CSF2

Summary

CSF2 (colony stimulating factor 2, HGNC:2434) is a protein-coding gene on chromosome 5q31.1, encoding Granulocyte-macrophage colony-stimulating factor (P04141). Cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes.

The protein encoded by this gene is a cytokine that controls the production, differentiation, and function of granulocytes and macrophages. The active form of the protein is found extracellularly as a homodimer. This gene has been localized to a cluster of related genes at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. Other genes in the cluster include those encoding interleukins 4, 5, and 13. This gene plays a role in promoting tissue inflammation. Elevated levels of cytokines, including the one produced by this gene, have been detected in SARS-CoV-2 infected patients that develop acute respiratory distress syndrome. Mice deficient in this gene or its receptor develop pulmonary alveolar proteinosis.

Source: NCBI Gene 1437 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 20 total
• Druggable target: yes
• MANE Select transcript: NM_000758

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2434
Approved symbol	CSF2
Name	colony stimulating factor 2
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	GM-CSF, GMCSF
Ensembl gene	ENSG00000164400
Ensembl biotype	protein_coding
OMIM	138960
Entrez	1437

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000296871

RefSeq mRNA: 1 — MANE Select: NM_000758 NM_000758

CCDS: CCDS4150

Canonical transcript exons

ENST00000296871 — 4 exons

Exon	Start	End
ENSE00001084066	132074081	132074122
ENSE00001084068	132074810	132074935
ENSE00001124346	132075745	132076170
ENSE00001124351	132073789	132073982

Expression profiles

Bgee: expression breadth broad, 64 present calls, max score 72.09.

FANTOM5 (CAGE): breadth broad, TPM avg 18.9773 / max 3544.2514, expressed in 483 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58423	18.9662	483
58424	0.0111	4

Top tissues by expression

261 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	72.09	gold quality
Brodmann (1909) area 10	UBERON:0013541	69.33	gold quality
endometrium epithelium	UBERON:0004811	68.66	silver quality
cartilage tissue	UBERON:0002418	67.74	gold quality
olfactory bulb	UBERON:0002264	67.59	gold quality
middle frontal gyrus	UBERON:0002702	65.29	gold quality
frontal pole	UBERON:0002795	62.94	gold quality
paraflocculus	UBERON:0005351	62.64	gold quality
tongue squamous epithelium	UBERON:0006919	58.81	gold quality
gluteal muscle	UBERON:0002000	58.80	gold quality
triceps brachii	UBERON:0001509	58.63	gold quality
upper lobe of left lung	UBERON:0008952	57.14	gold quality
upper lobe of lung	UBERON:0008948	57.04	gold quality
vastus lateralis	UBERON:0001379	56.74	gold quality
quadriceps femoris	UBERON:0001377	56.28	gold quality
metanephric glomerulus	UBERON:0004736	54.79	gold quality
lower lobe of lung	UBERON:0008949	53.99	silver quality
lung	UBERON:0002048	53.68	gold quality
thymus	UBERON:0002370	52.89	gold quality
gall bladder	UBERON:0002110	52.87	gold quality
stromal cell of endometrium	CL:0002255	52.66	gold quality
epithelial cell of pancreas	CL:0000083	51.63	gold quality
left ventricle myocardium	UBERON:0006566	51.25	gold quality
Brodmann (1909) area 46	UBERON:0006483	51.15	gold quality
deltoid	UBERON:0001476	50.72	gold quality
vermiform appendix	UBERON:0001154	49.94	gold quality
CA1 field of hippocampus	UBERON:0003881	49.85	gold quality
kidney epithelium	UBERON:0004819	49.84	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-10	yes	367.15
E-ANND-3	yes	5.20
E-HCAD-29	no	35043.55

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
HBG2	Activation
VTCN1	Repression

Upstream regulators (CollecTRI, top): AHR, AP1, CEBPA, CEBPB, CEBPD, CREBBP, CREM, CTCF, EGR3, ELF1, ELF4, ETS1, ETS2, FOS, GATA2, HMGA1, HSF1, IRF6, JUN, JUNB, KAT5, KAT7, MAF, MYB, MYC, NFAM1, NFATC1, NFATC2, NFKB1, NFKB2, NFKB, NR3C1, NR4A3, PBRM1, PRDM1, REL, RELA, RELB, RUNX1, RUNX2

miRNA regulators (miRDB)

19 targeting CSF2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-5585-3P	98.25	67.41	941
HSA-MIR-1470	98.11	63.53	399
HSA-MIR-6514-3P	97.52	66.50	808
HSA-MIR-663B	97.40	62.91	664
HSA-MIR-4281	92.91	63.60	271
HSA-MIR-4707-5P	90.95	65.69	110

Literature-anchored findings (GeneRIF, showing 40)

• inhibition of signaling by antisense oligodeoxynucleotides targeting the common beta chain of receptors (PMID:11763346)
• GM-CSF-driven apoptosis, but not TNF-driven apoptosis was reversibly associated with bcl-2-expression (bcl-2-dependent mechanism)in acute lymphoblastic leukaemia and non-Hodgkin’s lymphoma in children. (PMID:11855781)
• Protection of peritoneal macrophages by granulocyte/macrophage colony-stimulating factor (GM-CSF) against dexamethasone suppression of killing of Aspergillus, and the effect of human GM-CSF. (PMID:11880043)
• Adenomyotic glandular epithelium had greater expression of the GM-CSF ligand compared with autologous endometrium from premenopausal women (PMID:11963838)
• Activated eosinophils release small amounts of anti-apoptotic GM-CSF by stabilizing its coding mRNA. Review. (PMID:12022701)
• secretion from acute myelogenous leukemia blasts was up-regulated by leptin (PMID:12031914)
• B-CLL patients with progressive disease had a significantly increased number of T cells spontaneously producing IL-2, IL-4 and GM-CSF, suggesting a role for T cells in the pathogenesis of B-CLL. (PMID:12144536)
• GM-CSF induced human myelopoiesis is regulated by transforming growth factor-beta isoforms (PMID:12171249)
• GMCSF is induced in bronchial epithelial cells by the MAP kinase signaling system in response to air pollutants (PMID:12356579)
• GM-CSF plays a critical role in lung homeostasis by regulating levels of MCSF, MCP-1 and IL-8. (PMID:12356582)
• 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)
• data indicate that granulocyte-macrophage colony stimulating factor regulates cell viability in human embryos (PMID:12444058)
• GM-CSF inhibits prolonged glucocorticoid-induced activation of eosinophil c-Jun NH2-terminal kinase and preserves the expression of eosinophil antiapoptotic protein X-linked inhibitor of apoptosis. (PMID:12496443)
• signals for increased glucose transport via phosphatidylinositol 3-kinase- and hydrogen peroxide-dependent mechanisms (PMID:12538575)
• Granulocyte-macrophage colony-stimulating factor inhibited the platelet-activating factor acetylhydrolase secretion by decidual macrophages (PMID:12548211)
• GM-CSF-mediated antiapoptosis is mediated through protein synthesis-independent mechanisms and involves the Janus kinase-STAT pathway. (PMID:12568301)
• IL-6 and GM-CSF may be involved in the autoimmune mechanism of non-segmental vitiligo. (PMID:12615367)
• functional studies demonstrated GMCSF-dependent activation of IkappaB kinase activity in endothelial cells, degradation of IkappaB, and activation of NF-kappaB (PMID:12637324)
• GM-CSF is up-regulated by ETS2, a target of protein kinase C (PMID:12646185)
• GM-CSF exerts a dual effect: it stimulates cell division but contemporaneously up-regulates Jak-Stat-dependent proapoptotic proteins. (PMID:12663443)
• ICAM-3 is highly expressed on the surface of human eosinophils and has a role in the downregulation of GM-CSF production. (PMID:12743567)
• GMCSF is induced in lung fibroblasts by IL-beta, TNF-alpha, and macrophage contact. (PMID:12744771)
• Incubation of eosinophils with GMCSF leads to reduced expression of IL-5R alpha that is sustained for up to 5 days; in contrast, eosinophil IL-3R alpha expression is increased by GMCSF, whereas eosinophil GMCSF receptor alpha is down-regulated by GMCSF. (PMID:12759409)
• induces cell cycle progression via internal ribosome entry site-mediated translation of c-myc though the PI3K pathway in human factor-dependent leukemic cells (PMID:12855588)
• IL-10 is one of the cytokines up-regulating the GM-CSF expression in non-small cell lung cancer. (PMID:12926133)
• GM-CSF induces expression of surface and total class II major histocompatibility antigens crucial for antigen presentation in human monocytes. (PMID:12928384)
• immunolocalization studies confirmed the presence of granulocyte-macrophage colony stimulating factor(GM-CSF) in the germ cell line in bovine and human testes and addition of GM-CSF enhances several parameters of sperm motility (PMID:12935848)
• 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)
• The GM-CSF genotype is an important genetic marker predicting an individual’s predisposition to atopic dermatitis. (PMID:13679820)
• GMCSF was highly expressed in dendritic cells with a bicistronic retroviral vector. (PMID:14503968)
• neutralizing anti-GM-CSF autoantibodies develop specifically in patients with idiopathic pulmonary alveolar proteinosis (PMID:14512323)
• GMCSF displays additive effects with TNF-alpha on the common p47phox phosphorylated site and on fMLP-induced NADPH oxidase activation in human neutrophils, which is evidence for a common priming pathway. (PMID:14530365)
• Hematopoietin receptor superfamily. Comprised of cytokine-specific alpha chain and common beta chain for signaling. Contributes to differentiation and function of leukocytes. Protective immunity and pathophysiology of immunologic diseases. Review. (PMID:14564341)
• results suggest that in pulmonary alveolar proteinosis, GM-CSF synthesis is deficient and associated with negative regulation by IL-10 (PMID:14567558)
• long-term exposure of primitive human hematopoietic cells to elevated levels of human IL-3, GM-CSF and SF in vivo may deleteriously affect the stem cell compartment, while expanding terminal myelopoiesis. (PMID:14628073)
• Results identify several transcriptional targets of interleukin-5 and granulocyte macrophage-colony-stimulating factor in human eosinophils and suggest that a number of protein products are critical to the responsiveness of airway eosinophils. (PMID:14630612)
• GM-CSF elicits chemotaxis and chemokinesis of neutrophils by a process correlated with activity of the ribosomal p70 S6 kinase signaling pathway. (PMID:14662891)
• the GM-CSF ARE controls translation and mRNA decay by interfering with poly(A)-binding protein-mediated mRNA circularization. (PMID:14726527)
• Local injection of recombinant human GM-CSF may improve the healing of ischemic and even normal colon anastomoses. (PMID:14730225)
• Data characterize recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) for glycosylation sites and the definition of the glycosidic moiety, including the degree of site occupancy. (PMID:15009203)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Csf2	ENSMUSG00000018916
rattus_norvegicus	Csf2	ENSRNOG00000026805

Protein

Protein identifiers

Granulocyte-macrophage colony-stimulating factor — P04141 (reviewed: P04141)

Alternative names: Colony-stimulating factor, Molgramostin, Sargramostim

All UniProt accessions (1): P04141

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes.

Subunit / interactions. Monomer. The signaling GM-CSF receptor complex is a dodecamer of two head-to-head hexamers of two alpha, two beta, and two ligand subunits.

Subcellular location. Secreted.

Polymorphism. Variant Ile-117 may be a risk factor for atopic asthma.

Similarity. Belongs to the GM-CSF family.

RefSeq proteins (1): NP_000749* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000773	GM_colony-stim-fac	Family
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily

Pfam: PF01109

UniProt features (25 total): glycosylation site 6, helix 5, turn 3, strand 3, sequence variant 2, sequence conflict 2, disulfide bond 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
6BFS	X-RAY DIFFRACTION	2
5D70	X-RAY DIFFRACTION	2.06
5D71	X-RAY DIFFRACTION	2.25
2GMF	X-RAY DIFFRACTION	2.4
5D72	X-RAY DIFFRACTION	2.6
6BFQ	X-RAY DIFFRACTION	2.6
4RS1	X-RAY DIFFRACTION	2.68
1CSG	X-RAY DIFFRACTION	2.7
5C7X	X-RAY DIFFRACTION	2.95
4NKQ	X-RAY DIFFRACTION	3.3
9JKR	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04141-F1	88.30	0.77

Antibody-complex structures (SAbDab): 6 — 5C7X, 5D70, 5D71, 5D72, 6BFQ, 6BFS

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): 71–113, 105–138

Glycosylation sites (6): 22, 24, 26, 27, 44, 54

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6783783	Interleukin-10 signaling
R-HSA-8939246	RUNX1 regulates transcription of genes involved in differentiation of myeloid cells
R-HSA-912526	Interleukin receptor SHC signaling

MSigDB gene sets: 395 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CIRCADIAN_RHYTHM, GGGACCA_MIR133A_MIR133B, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_DENDRITIC_CELL_DIFFERENTIATION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_PODOSOME_ASSEMBLY, SWEET_KRAS_ONCOGENIC_SIGNATURE, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (33): histamine secretion (GO:0001821), embryonic placenta development (GO:0001892), immune response (GO:0006955), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), cell population proliferation (GO:0008283), positive regulation of cell population proliferation (GO:0008284), positive regulation of gene expression (GO:0010628), positive regulation of macrophage derived foam cell differentiation (GO:0010744), myeloid cell differentiation (GO:0030099), neutrophil differentiation (GO:0030223), monocyte differentiation (GO:0030224), macrophage differentiation (GO:0030225), positive regulation of cell migration (GO:0030335), positive regulation of interleukin-23 production (GO:0032747), response to silicon dioxide (GO:0034021), response to fluid shear stress (GO:0034405), granulocyte-macrophage colony-stimulating factor signaling pathway (GO:0038157), epithelial fluid transport (GO:0042045), myeloid dendritic cell differentiation (GO:0043011), regulation of circadian sleep/wake cycle, sleep (GO:0045187), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of leukocyte proliferation (GO:0070665), cellular response to lipopolysaccharide (GO:0071222), positive regulation of podosome assembly (GO:0071803), cellular response to granulocyte macrophage colony-stimulating factor stimulus (GO:0097011), dendritic cell differentiation (GO:0097028), cell surface receptor signaling pathway via STAT (GO:0097696), negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001240), signal transduction (GO:0007165), regulation of signal transduction (GO:0009966), regulation of gene expression (GO:0010468), regulation of cell population proliferation (GO:0042127), regulation of developmental process (GO:0050793)

GO Molecular Function (4): cytokine activity (GO:0005125), granulocyte macrophage colony-stimulating factor receptor binding (GO:0005129), growth factor activity (GO:0008083), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), granulocyte macrophage colony-stimulating factor receptor complex (GO:0030526)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by Interleukins	2
MAPK1/MAPK3 signaling	1
Transcriptional regulation by RUNX1	1
Interleukin-2 family signaling	1
Interleukin-3, Interleukin-5 and GM-CSF signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
myeloid leukocyte differentiation	3
mononuclear cell differentiation	2
receptor ligand activity	2
secretion	1
histamine transport	1
in utero embryonic development	1
placenta development	1
embryonic organ development	1
immune system process	1
response to stimulus	1
cell surface receptor signaling pathway via STAT	1
cellular process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
positive regulation of cell differentiation	1
hemopoiesis	1
cell differentiation	1
granulocyte differentiation	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
positive regulation of cytokine production	1
interleukin-23 production	1
regulation of interleukin-23 production	1
response to oxygen-containing compound	1
response to stress	1
cytokine-mediated signaling pathway	1
fluid transport	1
transepithelial transport	1
myeloid dendritic cell activation	1
dendritic cell differentiation	1
regulation of circadian sleep/wake cycle	1
circadian sleep/wake cycle, sleep	1
cytokine receptor binding	1

Protein interactions and networks

STRING

3852 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSF2	CSF3	P09919	998
CSF2	IL3	P08700	998
CSF2	CSF2RA	P15509	998
CSF2	IL2	P01585	996
CSF2	IL1B	P01584	996
CSF2	CCL11	P50877	996
CSF2	CSF2RB	P32927	995
CSF2	IL1A	P01583	992
CSF2	IL5	P05113	988
CSF2	IFNG	P01579	982
CSF2	CSF1R	P07333	974
CSF2	FGF2	P09038	964
CSF2	CSF1	P09603	963
CSF2	IL4	P05112	959
CSF2	FLT3LG	P49771	957

IntAct

31 interactions, top by confidence:

A	B	Type	Score
MEOX2	CSF2	psi-mi:“MI:0915”(physical association)	0.720
CSF2	MEOX2	psi-mi:“MI:0915”(physical association)	0.720
CSF2	A2M	psi-mi:“MI:0915”(physical association)	0.560
CSF2	DNM2	psi-mi:“MI:0915”(physical association)	0.560
CSF2	HTT	psi-mi:“MI:0915”(physical association)	0.560
CSF2	CSF2RB	psi-mi:“MI:0915”(physical association)	0.520
CSF2	CSF2RA	psi-mi:“MI:0915”(physical association)	0.400
CSF2	B4GALT5	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (16): MEOX2 (Two-hybrid), MEOX2 (Two-hybrid), CSF2RA (Reconstituted Complex), SDC2 (Reconstituted Complex), B4GALT5 (Affinity Capture-MS), S100P (Reconstituted Complex), S100A6 (Reconstituted Complex), CSF2 (Affinity Capture-RNA), CSF2 (Co-crystal Structure), PABPC1 (Affinity Capture-RNA), HNRNPA0 (Affinity Capture-RNA), HNRNPA2B1 (Affinity Capture-RNA), HNRNPA1 (Affinity Capture-RNA), ILF2 (Affinity Capture-RNA), SYNCRIP (Affinity Capture-RNA)

ESM2 similar proteins: A0A140LIA7, B6CKP4, O02720, O02750, O08987, O42164, P04141, P04401, P05113, P08700, P20109, P35225, P41159, P41160, P42203, P46652, P46685, P47966, P48093, P50595, P50596, P51492, P51748, P61126, Q0MUT8, Q1XG29, Q257X2, Q28504, Q28603, Q28809, Q29406, Q4KM46, Q588G0, Q5I6E4, Q5J732, Q62575, Q6EBC2, Q706D0, Q706D1, Q864V6

Diamond homologs: O62757, P01587, P04141, P11052, P28773, P48749, P48750, P51748, Q0MUT8, Q29118, Q60481

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
CSF2	up-regulates	CSF3R	binding
CSF2	“up-regulates activity”	CSF2RA	binding
CSF2	“up-regulates quantity by expression”	HBG2	“transcriptional regulation”
CSF2	up-regulates	CSF2RA/CSF2RB	binding
CSF2	up-regulates	CSF2RA	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

230 predictions. Top by Δscore:

Variant	Effect	Δscore
5:132073979:GATG:G	donor_gain	1.0000
5:132073980:ATG:A	donor_gain	1.0000
5:132073982:GGTA:G	donor_loss	1.0000
5:132073983:G:GG	donor_gain	1.0000
5:132074077:ACAG:A	acceptor_loss	1.0000
5:132074078:CA:C	acceptor_loss	1.0000
5:132074079:A:AG	acceptor_gain	1.0000
5:132074079:A:AT	acceptor_loss	1.0000
5:132074080:G:GC	acceptor_gain	1.0000
5:132074080:G:GT	acceptor_loss	1.0000
5:132074080:GAAT:G	acceptor_gain	1.0000
5:132074123:G:C	donor_loss	1.0000
5:132074123:G:GG	donor_gain	1.0000
5:132074124:T:A	donor_loss	1.0000
5:132074808:A:AG	acceptor_gain	1.0000
5:132074808:AG:A	acceptor_gain	1.0000
5:132074808:AGG:A	acceptor_loss	1.0000
5:132074809:G:GA	acceptor_gain	1.0000
5:132074809:GG:G	acceptor_gain	1.0000
5:132074809:GGA:G	acceptor_gain	1.0000
5:132074931:CCCCG:C	donor_gain	1.0000
5:132074932:CCCG:C	donor_gain	1.0000
5:132074932:CCCGG:C	donor_loss	1.0000
5:132074933:CCG:C	donor_gain	1.0000
5:132074934:CGG:C	donor_loss	1.0000
5:132074935:GGTG:G	donor_loss	1.0000
5:132074936:G:GG	donor_gain	1.0000
5:132074936:GTG:G	donor_loss	1.0000
5:132074937:T:A	donor_loss	1.0000
5:132075740:TAAAG:T	acceptor_loss	1.0000

AlphaMissense

944 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:132075805:T:C	F130L	0.951
5:132075807:T:A	F130L	0.951
5:132075807:T:G	F130L	0.951
5:132075797:T:C	L127P	0.950
5:132074889:T:C	L94S	0.937
5:132073938:G:C	A39P	0.925
5:132075789:A:C	K124N	0.923
5:132075789:A:T	K124N	0.923
5:132075784:T:C	F123L	0.922
5:132075786:C:A	F123L	0.922
5:132075786:C:G	F123L	0.922
5:132074832:G:C	R75P	0.917
5:132075806:T:G	F130C	0.917
5:132074821:C:G	C71W	0.909
5:132074819:T:C	C71R	0.906
5:132074923:C:G	C105W	0.905
5:132075806:T:C	F130S	0.902
5:132074921:T:C	C105R	0.896
5:132074819:T:A	C71S	0.893
5:132074820:G:C	C71S	0.893
5:132073827:T:A	W2R	0.889
5:132073827:T:C	W2R	0.889
5:132075785:T:C	F123S	0.884
5:132074111:T:C	F64L	0.879
5:132074113:T:A	F64L	0.879
5:132074113:T:G	F64L	0.879
5:132075809:T:C	L131P	0.879
5:132074921:T:A	C105S	0.877
5:132074922:G:C	C105S	0.877
5:132075834:G:C	W139C	0.874

dbSNP variants (sampled 300 via entrez): RS1000494540 (5:132072999 G>A), RS1002165189 (5:132074623 G>A,T), RS1002685758 (5:132072358 G>C,T), RS1002820215 (5:132072075 C>G), RS1003808899 (5:132073466 C>T), RS1004000822 (5:132074303 C>T), RS1005681615 (5:132076592 C>T), RS1006231606 (5:132076349 C>T), RS10072253 (5:132074075 C>T), RS1007293510 (5:132073179 T>A), RS1007993375 (5:132073042 C>A,T), RS1008265525 (5:132074276 C>T), RS1008298256 (5:132074537 C>A,T), RS1008928846 (5:132071832 G>A), RS1011208962 (5:132072099 A>T)

Disease associations

OMIM: gene MIM:138960 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001454_6	Rheumatoid arthritis	3.000000e-10
GCST001725_83	Inflammatory bowel disease	1.000000e-52
GCST002318_39	Rheumatoid arthritis	8.000000e-07
GCST002318_72	Rheumatoid arthritis	6.000000e-06
GCST004131_32	Inflammatory bowel disease	4.000000e-27
GCST004132_10	Crohn’s disease	6.000000e-36
GCST004133_36	Ulcerative colitis	2.000000e-06
GCST006959_100	Rheumatoid arthritis	8.000000e-06
GCST006959_123	Rheumatoid arthritis	1.000000e-06
GCST010701_41	Cortical surface area (MOSTest)	1.000000e-20
GCST010702_96	Subcortical volume (MOSTest)	2.000000e-08
GCST010703_160	Brain morphology (MOSTest)	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3712955 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

5 measured of 7 human assays (7 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CC-220 (Compound 6)	IC50	28 nM	US-9694015: Methods for the treatment of locally advanced breast cancer
3-(4-((4-(morpholinomethyl)benzyl)-oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione	IC50	190 nM	US-9694015: Methods for the treatment of locally advanced breast cancer
19171-19-8	IC50	230 nM	US-9694015: Methods for the treatment of locally advanced breast cancer
3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione	IC50	300 nM	US-9694015: Methods for the treatment of locally advanced breast cancer
(R)-3-(4-((4-(morpholinomethyl)benzyl)-oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione	IC50	450 nM	US-9694015: Methods for the treatment of locally advanced breast cancer

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	affects cotreatment, increases reaction, increases phosphorylation, decreases expression, decreases reaction (+5 more)	22
Particulate Matter	increases reaction, decreases expression, decreases reaction, increases secretion, increases expression (+2 more)	19
Dexamethasone	increases secretion, increases expression, affects binding, increases reaction, decreases expression (+3 more)	10
Silicon Dioxide	increases expression	8
sodium arsenite	affects cotreatment, decreases reaction, increases expression, increases secretion	7
Vehicle Emissions	decreases reaction, increases secretion, increases expression, increases reaction, decreases expression	7
Tobacco Smoke Pollution	increases secretion, decreases expression, decreases secretion, increases expression	7
Resveratrol	decreases reaction, increases expression, increases secretion	6
Beclomethasone	affects cotreatment, decreases secretion, decreases reaction, increases expression, increases secretion (+1 more)	6
titanium dioxide	affects binding, increases secretion, increases expression	5
Smoke	decreases expression, increases abundance, increases expression, decreases reaction, increases secretion	5
(+)-JQ1 compound	decreases reaction, increases expression, decreases expression	4
Acetylcysteine	decreases reaction, increases expression, increases secretion	4
Air Pollutants	increases expression, decreases reaction, decreases expression, affects cotreatment, increases abundance (+1 more)	4
Benzo(a)pyrene	decreases methylation, increases expression, affects methylation	4
Tetradecanoylphorbol Acetate	decreases reaction, affects expression, affects cotreatment, increases secretion, increases expression	4
Zymosan	increases reaction, increases secretion, increases expression	4
Budesonide	decreases reaction, increases secretion, decreases secretion, increases activity	4
Soot	increases expression, increases secretion	4
RTKI cpd	decreases reaction, increases secretion, affects binding, increases expression	3
Fluticasone	decreases secretion, increases activity, decreases reaction, increases secretion	3
Bleomycin	decreases reaction, increases expression	3
Histamine	increases reaction, increases expression, increases secretion	3
Peptidoglycan	increases secretion, increases expression, increases reaction	3
Quercetin	decreases reaction, increases secretion, decreases expression	3
Theophylline	increases reaction, decreases expression, affects cotreatment, decreases reaction, increases secretion (+1 more)	3
Ionomycin	affects cotreatment, decreases expression, increases expression, increases secretion, affects reaction (+1 more)	3
Asbestos, Crocidolite	increases expression	3
Cadmium Chloride	decreases reaction, increases expression, increases secretion	3
Antigens, Dermatophagoides	increases secretion, decreases reaction, increases expression	3

Cellosaurus cell lines

11 cell lines: 9 cancer cell line, 1 transformed cell line, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_4U13	SV-BR-1-GM	Cancer cell line	Female
CVCL_A8HT	K562/GM-CSF	Cancer cell line	Female
CVCL_B2VA	Abcam HEK293T CSF2 KO	Transformed cell line	Female
CVCL_B6KZ	Mel PG	Cancer cell line	Sex unspecified
CVCL_B6L1	Mel 26G	Cancer cell line	Sex unspecified
CVCL_B6L2	Mel IG	Cancer cell line	Female
CVCL_B6L4	Mel 31G	Cancer cell line	Sex unspecified
CVCL_B6LC	Mel ILG	Cancer cell line	Sex unspecified
CVCL_B6LQ	Mel KG	Cancer cell line	Sex unspecified
CVCL_C3LY	MVX-2	Telomerase immortalized cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.