCST008916_86	Asthma	6e-13
GCST004608_199	Granulocyte percentage of myeloid white cells	8e-13
GCST002318_48	Rheumatoid arthritis	2e-12
GCST008916_5	Asthma	2e-12
GCST004632_19	Lymphocyte percentage of white cells	6e-12
GCST004610_2	White blood cell count	1e-11
GCST004128_2	White blood cell count (neutrophil)	5e-11
GCST004126_2	White blood cell count	9e-11
GCST002557_6	Neutrophil count	1e-10

EFO canonical traits (from GWAS)

9 canonical traits:

EFO ID	Trait name
EFO:0004833	neutrophil count
EFO:0007997	granulocyte percentage of myeloid white cells
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:0004534	creatine kinase measurement
EFO:0006312	mitochondrial DNA measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases reaction, affects expression, decreases secretion, affects cotreatment, decreases expression (+5 more)	8
Lipopolysaccharides	increases expression, affects cotreatment, decreases reaction, increases secretion	5
Estradiol	affects expression, affects cotreatment, increases expression	4
Tretinoin	decreases reaction, decreases uptake, increases expression, increases reaction, decreases expression	4
nickel chloride	affects cotreatment, increases secretion, increases expression, increases reaction	3
Vehicle Emissions	increases abundance, increases expression, affects expression, affects cotreatment, decreases abundance (+1 more)	3
Cannabidiol	decreases reaction, increases expression	3
Dust	decreases expression, increases expression, increases secretion	3
Silicon Dioxide	increases secretion, increases expression	3
Tobacco Smoke Pollution	affects expression, increases expression, increases secretion	3
Asbestos, Crocidolite	increases secretion, decreases reaction, increases expression	3
titanium dioxide	affects binding, increases secretion, affects expression	2
sodium arsenite	increases expression	2
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	2
Resveratrol	decreases reaction, increases expression	2
Arsenic Trioxide	decreases uptake, increases expression, increases response to substance, increases reaction, increases uptake (+1 more)	2
Air Pollutants	increases abundance, increases expression	2
Benzo(a)pyrene	increases expression, affects methylation	2
Endosulfan	decreases expression, increases expression	2
Tetradecanoylphorbol Acetate	affects cotreatment, increases expression, affects expression	2
Asbestos, Serpentine	increases expression, increases secretion	2
Silver Compounds	increases secretion, affects cotreatment, increases expression, affects binding	2
Cadmium Chloride	increases expression	2
Interleukin 1 Receptor Antagonist Protein	decreases reaction, increases secretion, decreases secretion	2
Glupearl 19S	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
TL8-506	increases expression, affects cotreatment	1
7-ketocholesterol	increases expression, decreases reaction	1
2-anisidine	affects expression	1
propionaldehyde	increases expression	1

Cellosaurus cell lines

4 cell lines: 2 finite cell line, 1 spontaneously immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_6G75	IA1-7	Spontaneously immortalized cell line	Female
CVCL_B0ZB	Abcam K-562 CSF3 KO	Cancer cell line	Female
CVCL_B6BP	MSC G-CSF#1	Finite cell line	Male
CVCL_B6BQ	MSC G-CSF#2	Finite cell line	Male

Clinical trials (associated diseases)

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